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Sample records for ventilator-dependent amyotrophic lateral

  1. Unexpected death of a ventilator-dependent amyotrophic lateral sclerosis patient

    Directory of Open Access Journals (Sweden)

    M. di Paolo

    2013-07-01

    Full Text Available Background: Amyotrophic lateral sclerosis (ALS is a fatal, progressive, neurodegenerative disease and most patients affected die of respiratory compromise and/or pneumonia within 2–3 years of diagnosis. As ALS progresses, ventilator assistance is required. In the end stages of the disease, patients suffer from respiratory failure and may become ventilator-dependent. Deaths due to malfunction of mechanical ventilators are reported but there are very few forensic autopsy records. We report the case of a 69-year-old ALS female ventilator-dependent, trachostomised patient who was found dead by her husband, with the ventilator in “stand-by” mode. Method: A forensic autopsy was performed. Samples of internal organs were taken for histological and toxicological examination. The ventilator internal memory was also analysed and tested in order to find possible malfunction. Results: Gross examination did not reveal any sign of trauma but showed brain and lung congestion. Pulmonary histological examination revealed thickening of peribronchial interstitial space, alveolar over-distension, break of inter-alveolar walls and diffuse alveolar haemorrhages. Focal microhemorrhages were also detected in other organs. Analysis of the ventilator internal memory showed that during the night of death, there had been several voltage drops. Specific tests revealed malfunction of the internal battery which was unable to provide the necessary voltage, as a consequence the ventilator switched off, stopping ventilation. Battery malfunction reduced the volume of the ventilator alarm, which was not heard by the caregiver. Conclusion: Histological pattern, with acute pulmonary emphysema and focal polivisceral haemorrhages, is strongly suggestive of a death due to “acute” asphyxia. The authors also discuss the need for strict supervision and follow up of these ventilatory dependent patients and their devices. Resumo: Introdução: A Esclerose

  2. ALS (Amyotrophic Lateral Sclerosis)

    Science.gov (United States)

    ... Disorders » Patient & Caregiver Education » Fact Sheets Amyotrophic Lateral Sclerosis (ALS) Fact Sheet What is amyotrophic lateral sclerosis? ... I get more information? What is amyotrophic lateral sclerosis? Amyotrophic lateral sclerosis (ALS) is a group of ...

  3. Amyotrophic Lateral Sclerosis (ALS)

    Science.gov (United States)

    ... Division of Neuroscience Director, NIH BRAIN Initiative® Health Scientist Administrator Channels Synapses Circuits Cluster Scientific Director, Division of Intramural Research Featured Director's Message menu search Enter Search Term Submit Search Amyotrophic Lateral Sclerosis ( ...

  4. Genetics Home Reference: amyotrophic lateral sclerosis

    Science.gov (United States)

    ... Home Health Conditions Amyotrophic lateral sclerosis Amyotrophic lateral sclerosis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Amyotrophic lateral sclerosis (ALS) is a progressive disease that affects motor ...

  5. What causes amyotrophic lateral sclerosis?

    Science.gov (United States)

    Martin, Sarah; Al Khleifat, Ahmad; Al-Chalabi, Ammar

    2017-01-01

    Amyotrophic lateral sclerosis is a neurodegenerative disease predominantly affecting upper and lower motor neurons, resulting in progressive paralysis and death from respiratory failure within 2 to 3 years. The peak age of onset is 55 to 70 years, with a male predominance. The causes of amyotrophic lateral sclerosis are only partly known, but they include some environmental risk factors as well as several genes that have been identified as harbouring disease-associated variation. Here we review the nature, epidemiology, genetic associations, and environmental exposures associated with amyotrophic lateral sclerosis. PMID:28408982

  6. Optineurin and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Maruyama, Hirofumi; Kawakami, Hideshi

    2013-07-01

    Amyotrophic lateral sclerosis is a devastating disease, and thus it is important to identify the causative gene and resolve the mechanism of the disease. We identified optineurin as a causative gene for amyotrophic lateral sclerosis. We found three types of mutations: a homozygous deletion of exon 5, a homozygous Q398X nonsense mutation and a heterozygous E478G missense mutation within its ubiquitin-binding domain. Optineurin negatively regulates the tumor necrosis factor-α-induced activation of nuclear factor kappa B. Nonsense and missense mutations abolished this function. Mutations related to amyotrophic lateral sclerosis also negated the inhibition of interferon regulatory factor-3. The missense mutation showed a cyotoplasmic distribution different from that of the wild type. There are no specific clinical symptoms related to optineurin. However, severe brain atrophy was detected in patients with homozygous deletion. Neuropathologically, an E478G patient showed transactive response DNA-binding protein of 43 kDa-positive neuronal intracytoplasmic inclusions in the spinal and medullary motor neurons. Furthermore, Golgi fragmentation was identified in 73% of this patient's anterior horn cells. In addition, optineurin is colocalized with fused in sarcoma in the basophilic inclusions of amyotrophic lateral sclerosis with fused in sarcoma mutations, and in basophilic inclusion body disease. These findings strongly suggest that optineurin is involved in the pathogenesis of amyotrophic lateral sclerosis. © 2012 Japan Geriatrics Society.

  7. Amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Leigh P Nigel

    2009-02-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year and prevalence (average 5.2 per100,000 are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio~1.5:1. Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1–2 years. Paralysis is progressive and leads to death due to respiratory failure within 2–3 years for bulbar onset cases and 3–5 years for limb onset ALS cases. Most ALS cases are sporadic but 5–10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2–5% have mutations of the TARDBP (TDP-43 gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43

  8. Acoustic reflex patterns in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Canale, Andrea; Albera, Roberto; Lacilla, Michelangelo; Canosa, Antonio; Albera, Andrea; Sacco, Francesca; Chiò, Adriano; Calvo, Andrea

    2017-02-01

    The aim of the study is to investigate acoustic reflex testing in amyotrophic lateral sclerosis patients. Amplitude, latency, and rise time of stapedial reflex were recorded for 500 and 1000 Hz contralateral stimulus. Statistical analysis was performed by the Wilcoxon test and the level of significance was set at 5 %. Fifty-one amyotrophic lateral sclerosis patients and ten sex- and age-matched control subjects were studied. Patients were further divided in two groups: amyotrophic lateral sclerosis-bulbar (38 cases, with bulbar signs at evaluation) and amyotrophic lateral sclerosis-spinal (13 cases, without bulbar signs at evaluation). Stapedial reflex was present in all patients. There was a statistically significant difference in the mean amplitude, latency, and rise time between the amyotrophic lateral sclerosis patients as compared with the controls. Amplitude was lower in both the amyotrophic lateral sclerosis-bulbar and the amyotrophic lateral sclerosis-spinal patients than in the controls (p amyotrophic lateral sclerosis cases with bulbar signs and, moreover, suggesting a possible subclinical involvement of the stapedial motor neuron even in amyotrophic lateral sclerosis-spinal patients. Amplitude and rise time seem to be good sensitive parameters for investigating subclinical bulbar involvement.

  9. Clinical Neurogenetics: Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Harms, Matthew B.; Baloh, Robert H.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, about which our understanding is expanding rapidly as its genetic causes are uncovered. The pace of new gene discovery over the last 5 years has accelerated, providing new insights into the pathogenesis of disease and highlighting biological pathways for target for therapeutic development. This article reviews our current understanding of the heritability of ALS, provides an overview of each of the major ALS genes, highlighting their phenotypic characteristics and frequencies as a guide for clinicians evaluating patients with ALS. PMID:24176417

  10. Amyotrophic Lateral Sclerosis Regional Variants (Brachial Amyotrophic Diplegia, Leg Amyotrophic Diplegia, and Isolated Bulbar Amyotrophic Lateral Sclerosis).

    Science.gov (United States)

    Jawdat, Omar; Statland, Jeffrey M; Barohn, Richard J; Katz, Jonathan S; Dimachkie, Mazen M

    2015-11-01

    Amyotrophic lateral sclerosis (ALS), a rapidly progressive, invariably fatal disease, involves mixed upper and lower motor neurons in different spinal cord regions. Patients with bulbar onset progress more rapidly than patients with limb onset or with a lower motor neuron presentation. Recent descriptions of regional variants suggest some patients have ALS isolated to a single spinal region for many years, including brachial amyotrophic diplegia, leg amyotrophic diplegia, and isolated bulbar palsy. Clearer definitions of regional variants will have implications for prognosis, understanding the pathophysiology of ALS, identifying genetic factors related to slower disease progression, and future planning of clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. [Genetics of amyotrophic lateral sclerosis].

    Science.gov (United States)

    Corcia, Philippe; Blasco, Hélène; Camu, William

    2014-05-01

    Although the pathophysiology of amyotrophic lateral sclerosis remains currently unknown, involvement of genetic factors is worldwide accepted as a key clue in the motor neuron death. Since 1993 and the discovery of mutation in the SOD1 gene, number of genes linked to or promoting ALS had always growing. Among them, only four (SOD1, TARDBP, FUS and C9ORF72 genes) are unanimously recognized as convincing causative genetic factors for more than 60% of familial and probably 10% of sporadic ALS cases. Geographic origin of the studied populations tends to become one of the major items in the gene-ALS relationship: this was extremely stressed for C9ORF72. Concerning susceptibility genes factors, an increase of the risk of ALS is clearly shown for SMN1 and ATXN2 genes and accepted for some VEGF haplotypes. Finally, some modulating effects might also exist as underline for the relationships between ApoE and ALS that differ between European and North American studies. In inherited ALS, The European Federation of Neurological Societies (EFNS) edited rules that gave a legal frame to situations for which research of mutations were justified. Progress in the field of genetic raises major questions concerning the relevance of genetic studies from asymptomatic relatives. This first implies that the mutation identified in the proband case is perfectly characterized as a pathogenic mutation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  12. Amyotrophic Lateral Sclerosis: A Historical Perspective.

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    Katz, Jonathan S; Dimachkie, Mazen M; Barohn, Richard J

    2015-11-01

    This article looks back in time to see where the foundational basis for the understanding of amyotrophic lateral sclerosis originated. This foundation was created primarily in France by Jean-Martin Charcot and his fellow countrymen and disciples, along with key contributions from early clinicians in England and Germany. The early work on amyotrophic lateral sclerosis provides a useful foundation for today's clinicians with respect to tying together genetic and biologic aspects of the disorder that have been discovered over the past few decades. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Muscle ultrasonography to predict survival in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Arts, I.M.P.; Overeem, S.; Pillen, S.; Schelhaas, H.J.; Zwarts, M.J.

    2011-01-01

    The authors assessed the prognostic value of muscle ultrasonography in 31 patients with amyotrophic lateral sclerosis (ALS) and compared it with accepted prognostic variables like functional capacity (measured with the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS)) and muscle

  14. Traces of disease in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Verstraete, E.

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive disease of the motor system involving both upper motor neurons in the brain and lower motor neurons in the spinal cord. Patients suffer from progressive wasting and weakness of limb, bulbar and respiratory muscles. Onset and disease course in ALS

  15. Clinical psychology and amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Francesco Pagnini

    2010-07-01

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal and progressive disease, characterized by progressive muscles weakness, with consequent loss of physical capacities. Psychologists can play an important role in ALS care, by providing clinical activities in every step of the disease, including support and counseling activities directed to patients, their caregivers and to physicians.

  16. Towards gene therapy in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wisman, Liselijn Agatha Barendina

    2004-01-01

    Amyotrophic lateral sclerosis (ALS) is a paralytic neurodegenerative disorder, characterised by a specific loss of motoneurons. Although the exact pathogenesis is largely enigmatic, it is known that glutamate excitotoxicity plays an important role in motoneuron cell death. Glutamate is one of the

  17. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-01-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...

  18. Evaluation and management of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Valadi, Nojan

    2015-06-01

    Motor neuron diseases can cause progressive impairment of voluntary muscles of movement, respiration, speech, and swallowing. This review discusses the most common motor neuron disease, amyotrophic lateral sclerosis (ALS). It reviews the evaluation, diagnosis, and management of ALS, and its epidemiology, pathophysiology, and management. A coordinated approach by the primary care physician and neurologist is necessary with a focus on treatment options, durable medical equipment needs, and end-of-life discussions. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Psychiatric disorders prior to amyotrophic lateral sclerosis

    OpenAIRE

    Turner, M.; Goldacre, R; Talbot, K; Goldacre, MJ

    2016-01-01

    It is recognized that neuropsychiatric conditions are overrepresented in amyotrophic lateral sclerosis (ALS) patient kindreds and psychiatric symptoms may precede the onset of motor symptoms. Using a hospital record linkage database, hospitalization with a diagnosis of schizophrenia, bipolar disorder, depression, or anxiety was significantly associated with a first diagnosis of ALS within the following year. This is likely to specifically reflect the clinicopathological overlap of ALS with fr...

  20. The management of amyotrophic lateral sclerosis.

    LENUS (Irish Health Repository)

    Phukan, Julie

    2009-02-01

    The terms amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) refer to a condition characterized by motor system degeneration with relative preservation of other pathways. Although there have been advances in symptomatic treatment, ALS remains an incurable condition. Advances in ALS management prolong survival but simultaneously raise challenging ethical dilemmas for physicians, patients and their families. Here, we review current practice in the management of ALS including pharmacological treatment, nutritional management, respiratory care, and evolving strategies in the management of cognitive impairment.

  1. Stem cell therapy for amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Zhijuan Mao

    2015-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder characterized by the loss of motor neurons. Currently, no effective therapy is available to treat ALS, except for Riluzole, which has only limited clinical benefits. Stem-cell-based therapy has been intensively and extensively studied as a potential novel treatment strategy for ALS and has been shown to be effective, at least to some extent. In this article, we will review the current state of research on the use of stem cell therapy in the treatment of ALS and discuss the most promising stem cells for the treatment of ALS.

  2. Quantifying Disease Progression in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Simon, Neil G; Turner, Martin R; Vucic, Steve; Al-Chalabi, Ammar; Shefner, Jeremy; Lomen-Hoerth, Catherine; Kiernan, Matthew C

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) exhibits characteristic variability of onset and rate of disease progression, with inherent clinical heterogeneity making disease quantitation difficult. Recent advances in understanding pathogenic mechanisms linked to the development of ALS impose an increasing need to develop strategies to predict and more objectively measure disease progression. This review explores phenotypic and genetic determinants of disease progression in ALS, and examines established and evolving biomarkers that may contribute to robust measurement in longitudinal clinical studies. With targeted neuroprotective strategies on the horizon, developing efficiencies in clinical trial design may facilitate timely entry of novel treatments into the clinic. PMID:25223628

  3. Treatment of sialorrhea in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tysnes, O-B

    2008-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating progressive disease of all voluntary muscles. Bulbar symptoms with reduced ability to swallow occur frequently and may also be an early symptom. For some patients drooling may represent a severe social problem. To review the literature on treatment of sialorrhea in ALS and describe possible treatments. PubMed was searched combining the words amyotrophic or ALS with sialorrhea or drooling. Publications more recent than 2000 were selected. A total of 31 publications were found. Of these, 22 are from 2000 or later. Thirteen of the 22 most recent publications are original papers whereas 9 are review articles. Of the original articles, four describe treatment of sialorrhea with radiotherapy, five describe effects of botolinum toxin injections into the salivary grands and two describe serious side-effects of botolinum toxin injections for sialorrhea in ALS. The remaining original articles are case descriptions or practice surveys. The treatment of sialorrhea in ALS is discussed in the view of current knowledge.

  4. Amyotrophic lateral sclerosis: one or multiple causes?

    Directory of Open Access Journals (Sweden)

    Aline Furtado Bastos

    2011-04-01

    Full Text Available The Amyotrophic lateral sclerosis (ALS is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1, certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients.

  5. Amyotrophic lateral sclerosis: one or multiple causes?

    Science.gov (United States)

    Bastos, Aline Furtado; Orsini, Marco; Machado, Dionis; Mello, Mariana Pimentel; Nader, Sergio; Silva, Júlio Guilherme; da Silva Catharino, Antonio M.; de Freitas, Marcos R.G.; Pereira, Alessandra; Pessoa, Luciane Lacerda; Sztajnbok, Flavio R.; Leite, Marco Araújo; Nascimento, Osvaldo J.M.; Bastos, Victor Hugo

    2011-01-01

    The Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease in the adulthood, and it is characterized by rapid and progressive compromise of the upper and lower motor neurons. The majority of the cases of ALS are classified as sporadic and, until now, a specific cause for these cases still is unknown. To present the different hypotheses on the etiology of ALS. It was carried out a search in the databases: Bireme, Scielo and Pubmed, in the period of 1987 to 2011, using the following keywords: Amyotrophic lateral sclerosis, motor neuron disease, etiology, causes and epidemiology and its similar in Portuguese and Spanish. It did not have consensus as regards the etiology of ALS. Researches demonstrates evidences as regards intoxication by heavy metals, environmental and occupational causes, genetic mutations (superoxide dismutase 1), certain viral infections and the accomplishment of vigorous physical activity for the development of the disease. There is still no consensus regarding the involved factors in the etiology of ALS. In this way, new research about these etiologies are necessary, for a better approach of the patients, promoting preventive programs for the disease and improving the quality of life of the patients. PMID:21785676

  6. 78 FR 72573 - Specially Adapted Housing Eligibility for Amyotrophic Lateral Sclerosis Beneficiaries

    Science.gov (United States)

    2013-12-03

    ... veterans and active servicemembers with service- connected amyotrophic lateral sclerosis (ALS) rated... Amyotrophic Lateral Sclerosis Beneficiaries.'' Copies of comments received will be available for public... occasional locomotion by other methods may be possible. (d) Amyotrophic lateral sclerosis. VA considers Sec...

  7. High-fat and ketogenic diets in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Paganoni, Sabrina; Wills, Anne-Marie

    2013-08-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease. Epidemiologic data suggest that malnutrition is a common feature in amyotrophic lateral sclerosis and being overweight or obese confers a survival advantage in this patient population. In amyotrophic lateral sclerosis mouse models, a high-fat diet has been shown to lead to weight gain and prolonged survival. However, little research has been conducted to test whether nutritional interventions might ameliorate the disease course in humans. Here we review the currently available evidence supporting the potential role of dietary interventions as a therapeutic tool for amyotrophic lateral sclerosis. Ultimately, determining whether a high-fat or ketogenic diet could be beneficial in amyotrophic lateral sclerosis will require large randomized, placebo-controlled clinical trials.

  8. Amyotrophic lateral sclerosis associated with pregnancy.

    LENUS (Irish Health Repository)

    Tyagi, A

    2012-02-03

    Amyotrophic lateral sclerosis (ALS) is the most common, progressive motor neurone disease but is rare in the obstetric population. Only 4 cases have been described in the English literature since 1975. We describe a 29 year old woman who presented with ataxia, lower limb weakness and dysarthria 4 weeks after the birth of her first child. The symptoms had onset during the pregnancy but had not been considered remarkable. There were clinical features of upper and lower motor neurone involvement without any sensory loss. MRI of brain and spine was normal. CSF analysis was negative. EMG studies confirmed the presence of widespread anterior horn cell dysfunction compatible with ALS. The patient was commenced on Riluzole and has progressed clinically, at 12 months post diagnosis.

  9. [Amyotrophic lateral sclerosis and respiratory insufficiency].

    Science.gov (United States)

    Siirala, Waltteri; Korpela, Jaana; Vuori, Arno; Saaresranta, Tarja; Olkkola, Klaus T; Aantaa, Riku

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a disease causing degeneration of motor neurons, without any curative treatment. The most common cause of death is respiratory arrest due to atrophy of the respiratory musculature. ALS-associated respiratory insufficiency differs in mechanism from the more common causes of dyspnea, such as diseases of pulmonary or cardiac origin. Recognizing the respiratory insufficiency can be challenging for a clinician. It should be possible to predict the development of respiratory insufficiency in order to avoid leaving the treatment decisions concerning respiratory insufficiency to emergency services. Noninvasive ventilatory support can be used to alleviate the patient's dyspnea. It is actually recommended as the first-line treatment of ALS-associated respiratory insufficiency.

  10. Amyotrophic lateral sclerosis: a hormonal condition?

    Science.gov (United States)

    Blasco, Helene; Guennoc, Anne-Marie; Veyrat-Durebex, Charlotte; Gordon, Paul H; Andres, Christian R; Camu, William; Corcia, Philippe

    2012-10-01

    Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disorder in adults. This fatal condition, due to degeneration of upper and lower motor neurons in spinal and bulbar myotomes, leads to death from respiratory failure after median disease duration of 36 months. ALS is sporadic in more than 90% of cases and familial in the remaining cases. Most studies show male predominance with a gender ratio of 3:2, but gender differences are age related. The phenotype of ALS is also different in males and females with a predominance of limb onset in males and bulbar onset in females. While age and site of onset impact survival rate, and are both related to gender, gender by itself has not clearly been shown to have an effect on survival. Given this complex relationship between gender and ALS, we developed a hypothesis about hormone involvement in ALS aetiology by suggesting protective effect of oestrogens and adverse effect of androgens.

  11. Magnetic Resonance Imaging in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Katja Kollewe

    2012-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a rapidly progressing neurodegenerative disorder which is incurable to date. As there are many ongoing studies with therapeutic candidates, it is of major interest to develop biomarkers not only to facilitate early diagnosis but also as a monitoring tool to predict disease progression and to enable correct randomization of patients in clinical trials. Magnetic resonance imaging (MRI has made substantial progress over the last three decades and is a practical, noninvasive method to gain insights into the pathology of the disease. Disease-specific MRI changes therefore represent potential biomarkers for ALS. In this paper we give an overview of structural and functional MRI alterations in ALS with the focus on task-free resting-state investigations to detect cortical network failures.

  12. Neuroimaging Endpoints in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Menke, Ricarda A L; Agosta, Federica; Grosskreutz, Julian; Filippi, Massimo; Turner, Martin R

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative, clinically heterogeneous syndrome pathologically overlapping with frontotemporal dementia. To date, therapeutic trials in animal models have not been able to predict treatment response in humans, and the revised ALS Functional Rating Scale, which is based on coarse disability measures, remains the gold-standard measure of disease progression. Advances in neuroimaging have enabled mapping of functional, structural, and molecular aspects of ALS pathology, and these objective measures may be uniquely sensitive to the detection of propagation of pathology in vivo. Abnormalities are detectable before clinical symptoms develop, offering the potential for neuroprotective intervention in familial cases. Although promising neuroimaging biomarker candidates for diagnosis, prognosis, and disease progression have emerged, these have been from the study of necessarily select patient cohorts identified in specialized referral centers. Further multicenter research is now needed to establish their validity as therapeutic outcome measures.

  13. Neuromuscular Junction Dismantling in Amyotrophic Lateral Sclerosis

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    Valentina Cappello

    2017-10-01

    Full Text Available Neuromuscular junction assembly and plasticity during embryonic, postnatal, and adult life are tightly regulated by the continuous cross-talk among motor nerve endings, muscle fibers, and glial cells. Altered communications among these components is thought to be responsible for the physiological age-related changes at this synapse and possibly for its destruction in pathological states. Neuromuscular junction dismantling plays a crucial role in the onset of Amyotrophic Lateral Sclerosis (ALS. ALS is characterized by the degeneration and death of motor neurons leading to skeletal muscle denervation, atrophy and, most often, death of the patient within five years from diagnosis. ALS is a non-cell autonomous disease as, besides motor neuron degeneration, glial cells, and possibly muscle fibers, play a role in its onset and progression. Here, we will review the recent literature regarding the mechanisms leading to neuromuscular junction disassembly and muscle denervation focusing on the role of the three players of this peripheral tripartite synapse.

  14. Respiratory apraxia in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pinto, Susana; Pinto, Anabela; Atalaia, António; Peralta, Rita; de Carvalho, Mamede

    2007-06-01

    Respiratory dysfunction is a critical problem in amyotrophic lateral sclerosis (ALS). We report a patient with ALS who had respiratory apraxia. A 74-year-old female presented with progressive dysarthria and dysphagia. Clinical signs and evidence of widespread denervation on electromyography (EMG) confirmed the diagnosis of ALS. She had no signs of dementia. Irregular volitional inspiratory movements on verbal command were noticed, in contrast with rhythmic automatic inspiration - respiratory apraxia. Limb and buco-facial movements showed no signs of apraxia. EMG of respiratory muscles was normal, apart from irregular phasic activity of the diaphragm on volitional inspiration; this was confirmed by recording respiratory movements with a percutaneous sensor transducer. Sleep study was normal. She deteriorated rapidly; nonetheless, no clinical sign of dementia or other apraxic findings were observed. ALS, particularly when of bulbar onset, can cause respiratory apraxia and EMG of the respiratory muscles can be useful to detect this condition.

  15. A comprehensive review of amyotrophic lateral sclerosis

    Science.gov (United States)

    Zarei, Sara; Carr, Karen; Reiley, Luz; Diaz, Kelvin; Guerra, Orleiquis; Altamirano, Pablo Fernandez; Pagani, Wilfredo; Lodin, Daud; Orozco, Gloria; Chinea, Angel

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a late-onset fatal neurodegenerative disease affecting motor neurons with an incidence of about 1/100,000. Most ALS cases are sporadic, but 5–10% of the cases are familial ALS. Both sporadic and familial ALS (FALS) are associated with degeneration of cortical and spinal motor neurons. The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, genetic factors, symptoms, diagnostic, treatment, and even the available supplement and management of ALS. This will provide the reader with an advantage of receiving a broad range of information about the disease. PMID:26629397

  16. Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

    Science.gov (United States)

    Pandya, Rachna S.; Zhu, Haining; Li, Wei; Bowser, Robert; Friedlander, Robert M.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression. PMID:23864030

  17. Amyotrophic lateral sclerosis: update and new developments

    Science.gov (United States)

    Pratt, Ashley J; Getzoff, Elizabeth D; Perry, J Jefferson P

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease. It is typically characterized by adult-onset degeneration of the upper and lower motor neurons, and is usually fatal within a few years of onset. A subset of ALS patients has an inherited form of the disease, and a few of the known mutant genes identified in familial cases have also been found in sporadic forms of ALS. Precisely how the diverse ALS-linked gene products dictate the course of the disease, resulting in compromised voluntary muscular ability, is not entirely known. This review addresses the major advances that are being made in our understanding of the molecular mechanisms giving rise to the disease, which may eventually translate into new treatment options. PMID:23019386

  18. Motoneuron firing in amyotrophic lateral sclerosis (ALS

    Directory of Open Access Journals (Sweden)

    Mamede eDe Carvalho

    2014-09-01

    Full Text Available Amyotrophic lateral sclerosis is an inexorably progressive neurodegenerative disorder involving the classical motor system and the frontal effector brain, causing muscular weakness and atrophy, with variable upper motor neuron signs and often an associated fronto-temporal dementia. The physiological disturbance consequent on the motor system degeneration is beginning to be well understood. In this review we describe aspects of the motor cortical, neuronal and lower motor neuron dysfunction. We show how studies of the changes in the pattern of motor unit firing help delineate the underlying pathophysiological disturbance as the disease progresses. Such studies are beginning to illuminate the underlying disordered pathophysiological processes in the disease, and are important in designing new approaches to therapy and especially for clinical trials.

  19. What causes amyotrophic lateral sclerosis? [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Sarah Martin

    2017-03-01

    Full Text Available Amyotrophic lateral sclerosis is a neurodegenerative disease predominantly affecting upper and lower motor neurons, resulting in progressive paralysis and death from respiratory failure within 2 to 3 years. The peak age of onset is 55 to 70 years, with a male predominance. The causes of amyotrophic lateral sclerosis are only partly known, but they include some environmental risk factors as well as several genes that have been identified as harbouring disease-associated variation. Here we review the nature, epidemiology, genetic associations, and environmental exposures associated with amyotrophic lateral sclerosis.

  20. Radiotherapy reduces sialorrhea in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Neppelberg, E; Haugen, D F; Thorsen, L; Tysnes, O-B

    2007-12-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Sialorrhea is a frequent problem in ALS patients with bulbar symptoms, because of progressive weakness of oral, lingual and pharyngeal muscles. This prospective study aimed to investigate the putative effect of palliative single-dose radiotherapy on problematic sialorrhea in patients with ALS. Twenty patients with ALS and problematic drooling were included; 14 were given radiotherapy with a single fraction of 7.5 Grey (Gy). Five patients were treated with botulinum toxin A (BTX-A) injections (20 U) into the parotid glands; two of these were later given radiotherapy. Symptom assessment, clinical examination and measurements of salivary flow (ml/min) were performed before and after treatment (1-2 weeks, 3 months). Salivary secretion was significantly reduced after radiation treatment, with a mean reduction of 60% (1 week) and 51% (2 weeks). Three months post-treatment, 21% reduction of the salivary secretion was observed compared with salivation before treatment. Mean salivary flow was not reduced after BTX-A treatment in five patients. No serious side-effects were observed with either of the two treatment modalities. Single-dose radiotherapy (7.5 Gy) significantly reduces sialorrhea and is an effective and safe palliative treatment in patients with ALS.

  1. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

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    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  2. Nutrition management of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Greenwood, Daniel I

    2013-06-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease with high risk of malnutrition. Symptoms of dysphagia, depression, cognitive impairment, difficulty with self-feeding and meal preparation, hypermetabolism, anxiety, respiratory insufficiency, and fatigue with meals increase the risk of malnutrition. Malnutrition negatively affects prognosis and quality of life, making early and frequent nutrition assessment and intervention essential. Implementation of an adequate calorie diet, dietary texture modification, use of adaptive eating utensils, and placement of a feeding tube aid in preventing malnutrition. When nutrition status is compromised by dysphagia and weight loss (5%-10% of usual body weight) or body mass index 50%, a percutaneous endoscopic gastrostomy placement is indicated. When forced vital capacity is respiratory risk. Parenteral nutrition (PN) is indicated only when enteral nutrition (EN) is contraindicated or impossible. This article reviews the background of ALS, nutrition implications and risk of malnutrition, treatment strategies to prevent malnutrition, the role of EN and PN, and feeding tube placement methods according to disease stage.

  3. Selective attention impairment in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Volpato, Chiara; Prats Sedano, Maria Angeles; Silvoni, Stefano; Segato, Nicoletta; Cavinato, Marianna; Merico, Antonio; Piccione, Francesco; Palmieri, Arianna; Birbaumer, Niels

    2016-01-01

    Objective of this study was to evaluate attentional control mechanisms in amyotrophic lateral sclerosis (ALS) using an auditory event-related potentials (ERPs) paradigm. Fifteen mild to moderate ALS patients and 15 healthy controls were administered a brief neuropsychological test battery and an ERPs paradigm assessing selective attention. Four types of auditory stimuli were presented in random order: short standard (200 Hz, 200 ms), long standard (200 Hz, 500 ms), short deviant (1000 Hz, 200 ms) and long deviant (1000 Hz, 500 ms). Participants had to respond to the long deviant stimuli only. During the task the electroencephalogram (EEG) was recorded. The N200, P300 and re-orienting negativity (RON) ERP components were analysed. Compared to controls ALS patients showed reduced amplitudes and delayed latencies of N200, P300 and RON. These results could be attributable to both an alteration in change detection resulting in a reduction of the allocation and re-orientation of attentional resources or a general slowing or reduction of neural processing efficiency in the same system. The ERPs results support the hypothesis that ALS involves extramotor cognitive functions including auditory attentional processing at all processing stages, early (200 ms) and late (300-600 ms). These data prove the usefulness and sensitivity of the auditory ERPs in detection of cognitive functions in ALS patients.

  4. Stem cell treatment in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Mazzini, Letizia; Mareschi, Katia; Ferrero, Ivana; Vassallo, Elena; Oliveri, Giuseppe; Nasuelli, Nicola; Oggioni, Gaia Donata; Testa, Lucia; Fagioli, Franca

    2008-02-15

    Amyotrophic Lateral Sclerosis is a progressive fatal neurodegenerative disease that targets motor neurons. Its origin is unknown but a main role of reactive astrogliosis and microglia activation in the pathogenesis has been recently demonstrated. Surrounding neurons with healthy adjoining cells completely stops motor neuron death in some cases. Hence stem cell transplantation might represent a promising therapeutic strategy. In this study MSCs were isolated from bone marrow of 9 patients with definite ALS. Growth kinetics, immunophenotype, telomere length and karyotype were evaluated during in vitro expansion. No significant differences between donors or patients were observed. The patients received intraspinal injections of autologous MSCs at the thoracic level and monitored for 4 years. No significant acute or late side effects were evidenced. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. Four patients show a significant slowing down of the linear decline of the forced vital capacity and of the ALS-FRS score. Our results seem to demonstrate that MSCs represent a good chance for stem cell cell-based therapy in ALS and that intraspinal injection of MSCs is safe also in the long term. A new phase 1 study is carried out to verify these data in a larger number of patients.

  5. Redox Regulation in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Sonam Parakh

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

  6. Modelling amyotrophic lateral sclerosis: progress and possibilities

    Directory of Open Access Journals (Sweden)

    Philip Van Damme

    2017-05-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder that primarily affects the motor system and presents with progressive muscle weakness. Most patients survive for only 2-5 years after disease onset, often due to failure of the respiratory muscles. ALS is a familial disease in ∼10% of patients, with the remaining 90% developing sporadic ALS. Over the past decade, major advances have been made in our understanding of the genetics and neuropathology of ALS. To date, around 20 genes are associated with ALS, with the most common causes of typical ALS associated with mutations in SOD1, TARDBP, FUS and C9orf72. Advances in our understanding of the genetic basis of ALS have led to the creation of different models of this disease. The molecular pathways that have emerged from these systems are more heterogeneous than previously anticipated, ranging from protein aggregation and defects in multiple key cellular processes in neurons, to dysfunction of surrounding non-neuronal cells. Here, we review the different model systems used to study ALS and discuss how they have contributed to our current knowledge of ALS disease mechanisms. A better understanding of emerging disease pathways, the detrimental effects of the various gene mutations and the causes underlying motor neuron denegation in sporadic ALS will accelerate progress in the development of novel treatments.

  7. Amyotrophic Lateral Sclerosis: New Perpectives and Update

    Science.gov (United States)

    Orsini, Marco; Oliveira, Acary Bulle; Nascimento, Osvaldo J.M.; Reis, Carlos Henrique Melo; Leite, Marco Antonio Araujo; de Souza, Jano Alves; Pupe, Camila; de Souza, Olivia Gameiro; Bastos, Victor Hugo; de Freitas, Marcos R.G.; Teixeira, Silmar; Bruno, Carlos; Davidovich, Eduardo; Smidt, Benny

    2015-01-01

    Amyotrophic lateral sclerosis (ALS), Charcot’s disease or Lou Gehrig’s disease, is a term used to cover the spetrum of syndromes caracterized by progressive degeneration of motor neurons, a paralytic disorder caused by motor neuron degeneration. Currently, there are approximately 25,000 patients with ALS in the USA, with an average age of onset of 55 years. The incidence and prevalence of ALS are 1-2 and 4-6 per 100,000 each year, respectively, with a lifetime ALS risk of 1/600 to 1/1000. It causes progressive and cumulative physical disabilities, and leads to eventual death due to respiratory muscle failure. ALS is diverse in its presentation, course, and progression. We do not yet fully understand the causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. In this chapter, we will discuss the diagnosis, treatment, and how to cope with impaired function and end of life based on of our experience, guidelines, and clinical trials. Nowadays ALS seems to be a more complex disease than it did two decades – or even one decade – ago, but new insights have been plentiful. Clinical trials should be seen more as experiments on pathogenic mechanisms. A medication or combination of medications that targets more than one pathogenic pathway may slow disease progression in an additive or synergistic fashion. PMID:26487927

  8. Redox Regulation in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS. PMID:23533690

  9. Risk factors for amyotrophic lateral sclerosis

    Science.gov (United States)

    Ingre, Caroline; Roos, Per M; Piehl, Fredrik; Kamel, Freya; Fang, Fang

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. It is typically fatal within 2–5 years of symptom onset. The incidence of ALS is largely uniform across most parts of the world, but an increasing ALS incidence during the last decades has been suggested. Although recent genetic studies have substantially improved our understanding of the causes of ALS, especially familial ALS, an important role of non-genetic factors in ALS is recognized and needs further study. In this review, we briefly discuss several major genetic contributors to ALS identified to date, followed by a more focused discussion on the most commonly examined non-genetic risk factors for ALS. We first review factors related to lifestyle choices, including smoking, intake of antioxidants, physical fitness, body mass index, and physical exercise, followed by factors related to occupational and environmental exposures, including electromagnetic fields, metals, pesticides, β-methylamino-L-alanine, and viral infection. Potential links between ALS and other medical conditions, including head trauma, metabolic diseases, cancer, and inflammatory diseases, are also discussed. Finally, we outline several future directions aiming to more efficiently examine the role of non-genetic risk factors in ALS. PMID:25709501

  10. Controversies and priorities in amyotrophic lateral sclerosis

    Science.gov (United States)

    Turner, Martin R; Hardiman, Orla; Benatar, Michael; Brooks, Benjamin R; Chio, Adriano; de Carvalho, Mamede; Ince, Paul G; Lin, Cindy; Miller, Robert G; Mitsumoto, Hiroshi; Nicholson, Garth; Ravits, John; Shaw, Pamela J; Swash, Michael; Talbot, Kevin; Traynor, Bryan J; den Berg, Leonard H Van; Veldink, Jan H; Vucic, Steve; Kiernan, Matthew C

    2015-01-01

    Summary Two decades after the discovery that 20% of familial amyotrophic lateral sclerosis (ALS) cases were linked to mutations in the superoxide dismutase-1 (SOD1) gene, a substantial proportion of the remainder of cases of familial ALS have now been traced to an expansion of the intronic hexanucleotide repeat sequence in C9orf72. This breakthrough provides an opportunity to re-evaluate longstanding concepts regarding the cause and natural history of ALS, coming soon after the pathological unification of ALS with frontotemporal dementia through a shared pathological signature of cytoplasmic inclusions of the ubiquitinated protein TDP-43. However, with profound clinical, prognostic, neuropathological, and now genetic heterogeneity, the concept of ALS as one disease appears increasingly untenable. This background calls for the development of a more sophisticated taxonomy, and an appreciation of ALS as the breakdown of a wider network rather than a discrete vulnerable population of specialised motor neurons. Identification of C9orf72 repeat expansions in patients without a family history of ALS challenges the traditional division between familial and sporadic disease. By contrast, the 90% of apparently sporadic cases and incomplete penetrance of several genes linked to familial cases suggest that at least some forms of ALS arise from the interplay of multiple genes, poorly understood developmental, environmental, and age-related factors, as well as stochastic events. PMID:23415570

  11. Early saccades in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Burrell, James R; Carpenter, Roger H S; Hodges, John R; Kiernan, Matthew C

    2013-05-01

    Our objective was to correlate saccadic abnormalities, including early saccades, in patients with amyotrophic lateral sclerosis (ALS) with measures of motor and functional impairment. A portable saccadometer was used to record saccades in ALS patients and control subjects. The linear approach to threshold with ergodic rate model was used to characterize saccades, including sub-populations of early saccades. Patients with established cognitive impairment or frontotemporal dementia were excluded. Limb-onset (Limb ALS) and bulbar-onset (Bulbar ALS) patient groups were compared and saccadic abnormalities were correlated with measures of motor and functional impairment. In total, 48 participants were included in the study; 24 patients with ALS (15 males, 9 females; mean age 57.0 +/- 13.9 years; mean symptom duration 22.4 +/- 16.3 months, of whom 62.5% had Limb ALS) and 24 age-matched controls. Early saccades were increased in both Limb ALS and Bulbar ALS patients, but other saccadic parameters were normal in ALS. Saccadic abnormalities did not correlate with motor or functional impairment. In conclusion, ALS patients show increased early saccades, but exhibit no significant differences across ALS phenotypes.

  12. Spinal Cord Gray Matter Atrophy in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Paquin, M-Ê; El Mendili, M M; Gros, C; Dupont, S M; Cohen-Adad, J; Pradat, P-F

    2018-01-01

    There is an emerging need for biomarkers to better categorize clinical phenotypes and predict progression in amyotrophic lateral sclerosis. This study aimed to quantify cervical spinal gray matter atrophy in amyotrophic lateral sclerosis and investigate its association with clinical disability at baseline and after 1 year. Twenty-nine patients with amyotrophic lateral sclerosis and 22 healthy controls were scanned with 3T MR imaging. Standard functional scale was recorded at the time of MR imaging and after 1 year. MR imaging data were processed automatically to measure the spinal cord, gray matter, and white matter cross-sectional areas. A statistical analysis assessed the difference in cross-sectional areas between patients with amyotrophic lateral sclerosis and controls, correlations between spinal cord and gray matter atrophy to clinical disability at baseline and at 1 year, and prediction of clinical disability at 1 year. Gray matter atrophy was more sensitive to discriminate patients with amyotrophic lateral sclerosis from controls (P = .004) compared with spinal cord atrophy (P = .02). Gray matter and spinal cord cross-sectional areas showed good correlations with clinical scores at baseline (R = 0.56 for gray matter and R = 0.55 for spinal cord; P amyotrophic lateral sclerosis. © 2018 by American Journal of Neuroradiology.

  13. High content analysis in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Rinaldi, Federica; Motti, Dario; Ferraiuolo, Laura; Kaspar, Brian K

    2017-04-01

    Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive loss of motor neurons. Neurons, astrocytes, oligodendrocytes and microglial cells all undergo pathological modifications in the onset and progression of ALS. A number of genes involved in the etiopathology of the disease have been identified, but a complete understanding of the molecular mechanisms of ALS has yet to be determined. Currently, people affected by ALS have a life expectancy of only two to five years from diagnosis. The search for a treatment has been slow and mostly unsuccessful, leaving patients in desperate need of better therapies. Until recently, most pre-clinical studies utilized the available ALS animal models. In the past years, the development of new protocols for isolation of patient cells and differentiation into relevant cell types has provided new tools to model ALS, potentially more relevant to the disease itself as they directly come from patients. The use of stem cells is showing promise to facilitate ALS research by expanding our understanding of the disease and help to identify potential new therapeutic targets and therapies to help patients. Advancements in high content analysis (HCA) have the power to contribute to move ALS research forward by combining automated image acquisition along with digital image analysis. With modern HCA machines it is possible, in a period of just a few hours, to observe changes in morphology and survival of cells, under the stimulation of hundreds, if not thousands of drugs and compounds. In this article, we will summarize the major molecular and cellular hallmarks of ALS, describe the advancements provided by the in vitro models developed in the last few years, and review the studies that have applied HCA to the ALS field to date. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Cortical influences drive amyotrophic lateral sclerosis.

    Science.gov (United States)

    Eisen, Andrew; Braak, Heiko; Del Tredici, Kelly; Lemon, Roger; Ludolph, Albert C; Kiernan, Matthew C

    2017-11-01

    The early motor manifestations of sporadic amyotrophic lateral sclerosis (ALS), while rarely documented, reflect failure of adaptive complex motor skills. The development of these skills correlates with progressive evolution of a direct corticomotoneuronal system that is unique to primates and markedly enhanced in humans. The failure of this system in ALS may translate into the split hand presentation, gait disturbance, split leg syndrome and bulbar symptomatology related to vocalisation and breathing, and possibly diffuse fasciculation, characteristic of ALS. Clinical neurophysiology of the brain employing transcranial magnetic stimulation has convincingly demonstrated a presymptomatic reduction or absence of short interval intracortical inhibition, accompanied by increased intracortical facilitation, indicating cortical hyperexcitability. The hallmark of the TDP-43 pathological signature of sporadic ALS is restricted to cortical areas as well as to subcortical nuclei that are under the direct control of corticofugal projections. This provides anatomical support that the origins of the TDP-43 pathology reside in the cerebral cortex itself, secondarily in corticofugal fibres and the subcortical targets with which they make monosynaptic connections. The latter feature explains the multisystem degeneration that characterises ALS. Consideration of ALS as a primary neurodegenerative disorder of the human brain may incorporate concepts of prion-like spread at synaptic terminals of corticofugal axons. Further, such a concept could explain the recognised widespread imaging abnormalities of the ALS neocortex and the accepted relationship between ALS and frontotemporal dementia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. Rodent Models of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Philips, Thomas; Rothstein, Jeffrey D

    2015-06-01

    Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease affecting upper and lower motor neurons in the central nervous system. Patients with ALS develop extensive muscle wasting and atrophy leading to paralysis and death 3 to 5 years after disease onset. The condition may be familial (fALS 10%) or sporadic ALS (sALS, 90%). The large majority of fALS cases are due to genetic mutations in the Superoxide dismutase 1 gene (SOD1, 15% of fALS) and repeat nucleotide expansions in the gene encoding C9ORF72 (∼ 40% to 50% of fALS and ∼ 10% of sALS). Studies suggest that ALS is mediated through aberrant protein homeostasis (i.e., ER stress and autophagy) and/or changes in RNA processing (as in all non-SOD1-mediated ALS). In all of these cases, animal models suggest that the disorder is mediated non-cell autonomously, i.e., not only motor neurons are involved, but glial cells including microglia, astrocytes, and oligodendrocytes, and other neuronal subpopulations are also implicated in the pathogenesis. Provided in this unit is a review of ALS rodent models, including discussion of their relative advantages and disadvantages. Emphasis is placed on correlating the model phenotype with the human condition and the utility of the model for defining the disease process. Information is also presented on RNA processing studies in ALS research, with particular emphasis on the newest ALS rodent models. Copyright © 2013 John Wiley & Sons, Inc. All rights reserved.

  16. Lockhart Clarke's contribution to the description of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Turner, Martin R; Swash, Michael; Ebers, George C

    2010-11-01

    The definition of the clinicopathological entity of amyotrophic lateral sclerosis evolved over half a century. Although the definitive term amyotrophic lateral sclerosis that acknowledged both upper and lower motor neuron involvement was attributed to Jean-Martin Charcot in 1874, his initial case was published nearly a decade earlier; and it is accepted that, from at least the 1830s, several others (including Charles Bell, François-Amilcar Aran and Jean Cruveilhier) had already recognized a progressive lower motor neuron-only syndrome within a broader, clinically-defined group of disorders, termed progressive muscular atrophy. Although William Gowers first grouped the three phenotypes of amyotrophic lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy together as part of the same syndrome, the term motor neuron disease, as an over-arching label, was not suggested until nearly a century later by W. Russell Brain. Augustus Jacob Lockhart Clarke (1817-80) is best known for his descriptions of spinal cord anatomy. However, in two detailed case reports from the 1860s, he carried out rigorous post-mortem neuropathological studies of what appear to be classical cases of amyotrophic lateral sclerosis. Furthermore, he recognized the additional involvement of the corticospinal tracts that distinguished this from progressive muscular atrophy. Several aspects of the exquisite clinical histories documented as part of both studies, one by Charles Bland Radcliffe, resonate with contemporary debates concerning the evolution of disease in amyotrophic lateral sclerosis. These 'past masters' still have much to teach us.

  17. Quality of life of patients with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Sue Christine Siqueira

    2017-01-01

    Full Text Available Objective: to analyze the scientific evidence that evaluated the quality of life of patients with Amyotrophic Lateral Sclerosis through ALSAQ-40/ALSAQ-5. Methods: this is an integrative review carried out with eight articles in the database, using controlled keywords. Results: the most impaired domains of quality of life were physical mobility and activities of daily living. Patients with bulbar Amyotrophic Lateral Sclerosis, communication and feeding were more impaired. Problems with health care and lack of social support to the caregiver negatively impacted the patient´s quality of life. Emotional stress was correlated with communication, physical mobility and disease progression in patients with breathing and artificial feeding, but it is not directly related to the advances of physical deterioration, but rather how the patient processes the experiences. Conclusion: patients with Amyotrophic Lateral Sclerosis have a poorer quality of life regarding the motor aspect, and lack of caregiver support worsens the patient´s quality of life.

  18. Analysis of the pharyngoesophageal pressure profile in amyotrophic lateral sclerosis.

    Science.gov (United States)

    MacDougall, G; Wilson, J A; Pryde, A; Grant, R

    1995-02-01

    Treatment of dysphagia resulting from bulbar amyotrophic lateral sclerosis has included cricopharyngeal myotomy for many years but is successful in only a minority of cases. The purpose of this study was to explore the rationale for this procedure with modern manometric techniques. The results of pharyngoesophageal manometry in 13 patients with amyotrophic lateral sclerosis were compared with 13 age- and sex-matched healthy volunteers by Mann-Whitney analysis. There was no significant difference between patients and control subjects in distal esophageal or lower esophageal sphincter motility nor any pressure parameter of pharyngoesophageal motility. Separate analysis of the seven significantly dysphagic subjects showed a significantly reduced upper esophageal sphincter after-contraction amplitude during water and bread swallows in patients than in control subjects. These data suggest that the dysphagia of amyotrophic lateral sclerosis is not due to upper esophageal sphincter spasm and that treatment by cricopharyngeal myotomy may be inappropriate.

  19. Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

    2015-06-01

    Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the

  20. Coping strategies among patients with newly diagnosed amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jakobsson Larsson, Birgitta; Nordin, Karin; Askmark, Håkan; Nygren, Ingela

    2014-11-01

    To prospectively identify different coping strategies among newly diagnosed amyotrophic lateral sclerosis patients and whether they change over time and to determine whether physical function, psychological well-being, age and gender correlated with the use of different coping strategies. Amyotrophic lateral sclerosis is a fatal disease with impact on both physical function and psychological well-being. Different coping strategies are used to manage symptoms and disease progression, but knowledge about coping in newly diagnosed amyotrophic lateral sclerosis patients is scarce. This was a prospective study with a longitudinal and descriptive design. A total of 33 patients were included and evaluation was made at two time points, one to three months and six months after diagnosis. Patients were asked to complete the Motor Neuron Disease Coping Scale and the Hospital Anxiety and Depression Scale. Physical function was estimated using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale. The most commonly used strategies were support and independence. Avoidance/venting and information seeking were seldom used at both time points. The use of information seeking decreased between the two time points. Men did not differ from women, but patients ≤64 years used positive action more often than older patients. Amyotrophic Lateral Sclerosis Functional Rating Scale was positively correlated with positive action at time point 1, but not at time point 2. Patients' psychological well-being was correlated with the use of different coping strategies. Support and independence were the most used coping strategies, and the use of different strategies changed over time. Psychological well-being was correlated with different coping strategies in newly diagnosed amyotrophic lateral sclerosis patients. The knowledge about coping strategies in early stage of the disease may help the nurses to improve and develop the care and support for these patients. © 2014 John Wiley

  1. Vocal cord dysfunction in amyotrophic lateral sclerosis: four cases and a review of the literature

    NARCIS (Netherlands)

    van der Graaff, Maaike M.; Grolman, Wilko; Westermann, Erik J.; Boogaardt, Hans C.; Koelman, Hans; van der Kooi, Anneke J.; Tijssen, Marina A.; de Visser, Marianne

    2009-01-01

    We describe 4 patients with amyotrophic lateral sclerosis (ALS) and glottic narrowing due to vocal cord dysfunction, and review the literature found using the following search terms: amyotrophic lateral sclerosis, motor neuron disease, stridor, laryngospasm, vocal cord abductor paresis, and

  2. Muscle changes in amyotrophic lateral sclerosis: a longitudinal ultrasonography study

    NARCIS (Netherlands)

    Arts, I.M.P.; Overeem, S.; Pillen, S.; Schelhaas, H.J.; Zwarts, M.J.

    2011-01-01

    OBJECTIVE: We performed a longitudinal study to assess structural muscle changes in amyotrophic lateral sclerosis (ALS) using ultrasonography. METHODS: During a follow-up of 6 months, ultrasonography parameters (muscle thickness, echo intensity and fasciculations) were obtained from 6 muscle groups

  3. Premorbid body mass index and risk of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    O'Reilly, Eilis J.; Wang, Hao; Weisskopf, Marc G.; Fitzgerald, Kathryn C.; Falcone, Guido; McCullough, Marjorie L.; Thun, Michael; Park, Yikyung; Kolonel, Laurence N.; Ascherio, Alberto

    Our objective was to determine if amyotrophic lateral sclerosis (ALS) risk varies according to body mass index (BMI) captured up to three decades earlier. At baseline 537,968 females and 562,942 males in five ongoing cohorts reported height, current weight and weight at age 18/21 years. During 14-28

  4. Tele-treatment of patients with amyotrophic lateral sclerosis (ALS)

    NARCIS (Netherlands)

    Oude Nijeweme-d'Hollosy, Wendy; Janssen, Emile P.F.; Huis in 't Veld, M.H.A.; Spoelstra, Jos; Vollenbroek-Hutten, Miriam Marie Rosé; Hermens, Hermanus J.

    2006-01-01

    Management of patients with amyotrophic lateral sclerosis (ALS) mainly consists of (psycho) social support and advice on activities of daily living. We evaluated the effects of tele-treatment in addition to the conventional method of care in four patients with ALS. A Web application was built with

  5. Immunohistochemical characterization of the inflammatory infiltrate in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Troost, D.; van den Oord, J. J.; Vianney de Jong, J. M.

    1990-01-01

    In order to test the hypothesis that the immune system plays a role in the pathogenesis of amyotrophic lateral sclerosis (ALS), the cellular composition of the spinal cord inflammatory infiltrate was analysed in eight cases of sporadic ALS by a panel of monoclonal antibodies. The majority of the

  6. UBQLN2 in familial amyotrophic lateral sclerosis in the Netherlands

    NARCIS (Netherlands)

    van Doormaal, Perry T. C.; van Rheenen, Wouter; van Blitterswijk, Marka; Schellevis, Raymond D.; Schelhaas, Helenius J.; de Visser, Marianne; van der Kooi, Anneke J.; Veldink, Jan H.; van den Berg, Leonard H.

    2012-01-01

    Recently it was discovered that mutations in the UBQLN2 gene were a cause of an X-linked dominant type of familial amyotrophic lateral sclerosis (ALS). We investigated the frequency of mutations in this gene in a cohort of 92 families with ALS in the Netherlands. Eight families were excluded because

  7. NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Kenna, Kevin P.; van Doormaal, Perry T. C.; Dekker, Annelot M.; Ticozzi, Nicola; Kenna, Brendan J.; Diekstra, Frank P.; van Rheenen, Wouter; van Eijk, Kristel R.; Jones, Ashley R.; Keagle, Pamela; Shatunov, Aleksey; Sproviero, William; Smith, Bradley N.; van Es, Michael A.; Topp, Simon D.; Kenna, Aoife; Miller, Jack W.; Fallini, Claudia; Tiloca, Cinzia; McLaughlin, Russell L.; Vance, Caroline; Troakes, Claire; Colombrita, Claudia; Mora, Gabriele; Calvo, Andrea; Verde, Federico; Al-Sarraj, Safa; King, Andrew; Calini, Daniela; de Belleroche, Jacqueline; Baas, Frank; van der Kooi, Anneke J.; de Visser, Marianne; ten Asbroek, Anneloor L. M. A.; Sapp, Peter C.; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Muñoz-Blanco, José Luis; Strom, Tim M.; Meitinger, Thomas; Morrison, Karen E.; Lauria, Giuseppe; Williams, Kelly L.; Leigh, P. Nigel; Nicholson, Garth A.; Blair, Ian P.; Leblond, Claire S.; Dion, Patrick A.; Rouleau, Guy A.; Pall, Hardev; Shaw, Pamela J.; Turner, Martin R.; Talbot, Kevin; Taroni, Franco; Boylan, Kevin B.; van Blitterswijk, Marka; Rademakers, Rosa; Esteban-Pérez, Jesús; García-Redondo, Alberto; van Damme, Phillip; Robberecht, Wim; Chio, Adriano; Gellera, Cinzia; Drepper, Carsten; Sendtner, Michael; Ratti, Antonia; Glass, Jonathan D.; Mora, Jesús S.; Basak, Nazli A.; Hardiman, Orla; Ludolph, Albert C.; Andersen, Peter M.; Weishaupt, Jochen H.; Brown, Robert H.; Al-Chalabi, Ammar; Silani, Vincenzo; Shaw, Christopher E.; van den Berg, Leonard H.; Veldink, Jan H.; Landers, John E.; D'alfonso, Sandra; Mazzini, Letizia; Comi, Giacomo P.; del Bo, Roberto; Ceroni, Mauro; Gagliardi, Stella; Querin, Giorgia; Bertolin, Cinzia; Pensato, Viviana; Castellotti, Barbara; Corti, Stefania; Cereda, Cristina; Corrado, Lucia; Sorarù, Gianni

    2016-01-01

    To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a

  8. A randomized sequential trial of creatine in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Groeneveld, G. J.; Veldink, Jan H.; van der Tweel, Ingeborg; Kalmijn, Sandra; Beijer, Cornelis; de Visser, Marianne; Wokke, John H. J.; Franssen, Hessel; van den Berg, Leonard H.

    2003-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double-blind, placebo-controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival

  9. Characterizing Social Communication Changes in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Fisher, Fiona; Philpott, April; Andrews, Sophie C.; Maule, Roxanne; Douglas, Jacinta

    2017-01-01

    Background: Speech and language impairments are well-established in individuals with amyotrophic lateral sclerosis (ALS). However, knowledge about particular aspects of social communication and everyday conversational abilities is limited. Aims: To investigate self- and informant-report ratings of social communicative abilities in ALS participants…

  10. Amyotrophic lateral sclerosis: clinical features and current treatment approaches

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-06-01

    Full Text Available Amyotrophic lateral sclerosis also known as Lou Gehring's disease, is the most common motor neuron disease characterized by motor neuron degeneration in the primary cortex, brainstem and spinal cord. This leads to widespread paralysis, respiratory insufficiency and death within an average of 3-5 years from disease onset. Majority of cases is sporadic and only 10% have a family story. One of the most interesting discovery in the field of neurodegeneration in recent years is genetic mutation in the C9orf72 (chromosome 9 open reading frame 72 gene, the most common mutation found to be causative of frontotemporal dementia, amyotrophic lateral sclerosis and concomitant of these two diseases. Currently curative therapy for amyotrophic lateral sclerosis is lacking. To date, one medication, Riluzole, has been proved to prolong survival, approximately 3-5 months, in amyotrophic lateral sclerosis. Researches aim to slow disease progression by targeting known pathophysiological pathways or genetics defects. Only symptomatic care to improve quality of life and survival is suggested. These includes respiratory and nutrition support; dysphagia and gastrostomy management; communication and mobility programs; spasticity prevention; pain medication; management of cognitive dysfunction, depression, mood dysorders (especially apathy, fatigue, sleep disturbance and prevention of deep venous thrombosis. [Archives Medical Review Journal 2015; 24(2.000: 182-194

  11. Amyotrophic Lateral Sclerosis Patients' Perspectives on Use of Mechanical Ventilation.

    Science.gov (United States)

    Young, Jenny M.; And Others

    1994-01-01

    Interviewed 13 amyotrophic lateral sclerosis patients. All believed that they alone should make decision regarding use of mechanical ventilation. Factors they considered important were quality of life, severity of disability, availability of ventilation by means of nasal mask, possible admission to long-term care facility, ability to discontinue…

  12. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous

  13. Amyotrophic lateral sclerosis : moving towards a new classification system

    NARCIS (Netherlands)

    Al-Chalabi, Ammar; Hardiman, Orla; Kiernan, Matthew C; Chiò, Adriano; Rix-Brooks, Benjamin; van den Berg, Leonard H

    2016-01-01

    Amyotrophic lateral sclerosis is a progressive adult-onset neurodegenerative disease that primarily affects upper and lower motor neurons, but also frontotemporal and other regions of the brain. The extent to which each neuronal population is affected varies between individuals. The subsequent

  14. Structural MRI reveals cortical thinning in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Verstraete, E.; Veldink, J.H.; Hendrikse, J.; Schelhaas, H.J.; Heuvel, M.P. van den; Berg, L.H. van den

    2012-01-01

    OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a fatal disease characterised by combined upper and lower motor neuron degeneration. An early and accurate diagnosis is important for patient care and might facilitate the search for a more effective therapy. MRI was used to study the whole cortical

  15. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

    NARCIS (Netherlands)

    McLaughlin, Russell L.; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R.; O'Brien, Margaret; Kahn, René S.; Ophoff, Roel A.; Goris, An; Bradley, Daniel G.; Al-Chalabi, Ammar; van den Berg, Leonard H.; Luykx, Jurjen J.; Hardiman, Orla; Veldink, Jan H.; Shatunov, Aleksey; Dekker, Annelot M.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; van Doormaal, Perry T. C.; Sproviero, William; Jones, Ashley R.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Bauer, Denis; Kahlke, Tim; Williams, Kelly; Eftimov, Filip; Fogh, Isabella; Ticozzi, Nicola; Lin, Kuang; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Petri, Susanne; Abdulla, Susanna; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, Nazli; Meitinger, Thomas; Lichtner, Peter; Blagojevic-Radivojkov, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safa; Dürr, Alexandra; Wood, Nicholas; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöuthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; van der Kooi, Anneke J.; de Visser, Marianne; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; del Bo, Roberto; Comi, Giacomo P.; D'alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simon; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Blair, Ian; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Brown, Robert H.; Glass, Jonathan; Landers, John E.; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T. R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberley D.; Chan, Raymond C. K.; Chan, Ronald Y. L.; Chen, Eric Y. H.; Cheng, Wei; Cheung, Eric F. C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Lee, Jimmy; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik K. E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O'Callaghan, Eadbhard; O'Dushlaine, Colm; O'Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C. A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H. M.; Wormley, Brandon K.; Xi, Hualin Simon; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R.; Stefansson, Kari; Visscher, Peter M.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H. R.; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jönsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Riley, Brien P.; Rujescu, Dan; Sham, Pak C.; Sklar, Pamela; St Clair, David; Weinberger, Daniel R.; Wendland, Jens R.; Werge, Thomas; Daly, Mark J.; Sullivan, Patrick F.; O'Donovan, Michael C.

    2017-01-01

    We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide

  16. VCP mutations in familial and sporadic amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Koppers, M.; Blitterswijk, M.M. van; Vlam, L.; Rowicka, P.A.; Vught, P.W. van; Groen, E.J.; Spliet, W.G.; Engelen-Lee, J. van; Schelhaas, H.J.; Visser, M. de; Kooi, A.J. van der; Pol, W.L. van der; Pasterkamp, R.J.; Veldink, J.H.; Berg, L.H. van den

    2012-01-01

    Mutations in the valosin-containing protein (VCP) gene were recently reported to be the cause of 1%-2% of familial amyotrophic lateral sclerosis (ALS) cases. VCP mutations are known to cause inclusion body myopathy (IBM) with Paget's disease (PDB) and frontotemporal dementia (FTD). The presence of

  17. Risk factors for amyotrophic lateral sclerosis : Lifestyle, environment and genetics

    NARCIS (Netherlands)

    Seelen, M.

    2015-01-01

    In this thesis the results of studies aiming to identify risk factors for amyotrophic lateral sclerosis (ALS) are described. A population-based case-control design was used to perform (1) epidemiological risk factor studies, examining lifestyle factors and environmental exposures, and (2) genetic

  18. Spatiotemporal Coupling of the Tongue in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Kuruvilla, Mili S.; Green, Jordan R.; Yunusova, Yana; Hanford, Kathy

    2012-01-01

    Purpose: The primary aim of the investigation was to identify deficits in spatiotemporal coupling between tongue regions in amyotrophic lateral sclerosis (ALS). The relations between disease-related changes in tongue movement patterns and speech intelligibility were also determined. Methods: The authors recorded word productions from 11…

  19. Temporal lobe pathology in amyotrophic lateral sclerosis. Do amyotrophic lateral sclerosis and Alzheimer's disease share a common etiological factor?

    NARCIS (Netherlands)

    Smitt, P. A.; Troost, D.; Louwerse, E. S.; de Jong, J. M.; van Kessel, D. T.; de Leeuw, M. A.

    1993-01-01

    An autopsy study was performed on temporal lobe samples from 20 non-demented patients with amyotrophic lateral sclerosis (ALS), 17 age-matched non-demented controls and 4 Alzheimer's disease (AD) patients. Formalin fixed, paraffin embedded sections from the hippocampus with adjacent parahippocampal

  20. Natural compounds used as therapies targeting to amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nabavi, Seyed F; Daglia, Maria; D'Antona, Giuseppe; Sobarzo-Sánchez, Eduardo; Talas, Zeliha S; Nabavi, Seyed M

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease that occurs throughout the world with no racial, ethnic or socioeconomic boundaries. Despite its high morbidity and mortality, there are limited medications available for ALS that may increase survival in patients with amyotrophic lateral sclerosis by approximately 2-3 months. Inasmuch as negative effects of riluzole on muscle atrophy and wasting, weakness, muscle spasticity, dysarthria, dysphagia, and overall patient quality of life and its different adverse effects, much attention has been paid to natural products and herbal medicines. Overall scientific reports indicate that natural products have beneficial effects on patients with ALS low side effects and multiple targets. In the present paper, we review the scientific reports on beneficial role of natural polyphenolic compounds in treatment of ALS.

  1. The genetic basis of amyotrophic lateral sclerosis: recent breakthroughs

    Directory of Open Access Journals (Sweden)

    Eykens C

    2015-10-01

    Full Text Available Caroline Eykens,1,2 Wim Robberecht1–31Research Group Experimental Neurology, Department of Neurosciences, KU Leuven – University of Leuven, Leuven, Belgium; 2Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; 3Department of Neurology, University Hospitals Leuven, Leuven, BelgiumAbstract: Deciphering the genetic architecture of amyotrophic lateral sclerosis (ALS, an adult-onset neurodegenerative disorder of the motor neuron system, is important to understand the etiology of this fatal disease as well as to develop customized ALS therapies based on the patient's genetic fingerprint. In this review, we discuss the genetic basis of ALS, and attempt to link the causal genes to three highly interrelated pathogenic mechanisms: dysproteostasis, RNA dysregulation, and axon dysfunction. In addition, we address the clinical and biological implications of these genetic findings. Furthermore, we explore to what extent genetic knowledge can be converted into targeted and personalized treatments.Keywords: amyotrophic lateral sclerosis, frontotemporal dementia, genetics, disease modifiers, personalized medicine

  2. Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis

    OpenAIRE

    Devine, Matthew S.; Pannek, Kerstin; Coulthard, Alan; Pamela A. McCombe; Rose, Stephen E; Henderson, Robert D.

    2015-01-01

    Limb weakness in amyotrophic lateral sclerosis (ALS) is typically asymmetric. Previous studies have identified an effect of limb dominance on onset and spread of weakness, however relative atrophy of dominant and non-dominant brain regions has not been investigated. Our objective was to use voxel-based morphometry (VBM) to explore gray matter (GM) asymmetry in ALS, in the context of limb dominance. 30 ALS subjects were matched with 17 healthy controls. All subjects were right-handed. Each und...

  3. Tracheomegaly Secondary to Tracheotomy Tube Cuff in Amyotrophic Lateral Sclerosis

    OpenAIRE

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2015-01-01

    Abstract Tracheomegaly has not been reported in amyotrophic lateral sclerosis (ALS). Herein, the authors report a case of tracheomegaly secondary to tracheotomy tube cuff in a patient with ALS. To our knowledge, this is the first report of an ALS patient with tracheomegaly and of tracheomegaly being associated with tracheotomy tube cuff and home tracheotomy mechanical ventilator. The clinician should consider the possibility of tracheomegaly in the differential diagnosis, if a patient with AL...

  4. Nutritional care in motor neurone disease/ amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Cristina Cleide dos Santos Salvioni

    2014-02-01

    Full Text Available Patients with amyotrophic lateral sclerosis (ALS often present changes in nutritional status. Based on weight loss and on difficulty in nutritional management, this study aims to review the different possibilities and to present guidelines concerning nutritional treatment to such patients. Diet characteristics, types of treatment and nutritional therapy indicating administration routes and discussing the details of the disease are described herein. Nutritional therapy has been a substantial therapeutic resource for ALS development.

  5. Amyotrophic Lateral Sclerosis and Multiple Sclerosis Overlap: A Case Report

    OpenAIRE

    Francesca Trojsi; Anna Sagnelli; Giovanni Cirillo; Giovanni Piccirillo; Cinzia Femiano; Francesco Izzo; Maria Rosaria Monsurrò; Gioacchino Tedeschi

    2012-01-01

    The concurrence of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is extremely rare. We reported the case of a 33-year-old woman with a past history of paresthesias at the right hand, who developed progressive quadriparesis with muscular atrophy of limbs and, finally, bulbar signs and dyspnea. Clinical and neurophysiologic investigations revealed upper and lower motor neuron signs in the bulbar region and extremities, suggesting the diagnosis of ALS. Moreover, magnetic resona...

  6. The interaction between breathing and swallowing in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Erdem, Nazan Simsek; Karaali, Kamil; Ünal, Ali; Kızılay, Ferah; Öğüş, Candan; Uysal, Hilmi

    2016-12-01

    The aim of the study is to determine the association between respiratory swallow patterns in amyotrophic lateral sclerosis (ALS) patients. Furthermore, it aims to clarify the role of the dysphagia limit in defining the relationship between swallowing disorders and respiratory disorders. Functional rating scales were used to describe swallowing and respiratory function. Swallowing was observed using the dysphagia limit. Dysphagia limit is the volume at which a second or more swallows are required to swallow the whole bolus. Laryngeal and chest movement sensors, pulmonary function tests, submental, and diaphragm electromyography activity were used to evaluate the relationship between swallowing and respiratory phase. Of the 27 patients included in the study, 14 were dysphagic and 13 were non-dysphagic. Tests showed normal respiratory function in 11 of the non-dysphagic patients and 3 of the dysphagic patients. There was a high correlation between the dysphagia limit and Amyotrophic Lateral Sclerosis Functional Rating Scale swallowing parameters. Non-dysphagic patients were able to swallow during inspiration but only six patients in the dysphagic group were able to swallow during inspiration. The occurrence of dysphagia in ALS is related to piecemeal deglutition and respiration consistency during swallowing. Detecting the timing of disturbances in the relationship between swallowing and respiration may be a way of identifying dysphagia. Dysphagia limit may be a useful, complementary test for assessing swallowing disturbances in amyotrophic lateral sclerosis.

  7. Amyotrophic lateral sclerosis – a motor neuron disease. Case report

    Directory of Open Access Journals (Sweden)

    Maja Rubinowicz-Zasada

    2015-03-01

    Full Text Available Amyotrophic lateral sclerosis, also known as Charcot’s disease and motor neuron disease, is a progressive neurodegenerative disease that causes muscle weakness, paralysis, and ultimately, respiratory failure. The aetiology and the pathogenesis of the syndrome remain unknown. Most people live 2–5 years after their first signs of the disease. There is no cure or effective treatment. We present a case of a female patient affected by progressing Charcot’s disease. On the Amyotrophic Lateral Sclerosis Functional Rating Scale – Revised (ALSFRS-R, the patient obtained 21 points. Atrophy and muscle spasm were very extended. Electromyography revealed features of coexisting denervation and reinnervation in the examined muscles. A growing number of Charcot’s disease cases require multidirectional actions to meet patient’s physical, emotional, and nutritional needs. Amyotrophic lateral sclerosis is an incurable disease. However, it is possible to relieve its symptoms by applying systematic physical rehabilitation.

  8. Motor neuron disease (amyotrophic lateral sclerosis) arising from longstanding primary lateral sclerosis

    NARCIS (Netherlands)

    Bruyn, R. P.; Koelman, J. H.; Troost, D.; de Jong, J. M.

    1995-01-01

    Three men were initially diagnosed as having primary lateral sclerosis (PLS), but eventually developed amyotrophic lateral sclerosis (ALS) after 7.5, 9, and at least 27 years. Non-familial ALS and PLS might be different manifestations of a single disease or constitute completely distinct entities.

  9. Palliative care in amyotrophic lateral sclerosis: a review of current international guidelines and initiatives.

    LENUS (Irish Health Repository)

    Bede, Peter

    2011-04-01

    Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative condition. Optimal management requires a palliative approach from diagnosis with emphasis on patient autonomy, dignity and quality of life.

  10. Conjugal amyotrophic lateral sclerosis: a case report from Scotland.

    Science.gov (United States)

    Fernandes, P M; Macleod, M R; Bateman, A; Abrahams, S; Pal, S

    2017-03-29

    Conjugal amyotrophic lateral sclerosis is rare, with significant effects on psychological and care needs. We report a case of conjugal amyotrophic lateral sclerosis disease from central Scotland. This case is particularly unusual as both patients were diagnosed within an 18-month period and experienced the disease simultaneously, with similar symptomatology and progression. Patient A was a 71-year-old man who presented with unilateral arm weakness and wasting. Patient B was a 68-year-old woman who presented with unilateral shoulder and elbow weakness. Diagnosis of amyotrophic lateral sclerosis was made within a few months of presentation in both cases, based on typical clinical symptomatology together with supportive neurophysiological testing. Interventions included enteral feeding and non-invasive ventilation. The time period between symptom onset and death was 5 years for Patient A and 3.5 years for Patient B. This case illustrates two main points: the care issues surrounding cases of conjugal neurological disease, and the psychological issues in these patients. There are significant care issues arising when co-habiting couples both develop severe functionally limiting neurological diseases at the same time. The more slowly progressive nature of Patient A's disease may be at least partially explained by the support he was able to receive from Patient B before she developed symptoms. Secondly, there are important psychological effects of living with someone with the same - but more advanced - progressive and incurable neurological disease. Thus, Patient B was reluctant to have certain interventions that she had observed being given to her husband. Lastly, no plausible shared environmental risk factors were identified, implying that the co-occurrence of ALS in this couple was a random association.

  11. Side of Limb-Onset Predicts Laterality of Gray Matter Loss in Amyotrophic Lateral Sclerosis

    OpenAIRE

    Qiuli Zhang; Cuiping Mao; Jiaoting Jin; Chen Niu; Lijun Bai; Jingxia Dang; Ming Zhang

    2014-01-01

    Conflicting findings have been reported regarding the lateralized brain abnormality in patients with amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the probable lateralization of gray matter (GM) atrophy in ALS patients. We focused on the relationship between the asymmetry in decreased GM volume and the side of disease onset in patients with limb-onset. Structural imaging evaluation of normalized atrophy (SIENAX) and voxel-based morphometry (VBM) were used to asse...

  12. Energy Homeostasis and Abnormal RNA Metabolism in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Liu, Yu-Ju; Tsai, Po-Yi; Chern, Yijuang

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is clinically characterized by progressive muscle weakness and impaired voluntary movement due to the loss of motor neurons in the brain, brain stem and spinal cord. To date, no effective treatment is available. Ample evidence suggests that impaired RNA homeostasis and abnormal energy status are two major pathogenesis pathways in ALS. In the present review article, we focus on recent studies that report molecular insights of both pathways, and discuss the possibility that energy dysfunction might negatively regulate RNA homeostasis via the impairment of cytoplasmic-nuclear shuttling in motor neurons and subsequently contribute to the development of ALS. PMID:28522961

  13. FUS mutations in frontotemporal lobar degeneration with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Broustal, Oriane; Camuzat, Agnès; Guillot-Noël, Lena; Guy, Nathalie; Millecamps, Stéphanie; Deffond, Didier; Lacomblez, Lucette; Golfier, Véronique; Hannequin, Didier; Salachas, François; Camu, William; Didic, Mira; Dubois, Bruno; Meininger, Vincent; Le Ber, Isabelle; Brice, Alexis

    2010-01-01

    Rapid advances were made in the knowledge of amyotrophic lateral sclerosis (ALS) with the recent identification of TARDBP and FUS mutations in familial ALS. More recently, FUS-positive inclusions were found in a subset of TDP-43-negative frontotemporal lobar degeneration (FTLD) prompting us to analyze FUS in FTLD and FTLD-ALS patients. The p.Arg521His mutation was identified in a patient who initially had behavioral disorders and rapidly developed ALS. Although the frequency of mutations is low, our study enlarges the phenotypes associated with FUS mutations and shows that FUS could also play a direct pathogenic role in FTLD spectrum of diseases.

  14. Tracheomegaly Secondary to Tracheotomy Tube Cuff in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2015-01-01

    Abstract Tracheomegaly has not been reported in amyotrophic lateral sclerosis (ALS). Herein, the authors report a case of tracheomegaly secondary to tracheotomy tube cuff in a patient with ALS. To our knowledge, this is the first report of an ALS patient with tracheomegaly and of tracheomegaly being associated with tracheotomy tube cuff and home tracheotomy mechanical ventilator. The clinician should consider the possibility of tracheomegaly in the differential diagnosis, if a patient with ALS develops repeat air leakage around the tracheotomy tube or rupture of tracheotomy tube cuff. PMID:26496301

  15. Muscle ultrasound imaging in the diagnosis of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Yu. N. Rushkevich

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common form of motor neuron disease. This pathology is characterized by the involvement of central and peripheral motor neurons in the pathological process. One  f the specific symptoms of ALS is fasciculations - involuntary muscle contractions that may occasionally precede the development of muscle weakness and atrophies. This paper summarizes the accumulated practical experience in using muscle ultrasound study in the diagnosis of fasciculations and their prevalence as an early sign of anterior corneal lesion in ALS.

  16. Hirayama's Disease: A Rare Clinical Variant of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Swati C Aundhakar

    2017-01-01

    Full Text Available Hirayama's disease is a rare clinical variant of amyotrophic lateral sclerosis where distal muscles are involved more compared to proximal muscles and vice-versa occurs only in 10% cases and so it is differentiated from O'Sullivan McLeod syndrome which involves only small muscles of single limb. Here, we present a case of Hirayama's disease where disease achieved a plateau after 3 years with no further progression. His electrophysiological studies, and clinical picture, and magnetic resonance imaging findings were consistent with a diagnosis of Hirayama's disease.

  17. “Neuropathology of amyotrophic lateral sclerosis and its variants”

    Science.gov (United States)

    Saberi, Shahram; Stauffer, Jennifer E.; Schulte, Derek J.; Ravits, John

    2015-01-01

    Summary Amyotrophic lateral sclerosis (ALS) is a clinical syndrome named for its neuropathological hallmark: degeneration of motor neurons in the spinal anterior horn and motor cortex and loss of axons in the lateral columns of the spinal cord. The signature neuropathological molecular signature common to almost all sporadic ALS and most familial ALS is TDP-43 immunoreactive neuronal cytoplasmic inclusions. The neuropathological and molecular neuropathological features of ALS variants primarly lateral sclerosis and progressive muscular atrophy are less certain, but also appear to share the primary features of ALS. A number of genetic causes including mutations in SOD1, FUS, and C9orf72 comprise a disease spectrum and all demonstrate distinctive molecular and neuropathological signatures. Neuropathology will continue to play to a key role in solving the puzzle of ALS pathogenesis. PMID:26515626

  18. Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Giovanni Nardo

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC, a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%, and from patients with neurological disorders that may resemble ALS (91%, between two levels of disease severity (90%, and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

  19. Case-control study of amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Deapen, D.M.; Henderson, B.E.

    1986-05-01

    The authors conducted a study of 518 amyotrophic lateral sclerosis patients identified between 1977 and 1979 and 518 controls to investigate putative risk factors for this disease. Occupations at risk of electrical exposure were reported more often by patients (odds ratio (OR) = 3.8, 95% confidence interval (CI) = 1.4-13.0) as were electrical shocks producing unconsciousness (OR = 2.8, 95% CI = 1.0-9.9). Although an overall excess of physical trauma associated with unconsciousness was observed in the amyotrophic lateral sclerosis patients (OR = 1.6, 95% CI = 1.0-2.4), the effect was inversely associated with duration of the unconscious episodes, suggesting an effect of recall bias. Only slight differences were found for surgical traumata to the nervous system. Parkinsonism was reported more often among first degree relatives of cases (OR = 2.7, 95% CI = 1.1-7.6). The frequencies of prior poliomyelitis or other central nervous system diseases were similar for patients and controls. Occupational exposure to selected toxic substances was similar for patients and controls except for the manufacture of plastics (OR = 3.7, 95% CI = 1.0-20.5), although few details of these exposures were provided. No differences in occupations with exposure to animal skins or hides were observed.

  20. [Genetic coherence between hereditary amyotrophic lateral sclerosis and frontotemporal dementia].

    Science.gov (United States)

    Gjerde, Kristian Varden; Tysnes, Ole-Bjørn

    2014-02-11

    Amyotrophic lateral sclerosis (ALS) has traditionally been considered purely as a motor condition with a progressive loss of upper and lower motor neurons, and without cognitive or behavioural impairment. In 2011 a new genetic mutation that may cause both ALS and frontotemporal dementia (FTD) was detected. In light of this discovery, the article describes genetic and clinical characteristics of ALS and frontotemporal dementia. The article is based on a literature search in PubMed. Up to 50% of ALS patients develop some cognitive impairment, while 3-15% develop frontotemporal dementia. The recently discovered C9ORF72 mutation accounts for 20-50% of hereditary ALS and possibly up to 25% of sporadic cases. The mutation is the most common cause of ALS. Patients with C9ORF72 mutation are characterised by earlier disease onset, reduced survival after diagnosis, more frequent cognitive and behavioural dysfunction, and familial disposition for ALS and frontotemporal dementia. Cognitive and behavioural changes in amyotrophic lateral sclerosis are common, and can appear along a clinical continuum with development of frontotemporal dementia over time. Detection of the C9ORF72 mutation poses a challenge to our knowledge and management of patients with both hereditary and sporadic ALS.

  1. Motor neuron disease (amyotrophic lateral sclerosis) arising from longstanding primary lateral sclerosis.

    OpenAIRE

    Bruyn, R P; Koelman, J H; Troost, D.; de Jong, J M

    1995-01-01

    Three men were initially diagnosed as having primary lateral sclerosis (PLS), but eventually developed amyotrophic lateral sclerosis (ALS) after 7.5, 9, and at least 27 years. Non-familial ALS and PLS might be different manifestations of a single disease or constitute completely distinct entities. The clinical diagnosis of PLS predicts a median survival that is four to five times longer than in ALS.

  2. Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Louwerse, E. S.; Weverling, G. J.; Bossuyt, P. M.; Meyjes, F. E.; de Jong, J. M.

    1995-01-01

    BACKGROUND: Free radicals may play a role in the pathogenesis of amyotrophic lateral sclerosis. OBJECTIVE: To investigate the efficacy of the free radical scavenging agent acetylcysteine in patients with amyotrophic lateral sclerosis. DESIGN: Randomized, double-blind, placebo-controlled clinical

  3. 76 FR 78823 - Schedule for Rating Disabilities; Evaluation of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2011-12-20

    ... Sclerosis AGENCY: Department of Veterans Affairs. ACTION: Final rule. SUMMARY: The Department of Veterans... criterion provided for amyotrophic lateral sclerosis (ALS) to provide an evaluation of 100 percent for any... revise the evaluation criterion for amyotrophic lateral sclerosis (ALS) in the VA Schedule for Rating...

  4. 38 CFR 3.318 - Presumptive service connection for amyotrophic lateral sclerosis.

    Science.gov (United States)

    2010-07-01

    ... connection for amyotrophic lateral sclerosis. 3.318 Section 3.318 Pensions, Bonuses, and Veterans' Relief... sclerosis. (a) Except as provided in paragraph (b) of this section, the development of amyotrophic lateral sclerosis manifested at any time after discharge or release from active military, naval, or air service is...

  5. Structural MRI correlates of amyotrophic lateral sclerosis progression.

    Science.gov (United States)

    Senda, Joe; Atsuta, Naoki; Watanabe, Hirohisa; Bagarinao, Epifanio; Imai, Kazunori; Yokoi, Daichi; Riku, Yuichi; Masuda, Michihito; Nakamura, Ryoichi; Watanabe, Hazuki; Ito, Mizuki; Katsuno, Masahisa; Naganawa, Shinji; Sobue, Gen

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) presents with varying degrees of brain degeneration that can extend beyond the corticospinal tract (CST). Furthermore, the clinical course and progression of ALS varies widely. Brain degeneration detected using structural MRI could reflect disease progression. On study registration, 3-Tesla volumetric MRI and diffusion tensor imaging scans were obtained at baseline in 38 healthy controls and 67 patients with sporadic ALS. Patients had Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores of ≥36 and did not have the chromosome 9, open reading frame 72 repeat expansion. Six months later, changes in ALSFRS-R (ΔALSFRS-R) scores were calculated and patients were grouped into three categories, namely, patients with slow progression with ΔALSFRS-R scores ≤3 (n=19), intermediate progression with ΔALSFRS-R scores =4, 5 and 6 (n=36) and rapid progression with ΔALSFRS-R scores ≥7 (n=12). We analysed voxel-based morphometry and tract-based spatial statistics among these subgroups and controls. In comparison with controls, patients with ALS showed grey matter atrophy and decreased fractional anisotropy beyond the motor cortex and CST, especially in the frontotemporal lobes and basal ganglia. Moreover, the degree of change was highly proportional to ΔALSFRS-R at the 6-month assessment. A more rapid disease progression and poorer functional decline were associated with greater involvement of the extra-motor cortex and basal ganglia, suggesting that the spatial extent of brain involvement can be an indicator of the progression in ALS. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Nieves, Jeri W; Gennings, Chris; Factor-Litvak, Pam; Hupf, Jonathan; Singleton, Jessica; Sharf, Valerie; Oskarsson, Björn; Fernandes Filho, J Americo M; Sorenson, Eric J; D'Amico, Emanuele; Goetz, Ray; Mitsumoto, Hiroshi

    2016-12-01

    There is growing interest in the role of nutrition in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS). To evaluate the associations between nutrients, individually and in groups, and ALS function and respiratory function at diagnosis. A cross-sectional baseline analysis of the Amyotrophic Lateral Sclerosis Multicenter Cohort Study of Oxidative Stress study was conducted from March 14, 2008, to February 27, 2013, at 16 ALS clinics throughout the United States among 302 patients with ALS symptom duration of 18 months or less. Nutrient intake, measured using a modified Block Food Frequency Questionnaire (FFQ). Amyotrophic lateral sclerosis function, measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), and respiratory function, measured using percentage of predicted forced vital capacity (FVC). Baseline data were available on 302 patients with ALS (median age, 63.2 years [interquartile range, 55.5-68.0 years]; 178 men and 124 women). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALSFRS-R scores or percentage FVC. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores (β [SE], 2.7 [0.69] and 2.9 [0.9], respectively) and percentage FVC (β [SE], 12.1 [2.8] and 11.5 [3.4], respectively) (all P < .001). Positive and significant associations with ALSFRS-R scores (β [SE], 1.5 [0.61]; P = .02) and percentage FVC (β [SE], 5.2 [2.2]; P = .02) for selected vitamins were found in exploratory analyses. Antioxidants, carotenes, fruits, and vegetables were associated with higher ALS function at baseline by regression of nutrient indices and weighted quantile sum regression analysis. We also demonstrated the usefulness of the weighted quantile sum regression method in the evaluation of diet. Those responsible for nutritional

  7. Is amyotrophic lateral sclerosis/frontotemporal dementia an autophagy disease?

    Science.gov (United States)

    Deng, Zhiqiang; Sheehan, Patricia; Chen, Shi; Yue, Zhenyu

    2017-12-28

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative disorders that share genetic risk factors and pathological hallmarks. Intriguingly, these shared factors result in a high rate of comorbidity of these diseases in patients. Intracellular protein aggregates are a common pathological hallmark of both diseases. Emerging evidence suggests that impaired RNA processing and disrupted protein homeostasis are two major pathogenic pathways for these diseases. Indeed, recent evidence from genetic and cellular studies of the etiology and pathogenesis of ALS-FTD has suggested that defects in autophagy may underlie various aspects of these diseases. In this review, we discuss the link between genetic mutations, autophagy dysfunction, and the pathogenesis of ALS-FTD. Although dysfunction in a variety of cellular pathways can lead to these diseases, we provide evidence that ALS-FTD is, in many cases, an autophagy disease.

  8. Axonal Excitability in Amyotrophic Lateral Sclerosis : Axonal Excitability in ALS.

    Science.gov (United States)

    Park, Susanna B; Kiernan, Matthew C; Vucic, Steve

    2017-01-01

    Axonal excitability testing provides in vivo assessment of axonal ion channel function and membrane potential. Excitability techniques have provided insights into the pathophysiological mechanisms underlying the development of neurodegeneration and clinical features of amyotrophic lateral sclerosis (ALS) and related neuromuscular disorders. Specifically, abnormalities of Na+ and K+ conductances contribute to development of membrane hyperexcitability in ALS, thereby leading to symptom generation of muscle cramps and fasciculations, in addition to promoting a neurodegenerative cascade via Ca2+-mediated processes. Modulation of axonal ion channel function in ALS has resulted in significant symptomatic improvement that has been accompanied by stabilization of axonal excitability parameters. Separately, axonal ion channel dysfunction evolves with disease progression and correlates with survival, thereby serving as a potential therapeutic biomarker in ALS. The present review provides an overview of axonal excitability techniques and the physiological mechanisms underlying membrane excitability, with a focus on the role of axonal ion channel dysfunction in motor neuron disease and related neuromuscular diseases.

  9. Management and therapeutic perspectives in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Mathis, Stéphane; Couratier, Philippe; Julian, Adrien; Vallat, Jean-Michel; Corcia, Philippe; Le Masson, Gwendal

    2017-03-01

    Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder affecting both upper and lower motor neurons. Despite much research and effort, no clear insights into a unifying hypothesis for the pathogenesis has so far emerged for this disease. Areas covered: We review the main pathophysiological hypotheses and the potential therapeutic targets in ALS, as well as the management of these patients (in order to improve their survival and quality of life). Expert commentary: ALS is a complex neurodegenerative disease, these days considered as a multisystem disorder with predominant motor symptoms (and various clinical forms). Further comprehension of the pathophysiology of this disease is required, although pathophysiological mechanisms (such as TDP-43) show promise in the search for new therapies. There is still no curative treatment for ALS, but the emergence of multidisciplinary specialized ALS clinics has increased both the quality of life and the survival of these patients.

  10. Mortality from amyotrophic lateral sclerosis in Finland, 1986-1995

    DEFF Research Database (Denmark)

    Maasilta, P.; Jokelainen, M.; Löytönen, M.

    2001-01-01

    Objective - To study the possible changes, between 1986 and 1995, in the mortality due to amyotrophic lateral sclerosis (ALS) among Finnish patients. Materials and methods - A total of 1000 deaths from ALS were extracted from the Finnish Death Certificate Register for the study years. General...... population data were obtained from the Statistical Yearbooks of Finland. Results - From a death rate of 1.54/100,000 in 1986 an increase to 2.27/100,000 in 1995 was observed. Since 1963 the number of ALS deaths has tripled. The documented increased life-expectancy in Finland correlates with the ALS death...... rate, at least partly explaining the increase. Contrary to other countries, on the whole equal numbers of men and women died of ALS. Women tended to be older than men when they died of ALS. Conclusion - In accordance with other countries ALS mortality in Finland is steadily increasing....

  11. Telomerase expression in amyotrophic lateral sclerosis (ALS) patients.

    Science.gov (United States)

    De Felice, Bruna; Annunziata, Anna; Fiorentino, Giuseppe; Manfellotto, Francesco; D'Alessandro, Raffaella; Marino, Rita; Borra, Marco; Biffali, Elio

    2014-10-01

    Telomerase and telomeric complex have been linked to a variety of disease states related to neurological dysfunction. In amyotrophic lateral sclerosis (ALS) patients, telomerase activity, as human telomerase reverse transcriptase (hTERT) expression, has not been characterized yet. Here, for the first time, we characterized telomerase and related pathway in blood sample and spinal cord from ALS patients compared with healthy controls. We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS. As a consequence of the reduced telomerase activity, we identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy control group.

  12. Therapeutic targeting of epigenetic components in amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Lee, J; Ryu, H; Keum, G; Yoon, Y J; Kowall, N W; Ryu, H

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease characterized by degeneration of motor neuron and glial activation followed by the progressive muscle loss and paralysis. Numerous distinct therapeutic interventions have been examined but currently ALS does not have a cure or an efficacious treatment for the disorder. Glutamate- induced excitotoxicity, inflammation, mitochondrial dysfunction, oxidative stress, protein aggregation, transcription deregulation, and epigenetic modifications are associated with the pathogenesis of ALS and known to be therapeutic targets in ALS. In this review, we discuss translational pharmacological studies targeting epigenetic components to ameliorate ALS. Understanding of the epigenetic mechanisms will provide novel insights that will further identify potential biological markers and therapeutic approaches for treating ALS. A combination of treatments that modulate epigenetic components and multiple targets may prove to be the most effective therapy for ALS.

  13. Cardiometabolic health and risk of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Timmins, Hannah C; Saw, Wilfred; Cheah, Benjamin C; Lin, Cindy S Y; Vucic, Steve; Ahmed, Rebekah M; Kiernan, Matthew C; Park, Susanna B

    2017-10-01

    Patients diagnosed with amyotrophic lateral sclerosis (ALS) generally have a limited medical history and a normal body mass index, raising the possibility of a premorbid ALS phenotype. The prevalence of cardiometabolic factors was analyzed in 58 ALS patients via comprehensive cardiovascular assessments and compared with Australian population norms. ALS patients had good cardiac fitness and no reported cardiovascular events. Average blood pressure, heart rate, PR interval, and corrected QT interval were in the normal range. There were significantly fewer obese women in the ALS cohort (13.6%, P ALS cohort (55.8%, P ≤ 0.001), and the prevalence of dyslipidemia was lower (38.7%) compared with the general population (74.4%, P ALS patients had good cardiometabolic health, with evidence of a reduced vascular risk profile. Muscle Nerve 56: 721-725, 2017. © 2016 Wiley Periodicals, Inc.

  14. Optimizing muscle selection for electromyography in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Babu, Suma; Pioro, Erik P; Li, Jianbo; Li, Yuebing

    2017-07-01

    We compared the yield of limb and thoracic paraspinal muscle examination for revealing lower motor neuron (LMN) dysfunction on electromyography (EMG) in amyotrophic lateral sclerosis (ALS). A retrospective review of 354 patients with clinically definite or probable ALS was performed. Seventeen limb muscles and thoracic paraspinal muscles were evaluated for the presence of both active and chronic denervation. Distal limb muscles showed the highest electrodiagnostic sensitivities of LMN dysfunction in ALS regardless of onset region and diagnostic certainty at the time of diagnosis. Electrodiagnostic yield is higher in muscles from the onset limb. Noncontiguous spread of lower motor neuron degeneration is present in ALS. Optimally selected 6 upper and 5 lower extremity muscles yielded >98% of potential positive cervical or lumbosacral segments. An algorithmic approach to needle EMG in ALS based on pretest probability of individual muscles optimizes electrodiagnostic yield, thus possibly minimizing test duration and patient discomfort. Muscle Nerve 56: 36-44, 2017. © 2016 Wiley Periodicals, Inc.

  15. Amyotrophic lateral sclerosis surveillance in Baltimore and Philadelphia.

    Science.gov (United States)

    Jordan, Heather; Rechtman, Lindsay; Wagner, Laurie; Kaye, Wendy E

    2015-06-01

    Limited epidemiological data on amyotrophic lateral sclerosis (ALS) exist in defined geographic areas in the United States. Neurologists submitted case reports for patients under their care between January 1, 2009, and December 31, 2011, who met the El Escorial criteria. Diagnosis was confirmed for a sample of cases by the consulting neurologist. Death certificate data were used for supplemental case identification. The 248 reported cases were most likely to be 50-69 years old, men, white, and non-Hispanic. The total crude average annual incidence rate was 1.46 per 100,000 person-years. The reported demographic characteristics were consistent with previously published findings. The crude annual incidence was slightly lower than the expected rate of 1.6 but was within the range reported previously (0.7-2.5). These findings help quantify the burden of ALS in the United States. © 2014 The Authors. Muscle & Nerve Published by Wiley Periodicals, Inc.

  16. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Directory of Open Access Journals (Sweden)

    Alok Kumar

    2013-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.

  17. Protein Homeostasis in Amyotrophic Lateral Sclerosis: Therapeutic Opportunities?

    Science.gov (United States)

    Webster, Christopher P.; Smith, Emma F.; Shaw, Pamela J.; De Vos, Kurt J.

    2017-01-01

    Protein homeostasis (proteostasis), the correct balance between production and degradation of proteins, is essential for the health and survival of cells. Proteostasis requires an intricate network of protein quality control pathways (the proteostasis network) that work to prevent protein aggregation and maintain proteome health throughout the lifespan of the cell. Collapse of proteostasis has been implicated in the etiology of a number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), the most common adult onset motor neuron disorder. Here, we review the evidence linking dysfunctional proteostasis to the etiology of ALS and discuss how ALS-associated insults affect the proteostasis network. Finally, we discuss the potential therapeutic benefit of proteostasis network modulation in ALS. PMID:28512398

  18. Nigrostriatal dysfunction in patients with amyotrophic lateral sclerosis and parkinsonism.

    Science.gov (United States)

    Park, Hee Kyung; Lim, Young-Min; Kim, Jae Seung; Lee, Myoung C; Kim, Seung Min; Kim, Bum Joon; Kim, Kwang-Kuk

    2011-02-15

    The pathomechanism of amyotrophic lateral sclerosis (ALS) with parkinsonism (ALS-P) has not been clarified. We report two patients with ALS-P who showed dysfunction of the nigrostriatal system. The first patient showed tremor dominant, asymmetric parkinsonism which was more severe on the right side, while the second patient exhibited predominant freezing of gait. Both patients showed reduced uptake of [¹⁸F] N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane (¹⁸F-FP-CIT) in the posterior parts of bilateral putamina on positron emission tomography (PET). Based on our PET findings, we suggest that presynaptic nigrostriatal dysfunction may be involved in the pathomechanism of parkinsonism combined with ALS. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. A clustering of conjugal amyotrophic lateral sclerosis in southeastern France.

    Science.gov (United States)

    Corcia, Philippe; Jafari-Schluep, Helene-Farnase; Lardillier, Dominique; Mazyad, Hassan; Giraud, Pieric; Clavelou, Pierre; Pouget, Jean; Camu, William

    2003-04-01

    The origin of amyotrophic lateral sclerosis (ALS) remains largely unknown but seems to be multifactorial. We believe that ALS clusters may help clinicians understand or analyze the role of environmental factors in ALS pathogenesis. To describe a cluster of conjugal ALS in southeastern France. We describe 9 couples in which both spouses were affected by ALS. Eight of the 9 had lived in southeastern France. In all cases, the spouses were married for more than 10 years. Three couples lived in the same département and 2 of them in the same city. To our knowledge, such a large cluster of conjugal ALS cases has not been previously reported. No precise environmental factors could be identified at the origin of these conjugal cases. We suggest that genetic and environmental factors, or both, may explain the occurrence of this cluster of ALS.

  20. Localized muscle impedance abnormalities in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tarulli, Andrew W; Garmirian, Lindsay P; Fogerson, Patricia M; Rutkove, Seward B

    2009-03-01

    To assess changes in electrical impedance myography (EIM) parameters in amyotrophic lateral sclerosis (ALS). Ten patients with ALS and a cohort of normal subjects underwent EIM testing of tibialis anterior. Montages using voltage and current electrodes placed at a distance (far) and in close proximity (near) were compared. The EIM parameters, resistance (R), reactance (X), and phase (theta) in the patients with ALS, were compared with normal values. theta measured at 50 kHz using the near montage was most sensitive to the presence of ALS, with 9 of 10 patients with ALS having smaller theta values than the calculated lower limit of normal. theta using the far montage and X using both the near and far montages were also sensitive to disease, whereas R did not seem to be useful. EIM is sensitive to muscle abnormalities in ALS, with theta measured with near montages providing the best results.

  1. An Amyotrophic Lateral Sclerosis Like Symptoms Associated with Lead Toxicity

    Directory of Open Access Journals (Sweden)

    Mahmoud Abedini

    2017-03-01

    Full Text Available Abstract Lead is a heavy metal that affects many organs such as nervous system, liver, and kidney. The most important affected organ is central nervous system. The present study reported a case similar to Amyotrophic lateral sclerosis (ALS due to lead exposure in an opium addicted person. The patient complaint was the weakness of upper and lower limbs in addition to the unsteadiness of gait. Nerve conduction studies showed normal sensory and motor action potential but needle electromyography showed fasciculation in distal and proximal muscles. The patient was encephalopathic and had psychiatric disorder. The blood lead level was also found to be higher than the normal upper limit. Hence, lead poisoning could occur in a patient addicted to opium with symptoms similar to ALS.

  2. Comprehensive care of amyotrophic lateral sclerosis patients: a care model.

    Science.gov (United States)

    Güell, Maria Rosa; Antón, Antonio; Rojas-García, Ricardo; Puy, Carmen; Pradas, Jesus

    2013-12-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that presents with muscle weakness, causing progressive difficulty in movement, communication, eating and ultimately, breathing, creating a growing dependence on family members and other carers. The ideal way to address the problems associated with the disease, and the decisions that must be taken, is through multidisciplinary teams. The key objectives of these teams are to optimise medical care, facilitate communication between team members, and thus to improve the quality of care. In our centre, we have extensive experience in the care of patients with ALS through an interdisciplinary team whose aim is to ensure proper patient care from the hospital to the home setting. In this article, we describe the components of the team, their roles and our way of working. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  3. Comprehensive Rehabilitative Care Across the Spectrum of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Paganoni, Sabrina; Karam, Chafic; Joyce, Nanette; Bedlack, Richard; Carter, Gregory T

    2016-01-01

    Background Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) is a neurodegenerative disease that results in progressive muscle weakness and wasting. There is no known cure and the disease is uniformly fatal. Purpose This review discusses current concepts in ALS care, from breaking the diagnosis to end-of-life care. People with ALS have several multidisciplinary needs due to a complex and dynamic disease process. They benefit from rehabilitation interventions that are individualized and have the goal of optimizing independence, function, and safety. These strategies also help minimize symptomatic burden and maximize quality of life. Conclusion Patient-centered, multidisciplinary care has a significant impact on the life of people with ALS and is the current standard of care for this patient population. PMID:26409693

  4. Common Molecular Pathways in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.

    Science.gov (United States)

    Weishaupt, Jochen H; Hyman, Tony; Dikic, Ivan

    2016-09-01

    Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative diseases in which predominantly motor neurons and cerebral cortex neurons, respectively, are affected. Several novel ALS and FTD disease genes have been recently discovered, pointing toward a few overarching pathways in ALS/FTD pathogenesis. Nevertheless, a precise picture of how various cellular processes cause neuronal death, or how different routes leading to ALS and FTD are functionally connected is just emerging. Moreover, how the most recent milestone findings in the ALS/FTD field might lead to improved diagnosis and treatment is actively being explored. We highlight some of the most exciting recent topics in the field, which could potentially facilitate the identification of further links between the pathogenic ALS/FTD pathways related to autophagy, vesicle trafficking, and RNA metabolism. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Progress in clinical diagnosis of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    YANG Qiong

    2012-06-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease, mainly involving the pyramidal tract, brain stem and spinal cord anterior horn cells, manifests as progressive muscle atrophy, weakness and cramps, as well as cognitive impairment, and may overlap with frontotemporal dementia. ALS is familial in 5% of cases, whose clinical manifestations are similar to sporadic. The diagnosis is made mainly based on clinical manifestations, using internationally recognized consensus standard, after rule out conditions that can mimic ALS. Genetic testing provides a new way to accelerate the diagnostic process for early intervention. Part of the gene mutations are associated with specific phenotypes. According to this, prognosis assessment and genetic counseling are able to carry out.

  6. Amyotrophic Lateral Sclerosis and Multiple Sclerosis Overlap: A Case Report

    Directory of Open Access Journals (Sweden)

    Francesca Trojsi

    2012-01-01

    Full Text Available The concurrence of amyotrophic lateral sclerosis (ALS and multiple sclerosis (MS is extremely rare. We reported the case of a 33-year-old woman with a past history of paresthesias at the right hand, who developed progressive quadriparesis with muscular atrophy of limbs and, finally, bulbar signs and dyspnea. Clinical and neurophysiologic investigations revealed upper and lower motor neuron signs in the bulbar region and extremities, suggesting the diagnosis of ALS. Moreover, magnetic resonance imaging (MRI and cerebrospinal fluid (CSF analysis demonstrated 3 periventricular and juxtacortical lesions, hyperintense in T2 and FLAIR sequences, and 3 liquoral immunoglobulin G (IgG oligoclonal bands, consistent with diagnosis of primary progressive MS (PPMS. This unusual overlap of ALS and MS leads to the discussion of a hypothetical common pathological process of immunological dysfunction in these two disorders, although the role of immune response in ALS remains ambivalent and unclear.

  7. Amyotrophic Lateral Sclerosis: What Nurses Need to Know.

    Science.gov (United States)

    Bellomo, Tamara L; Cichminski, Lucille

    2017-03-01

    A MOTHER OF THREE teenage children, Mrs. S, 49, presented to her healthcare provider with bilateral leg twitching and weakness, difficulty swallowing, and fatigue that's worsened over the past few weeks. While she was on her daily morning walk, she tripped and fell. She experienced a small laceration to her leg, prompting her visit to the healthcare facility. Her husband said that she'd had periods of slurred speech over the past few months as well. She was alert and oriented, and her vital signs were all within normal limits.After an exam, her healthcare provider referred her to a neurologist who ordered magnetic resonance imaging (MRI), an electromyogram, and a full bloodwork panel. After multiple visits to rule out other causes, Mrs. S received the devastating diagnosis of amyotrophic lateral sclerosis (ALS).

  8. Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

    Science.gov (United States)

    Kumar, Alok; Ghosh, Devlina; Singh, R. L.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients. PMID:26317018

  9. Amyotrophic Lateral Sclerosis: A Focus on Disease Progression

    Science.gov (United States)

    Calvo, Ana C.; Manzano, Raquel; Mendonça, Deise M. F.; Muñoz, María J.; Zaragoza, Pilar

    2014-01-01

    Since amyotrophic lateral sclerosis (ALS) was discovered and described in 1869 as a neurodegenerative disease in which motor neuron death is induced, a wide range of biomarkers have been selected to identify therapeutic targets. ALS shares altered molecular pathways with other neurodegenerative diseases, such as Alzheimer's, Huntington's, and Parkinson's diseases. However, the molecular targets that directly influence its aggressive nature remain unknown. What is the first link in the neurodegenerative chain of ALS that makes this disease so peculiar? In this review, we will discuss the progression of the disease from the viewpoint of the potential biomarkers described to date in human and animal model samples. Finally, we will consider potential therapeutic strategies for ALS treatment and future, innovative perspectives. PMID:25157374

  10. Intrinsic disorder in proteins involved in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Santamaria, Nikolas; Alhothali, Marwa; Alfonso, Maria Harreguy; Breydo, Leonid; Uversky, Vladimir N

    2017-04-01

    Five structurally and functionally different proteins, an enzyme superoxide dismutase 1 (SOD1), a TAR-DNA binding protein-43 (TDP-43), an RNA-binding protein FUS, a cofilin-binding protein C9orf72, and polypeptides generated as a result of its intronic hexanucleotide expansions, and to lesser degree actin-binding profilin-1 (PFN1), are considered to be the major drivers of amyotrophic lateral sclerosis. One of the features common to these proteins is the presence of significant levels of intrinsic disorder. The goal of this study is to consider these neurodegeneration-related proteins from the intrinsic disorder perspective. To this end, we employed a broad set of computational tools for intrinsic disorder analysis and conducted intensive literature search to gain information on the structural peculiarities of SOD1, TDP-43, FUS, C9orf72, and PFN1 and their intrinsic disorder predispositions, and the roles of intrinsic disorder in their normal and pathological functions.

  11. Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole

    Directory of Open Access Journals (Sweden)

    Corcia P

    2012-08-01

    Full Text Available Philippe Corcia,1 Paul H Gordon21Centre SLA, CHRU de Tours, Tours, France; UMR INSERM U930, Université François Rabelais de Tours (PC, Tours, France; 2AP-HP, Hôpital de la Pitié-Salpêtrière, Département des Maladies du Système Nerveux (PHG, Paris, FranceAbstract: Amyotrophic lateral sclerosis (ALS is a neurodegenerative disorder that leads to progressive weakness from loss of motor neurons and death on average in less than 3 years after symptom onset. No clear causes have been found and just one medication, riluzole, extends survival. Researchers have identified some of the cellular processes that occur after disease onset, including mitochondrial dysfunction, protein aggregation, oxidative stress, excitotoxicity, inflammation, and apoptosis. Mitochondrial disease may be a primary event in neurodegeneration or occur secondary to other cellular processes, and may itself contribute to oxidative stress, excitotoxicity, and apoptosis. Clinical trials currently aim to slow disease progression by testing drugs that impact one or more of these pathways. While every agent tested in the 18 years after the approval of riluzole has been ineffective, basic and clinical research methods in ALS have become dramatically more sophisticated. Dexpramipexole (RPPX, the R(+ enantiomer of pramiprexole, which is approved for symptomatic treatment of Parkinson disease, carries perhaps the currently largest body of pre- and early clinical data that support testing in ALS. The neuroprotective properties of RPPX in various models of neurodegeneration, including the ALS murine model, may be produced through protective actions on mitochondria. Early phase trials in human ALS suggest that the drug can be taken safely by patients in doses that provide neuroprotection in preclinical models. A Phase III trial to test the efficacy of RPPX in ALS is underway.Keywords: dexpramipexole, amyotrophic lateral sclerosis, survival, clinical trials, neurodegeneration

  12. Surgical improvement of speech disorder caused by amyotrophic lateral sclerosis.

    Science.gov (United States)

    Saigusa, Hideto; Yamaguchi, Satoshi; Nakamura, Tsuyoshi; Komachi, Taro; Kadosono, Osamu; Ito, Hiroyuki; Saigusa, Makoto; Niimi, Seiji

    2012-12-01

    Amyotrophic lateral sclerosis (ALS) is a progressive debilitating neurological disease. ALS disturbs the quality of life by affecting speech, swallowing and free mobility of the arms without affecting intellectual function. It is therefore of significance to improve intelligibility and quality of speech sounds, especially for ALS patients with slowly progressive courses. Currently, however, there is no effective or established approach to improve speech disorder caused by ALS. We investigated a surgical procedure to improve speech disorder for some patients with neuromuscular diseases with velopharyngeal closure incompetence. In this study, we performed the surgical procedure for two patients suffering from severe speech disorder caused by slowly progressing ALS. The patients suffered from speech disorder with hypernasality and imprecise and weak articulation during a 6-year course (patient 1) and a 3-year course (patient 2) of slowly progressing ALS. We narrowed bilateral lateral palatopharyngeal wall at velopharyngeal port, and performed this surgery under general anesthesia without muscle relaxant for the two patients. Postoperatively, intelligibility and quality of their speech sounds were greatly improved within one month without any speech therapy. The patients were also able to generate longer speech phrases after the surgery. Importantly, there was no serious complication during or after the surgery. In summary, we performed bilateral narrowing of lateral palatopharyngeal wall as a speech surgery for two patients suffering from severe speech disorder associated with ALS. With this technique, improved intelligibility and quality of speech can be maintained for longer duration for the patients with slowly progressing ALS.

  13. Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Saccon, Rachele A; Bunton-Stasyshyn, Rosie K A; Fisher, Elizabeth M C; Fratta, Pietro

    2013-08-01

    Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a--still unknown--toxic gain of function, and the possibility that loss of function plays a role in amyotrophic lateral sclerosis pathogenesis was abandoned. Although loss of function is not causative for amyotrophic lateral sclerosis, here we re-examine two decades of evidence regarding whether loss of function may play a modifying role in SOD1-amyotrophic lateral sclerosis. From analysing published data from patients with SOD1-amyotrophic lateral sclerosis, we find a marked loss of SOD1 enzyme activity arising from almost all mutations. We continue to examine functional data from all Sod1 knockout mice and we find obvious detrimental effects within the nervous system with, interestingly, some specificity for the motor system. Here, we bring together historical and recent experimental findings to conclude that there is a possibility that SOD1 loss of function may play a modifying role in amyotrophic lateral sclerosis. This likelihood has implications for some current therapies aimed at knocking down the level of mutant protein in patients with SOD1-amyotrophic lateral sclerosis. Finally, the wide-ranging phenotypes that result from loss of function indicate that SOD1 gene sequences should be screened in diseases other than amyotrophic lateral sclerosis.

  14. Rapid voice tremor, or "flutter," in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Aronson, A E; Ramig, L O; Winholtz, W S; Silber, S R

    1992-06-01

    In an attempt to clarify the origin and frequency characteristics of a rapid voice tremor, or "flutter," in patients with amyotrophic lateral sclerosis (ALS), eight patients (four men and four women; ages 42 to 70 years) who had ALS and rapid voice tremor and an age- and sex-matched control group of eight subjects were asked to sustain the vowel /a/ and their voices were recorded for later analysis. Each segment of phonation was demodulated into amplitude and frequency components. From each subject's 8-second amplitude and frequency signals, a fast Fourier transform analysis was done on a 1-second segment previously identified perceptually as having the most apparent tremor or flutter. The results showed that patients with ALS had multiple combinations of levels and frequencies for amplitude and frequency modulations in comparison with control subjects, who had consistently low levels of modulations. In an attempt to quantify the tremor or flutter in ALS, amplitude and frequency modulations were not clearly or predominantly represented at one point along the spectrum. Nevertheless, these frequency and amplitude modulations are more prominent in patients with ALS than in normal subjects. The origins of these aberrant frequency and amplitude modulations in ALS patients remain obscure, although speculation is that they are of peripheral rather than central nervous system origin.

  15. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

    Science.gov (United States)

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2016-02-01

    Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. Oral appliance to assist non-invasive ventilation in a patient with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Veldhuis, Steffanie K. B.; Doff, Michiel H. J.; Stegenga, Boudewijn; Nieuwenhuis, Jellie A.; Wijkstra, Peter J.

    From the moment the respiratory muscle groups are affected in amyotrophic lateral sclerosis (ALS), respiratory complications will be the major cause of morbidity and mortality. Untreated respiratory muscle impairment leads to respiratory insufficiency and additionally to difficulties in airway

  17. Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis: report of two new cases and review of literature

    OpenAIRE

    Padovan, Melissa; Caniatti, Luisa Maria; Trotta, Francesco; Govoni, Marcello

    2011-01-01

    Abstract To describe a rare association between rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). Two new cases of patients with RA who developed amyotrophic lateral sclerosis (ALS), one receiving anti-TNF? agents, were reported. Only other five cases of this rare association have been previously described in literature. The simultaneous presence of the two diseases represents a difficult diagnostic challenge because RA may mimic some musculoskeletal symptoms of AL...

  18. Frontostriatal deficit in Motor Neuron Disease/Amyotrophic Lateral Sclerosis (MND/ALS)

    OpenAIRE

    Buoiano, Dr. G; Bongioanni, Dr. P; Magoni, Dr. M; Carboncini, Dr. MC; Rossi, Dr. B

    2003-01-01

    So far, cognitive derangements in MND/ALS have not been widely studied. Nevertheless, it seems that in subgroups of patients cognitive functions are impaired in different degree, so that often at least two sub-types of the syndrome are reported: Motor Neuron Disease/Amyotrophic Lateral Sclerosis/Dementia Syndrome (MND/ALS/DS) and Motor Neuron Disease/Amyotrophic Lateral Sclerosis/ Aphasia Syndrome (MND/ALS/AS. A third subtype showing both symptoms of cognitive impairment may be identified in...

  19. A patient with amyotrophic lateral sclerosis and atypical clinical and electrodiagnostic features: a case report

    OpenAIRE

    Venizelos Alexander; Park Youngsook; Fisher Morris A

    2011-01-01

    Abstract Introduction Amyotrophic lateral sclerosis is a rapidly progressive, fatal neurodegenerative disorder for which there is no effective treatment. The diagnosis is dependent on the clinical presentation and consistent electrodiagnostic studies. Typically, there is a combination of upper and lower motor neuron signs as well as electrodiagnostic studies indicative of diffuse motor axonal injury. The presentation of amyotrophic lateral sclerosis, however, may be variable. At the same time...

  20. Early Dropped Head Syndrome In A Case With Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Shanbhogue K R

    2005-01-01

    Full Text Available We Report a case of "Dropped head syndrome" [DHS] due to Amyotrophic lateral sclerosis [ALS]. A thirty seven year old gentleman was admitted with progressive limb and bulbar weakness of 10 months duration. He developed drooping of the head six months after the onset of illness. After clinical examination and investigation a diagnosis of Amyotrophic lateral sclerosis was made based on El Escorial criteria.

  1. Dropped head and man-in-barrel syndrome in amyotrophic lateral sclerosis

    OpenAIRE

    Almeida, Rui; Felix, Ana Catarina; Andr?, Ana Lu?sa; Nzwalo, Hip?lito

    2017-01-01

    Abstract We report a case of progressive symmetric brachial weakness followed by cervical muscle weakness. The electromyogram confirmed the diagnosis of amyotrophic lateral sclerosis. After 3 years the patient remained able to walk unassisted and without significant bulbar manifestations or upper neuron signs. The concomitant presence of dropped head syndrome and man-in-barrel syndrome in an amyotrophic lateral sclerosis patient makes our case unique.

  2. Targeted Riluzole Delivery by Antioxidant Nanovectors for Treating Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2015-06-01

    AWARD NUMBER: W81XWH-12-1-0612 TITLE: Targeted Riluzole Delivery by Antioxidant Nanovectors for Treating Amyotrophic Lateral Sclerosis...29 Mar 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeted Riluzole Delivery by Antioxidant Nanovectors for Treating Amyotrophic Lateral...potent antioxidant capabilities, and 2) possess the ability to serve as carriers for other potentially therapeutic molecules by James Tour, PhD of

  3. Longitudinal changes in discourse production in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Roberts-South, Angela; Findlater, Kate; Strong, Michael J; Orange, J B

    2012-02-01

    Amyotrophic lateral sclerosis (ALS) is a multisystem disease that significantly impacts communication as a function of changes in motor speech, cognition, and language skills. Although discourse tasks have been used to assess language in a variety of acquired disorders, little work to date has been published on changes in discourse in ALS and even less work has evaluated these changes with disease progression. In the present study, discourse samples (gained from a picture description task) as well as standardized language test measures obtained from 16 individuals with ALS without dementia and 12 healthy controls (collected over a duration of 24 months). Discourse samples were analyzed for both productivity and content. Results indicate that there were no differences for ALS versus controls for any of the standardized language tests. However, findings suggest that discourse analysis methods may be more sensitive for identifying subtle language deficits in ALS. Overall, discourse productivity appears less impaired than discourse content for individuals with ALS. Although there was a general trend for decline in language performance over the study duration, there was the suggestion of subgroups of language performance among ALS participants. The results suggest that subtle cognitive language deficits that affect discourse emerge early in ALS and progress with disease progression. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  4. Identification of new mutations in familial amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Siddique, T.; Deng, H.X.; Hentati, A. [Northwestern Univ. Medical School, Chicago, IL (United States)] [and others

    1994-09-01

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease due to motor neuron death in the cortex, brain stem and spinal cord. Ten percent of ALS cases are familial (FALS). Previously a subset of FALS families have been mapped to chromosome 21 and mutations in the Cu,Zn superoxide dismutase gene have been identified in those families. Nineteen different mutations at 16 distinct codons have been documented, of which 12 different mutations were identified in our 29 FALS families. These mutations account for about twenty percent of all FALS families screened. The mutations identified in our FALS families are A4V, A4T, G37R, G41D, H43R, G85R, G93A, E100G, L106V, I113T, L144F, and V148G. Mutation A4V is the most frequent one which occurred in 14 out of our 29 FALS families. In further screening of our FALS families, two new mutations, V14M and L84V, have been identified. Thus a total of 21 different mutations at 18 distinct codon sites have been identified in SOD1.

  5. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

    Science.gov (United States)

    McLaughlin, Russell L.; Schijven, Dick; van Rheenen, Wouter; van Eijk, Kristel R.; O'Brien, Margaret; Kahn, René S.; Ophoff, Roel A.; Goris, An; Bradley, Daniel G.; Al-Chalabi, Ammar; van den Berg, Leonard H.; Luykx, Jurjen J.; Hardiman, Orla; Veldink, Jan H.; Shatunov, Aleksey; Dekker, Annelot M.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; van Doormaal, Perry T. C.; Sproviero, William; Jones, Ashley R.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Bauer, Denis; Kahlke, Tim; Williams, Kelly; Eftimov, Filip; Fogh, Isabella; Ticozzi, Nicola; Lin, Kuang; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Petri, Susanne; Abdulla, Susanna; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, Nazli; Meitinger, Thomas; Lichtner, Peter; Blagojevic-Radivojkov, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safa; Dürr, Alexandra; Wood, Nicholas; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöuthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; van der Kooi, Anneke J.; de Visser, Marianne; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P.; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simon; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Blair, Ian; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Brown, Robert H.; Glass, Jonathan; Landers, John E.; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T. R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberley D.; Chan, Raymond C. K.; Chan, Ronald Y. L.; Chen, Eric Y. H.; Cheng, Wei; Cheung, Eric F. C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Giegling, Ina; Giusti-Rodríguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julià, Antonio; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kähler, Anna K.; Laurent, Claudine; Lee, Jimmy; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lönnqvist, Jouko; Macek, Milan; Magnusson, Patrik K. E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Müller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O'Callaghan, Eadbhard; O'Dushlaine, Colm; O'Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietiläinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C. A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Söderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H. M.; Wormley, Brandon K.; Xi, Hualin Simon; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R.; Stefansson, Kari; Visscher, Peter M.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H. R.; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tõnu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jönsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Riley, Brien P.; Rujescu, Dan; Sham, Pak C.; Sklar, Pamela; St Clair, David; Weinberger, Daniel R.; Wendland, Jens R.; Werge, Thomas; Daly, Mark J.; Sullivan, Patrick F.; O'Donovan, Michael C.

    2017-03-01

    We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6 P=1 × 10-4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10-7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.

  6. Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Vu, Lucas T; Bowser, Robert

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients. Significant progress has been made using cerebrospinal fluid, serum, and plasma in the search for ALS biomarkers, with urine and saliva biomarkers still in earlier stages of development. A few of these biomarker candidates have demonstrated use in patient stratification, predicting disease course (fast vs slow progression) and severity, or have been used in preclinical and clinical applications. However, while ALS biomarker discovery has seen tremendous advancements in the last decade, validating biomarkers and moving them towards the clinic remains more elusive. In this review, we highlight biomarkers that are moving towards clinical utility and the challenges that remain in order to implement biomarkers at all stages of the ALS drug development process.

  7. Respiratory insufficiency with preserved diaphragmatic function in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Yamauchi, Rika; Imai, Tomihiro; Tsuda, Emiko; Hozuki, Takayoshi; Yamamoto, Daisuke; Shimohama, Shun

    2014-01-01

    We performed a longitudinal study to elucidate the correlation between respiratory insufficiency and respiratory biomarkers, including diaphragmatic compound muscle action potential (DCMAP), at the initiation of noninvasive ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). The patients were assessed at least every six months. Additional assessments were performed at the start of respiratory therapy when the patients met the criteria for the initiation of NIV. Each assessment consisted of a full neurological examination, a phrenic nerve conduction study, respiratory function tests, and nocturnal pulsed oximetry. We enrolled 43 patients with either definite or probable ALS as defined by the revised El Escorial criteria. The patients were divided into two groups according to the timing of the initiation of respiratory therapy. Seventeen patients (group A) met the criteria for NIV initiation when their DCMAP remained normal. Twenty-six patients (group B) met the criteria when their DCMAP decreased below normal limits. Although respiratory function parameters were significantly worse in group B compared with group A at NIV initiation, more than 80% of the patients in both groups developed nocturnal desaturation during sleep. DCMAP is not always a reliable indicator for determining the optimal timing for NIV initiation during the progression of respiratory insufficiency in ALS. Physicians should be aware of the risk of respiratory insufficiency during sleep in patients with ALS.

  8. Meta-analysis of social cognition in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bora, Emre

    2017-03-01

    Amyotrophic lateral sclerosis (ALS) is associated with executive dysfunction and behavioural impairment. Recent studies suggested that social cognitive deficits might also be a prominent feature of ALS. Current meta-analysis aimed to summarize available evidence for deficits in social cognition including theory of mind (ToM) and emotion recognition in ALS. In this meta-analysis of 15 studies, facial emotion recognition and ToM performances of 389 patients with ALS and 471 healthy controls were compared. ALS was associated with significant impairments with medium effect sizes in ToM (d = .65) and facial emotion recognition (d = .69). Among individual emotions recognition of disgust and surprise were particularly impaired. Deficits in perspective taking (d = .73) aspects of ToM (ToM-PT) was more pronounced in comparison to decoding (d = .28) aspects of ToM (ToM-decoding). The severity of social cognitive impairment was similar to level of executive dysfunction and there was a significant relationship between social cognition and executive dysfunction. Deficits in social cognition are part of the cognitive phenotype of ALS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Morphometric correlates of dysarthric deficit in amyotrophic lateral sclerosis.

    Science.gov (United States)

    De Marco, Matteo; Merico, Antonio; Berta, Giulia; Segato, Nicoletta; Citton, Valentina; Baglione, Alessandro; Venneri, Annalena

    2015-01-01

    Our objective was to investigate the volumetric correlates of speech in amyotrophic lateral sclerosis (ALS). Twenty-three ALS patients had a structural 3D MRI scan, neuropsychological, linguistic and speech assessments. Twenty-three healthy adults of comparable age, education, white-matter hyperintensity load and intracranial volumes were also recruited. Between-group differences in grey matter and white matter (WM) were examined to characterize ALS patients accurately. The association between residual speech and volumetric maps was studied in these patients. Results demonstrated that ALS patients showed a pattern of WM reduction, which was located in peri-cortical motor/premotor fibres bilaterally, and in a large volume extending from the pons/midbrain to the cerebellum. A speech composite score was computed, and this was positively associated with premotor/supplementary-motor WM bilaterally, and right cerebellar WM. Since premotor associations were found in volumes where ALS patients showed WM reduction, this region is believed to be directly involved in speech execution in this group. Since cerebellar associations were instead found in volumes free from shrinkage, this region is interpreted as playing a modulatory role, compensating for the impact of ALS pathology.

  10. Black hairy tongue in a patient with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Erriu, Matteo; Pili, Francesca Maria Giovanna; Denotti, Gloria; Garau, Valentino

    2016-01-01

    Black hairy tongue (BHT) is a condition characterized by the elongation of filiform papillae associated with a marked discoloration, from yellowish-brown to black, and a thick lingual coating. BHT is usually observed in the elderly and in patients with limited self-sufficiency, as a consequence of poor oral hygiene. In this perspective, the patients affected by amyotrophic lateral sclerosis (ALS) represent a high-risk category for the occurrence of BHT. The fast and inexorable loss of their self-sufficiency due to progressive muscle atrophy as well as the impropriate education of healthcare assistants have demonstrated to have significant reflection on the maintenance of an adequate standard of oral hygiene. This paper firstly described a case of BHT in a patient affected by ALS. A case of BHT in a patient (Caucasic, male, 63 years old) affected by ALS was described. The primary goal of the work was to teach and motivate the patient to the use of the tongue cleaner in association with the local application of chlorexidine 0.20%. Furthermore, in order to support the patient with accurate domiciliary oral hygiene, a proper training for his health-care assistant was provided. The maintenance of the oral health of ALS patient is fundamental to prevent systemic complications that could jeopardize the already fragile physical balance of these patients. The dedicated monitoring by a dentist or a dental hygienist would seem essential in order to achieve this objective.

  11. Apathy is associated with poor prognosis in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Caga, J; Turner, M R; Hsieh, S; Ahmed, R M; Devenney, E; Ramsey, E; Zoing, M C; Mioshi, E; Kiernan, M C

    2016-05-01

    Apathy is the most commonly reported behavioural change in amyotrophic lateral sclerosis (ALS). However, the degree to which it affects prognosis and overlaps with depression in this population is unknown. The present study examined the relationship between level of apathy, mortality and survival time and whether apathy was linked to specific symptom clusters of depression. A cohort of 76 consecutive ALS patients attending specialized multidisciplinary clinics were classified according to level of apathy. The effects of clinical factors and apathy on survival time were analysed using univariate and multivariate methods. The majority of patients with moderate to severe apathy died during the study (P = 0.003) and had a median survival time of 21.7 months, considerably shorter than patients with mild apathy (46.9 months) and no apathy (51.9 months) (P = 0.0001). Apathy remained a significant predictor of survival even after controlling for clinical factors and symptom duration at the time of study entry (hazard ratio 3.8, 95% confidence interval 1.9-7.5, P = 0.0001). Depression with demoralization was not associated with level of apathy (P = 0.172) whereas depression with anhedonia was more common in patients with apathy than in those without apathy (P = 0.006). The presence of severe apathy is an independent, negative prognostic factor in ALS. © 2016 EAN.

  12. Mitochondria and endoplasmic reticulum crosstalk in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Manfredi, Giovanni; Kawamata, Hibiki

    2016-06-01

    Physical and functional interactions between mitochondria and the endoplasmic reticulum (ER) are crucial for cell life. These two organelles are intimately connected and collaborate to essential processes, such as calcium homeostasis and phospholipid biosynthesis. The connections between mitochondria and endoplasmic reticulum occur through structures named mitochondria associated membranes (MAMs), which contain lipid rafts and a large number of proteins, many of which serve multiple functions at different cellular sites. Growing evidence strongly suggests that alterations of ER-mitochondria interactions are involved in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), a devastating and rapidly fatal motor neuron disease. Mutations in proteins that participate in ER-mitochondria interactions and MAM functions are increasingly being associated with genetic forms of ALS and other neurodegenerative diseases. This evidence strongly suggests that, rather than considering the two organelles separately, a better understanding of the disease process can derive from studying the alterations in their crosstalk. In this review we discuss normal and pathological ER-mitochondria interactions and the evidence that link them to ALS. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Dysphagia in amyotrophic lateral sclerosis: prevalence and clinical findings.

    Science.gov (United States)

    Ruoppolo, G; Schettino, I; Frasca, V; Giacomelli, E; Prosperini, L; Cambieri, C; Roma, R; Greco, A; Mancini, P; De Vincentiis, M; Silani, V; Inghilleri, M

    2013-12-01

    To characterize swallowing deficits in amyotrophic lateral sclerosis (ALS); investigate the delay in dysphagia onset; estimate correlations between dysphagia severity and patients' functional status; identify the symptom(s) most likely to predict dysphagia. A group of 49 consecutive patients with ALS, 14 with bulbar onset and 35 with spinal onset, underwent swallowing evaluation including bedside and fiberoptic endoscopic examination to detect dysphagia. Patients with dysphagia were more likely than those without to have bulbar onset ALS (P = 0.02); more severely impaired chewing (P = 0.01); and tongue muscle deficits (P = 0.001). The only variable measured at first examination significantly associated with dysphagia was a more than mild tongue muscle deficit. The only variable useful in predicting dysphagia was a chewing deficit. In 10 of the 49 patients studied, swallowing evaluation disclosed an impaired cough reflex. Dysphagia in patients with ALS correlates significantly with bulbar onset and with oral swallowing impairment. Fiberoptic swallowing evaluation is a useful tool for detecting swallowing deficits and laryngeal sensitivity in patients with ALS. An impaired cough reflex is an unexpected finding in many patients with ALS. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Discontinuation of mechanical ventilation in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Borasio, G D; Voltz, R

    1998-11-01

    Mechanical ventilation, both invasive and non-invasive, may be an effective means of improving the quality of life and prolonging the survival of patients suffering from amyotrophic lateral sclerosis (ALS). However, the attitude towards this palliative measure varies greatly between different centres and countries. One of the arguments cited against this procedure is the fear that a patient might request the physician to discontinue life support. We believe that the question of withdrawal of mechanical ventilation can only be meaningfully addressed in the general context of palliative care. Here, we review possible modes of action in response to a patient's request for life support withdrawal and their medical, legal and ethical implications. We propose that the following goals should be pursued: (1) prevention of unwanted ventilation by early, open discussion with patient and relatives, (2) delivery of optimal palliative care by the caring team, (3) recognition of the patient's right to withdraw his/her consent to an invasive medical procedure. If these goals have been met, it may be medically, legally and ethically justified for the physician to take all necessary steps to ensure a peaceful death after discontinuation of life support.

  15. Disorders of emotional processing in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Sedda, Anna

    2014-12-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative brain disease characterized by motor, behavioural and cognitive deficits. Only recently, emotional processing disorders have been shown in this disease. The interest in affective processing in ALS is growing given that basic emotion impairments could impact copying strategies and mood. Studies explore both basic emotion recognition and social cognition. Results are congruent on arousal and valence detection impairments, independently from the stimulus modality (verbal or visual). Further, recognition of facial expressions of anger, sadness and disgust is impaired in ALS, even when cognition is preserved. Clinical features such as type of onset and severity of the disease could be the cause of the heterogeneity in emotional deficits profiles between patients. Finally, a study employing diffusion tensor imaging showed that emotional dysfunctions in ALS are related to right hemispheric connective bundles impairments, involving the inferior longitudinal fasciculus and the inferior frontal occipital fasciculus. Research on emotional processing in ALS is still in its infancy and results are mixed. Future research including more detailed clinical profiles of patients and measures of brain connectivity will provide useful information to understand heterogeneity of results in ALS.

  16. Amyotrophic lateral sclerosis: improving care with a multidisciplinary approach

    Science.gov (United States)

    Hogden, Anne; Foley, Geraldine; Henderson, Robert D; James, Natalie; Aoun, Samar M

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, leading to death within an average of 2–3 years. A cure is yet to be found, and a single disease-modifying treatment has had a modest effect in slowing disease progression. Specialized multidisciplinary ALS care has been shown to extend survival and improve patients’ quality of life, by providing coordinated interprofessional care that seeks to address the complex needs of this patient group. This review examines the nature of specialized multidisciplinary care in ALS and draws on a broad range of evidence that has shaped current practice. The authors explain how multidisciplinary ALS care is delivered. The existing models of care, the role of palliative care within multidisciplinary ALS care, and the costs of formal and informal care are examined. Critical issues of ALS care are then discussed in the context of the support rendered by multidisciplinary-based care. The authors situate the patient and family as key stakeholders and decision makers in the multidisciplinary care network. Finally, the current challenges to the delivery of coordinated interprofessional care in ALS are explored, and the future of coordinated interprofessional care for people with ALS and their family caregivers is considered. PMID:28579792

  17. A(a)LS: Ammonia-induced amyotrophic lateral sclerosis

    Science.gov (United States)

    Parekh, Bhavin

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a dreadful, devastating and incurable motor neuron disease. Aetiologically, it is a multigenic, multifactorial and multiorgan disease. Despite intense research, ALS pathology remains unexplained. Following extensive literature review, this paper posits a new integrative explanation. This framework proposes that ammonia neurotoxicity is a main player in ALS pathogenesis. According to this explanation, a combination of impaired ammonia removal— mainly because of impaired hepatic urea cycle dysfunction—and increased ammoniagenesis— mainly because of impaired glycolytic metabolism in fast twitch skeletal muscle—causes chronic hyperammonia in ALS. In the absence of neuroprotective calcium binding proteins (calbindin, calreticulin and parvalbumin), elevated ammonia—a neurotoxin—damages motor neurons. Ammonia-induced motor neuron damage occurs through multiple mechanisms such as macroautophagy-endolysosomal impairment, endoplasmic reticulum (ER) stress, CDK5 activation, oxidative/nitrosative stress, neuronal hyperexcitability and neuroinflammation. Furthermore, the regional pattern of calcium binding proteins’ loss, owing to either ER stress and/or impaired oxidative metabolism, determines clinical variability of ALS. Most importantly, this new framework can be generalised to explain other neurodegenerative disorders such as Huntington’s disease and Parkinsonism. PMID:27785351

  18. Cortical hyperexcitability and disease spread in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Menon, P; Geevasinga, N; van den Bos, M; Yiannikas, C; Kiernan, M C; Vucic, S

    2017-06-01

    Amyotrophic lateral sclerosis (ALS) is characterized by focal disease onset with a predominantly contiguous pattern of disease spread. The pathophysiological mechanisms underlying disease progression in ALS have not been elucidated. Given that cortical hyperexcitability has been identified as an important pathogenic mechanism in ALS, the aim of the present study was to determine whether changes in cortical function could mediate disease spread in ALS. Threshold-tracking transcranial magnetic stimulation was undertaken in 50 patients with sporadic ALS with recording of responses over both abductor pollicis brevis muscles, with results matched to clinical assessments and concurrent neurophysiological investigation of lower motor neuron function. Subsequently, patients were followed longitudinally to map patterns of clinical disease progression. Cortical dysfunction was evident over both motor cortices, with hyperexcitability more prominent over the dominant motor cortex, contralateral to the site of disease onset, with reduction of resting motor threshold (F = 3.83, P side of symptom onset, and contributes to a contiguous pattern of spread in sporadic ALS. © 2017 EAN.

  19. Trigemino-cervical response in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Xu, Y; Fan, D; Zhang, J; Zheng, J; Zhang, S; Kang, D

    2005-03-01

    The trigemino-cervical response (TCR) was investigated in the patients with amyotrophic lateral sclerosis (ALS) to evaluate its effect for disclosing the bulbar involvement in this disorder. We studied 100 normal subjects and 45 patients with ALS. In all normal subjects, stimulation of the infraorbital nerve on one side produced bilateral short latency waves, which consisted of a positive/negative wave described with the mean peak latency (P20/N30). The mean square root of the ratio between the amplitude of P20/N30 and the mean rectified surface EMG activity preceding the stimulus was described by A value. The latency of P20 in controls was 18.5 +/- 1.4 ms, N30 was 28.8 +/- 2.8 ms, and the A value was 1.6 +/- 0.5, respectively. In ALS patients, twelve showed absent, seventeen were delayed in the latencies, six were above normal asymmetry on two sides, and ten showed normal. The latency of P20 in ALS patients was 22.9 +/- 9.4 ms, N30 was 33.7 +/- 11.2 ms, and the A value was 1.5 +/- 0.8, respectively. The parameters of the latencies of TCR between ALS patients and the normal controls were statistically different (P < 0.05). TCR can be reliably measured in all normal subjects and help in disclosing lower brainstem lesions in ALS patients, even without bulbar symptoms.

  20. [Single fibre electromyography in 18 patients with amyotrophic lateral sclerosis].

    Science.gov (United States)

    Dinca-Avarvarei, L; Patrignani-Ochoa, J H; Castilla-Garrido, J M; Jiménez-Castellano Ballesteros, R; Ugarte-Monasterio, J

    Single fibre electromyography (SFEMG) is a method that complements conventional electromyography and studies the activity of individual muscle fibres and of the neuromuscular junction. AIMS. We attempt to demonstrate the presence of reinnervation disorders by studying Jitter, fibre density (FD) and the presence of neurogenic blocks in patients with amyotrophic lateral sclerosis (ALS). SFEMG was carried out on 18 patients diagnosed with ALS. All the patients were submitted to a voluntary SFEMG in the extensor digitorum communis muscle of the fingers on the most affected side. The SFEMG in the extensor digitorum communis muscle of the fingers showed alterations in 13 out of the 18 patients studied (72%). FD was the most reliable parameter for translation of the motor neuron instability and increased in all cases. This was followed by the mean and the maximum individual (62%) Jitter and, lastly, the percentage of blocks (38%). In ALS, the parameters studied with SFEMG were modified in 72% of the cases studied. There is an overall correlation between the length of time the patient has had the disease and the modifications in the SFEMG (21.5 versus 13.7 months). The degree of clinical involvement is higher (6.5/13) in those who present an altered SFEMG compared to those who present a normal SFEMG (5.3/13).

  1. A predictive model for amyotrophic lateral sclerosis (ALS) diagnosis.

    Science.gov (United States)

    Gupta, P K; Prabhakar, S; Sharma, S; Anand, A

    2012-01-15

    The clinical diagnosis of amyotrophic lateral sclerosis (ALS) usually takes several months. The delay in diagnosis compromises the effective therapeutic interventions. Therefore, the present study was aimed to develop a statistical model for predicting the risk of ALS at earlier stages for better management of ALS patients. The study recruited 44 sporadic ALS patients and 29 normal controls. Thirteen different independent variables (predictors) which were believed to be associated with ALS were included in the study. Forward stepwise (likelihood ratio) binary logistic regression was used to find significant variables and probability of disease prediction. The Hosmer-Lemeshow goodness of fit statistic (χ(2)=4.379, df=8, p=0.821) indicate the appropriateness of forward stepwise (likelihood ratio) binary logistic regression model. Serum chemokine ligand-2, chemokine ligand-2 mRNA, vascular endothelial growth factor-A mRNA, smoking and alcohol consumption are the independent variables found significant to predict risk of ALS (pside diagnostic utility of these variables needs to be validated further in larger ALS cohorts. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Longitudinal diffusion tensor imaging in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Keil Carsten

    2012-11-01

    Full Text Available Abstract Background Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disorder, caused by progressive loss of motor neurons. Changes are widespread in the subcortical white matter in ALS. Diffusion tensor imaging (DTI detects pathological changes in white matter fibres in vivo, based on alterations in the degree (diffusivity, ADC and directedness (fractional anisotropy, FA of proton movement. Methods 24 patients with ALS and 24 age-matched controls received 1.5T DTI. FA and ADC were analyzed using statistical parametric mapping. In 15 of the 24 ALS patients, a second DTI was obtained after 6 months. Results Decreased FA in the corticospinal tract (CST and frontal areas confirm existing results. With a direct comparison of baseline and follow-up dataset, the progression of upper motor neuron degeneration, reflected in FA decrease, could be captured along the CST and in frontal areas. The involvement of cerebellum in the pathology of ALS, as suspected from functional MRI studies, could be confirmed by a reduced FA (culmen, declive. These structural changes correlated well with disease duration, ALSFRS-R, and physical and executive functions. Conclusion DTI detects changes that are regarded as prominent features of ALS and thus, shows promise in its function as a biomarker. Using the technique herein, we could demonstrate DTI changes at follow-up which correlated well with clinical progression.

  3. Blood Lead, Bone Turnover, and Survival in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Fang, Fang; Peters, Tracy L; Beard, John D; Umbach, David M; Keller, Jean; Mariosa, Daniela; Allen, Kelli D; Ye, Weimin; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

    2017-11-01

    Blood lead and bone turnover may be associated with the risk of amyotrophic lateral sclerosis (ALS). We aimed to assess whether these factors were also associated with time from ALS diagnosis to death through a survival analysis of 145 ALS patients enrolled during 2007 in the National Registry of Veterans with ALS. Associations of survival time with blood lead and plasma biomarkers of bone resorption (C-terminal telopeptides of type I collagen (CTX)) and bone formation (procollagen type I amino-terminal peptide (PINP)) were estimated using Cox models adjusted for age at diagnosis, diagnostic certainty, diagnostic delay, site of onset, and score on the Revised ALS Functional Rating Scale. Hazard ratios were calculated for each doubling of biomarker concentration. Blood lead, plasma CTX, and plasma PINP were mutually adjusted for one another. Increased lead (hazard ratio (HR) = 1.38; 95% confidence interval (CI): 1.03, 1.84) and CTX (HR = 2.03; 95% CI: 1.42, 2.89) were both associated with shorter survival, whereas higher PINP was associated with longer survival (HR = 0.59; 95% CI: 0.42, 0.83), after ALS diagnosis. No interactions were observed between lead or bone turnover and other prognostic indicators. Lead toxicity and bone metabolism may be involved in ALS pathophysiology. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  4. The corticospinal tract in amyotrophic lateral sclerosis: an MRI study

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    Hofmann, E.; Warmuth-Metz, M. [Department of Neuroradiology, University of Wuerzburg (Germany); Ochs, G.; Pelzl, A. [Department of Neurology, University of Wuerzburg, Wuerzburg (Germany)

    1998-02-01

    Cortical motor neurone loss and corticospinal tract (CST) degeneration are typical of amyotrophic lateral sclerosis (ALS). It is a matter of debate whether qualitative assessment of the CST by MRI is useful in the diagnosis. It is also an open question whether quantitative determination of the T2 relaxation times can improve its value. Signal intensity along the CST on 14 consecutive slices was assessed using arbitrary visual rating on double-echo T2-weighted and proton-density spin-echo images of 21 patients with ALS and 21 age- and sex-matched controls. T2 was determined quantitatively. On the T2-weighted images the patients` ratings did not differ from that of controls. The T2 of patients and controls showed no statistical difference in any slice. There was no correlation between T2 and patient age, duration of the disease, or predominant bulbar, lower or upper motor neurone signs. The only correlation between MRI findings and disease was on the proton-density images: all cases in which the CST was poorly seen were controls; a clearly high-signal CST was seen only in the patients. High conspicuity of the CST was thus specific but not sensitive for the diagnosis of ALS. T2-weighted images and measurement of T2 were not useful for diagnosis. (orig.) With 2 figs., 1 tab., 26 refs.

  5. Vitamin D as a potential therapy in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Gianforcaro, Alexandro; Hamadeh, Mazen J

    2014-02-01

    Vitamin D has been demonstrated to influence multiple aspects of amyotrophic lateral sclerosis (ALS) pathology. Both human and rodent central nervous systems express the vitamin D receptor (VDR) and/or its enzymatic machinery needed to fully activate the hormone. Clinical research suggests that vitamin D treatment can improve compromised human muscular ability and increase muscle size, supported by loss of motor function and muscle mass in animals following VDR knockout, as well as increased muscle protein synthesis and ATP production following vitamin D supplementation. Vitamin D has also been shown to reduce the expression of biomarkers associated with oxidative stress and inflammation in patients with multiple sclerosis, rheumatoid arthritis, congestive heart failure, Parkinson's disease and Alzheimer's disease; diseases that share common pathophysiologies with ALS. Furthermore, vitamin D treatment greatly attenuates hypoxic brain damage in vivo and reduces neuronal lethality of glutamate insult in vitro; a hallmark trait of ALS glutamate excitotoxicity. We have recently shown that high-dose vitamin D3 supplementation improved, whereas vitamin D3 restriction worsened, functional capacity in the G93A mouse model of ALS. In sum, evidence demonstrates that vitamin D, unlike the antiglutamatergic agent Riluzole, affects multiple aspects of ALS pathophysiology and could provide a greater cumulative effect. © 2014 John Wiley & Sons Ltd.

  6. Assessment of the upper motor neuron in amyotrophic lateral sclerosis.

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    Huynh, William; Simon, Neil G; Grosskreutz, Julian; Turner, Martin R; Vucic, Steve; Kiernan, Matthew C

    2016-07-01

    Clinical signs of upper motor neuron (UMN) involvement are an important component in supporting the diagnosis of amyotrophic lateral sclerosis (ALS), but are often not easily appreciated in a limb that is concurrently affected by muscle wasting and lower motor neuron degeneration, particularly in the early symptomatic stages of ALS. Whilst recent criteria have been proposed to facilitate improved detection of lower motor neuron impairment through electrophysiological features that have improved diagnostic sensitivity, assessment of upper motor neuron involvement remains essentially clinical. As a result, there is often a significant diagnostic delay that in turn may impact institution of disease-modifying therapy and access to other optimal patient management. Biomarkers of pathological UMN involvement are also required to ensure patients with suspected ALS have timely access to appropriate therapeutic trials. The present review provides an analysis of current and recently developed assessment techniques, including novel imaging and electrophysiological approaches used to study corticomotoneuronal pathology in ALS. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  7. Cystatin C: a candidate biomarker for amyotrophic lateral sclerosis.

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    Meghan E Wilson

    2010-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development. The cysteine protease inhibitor cystatin C has recently gained interest as a candidate diagnostic biomarker for ALS, but further studies are required to fully characterize its biomarker utility. We used quantitative enzyme-linked immunosorbent assay (ELISA to assess initial and longitudinal cerebrospinal fluid (CSF and plasma cystatin C levels in 104 ALS patients and controls. Cystatin C levels in ALS patients were significantly elevated in plasma and reduced in CSF compared to healthy controls, but did not differ significantly from neurologic disease controls. In addition, the direction of longitudinal change in CSF cystatin C levels correlated to the rate of ALS disease progression, and initial CSF cystatin C levels were predictive of patient survival, suggesting that cystatin C may function as a surrogate marker of disease progression and survival. These data verify prior results for reduced cystatin C levels in the CSF of ALS patients, identify increased cystatin C levels in the plasma of ALS patients, and reveal correlations between CSF cystatin C levels to both ALS disease progression and patient survival.

  8. Further development of biomarkers in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blasco, H; Vourc'h, P; Pradat, P F; Gordon, P H; Andres, C R; Corcia, P

    2016-08-01

    Amyotrophic lateral sclerosis (ALS) is an idiopathic neurodegenerative disease usually fatal in less than three years. Even if standard guidelines are available to diagnose ALS, the mean diagnosis delay is more than one year. In this context, biomarker discovery is a priority. Research has to focus on new diagnostic tools, based on combined explorations. In this review, we specifically focus on biology and imaging markers. We detail the innovative field of 'omics' approach and imaging and explain their limits to be useful in routine practice. We describe the most relevant biomarkers and suggest some perspectives for biomarker research. Expert commentary: The successive failures of clinical trials in ALS underline the need for new strategy based on innovative tools to stratify patients and to evaluate their responses to treatment. Biomarker data may be useful to improve the designs of clinical trials. Biomarkers are also needed to better investigate disease pathophysiology, to identify new therapeutic targets, and to improve the performance of clinical assessments for diagnosis and prognosis in the clinical setting. A consensus on the best management of neuroimaging and 'omics' methods is necessary and a systematic independent validation of findings may add robustness to future studies.

  9. Emerging molecular biomarker targets for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Costa, Júlia; de Carvalho, Mamede

    2016-04-01

    Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disease that affects upper (UMN) and lower motor (LMN) neurons. It is associated with a short survival and there is no effective treatment, in spite of a large number of clinical trials. Strong efforts have been made to identify novel disease biomarkers to support diagnosis, provide information on prognosis, to measure disease progression in trials and increase our knowledge on disease pathogenesis. Electromyography by testing the function of the LMN can be used as a biomarker of its dysfunction. A number of electrophysiological and neuroimaging methods have been explored to identify a reliable marker of UMN degeneration. Recently, strong evidence from independent groups, large cohorts of patients and multicenter studies indicate that neurofilaments are very promising diagnostic biomarkers, in particular cerebrospinal fluid and blood levels of phosphoneurofilament heavy chain and neurofilament light chain. Furthermore, their increased levels are associated with poor prognosis. Additional studies have been performed aiming to identify other biomarkers, which alone or in combination with neurofilaments could increase the sensitivity and the specificity of the assays. Emerging molecular marker targets are being discovered, but more studies with standardized methods are required in larger cohorts of ALS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Blood Biomarkers for Amyotrophic Lateral Sclerosis: Myth or Reality?

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    Laura Robelin

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal condition primarily characterized by the selective loss of upper and lower motor neurons. At present, the diagnosis and monitoring of ALS is based on clinical examination, electrophysiological findings, medical history, and exclusion of confounding disorders. There is therefore an undeniable need for molecular biomarkers that could give reliable information on the onset and progression of ALS in clinical practice and therapeutic trials. From a practical point of view, blood offers a series of advantages, including easy handling and multiple testing at a low cost, that make it an ideal source of biomarkers. In this review, we revisited the findings of many studies that investigated the presence of systemic changes at the molecular and cellular level in patients with ALS. The results of these studies reflect the diversity in the pathological mechanisms contributing to disease (e.g., excitotoxicity, oxidative stress, neuroinflammation, metabolic dysfunction, and neurodegeneration, among others and provide relatively successful evidence of the usefulness of a wide-ranging panel of molecules as potential biomarkers. More studies, hopefully internationally coordinated, would be needed, however, to translate the application of these biomarkers into benefit for patients.

  11. Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis

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    Matthew S. Devine

    2015-01-01

    Full Text Available Limb weakness in amyotrophic lateral sclerosis (ALS is typically asymmetric. Previous studies have identified an effect of limb dominance on onset and spread of weakness, however relative atrophy of dominant and non-dominant brain regions has not been investigated. Our objective was to use voxel-based morphometry (VBM to explore gray matter (GM asymmetry in ALS, in the context of limb dominance. 30 ALS subjects were matched with 17 healthy controls. All subjects were right-handed. Each underwent a structural MRI sequence, from which GM segmentations were generated. Patterns of GM atrophy were assessed in ALS subjects with first weakness in a right-sided limb (n = 15 or left-sided limb (n = 15. Within each group, a voxelwise comparison was also performed between native and mirror GM images, to identify regions of hemispheric GM asymmetry. Subjects with ALS showed disproportionate atrophy of the dominant (left motor cortex hand area, irrespective of the side of first limb weakness (p < 0.01. Asymmetric atrophy of the left somatosensory cortex and temporal gyri was only observed in ALS subjects with right-sided onset of limb weakness. Our VBM protocol, contrasting native and mirror images, was able to more sensitively detect asymmetric GM pathology in a small cohort, compared with standard methods. These findings indicate particular vulnerability of dominant upper limb representation in ALS, supporting previous clinical studies, and with implications for cortical organisation and selective vulnerability.

  12. Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Devine, Matthew S; Pannek, Kerstin; Coulthard, Alan; McCombe, Pamela A; Rose, Stephen E; Henderson, Robert D

    2015-01-01

    Limb weakness in amyotrophic lateral sclerosis (ALS) is typically asymmetric. Previous studies have identified an effect of limb dominance on onset and spread of weakness, however relative atrophy of dominant and non-dominant brain regions has not been investigated. Our objective was to use voxel-based morphometry (VBM) to explore gray matter (GM) asymmetry in ALS, in the context of limb dominance. 30 ALS subjects were matched with 17 healthy controls. All subjects were right-handed. Each underwent a structural MRI sequence, from which GM segmentations were generated. Patterns of GM atrophy were assessed in ALS subjects with first weakness in a right-sided limb (n = 15) or left-sided limb (n = 15). Within each group, a voxelwise comparison was also performed between native and mirror GM images, to identify regions of hemispheric GM asymmetry. Subjects with ALS showed disproportionate atrophy of the dominant (left) motor cortex hand area, irrespective of the side of first limb weakness (p < 0.01). Asymmetric atrophy of the left somatosensory cortex and temporal gyri was only observed in ALS subjects with right-sided onset of limb weakness. Our VBM protocol, contrasting native and mirror images, was able to more sensitively detect asymmetric GM pathology in a small cohort, compared with standard methods. These findings indicate particular vulnerability of dominant upper limb representation in ALS, supporting previous clinical studies, and with implications for cortical organisation and selective vulnerability.

  13. Amyotrophic lateral sclerosis: an emerging era of collaborative gene discovery.

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    Katrina Gwinn

    2007-12-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common form of motor neuron disease (MND. It is currently incurable and treatment is largely limited to supportive care. Family history is associated with an increased risk of ALS, and many Mendelian causes have been discovered. However, most forms of the disease are not obviously familial. Recent advances in human genetics have enabled genome-wide analyses of single nucleotide polymorphisms (SNPs that make it possible to study complex genetic contributions to human disease. Genome-wide SNP analyses require a large sample size and thus depend upon collaborative efforts to collect and manage the biological samples and corresponding data. Public availability of biological samples (such as DNA, phenotypic and genotypic data further enhances research endeavors. Here we discuss a large collaboration among academic investigators, government, and non-government organizations which has created a public repository of human DNA, immortalized cell lines, and clinical data to further gene discovery in ALS. This resource currently maintains samples and associated phenotypic data from 2332 MND subjects and 4692 controls. This resource should facilitate genetic discoveries which we anticipate will ultimately provide a better understanding of the biological mechanisms of neurodegeneration in ALS.

  14. [Amyotrophic lateral sclerosis in literature, cinema and television].

    Science.gov (United States)

    Collado-Vázquez, Susana; Carrillo, Jesús María

    2014-07-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course that affects the corticospinal and spinal cord motor neurons, the main manifestations of which are muscular weakness, amyotrophy and hyperreflexia. It has an incidence of 0.4-2.4 cases/100,000 inhabitants/year, and a prevalence of 4-6 cases/100,000 inhabitants. It is more frequent in adult males over 50 years of age. A number of different neurological diseases have been portrayed in literature, cinema and television, including ALS, which has been presented correctly and realistically. To analysis how literature, cinema and television have addressed ALS. Several different literary works have dealt with ALS, such as El desencuentro, Lou Gehrig: the luckiest man or Tuesdays with Morrie; the cinema has also depicted this disease in films such as The pride of the Yankees, My love beside me (closer to Heaven) or Right to die; and on television this disease has been shown in series, documentaries and television films, such as: Tuesdays with Morrie, Jenifer or A love affair: the Eleanor and Lou Gehrig Story. Most of the works are of a biographical and testimonial nature, and portray the disease realistically, with the intention of making ALS more widely known and raising the population's awareness about the condition. Literature, cinema and television have portrayed ALS in a realistic and believable manner, unlike some other diseases of a neurological origin.

  15. Widespread temporo-occipital lobe dysfunction in amyotrophic lateral sclerosis

    Science.gov (United States)

    Loewe, Kristian; Machts, Judith; Kaufmann, Jörn; Petri, Susanne; Heinze, Hans-Jochen; Borgelt, Christian; Harris, Joseph Allen; Vielhaber, Stefan; Schoenfeld, Mircea Ariel

    2017-01-01

    Recent studies suggest that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) lie on a single clinical continuum. However, previous neuroimaging studies have found only limited involvement of temporal lobe regions in ALS. To better delineate possible temporal lobe involvement in ALS, the present study aimed to examine changes in functional connectivity across the whole brain, particularly with regard to extra-motor regions, in a group of 64 non-demented ALS patients and 38 healthy controls. To assess between-group differences in connectivity, we computed edge-level statistics across subject-specific graphs derived from resting-state functional MRI data. In addition to expected ALS-related decreases in functional connectivity in motor-related areas, we observed extensive changes in connectivity across the temporo-occipital cortex. Although ALS patients with comorbid FTD were deliberately excluded from this study, the pattern of connectivity alterations closely resembles patterns of cerebral degeneration typically seen in FTD. This evidence for subclinical temporal dysfunction supports the idea of a common pathology in ALS and FTD.

  16. Writing Errors and Anosognosia in Amyotrophic Lateral Sclerosis with Dementia

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    Hiroo Ichikawa

    2008-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS with dementia (ALS-D is known to exhibit characteristics of frontotemporal dementia. However, in clinical situations, it is often difficult to evaluate their cognitive functions because of impaired voluntary speech and physical disabilities. In order to identify characteristic and diagnostic cognitive symptoms of relatively advanced ALS-D patients, we retrospectively reviewed the clinical features of seven cases of clinically definitive ALS who had dementia, impaired voluntary speech, and physical disability. Their medical records showed that six out of seven patients made writing errors, and all of the patients demonstrated anosognosia. The writing errors consisted of paragraphia such as substitution, omission, or syntactic errors with individual differences in error types. Dissociation between kana and kanji were also observed. Anosognosia was evaluated by a self-rating scale with which the patients and the medical staff evaluated the patient's physical ability; the results indicated a large discrepancy between the evaluation by the patients and the medical staff. We emphasize that aphasic writing errors have been underestimated, particularly in ALS-D patients with impaired voluntary speech. We also reported that anosognosia was the most important and quantifiable symptom in ALS-D. The relationship between writing errors and anosognosia should be investigated further.

  17. Clinical Significance of TDP-43 Neuropathology in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Cykowski, Matthew D; Powell, Suzanne Z; Peterson, Leif E; Appel, Joan W; Rivera, Andreana L; Takei, Hidehiro; Chang, Ellen; Appel, Stanley H

    2017-05-01

    To determine the significance of TAR DNA binding protein 43 kDa (TDP-43) pathology in amyotrophic lateral sclerosis (ALS), we examined the whole brains and spinal cords of 57 patients (35 men; 22 women; mean age 63.3 years; 15 patients with c9orf72-associated ALS [c9ALS]). TDP-43 pathologic burden was determined relative to symptom onset site, disease duration, progression rate, cognitive status, and c9ALS status. There was a trend for greater TDP-43 pathologic burden in cognitively impaired patients (p = 0.07), though no association with disease duration or progression rate was seen. Shorter disease duration (p = 0.0016), more severe striatal pathology (p = 0.0029), and a trend toward greater whole brain TDP-43 pathology (p = 0.059) were found in c9ALS. Cluster analysis identified "TDP43-limited," "TDP43-moderate," and "TDP43-severe" subgroups. The TDP43-limited group contained more cognitively intact (p = 0.005) and lower extremity onset site (p = 0.019) patients, while other subgroups contained more cognitively impaired patients. We conclude that TDP-43 pathologic burden in ALS is associated with cognitive impairment and c9ALS, but not duration of disease or rate of progression. Further, we demonstrate a subgroup of patients with low TDP-43 burden, lower extremity onset, and intact cognition, which requires further investigation. © 2017 American Association of Neuropathologists, Inc.

  18. Intraspinal Stem Cell Transplantation for Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Chen, Kevin S.; Sakowski, Stacey A.; Feldman, Eva L.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder in which the loss of upper and lower motor neurons produces progressive weakness and eventually death. In the decades since the approval of riluzole, the only FDA approved medication to moderately slow progression of ALS, no new therapeutics have arisen to alter the course of the disease. This is partly due to our incomplete understanding of the complex pathogenesis of motor neuron degeneration. Stem cells have emerged as an attractive option in treating ALS since they come armed with equally complex cellular machinery and may modulate the local microenvironment in many ways to rescue diseased motor neurons. While various stem cell types are being evaluated in preclinical and early clinical applications, here we review the preclinical strategies and advances supporting the recent clinical translation of neural progenitor cell therapy for ALS. Specifically, we focus on the use of spinal cord neural progenitor cells and the pipeline starting from preclinical studies to the designs of the Phase I and IIa clinical trials involving direct intraspinal transplantation in humans. PMID:26696091

  19. 25 years of neuroimaging in amyotrophic lateral sclerosis

    Science.gov (United States)

    Foerster, Bradley R.; Welsh, Robert C.; Feldman, Eva L.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease for which a precise cause has not yet been identified. Standard CT or MRI evaluation does not demonstrate gross structural nervous system changes in ALS, so conventional neuroimaging techniques have provided little insight into the pathophysiology of this disease. Advanced neuroimaging techniques—such as structural MRI, diffusion tensor imaging and proton magnetic resonance spectroscopy—allow evaluation of alterations of the nervous system in ALS. These alterations include focal loss of grey and white matter and reductions in white matter tract integrity, as well as changes in neural networks and in the chemistry, metabolism and receptor distribution in the brain. Given their potential for investigation of both brain structure and function, advanced neuroimaging methods offer important opportunities to improve diagnosis, guide prognosis, and direct future treatment strategies in ALS. In this article, we review the contributions made by various advanced neuroimaging techniques to our understanding of the impact of ALS on different brain regions, and the potential role of such measures in biomarker development. PMID:23917850

  20. Ethical considerations in the management of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Eisen, Andrew; Krieger, Charles

    2013-11-01

    This article examines some of the ethical concerns relevant for the management of amyotrophic lateral sclerosis (ALS). We emphasize the importance for providing a competent assessment of the clinical deficit to correctly identify the disease and to avoid incorrect diagnoses. Conveying the diagnosis to the patient and their family requires empathy and it is important to remain supportive and positive, even in the face of this incurable disease. The essence of care in ALS is to permit the patient to have optimal function for their level of ability. This may require the use of gastrostomy and non-invasive or permanent ventilation. Employment of a multi-disciplinary team will permit optimization of patient care to achieve a good quality of life for as long as possible. The patient should also be informed of the risks associated with unproven therapies and the risks and potential benefits of therapeutic trials. The wishes of patients in regard to gastrostomy, long-term ventilation and end-of life decisions must be considered in an unbiased fashion. Recent advances in the genetics of familial ALS (FALS) have demonstrated some overlap between FALS, sporadic ALS and fronto-temporal lobar dementia (FTLD). The interpretation and dissemination of the results of genetic testing although important can induce confusion, considerable anxiety and guilt in patients and their families and proper counseling is imperative. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Dysregulation of chromatin remodelling complexes in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tibshirani, Michael; Zhao, Beibei; Gentil, Benoit J; Minotti, Sandra; Marques, Christine; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Rouaux, Caroline; Robertson, Janice; Durham, Heather D

    2017-11-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS. When plasmids encoding wild-type or mutant human FUS or TDP-43 were expressed in motor neurons of dissociated spinal cord cultures prepared from E13 mice, mutant proteins in particular accumulated in the cytoplasm. Immunolabelling of nBAF subunits was reduced in proportion to loss of nuclear FUS or TDP-43 and depletion of Brg1 was associated with nuclear retention of Brg1 mRNA. Dendritic attrition (loss of intermediate and terminal dendritic branches) occurred in motor neurons expressing mutant, but not wild-type, FUS or TDP-43. This attrition was delayed by ectopic over-expression of Brg1 and was reproduced by inhibiting Brg1 activity either through genetic manipulation or treatment with the chemical inhibitor, (E)-1-(2-Hydroxyphenyl)-3-((1R, 4R)-5-(pyridin-2-yl)-2, 5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one, demonstrating the importance of Brg1 to maintenance of dendritic architecture. Loss of nBAF subunits was also documented in spinal motor neurons in autopsy tissue from familial amyotrophic sclerosis (chromosome 9 open reading frame 72 with G4C2 nucleotide expansion) and from sporadic cases with no identified mutation, pointing to dysfunction of nBAF chromatin remodelling in multiple forms of ALS. © The Author 2017. Published by Oxford University Press. All rights reserved

  2. Microstructural Correlates of Emotional Attribution Impairment in Non-Demented Patients with Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Crespi, Chiara; Cerami, Chiara; Dodich, Alessandra; Canessa, Nicola; Iannaccone, Sandro; Corbo, Massimo; Lunetta, Christian; Falini, Andrea; Cappa, Stefano F

    2016-01-01

    Impairments in the ability to recognize and attribute emotional states to others have been described in amyotrophic lateral sclerosis patients and linked to the dysfunction of key nodes of the emotional empathy network. Microstructural correlates of such disorders are still unexplored. We investigated the white-matter substrates of emotional attribution deficits in a sample of amyotrophic lateral sclerosis patients without cognitive decline. Thirteen individuals with either probable or definite amyotrophic lateral sclerosis and 14 healthy controls were enrolled in a Diffusion Tensor Imaging study and administered the Story-based Empathy Task, assessing the ability to attribute mental states to others (i.e., Intention and Emotion attribution conditions). As already reported, a significant global reduction of empathic skills, mainly driven by a failure in Emotion Attribution condition, was found in amyotrophic lateral sclerosis patients compared to healthy subjects. The severity of this deficit was significantly correlated with fractional anisotropy along the forceps minor, genu of corpus callosum, right uncinate and inferior fronto-occipital fasciculi. The involvement of frontal commissural fiber tracts and right ventral associative fronto-limbic pathways is the microstructural hallmark of the impairment of high-order processing of socio-emotional stimuli in amyotrophic lateral sclerosis. These results support the notion of the neurofunctional and neuroanatomical continuum between amyotrophic lateral sclerosis and frontotemporal dementia.

  3. Neuron-specific antioxidant OXR1 extends survival of a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Liu, Kevin X; Edwards, Benjamin; Lee, Sheena; Finelli, Mattéa J; Davies, Ben; Davies, Kay E; Oliver, Peter L

    2015-05-01

    Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder characterized by the progressive loss of spinal motor neurons. While the aetiological mechanisms underlying the disease remain poorly understood, oxidative stress is a central component of amyotrophic lateral sclerosis and contributes to motor neuron injury. Recently, oxidation resistance 1 (OXR1) has emerged as a critical regulator of neuronal survival in response to oxidative stress, and is upregulated in the spinal cord of patients with amyotrophic lateral sclerosis. Here, we tested the hypothesis that OXR1 is a key neuroprotective factor during amyotrophic lateral sclerosis pathogenesis by crossing a new transgenic mouse line that overexpresses OXR1 in neurons with the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. Interestingly, we report that overexpression of OXR1 significantly extends survival, improves motor deficits, and delays pathology in the spinal cord and in muscles of SOD1(G93A) mice. Furthermore, we find that overexpression of OXR1 in neurons significantly delays non-cell-autonomous neuroinflammatory response, classic complement system activation, and STAT3 activation through transcriptomic analysis of spinal cords of SOD1(G93A) mice. Taken together, these data identify OXR1 as the first neuron-specific antioxidant modulator of pathogenesis and disease progression in SOD1-mediated amyotrophic lateral sclerosis, and suggest that OXR1 may serve as a novel target for future therapeutic strategies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  4. Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Álvarez, N; Díez, L; Avellaneda, C; Serra, M; Rubio, M Á

    Pyramidal signs (hyperreflexia, spasticity, Babinski sign) are essential for the diagnosis of amyotrophic lateral sclerosis (ALS). However, these signs are not always present at onset and may vary over time, besides which their role in disease evolution is controversial. Our goal was to describe which pyramidal signs were present and how they evolved in a cohort of patients with ALS, as well as their role in prognosis. Retrospective analysis of prospectively collected patients diagnosed with ALS in our centre from 1990 to 2015. Of a total of 130 patients with ALS, 34 (26.1%) patients showed no pyramidal signs at the first visit while 15 (11.5%) had a complete pyramidal syndrome. Of those patients without initial pyramidal signs, mean time of appearance of the first signs was 4.5 months. Babinski sign was positive in 64 (49.2%) patients, hyperreflexia in 90 (69.2%) and 22 (16.9%) patients had spasticity. Pyramidal signs tended to remain unchanged over time, although they seem to appear at later stages or even disappear with time in some patients. We found no association between survival and the presence of changes to pyramidal signs, although decreased spasticity was associated with greater clinical deterioration (ALSFR scale) (P<.001). A quarter of patients with ALS initially showed no pyramidal signs and in some cases they even disappear over time. These data support the need for tools that assess the pyramidal tract. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. MRI and clinical features in amyotrophic lateral sclerosis

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    Waragai, M. [Department of Neurology, Chiba University (Japan)

    1997-12-01

    MRI of the brain and spinal cord was performed in 21 patients with amyotrophic lateral sclerosis (ALS), 8 normal volunteers and 16 neurological disease controls. High signal was seen in the intracranial corticospinal tract in 16 of the 21 patients on T2-weighted and in 10 on proton density (PD)-weighted images. In one patient, the high signal on T2-weighted images became less marked with progression of the disease. Low signal intensity was seen in the motor cortex in 12 of the 21 patients. High signal in the anterolateral column of the spinal cord on T1 weighted images was seen in 14, and high signal in the lateral corticospinal tract on T2 weighted images was seen in 7 of the 21 patients. The relationship between the abnormal images and upper motor neurone signs remained unclear. High signal intensity was seen in the corticospinal tract in the brain on T2-weighted images in two normal volunteers and four disease controls, and on PD weighted images in three disease controls.Low signal intensity in the motor cortex on T2 weighted images was seen in three normal volunteers and four disease controls. However, high signal intensity was seen in the intracranial corticospinal tract on T1 weighted images in five patients with ALS who showed pronounced upper motor neurone signs including spastic paraparesis, but not in controls. Thus, abnormalities on MRI in the brain and spinal cord should be considered in the diagnosis of ALS, and high signal intensity of the intracranial corticospinal tract on T1-weighted images may reflect the severe pathological changes of the upper motor neurones in ALS. (orig.) With 3 figs., 1 tab., 19 refs.

  6. Which equation best predicts energy expenditure in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Ellis, Amy C; Rosenfeld, Jeffrey

    2011-11-01

    The purpose of this study was to compare measured resting energy expenditure (REE) with estimates from three common prediction equations with the goal of determining which equation best estimates REE in amyotrophic lateral sclerosis (ALS). Cross-sectional measurements of REE from indirect calorimetry were compared to calculations from the Harris Benedict, Mifflin-St Jeor, and Ireton-Jones equations. Additional measurements to identify predictors of REE included pulmonary function tests, fat-free mass by bioelectrical impedance, and anthropometrics. Participants were 56 men and women with ALS. For comparison, subjects were categorized by disease progression into three groups. Pearson correlations and paired t tests were used to compare measured REE with predicted REE from each equation, and the accuracy of each equation was quantified by the root mean squared prediction error and the percentage of REE estimates within 10% of measured values. Bias for each equation was calculated as the mean percentage difference between calculated and measured REE. Multiple linear regression was used to determine the best predictor variables for REE. Across the disease spectrum, the Harris Benedict and Mifflin-St Jeor equations provided clinically acceptable estimates of REE, whereas the Ireton-Jones equations consistently overestimated REE. The best predictors of REE among this cohort were fat-free mass, sex, and age. When estimating energy requirements for patients with ALS, clinicians should choose prediction equations that incorporate sex and age as predictor variables, such as the Harris Benedict and Mifflin-St Jeor equations. Copyright © 2011 American Dietetic Association. Published by Elsevier Inc. All rights reserved.

  7. Apelin deficiency accelerates the progression of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Atsushi Kasai

    Full Text Available Amyotrophic lateral sclerosis (ALS is a neurodegenerative disease characterized by the selective loss of motor neurons. Recent studies have implicated that chronic hypoxia and insufficient vascular endothelial growth factor (VEGF-dependent neuroprotection may lead to the degeneration of motor neurons in ALS. Expression of apelin, an endogenous ligand for the G protein-coupled receptor APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin protects neurons against glutamate-induced excitotoxicity. Here, we examined whether apelin is an endogenous neuroprotective factor using SOD1(G93A mouse model of ALS. In mouse CNS tissues, the highest expressions of both apelin and APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA expression in the spinal cord of wild-type mice was not changed from 4 to 18 weeks age, that of SOD1(G93A mice was reduced along with the paralytic phenotype. In addition, double mutant apelin-deficient and SOD1(G93A displayed the disease phenotypes earlier than SOD1(G93A littermates. Immunohistochemical observation revealed that the number of motor neurons was decreased and microglia were activated in the spinal cord of the double mutant mice, indicating that apelin deficiency pathologically accelerated the progression of ALS. Furthermore, we showed that apelin enhanced the protective effect of VEGF on H(2O(2-induced neuronal death in primary neurons. These results suggest that apelin/APJ system in the spinal cord has a neuroprotective effect against the pathogenesis of ALS.

  8. Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: effect on survival.

    Science.gov (United States)

    Spataro, Rossella; Ficano, Leonardo; Piccoli, Federico; La Bella, Vincenzo

    2011-05-15

    Percutaneous endoscopic gastrostomy (PEG) is offered to amyotrophic lateral sclerosis (ALS) patients with severe dysphagia. Immediate benefits of PEG are adequate food intake and weight stabilization. However, the impact of PEG on survival is still uncertain. In this work we retrospectively evaluated the effect of PEG on survival in a cohort of ALS patients followed in a tertiary referral centre. Between 2000 and 2007, 150 dysphagic ALS patients were followed until death or tracheostomy. PEG was placed in 76 patients who accepted the procedure and survival was analysed using the Kaplan-Meier life-table method. In ALS patients submitted to PEG, no major complications were observed. Total median survival time from symptom onset was 38 months for PEG users as compared to 32 months for the remaining dysphagic patients who declined the procedure (p=0.05). Among bulbar-onset patients, PEG users showed a median survival time longer than those with no PEG (28 months vs. 25 months), even though the difference was not significant. Conversely, dysphagic spinal-onset patients with PEG lived significantly longer than those who refused this palliative care (44 months vs. 36 months, p=0.046). Survival in patients with PEG was not affected by the severity of the respiratory impairment, as measured by forced vital capacity. This study demonstrates that PEG improves survival in dysphagic ALS patients, with few side effects. The procedure is safe and applicable even to patients with impaired respiratory function. PEG remains a milestone in palliative care in dysphagic ALS patients. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis

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    Matias-Guiu, Jordi A.; Pytel, Vanesa; Galan, Lucia; Valles-Salgado, Maria; Guerrero, Antonio; Moreno-Ramos, Teresa; Matias-Guiu, Jorge [Hospital Clinico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Department of Neurology, Madrid (Spain); Cabrera-Martin, Maria Nieves; Carreras, Jose Luis [Hospital Clinico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense de Madrid, Department of Nuclear Medicine, Madrid (Spain)

    2016-10-15

    We aimed to study brain metabolism and presence of beta-amyloid deposits using positron emission tomography (PET) in patients with amyotrophic lateral sclerosis (ALS). This prospective cross-sectional study included 18 patients with definite or probable ALS according to the revised El Escorial diagnostic criteria, and 24 healthy controls. Patients underwent neurological and neuropsychological assessments, PET with {sup 18}F-fluorodeoxyglucose (FDG), and amyloid-PET with {sup 18}F-florbetaben. Patients with ALS showed hypometabolism in the frontal area and hypermetabolism in the cerebellum compared to healthy controls. Four patients (22 %) displayed cognitive impairment and decreased metabolism in the frontal area extending bilaterally to the parietal regions, and increased metabolism in the posterior area of the cerebellum. In patients with no cognitive impairment, metabolism was lower in the left superior frontal gyrus and higher in the anterior and posterior lobes of the cerebellum. In the individual analysis, six patients (35 %) displayed more anterior involvement with hypometabolism affecting the superior frontal, medial, and inferior gyri; six patients (35 %) exhibited a more posterior pattern with hypometabolism in the precentral and postcentral gyri and in the superior and inferior parietal lobules; two patients (11 %) showed a mixed pattern; and three patients (17 %) showed no alterations in brain metabolism. Three (16 %) showed increased {sup 18}F-florbetaben uptake compared to controls. We have identified two main patterns of brain metabolism with an association to cognitive status. Only a subgroup of patients showed an increased uptake of the amyloid tracer. Our results suggest that ALS is heterogeneous from a clinical, metabolic, and molecular standpoint. (orig.)

  10. Amyotrophic lateral sclerosis: improving care with a multidisciplinary approach

    Directory of Open Access Journals (Sweden)

    Hogden A

    2017-05-01

    Full Text Available Anne Hogden,1 Geraldine Foley,2 Robert D Henderson,3 Natalie James,4 Samar M Aoun5 1Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia; 2Discipline of Occupational Therapy, School of Medicine, Trinity College Dublin, the University of Dublin, Republic of Ireland; 3Neurology, Royal Brisbane & Women’s Hospital, Brisbane, QLD, 4Motor Neurone Disease (MND Service, Communication and Assistive Technology (CAT Clinic, St Joseph’s Hospital, St Vincent’s Health Network, Sydney, NSW, 5School of Nursing, Midwifery and Paramedicine, Faculty of Health Sciences, Curtin University, Perth, WA, Australia Abstract: Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease, leading to death within an average of 2–3 years. A cure is yet to be found, and a single disease-modifying treatment has had a modest effect in slowing disease progression. Specialized multidisciplinary ALS care has been shown to extend survival and improve patients’ quality of life, by providing coordinated interprofessional care that seeks to address the complex needs of this patient group. This review examines the nature of specialized multidisciplinary care in ALS and draws on a broad range of evidence that has shaped current practice. The authors explain how multidisciplinary ALS care is delivered. The existing models of care, the role of palliative care within multidisciplinary ALS care, and the costs of formal and informal care are examined. Critical issues of ALS care are then discussed in the context of the support rendered by multidisciplinary-based care. The authors situate the patient and family as key stakeholders and decision makers in the multidisciplinary care network. Finally, the current challenges to the delivery of coordinated interprofessional care in ALS are explored, and the future of coordinated interprofessional care for people with ALS and their family caregivers is considered. Keywords: quality of life

  11. Misregulation of iron homeostasis in amyotrophic lateral sclerosis

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    Anna Gajowiak

    2016-06-01

    Full Text Available Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood-cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS. ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1 gene. Mutations in the SOD1 gene constituteone of the most common genetic causes of the inherited form of ALS. However, it should beconsidered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymaticactivity, a condition which does not occur in human pathology and which may itself changethe expression of iron metabolism genes.

  12. Death with dignity in Washington patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Wang, Leo H; Elliott, Michael A; Jung Henson, Lily; Gerena-Maldonado, Elba; Strom, Susan; Downing, Sharon; Vetrovs, Jennifer; Kayihan, Paige; Paul, Piper; Kennedy, Kate; Benditt, Joshua O; Weiss, Michael D

    2016-11-15

    To describe the amyotrophic lateral sclerosis (ALS) patients who sought medication under the Washington State Death with Dignity (DWD) Act since its inception in 2009. Chart review at 3 tertiary medical centers in the Seattle/Puget Sound region and comparison to publicly available data of ALS and all-cause DWD cohorts from Washington and Oregon. In Washington State, 39 patients with ALS requested DWD from the University of Washington, Virginia Mason, and Swedish Medical Centers beginning in 2009. The median age at death was 65 years (range 46-86). Seventy-seven percent of the patients used the prescriptions. All of the patients who used the medications passed away without complications. The major reasons for patients to request DWD as reported by participating physicians were loss of autonomy and dignity and decrease in enjoyable activities. Inadequate pain control, financial cost, and loss of bodily control were less commonly indicated. These findings were similar to those of the 92 patients who sought DWD in Oregon. In Washington and Oregon, the percentage of patients with ALS seeking DWD is higher compared to the cancer DWD cohort. Furthermore, compared to the all-cause DWD cohort, patients with ALS are more likely to be non-Hispanic white, married, educated, enrolled in hospice, and to have died at home. Although a small number, ALS represents the disease with the highest proportion of patients seeking to participate in DWD. Patients with ALS who choose DWD are well-educated and have access to palliative or life-prolonging care. The use of the medications appears to be able to achieve the patients' goals without complications. © 2016 American Academy of Neurology.

  13. Multimodal emotion processing deficits are present in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Andrews, Sophie C; Staios, Mathew; Howe, Jim; Reardon, Katrina; Fisher, Fiona

    2017-03-01

    Emotion processing abilities might be reduced in amyotrophic lateral sclerosis (ALS). Previous studies of emotion processing in ALS have inconsistent results, and are limited by variations in task difficulty, modalities examined, and participants' cognitive status. The current study used a battery of emotion processing tasks at differing levels of difficulty and across different modalities (facial affect and voice prosody) to assess the extent of emotion processing deficits in nondemented ALS. 33 ALS participants with intact basic cognition and 22 healthy controls completed the abbreviated Comprehensive Affect Testing System (CATS), which assesses simple and complex facial affect recognition, affective prosody recognition, cross-modal face-prosody integration, and semantic comprehension of affect. Participants also completed measures of executive function, mood, and functional impairment. ALS participants showed impairments on complex facial affect recognition, affective prosody recognition, and cross-modal integration. In contrast, simple facial affect recognition and semantic comprehension of affect were intact. ALS participants did not have significant mood symptoms, and neither mood nor functional impairment was related to emotion processing. Performance on the cross-modal composite was related to executive function, however, this relationship was not apparent for facial or prosody recognition within a single modality. These results indicate that people living with ALS without dementia often have subtle difficulties with recognizing emotions in both faces and voices, even in the context of intact basic cognition. Clinicians should be aware of the potential for these emotion processing difficulties to be present in ALS and to affect interpersonal behavior and quality of life. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Implications of white matter damage in amyotrophic lateral sclerosis

    Science.gov (United States)

    Zhou, Ting; Ahmad, Tina Khorshid; Gozda, Kiana; Truong, Jessica; Kong, Jiming; Namaka, Michael

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, which involves the progressive degeneration of motor neurons. ALS has long been considered a disease of the grey matter; however, pathological alterations of the white matter (WM), including axonal loss, axonal demyelination and oligodendrocyte death, have been reported in patients with ALS. The present review examined motor neuron death as the primary cause of ALS and evaluated the associated WM damage that is guided by neuronal-glial interactions. Previous studies have suggested that WM damage may occur prior to the death of motor neurons, and thus may be considered an early indicator for the diagnosis and prognosis of ALS. However, the exact molecular mechanisms underlying early-onset WM damage in ALS have yet to be elucidated. The present review explored the detailed anatomy of WM and identified several pathological mechanisms that may be implicated in WM damage in ALS. In addition, it associated the pathophysiological alterations of WM, which may contribute to motor neuron death in ALS, with similar mechanisms of WM damage that are involved in multiple sclerosis (MS). Furthermore, the early detection of WM damage in ALS, using neuroimaging techniques, may lead to earlier therapeutic intervention, using immunomodulatory treatment strategies similar to those used in relapsing-remitting MS, aimed at delaying WM damage in ALS. Early therapeutic approaches may have the potential to delay motor neuron damage and thus prolong the survival of patients with ALS. The therapeutic interventions that are currently available for ALS are only marginally effective. However, early intervention with immunomodulatory drugs may slow the progression of WM damage in the early stages of ALS, thus delaying motor neuron death and increasing the life expectancy of patients with ALS. PMID:28791401

  15. DREAM-Dependent Activation of Astrocytes in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Larrodé, Pilar; Calvo, Ana Cristina; Moreno-Martínez, Laura; de la Torre, Miriam; Moreno-García, Leticia; Molina, Nora; Castiella, Tomás; Iñiguez, Cristina; Pascual, Luis Fernando; Mena, Francisco Javier Miana; Zaragoza, Pilar; Y Cajal, Santiago Ramón; Osta, Rosario

    2017-08-24

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin and characterized by a relentless loss of motor neurons that causes a progressive muscle weakness until death. Among the several pathogenic mechanisms that have been related to ALS, a dysregulation of calcium-buffering proteins in motor neurons of the brain and spinal cord can make these neurons more vulnerable to disease progression. Downstream regulatory element antagonist modulator (DREAM) is a neuronal calcium-binding protein that plays multiple roles in the nucleus and cytosol. The main aim of this study was focused on the characterization of DREAM and glial fibrillary acid protein (GFAP) in the brain and spinal cord tissues from transgenic SOD1G93A mice and ALS patients to unravel its potential role under neurodegenerative conditions. The DREAM and GFAP levels in the spinal cord and different brain areas from transgenic SOD1G93A mice and ALS patients were analyzed by Western blot and immunohistochemistry. Our findings suggest that the calcium-dependent excitotoxicity progressively enhanced in the CNS in ALS could modulate the multifunctional nature of DREAM, strengthening its apoptotic way of action in both motor neurons and astrocytes, which could act as an additional factor to increase neuronal damage. The direct crosstalk between astrocytes and motor neurons can become vulnerable under neurodegenerative conditions, and DREAM could act as an additional switch to enhance motor neuron loss. Together, these findings could pave the way to further study the molecular targets of DREAM to find novel therapeutic strategies to fight ALS.

  16. Alzheimer disease and amyotrophic lateral sclerosis: an etiopathogenic connection.

    Science.gov (United States)

    Wang, Xiaochuan; Blanchard, Julie; Grundke-Iqbal, Inge; Wegiel, Jerzy; Deng, Han-Xiang; Siddique, Teepu; Iqbal, Khalid

    2014-02-01

    The etiopathogenesis of neither the sporadic form of Alzheimer disease (AD) nor of amyotrophic lateral sclerosis (ALS) is well understood. The activity of protein phosphatase-2A (PP2A), which regulates the phosphorylation of tau and neurofilaments, is negatively regulated by the myeloid leukemia-associated protein SET, also known as inhibitor-2 of PP2A, I2(PP2A). In AD brain, PP2A activity is compromised, probably because I2(PP2A) is overexpressed and is selectively cleaved at asparagine 175 into an N-terminal fragment, I2NTF, and a C-terminal fragment, I2CTF, and both fragments inhibit PP2A. Here, we analyzed the spinal cords from ALS and control cases for I2(PP2A) cleavage and PP2A activity. As observed in AD brain, we found a selective increase in the cleavage of I2(PP2A) into I2NTF and I2CTF and inhibition of the activity and not the expression of PP2A in the spinal cords of ALS cases. To test the hypothesis that both AD and ALS could be triggered by I2CTF, a cleavage product of I2(PP2A), we transduced by intracerebroventricular injections newborn rats with adeno-associated virus serotype 1 (AAV1) containing human I2CTF. AAV1-I2CTF produced reference memory impairment and tau pathology, and intraneuronal accumulation of Aβ by 5-8 months, and motor deficit and hyperphosphorylation and proliferation of neurofilaments, tau and TDP-43 pathologies, degeneration and loss of motor neurons and axons in the spinal cord by 10-14 months in rats. These findings suggest a previously undiscovered etiopathogenic relationship between sporadic forms of AD and ALS that is linked to I2(PP2A) and the potential of I2(PP2A)-based therapeutics for these diseases.

  17. "Understanding my ALS". Experiences and reflections of persons with amyotrophic lateral sclerosis and relatives on participation in peer group rehabilitation

    DEFF Research Database (Denmark)

    Madsen, Louise Sofia; Jeppesen, Jørgen; Handberg, Charlotte

    2018-01-01

    rehabilitation for persons with amyotrophic lateral sclerosis and relatives indicates that programme participation leads to positive experiences in terms of living a shared meaningful life despite severe disability. The findings may guide practice to develop longitudinal peer group rehabilitation programmes...... with joint inclusion of persons with amyotrophic lateral sclerosis and relatives. Implications for Rehabilitation Peer group rehabilitation may facilitate an increased and personalised understanding of what it means to live with amyotrophic lateral sclerosis. A programme design with six months of sequential...

  18. Antecedent disease and Amyotrophic Lateral Sclerosis: What is protecting whom?

    Directory of Open Access Journals (Sweden)

    Sabrina K Hollinger

    2016-03-01

    Full Text Available Multiple studies have shown that antecedent diseases are less prevalent in Amyotrophic Lateral Sclerosis (ALS patients than the general age-matched population, which suggests possible neuroprotection. Antecedent disease could be protective against ALS or, conversely, the asymptomatic early physiological underpinnings of ALS could be protective against other antecedent disease. Elucidating the impact of antecedent disease on ALS is critical for assessing diagnostic risk factors, prognostic outcomes, and intervention timing. The objective of this study was to examine the relationship between antecedent conditions and ALS onset age and disease duration. Medical history surveys for 1,439 Emory ALS Clinic patients (Atlanta, GA, USA were assessed for antecedent hypertension, hyperlipidemia, diabetes, obesity, asthma, arthritis, chronic obstructive pulmonary disease (COPD, thyroid, kidney, liver, and other non-ALS neurological disease. The ALS onset age and disease duration is compared between the antecedent and non-antecedent populations using Chi square, Kaplan Meier, and ordinal logistic regression. When controlled for confounders, antecedent hypertension (high blood pressure, hyperlipidemia (high cholesterol, arthritis, COPD, thyroid disease and non-ALS neurological disease are found to be statistically associated with a delayed onset age whereas antecedent obesity (body mass index, BMI > 30 was correlated with earlier ALS onset age. With the potential exceptions of liver disease and diabetes (the latter without other common co-morbid conditions, antecedent disease is associated with overall shorter disease duration. The unique potential relationship between antecedent liver disease and longer ALS disease duration warrants further investigation, especially given liver disease was found to be a factor of 4-7 times less prevalent in ALS. Notably, most conditions associated with delayed ALS onset are also associated with shorter disease duration

  19. c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2015-03-01

    1 AWARD NUMBER: W81XWH-12-1-0431 TITLE: “c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Sclerosis ” PRINCIPAL...TITLE AND SUBTITLE “c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Scelerosis” 5a. CONTRACT NUMBER 5b. GRANT NUMBER... Lateral   Sclerosis ”   Final  Report:  Project  Period  Sept  2012-­‐Dec  2014     Personnel  List:     Feng,  Yangbo

  20. TDP-43 protein variants as biomarkers in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Williams, Stephanie M; Khan, Galam; Harris, Brent T; Ravits, John; Sierks, Michael R

    2017-01-25

    TDP-43 aggregates accumulate in individuals affected by amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases, representing potential diagnostic and therapeutic targets. Using an atomic force microscopy based biopanning protocol developed in our lab, we previously isolated 23 TDP-43 reactive antibody fragments with preference for human ALS brain tissue relative to frontotemporal dementia, a related neurodegeneration, and healthy samples from phage-displayed single chain antibody fragment (scFv) libraries. Here we further characterize the binding specificity of these different scFvs and identify which ones have promise for detecting ALS biomarkers in human brain tissue and plasma samples. We developed a sensitive capture ELISA for detection of different disease related TDP-43 variants using the scFvs identified from the ALS biopanning. We show that a wide variety of disease selective TDP-43 variants are present in ALS as the scFvs show different reactivity profiles amongst the ALS cases. When assaying individual human brain tissue cases, three scFvs (ALS-TDP6, ALS-TDP10 and ALS-TDP14) reacted with all the ALS cases and 12 others reacted with the majority of the ALS cases, and none of the scFvs reacted with any control samples. When assaying individual human plasma samples, 9 different scFvs reacted with all the sporadic ALS samples and again none of them reacted with any control samples. These 9 different scFvs had different patterns of reactivity with plasma samples obtained from chromosome 9 open reading frame 72 (c9orf72) cases indicating that these familial ALS genetic variants may display different TDP-43 pathology than sporadic ALS cases. These results indicated that a range of disease specific TDP-43 variants are generated in ALS patients with different variants being generated in sporadic and familial cases. We show that a small panel of scFvs recognizing different TDP-43 variants can generate a neuropathological and plasma biomarker

  1. Anti-ganglioside antibodies in amyotrophic lateral sclerosis revisited.

    Directory of Open Access Journals (Sweden)

    Katja Kollewe

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a devastating neurodegenerative disorder with typical onset in the 5th- 6th decade of life. The hypothesis of an autoimmune origin of ALS receives less attention today, but immunological phenomena still seem to be involved and mechanisms such as protective autoimmunity may be important. Detection of antibodies against a variety of gangliosides has been repeatedly described in ALS-patients by several authors, but widely differing frequencies and titres have been reported. Therefore, we investigated the presence of six common antibodies with a commercially available test panel for GA1, GM1, GM2, GD1a, GD1b and GQ1b in a large group of clinically well-characterized ALS patients and compared them to a collective of 200 healthy blood donors.IgG and IgM antibodies to the six gangliosides asialoGM1 (GA1, GM1, GM2, GD1a, GD1b, GQ1b were determined by GanglioCombi ELISA in sera of 84 ALS patients. Results were expressed as a %-ratio of a highly positive control and categorized as negative (100%. The values obtained from 200 Swiss blood donors served as a reference group.In twenty-two (26.2% ALS-patients elevated anti-ganglioside antibodies could be detected: Taking all subspecific antibodies together, IgG antibodies were found in 9/84 (10.7% and IgM in 15/84 (17.9% patients. There was no correlation between age, gender, site of onset or survival and anti-ganglioside-positive/-negative titres in ALS-patients. No statistically significant difference in the frequency of anti-ganglioside antibodies compared to the group of healthy blood donors was found.Even with this more comprehensive approach, anti-ganglioside antibody frequencies and patterns in our ALS cohort closely resembled the values measured in healthy controls. In accordance with other studies, we did not observe any association of a distinct ALS phenotype with elevated anti-ganglioside antibodies or an impact on survival.

  2. TDP-43 pathology in the basal forebrain and hypothalamus of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Cykowski, Matthew D; Takei, Hidehiro; Schulz, Paul E; Appel, Stanley H; Powell, Suzanne Z

    2014-12-24

    Amyotrophic lateral sclerosis is a neurodegenerative disease characterized clinically by motor symptoms including limb weakness, dysarthria, dysphagia, and respiratory compromise, and pathologically by inclusions of transactive response DNA-binding protein 43 kDa (TDP-43). Patients with amyotrophic lateral sclerosis also may demonstrate non-motor symptoms and signs of autonomic and energy dysfunction as hypermetabolism and weight loss that suggest the possibility of pathology in the forebrain, including hypothalamus. However, this region has received little investigation in amyotrophic lateral sclerosis. In this study, the frequency, topography, and clinical associations of TDP-43 inclusion pathology in the basal forebrain and hypothalamus were examined in 33 patients with amyotrophic lateral sclerosis: 25 men and 8 women; mean age at death of 62.7 years, median disease duration of 3.1 years (range of 1.3 to 9.8 years). TDP-43 pathology was present in 11 patients (33.3%), including components in both basal forebrain (n=10) and hypothalamus (n=7). This pathology was associated with non-motor system TDP-43 pathology (Χ2=17.5, p=0.00003) and bulbar symptoms at onset (Χ2=4.04, p=0.044), but not age or disease duration. Furthermore, TDP-43 pathology in the lateral hypothalamic area was associated with reduced body mass index (W=11, p=0.023). This is the first systematic demonstration of pathologic involvement of the basal forebrain and hypothalamus in amyotrophic lateral sclerosis. Furthermore, the findings suggest that involvement of the basal forebrain and hypothalamus has significant phenotypic associations in amyotrophic lateral sclerosis, including site of symptom onset, as well as deficits in energy metabolism with loss of body mass index.

  3. The Big Bluff of Amyotrophic Lateral Sclerosis Diagnosis: The Role of Neurodegenerative Disease Mimics.

    Science.gov (United States)

    Bicchi, Ilaria; Emiliani, Carla; Vescovi, Angelo; Martino, Sabata

    2015-01-01

    Neurodegenerative diseases include a significant number of pathologies affecting the nervous system. Generally, the primary cause of each disease is specific; however, recently, it was shown that they may be correlated at molecular level. This aspect, together with the exhibition of similar symptoms, renders the diagnosis of these disorders difficult. Amyotrophic lateral sclerosis is one of these pathologies. Herein, we report several cases of amyotrophic lateral sclerosis misdiagnosed as a consequence of features that are common to several neurodegenerative diseases, such as Parkinson's, Huntington's and Alzheimer's disease, spinal muscular atrophy, progressive bulbar palsy, spastic paraplegia and frontotemporal dementia, and mostly with the lysosomal storage disorder GM2 gangliosidosis. Overall reports highlight that the differential diagnosis for amyotrophic lateral sclerosis should include correlated mechanisms. © 2015 S. Karger AG, Basel.

  4. Side of limb-onset predicts laterality of gray matter loss in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhang, Qiuli; Mao, Cuiping; Jin, Jiaoting; Niu, Chen; Bai, Lijun; Dang, Jingxia; Zhang, Ming

    2014-01-01

    Conflicting findings have been reported regarding the lateralized brain abnormality in patients with amyotrophic lateral sclerosis (ALS). In this study, we aimed to investigate the probable lateralization of gray matter (GM) atrophy in ALS patients. We focused on the relationship between the asymmetry in decreased GM volume and the side of disease onset in patients with limb-onset. Structural imaging evaluation of normalized atrophy (SIENAX) and voxel-based morphometry (VBM) were used to assess differences in global and local brain regions in patients with heterogeneous body onset and subgroups with different side of limb-onset. We found global brain atrophy and GM losses in the frontal and parietal areas in each patient group as well as left predominant GM losses in the total cohort. The intriguing findings in subgroup analyses demonstrated that the motor cortex in the contralateral hemisphere of the initially involved limb was most affected. We also found that regional brain atrophy was related to disease progression rate. Our observations suggested that side of limb-onset can predict laterality of GM loss in ALS patients and disease progression correlates with the extent of cortical abnormality.

  5. Side of Limb-Onset Predicts Laterality of Gray Matter Loss in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Qiuli Zhang

    2014-01-01

    Full Text Available Conflicting findings have been reported regarding the lateralized brain abnormality in patients with amyotrophic lateral sclerosis (ALS. In this study, we aimed to investigate the probable lateralization of gray matter (GM atrophy in ALS patients. We focused on the relationship between the asymmetry in decreased GM volume and the side of disease onset in patients with limb-onset. Structural imaging evaluation of normalized atrophy (SIENAX and voxel-based morphometry (VBM were used to assess differences in global and local brain regions in patients with heterogeneous body onset and subgroups with different side of limb-onset. We found global brain atrophy and GM losses in the frontal and parietal areas in each patient group as well as left predominant GM losses in the total cohort. The intriguing findings in subgroup analyses demonstrated that the motor cortex in the contralateral hemisphere of the initially involved limb was most affected. We also found that regional brain atrophy was related to disease progression rate. Our observations suggested that side of limb-onset can predict laterality of GM loss in ALS patients and disease progression correlates with the extent of cortical abnormality.

  6. The Use of Peripherally Inserted Central Catheter in Amyotrophic Lateral Sclerosis Patients at a Later Stage.

    Science.gov (United States)

    Juntas-Morales, Raul; Pageot, Nicolas; Alphandéry, Sébastien; Camu, William

    2017-01-01

    To describe the use of peripherally inserted central catheter (PICC), in amyotrophic lateral sclerosis (ALS) at a later stage. Twenty-five ALS patients in the later stages of the disease underwent PICC insertion followed by parenteral nutrition (PN). For all of them, gastrostomy was non-feasible. Patients were followed until death and monitored for complications. PICC insertion was successful in all patients. Three months after insertion, the mean body weight increased by 4.5% (p = 0.0057). PICC could be maintained until death in all but 1 patient. The mean delay between insertion and death was 4.5 months, but PN was administered for more than 1 year in 2 patients. Complications were noted in 6 patients: sepsis (n = 4), venous thrombosis (n = 1), and upper limb oedema (n = 1), none of them resulting in death. PICC insertion for PN at a later stage of ALS, in patients for whom gastrostomy is non-feasible, appears to be a useful option compared to the central venous catheter. © 2016 S. Karger AG, Basel.

  7. Dietary BMAA exposure in an amyotrophic lateral sclerosis cluster from southern France.

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    Estelle Masseret

    Full Text Available BACKGROUND: Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. OBJECTIVES: We aimed at identifying cluster(s of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s, for the existence of a potential dietary source of BMAA. METHODS: A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations. RESULTS: We found one significant amyotrophic lateral sclerosis cluster (p = 0.0024, surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g and oysters (0.6 µg/g to 1.6 µg/g. The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded. CONCLUSIONS: While it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.

  8. Dietary BMAA Exposure in an Amyotrophic Lateral Sclerosis Cluster from Southern France

    Science.gov (United States)

    Masseret, Estelle; Banack, Sandra; Boumédiène, Farid; Abadie, Eric; Brient, Luc; Pernet, Fabrice; Juntas-Morales, Raoul; Pageot, Nicolas; Metcalf, James; Cox, Paul; Camu, William

    2013-01-01

    Background Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. Objectives We aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA. Methods A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations. Results We found one significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g) and oysters (0.6 µg/g to 1.6 µg/g). The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded. Conclusions While it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder. PMID:24349504

  9. Dietary BMAA exposure in an amyotrophic lateral sclerosis cluster from southern France.

    Science.gov (United States)

    Masseret, Estelle; Banack, Sandra; Boumédiène, Farid; Abadie, Eric; Brient, Luc; Pernet, Fabrice; Juntas-Morales, Raoul; Pageot, Nicolas; Metcalf, James; Cox, Paul; Camu, William

    2013-01-01

    Dietary exposure to the cyanotoxin BMAA is suspected to be the cause of amyotrophic lateral sclerosis in the Western Pacific Islands. In Europe and North America, this toxin has been identified in the marine environment of amyotrophic lateral sclerosis clusters but, to date, only few dietary exposures have been described. We aimed at identifying cluster(s) of amyotrophic lateral sclerosis in the Hérault district, a coastal district from Southern France, and to search, in the identified area(s), for the existence of a potential dietary source of BMAA. A spatio-temporal cluster analysis was performed in the district, considering all incident amyotrophic lateral sclerosis cases identified from 1994 to 2009 by our expert center. We investigated the cluster area with serial collections of oysters and mussels that were subsequently analyzed blind for BMAA concentrations. We found one significant amyotrophic lateral sclerosis cluster (p = 0.0024), surrounding the Thau lagoon, the most important area of shellfish production and consumption along the French Mediterranean coast. BMAA was identified in mussels (1.8 µg/g to 6.0 µg/g) and oysters (0.6 µg/g to 1.6 µg/g). The highest concentrations of BMAA were measured during summer when the highest picocyanobacteria abundances were recorded. While it is not possible to ascertain a direct link between shellfish consumption and the existence of this ALS cluster, these results add new data to the potential association of BMAA with sporadic amyotrophic lateral sclerosis, one of the most severe neurodegenerative disorder.

  10. Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Smith, Bradley N.; Topp, Simon D.; Fallini, Claudia; Shibata, Hideki; Chen, Han-Jou; Troakes, Claire; King, Andrew; Ticozzi, Nicola; Kenna, Kevin P.; Soragia-Gkazi, Athina; Miller, Jack W.; Sato, Akane; Dias, Diana Marques; Jeon, Maryangel; Vance, Caroline; Wong, Chun Hao; de Majo, Martina; Kattuah, Wejdan; Mitchell, Jacqueline C.; Scotter, Emma L.; Parkin, Nicholas W.; Sapp, Peter C.; Nolan, Matthew; Nestor, Peter J.; Simpson, Michael; Weale, Michael; Lek, Monkel; Baas, Frank; Vianney de Jong, J. M.; ten Asbroek, Anneloor L. M. A.; Redondo, Alberto Garcia; Esteban-Pérez, Jesús; Tiloca, Cinzia; Verde, Federico; Duga, Stefano; Leigh, Nigel; Pall, Hardev; Morrison, Karen E.; Al-Chalabi, Ammar; Shaw, Pamela J.; Kirby, Janine; Turner, Martin R.; Talbot, Kevin; Hardiman, Orla; Glass, Jonathan D.; de Belleroche, Jacqueline; Maki, Masatoshi; Moss, Stephen E.; Miller, Christopher; Gellera, Cinzia; Ratti, Antonia; Al-Sarraj, Safa; Brown, Robert H.; Silani, Vincenzo; Landers, John E.; Shaw, Christopher E.

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. We screened 751 familial ALS patient whole-exome sequences and identified six mutations including p.D40G in the ANXA11 gene in 13 individuals. The p.D40G mutation was absent from 70,000 control whole-exome sequences. This

  11. Molecular classification of amyotrophic lateral sclerosis by unsupervised clustering of gene expression in motor cortex

    NARCIS (Netherlands)

    Aronica, E.; Baas, F.; Iyer, A.; ten Asbroek, A.L.M.A.; Morello, G.; Cavallaro, S.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disease, caused by the loss of motor neurons in the brain and spinal cord. Although 10% of ALS cases are familial (FALS), the majority are sporadic (SALS) and probably associated to a multifactorial

  12. VAPB and C9orf72 mutations in 1 familial amyotrophic lateral sclerosis patient

    NARCIS (Netherlands)

    van Blitterswijk, Marka; van Es, Michael A.; Koppers, Max; van Rheenen, Wouter; Medic, Jelena; Schelhaas, Helenius J.; van der Kooi, Anneke J.; de Visser, Marianne; Veldink, Jan H.; van den Berg, Leonard H.

    2012-01-01

    Previously, we have reported amyotrophic lateral sclerosis (ALS) families with multiple mutations in major ALS-associated genes. These findings provided evidence for an oligogenic basis of ALS. In our present study, we screened a cohort of 755 sporadic ALS patients, 111 familial ALS patients (97

  13. Aberrant myelinated neurites in the anterior horns of a patient with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Troost, D.; Louwerse, E. S.; de Jong, J. M.; van Leersum, G. S.; van Raalte, J. A.

    1989-01-01

    A case of amyotrophic lateral sclerosis revealed the classical pathologic features of ALS, i.e. neuronal loss in the anterior horns and pyramidal tract degeneration. In addition to the pathological hallmarks of Alzheimer's disease, senile plaques, neurofibrillary tangles and granulovacuolar changes

  14. Myasthenia gravis with muscle specific kinase antibodies mimicking amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Huijbers, Maartje G.; Niks, Erik H.; Klooster, Rinse; de Visser, Marianne; Kuks, Jan B.; Veldink, Jan H.; Klarenbeek, Pim; van Damme, Philip; de Baets, Marc H.; van der Maarel, Silvère M.; van den Berg, Leonard H.; Verschuuren, Jan J.

    2016-01-01

    Muscle-specific kinase (MuSK) myasthenia gravis (MG) is hallmarked by the predominant involvement of bulbar muscles and muscle atrophy. This might mimic amyotrophic lateral sclerosis (ALS) presenting with bulbar weakness. We encountered four cases of MuSK MG patients with an initial misdiagnosis of

  15. Exposure to chemicals and metals and risk of amyotrophic lateral sclerosis: a systematic review

    NARCIS (Netherlands)

    Sutedja, N.A.; Veldink, J.H.; Fischer, K.; Kromhout, H.|info:eu-repo/dai/nl/074385224; Heederik, D.J.J.|info:eu-repo/dai/nl/072910542; Huisman, M.H.B.; Wokke, J.H.J.; van den Berg, L.H.

    2009-01-01

    Environmental exposure to chemicals and metals may contribute to the risk of sporadic amyotrophic lateral sclerosis (ALS). Two systematic reviews of the literature on these topics performed according to the well-established MOOSE guidelines are presented. Literature cited in MEDLINE, EMBASE, CINAHL,

  16. Ethnic and demographic incidence of amyotrophic lateral sclerosis (ALS) in Brazil: A population based study.

    Science.gov (United States)

    Moura, Mirian Conceicao; Casulari, Luiz Augusto; Carvalho Garbi Novaes, Maria Rita

    2016-01-01

    Our objectives were to examine demographic and ethnic factors associated with amyotrophic lateral sclerosis in Brazil. The method used was a retrospective study of death certificates performed in June 2015, identifying the incidence of amyotrophic lateral sclerosis over 10 years, from January 2004 to December 2013, related to gender, age and race. Results revealed 8942 death certificates with 8152 as the underlying cause and 790 as a secondary cause. The average age was 62.7 ± 13.2 years, with a predominance of males (1·3:1). The adjusted mortality rate over 20 years was 0.61 to 0.89/100,000 person-years, and over 45 years was 1.77 to 2.3/100,000 person-years. There was a predominance of amyotrophic lateral sclerosis in Caucasians compared to the general population above 20 years (2010 Census), with an odds ratio (OR) of 2.92 (95% CI 2.78-3.07). The OR in blacks was 0.04 (95% CI: 0.03-0.04), in mestizos was 0.05 (0.04-0.07), and in Indians was 0.02 (0.01-0.04). The mean age was lower than in European populations (48.5 ± 12.3 years) (p amyotrophic lateral sclerosis in Brazil is close to other Latin American populations, with a lower age at death and clear predominance in Caucasians.

  17. UNC13A is a modifier of survival in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Diekstra, Frank P.; van Vught, Paul W. J.; van Rheenen, Wouter; Koppers, Max; Pasterkamp, R. Jeroen; van Es, Michael A.; Schelhaas, Helenius J.; de Visser, Marianne; Robberecht, Wim; van Damme, Philip; Andersen, Peter M.; van den Berg, Leonard H.; Veldink, Jan H.

    2012-01-01

    A large genome-wide screen in patients with sporadic amyotrophic lateral sclerosis (ALS) showed that the common variant rs12608932 in gene UNC13A was associated with disease susceptibility. UNC13A regulates the release of neurotransmitters, including glutamate. Genetic risk factors that, in

  18. The costs of amyotrophic lateral sclerosis, according to type of care

    NARCIS (Netherlands)

    Van Der Steen, Irene; Van Den Berg, Jan-Paul; Buskens, Erik; Lindeman, Eline; Van Den Berg, Leonard H.

    2009-01-01

    Our objective was to estimate the economic burden of patients with amyotrophic lateral sclerosis (ALS) and to examine the effect of treatment in a multidisciplinary ALS treatment centre versus general care on costs and to describe differences in costs according to clinical characteristics. In a

  19. Is chronic ventilatory support really effective in patients with amyotrophic lateral sclerosis?

    NARCIS (Netherlands)

    Hazenberg, A.; Kerstjens, H. A. M.; Prins, S. C. L.; Vermeulen, K. M.; Wijkstra, P. J.

    2016-01-01

    Most patients with amyotrophic lateral sclerosis (ALS) develop respiratory insufficiency in the advanced stage of their disease. Non-invasive ventilation (NIV) is commonly regarded to be a treatment that is effective in reducing these complaints. To assess whether the effect of NIV on gas exchange

  20. Rare and common paraoxonase gene variants in amyotrophic lateral sclerosis patients

    NARCIS (Netherlands)

    van Blitterswijk, Marka; Blokhuis, Anna; van Es, Michael A.; van Vught, Paul W. J.; Rowicka, Paulina A.; Schelhaas, Helenius J.; van der Kooi, Anneke J.; de Visser, Marianne; Veldink, Jan H.; van den Berg, Leonard H.

    2012-01-01

    Polymorphisms in the paraoxonase family (PON) have been reported in patients with amyotrophic lateral sclerosis (ALS), but a recent meta-analysis did not show a clear association. Recently, PON mutations have also been identified in ALS patients. In this study, we assessed the frequency of PON

  1. Amyotrophic lateral sclerosis presenting with orthopnea in a patient with COPD and obstructive sleep apnea

    Directory of Open Access Journals (Sweden)

    T.L.N. Swamy

    2011-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease (MND is a relentlessly progressive neurological disorder causing peripheral muscular weakness and resultant respiratory failure. In this article, we report a case of ALS with chronic obstructive pulmonary disease (COPD and obstructive sleep apnea (OSA with orthopnea as initial symptoms.

  2. Lower motor neuron involvement examined by quantitative electromyography in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Krarup, Christian

    2011-01-01

    Objective The diagnosis of amyotrophic lateral sclerosis (ALS) includes demonstration of lower motor neuron (LMN) and upper motor neuron (UMN) involvement of bulbar and spinal muscles. Electromyography (EMG) is essential to confirm LMN affection in weak muscles, and to demonstrate changes...

  3. Needs of informal caregivers across the caregiving course in amyotrophic lateral sclerosis: a qualitative analysis.

    LENUS (Irish Health Repository)

    Galvin, Miriam

    2018-01-27

    Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a debilitating terminal condition. Informal caregivers are key figures in ALS care provision. The physical, psychological and emotional impact of providing care in the home requires appropriate assistance and support. The objective of this analysis is to explore the needs of informal ALS caregivers across the caregiving course.

  4. Lingual-Alveolar Contact Pressure during Speech in Amyotrophic Lateral Sclerosis: Preliminary Findings

    Science.gov (United States)

    Searl, Jeff; Knollhoff, Stephanie; Barohn, Richard J.

    2017-01-01

    Purpose: This preliminary study on lingual-alveolar contact pressures (LACP) in people with amyotrophic lateral sclerosis (ALS) had several aims: (a) to evaluate whether the protocol induced fatigue, (b) to compare LACP during speech (LACP-Sp) and during maximum isometric pressing (LACP-Max) in people with ALS (PALS) versus healthy controls, (c)…

  5. Acute deterioration of bulbar function after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Meijer, J.W.; Kuijk, A.A. van; Geurts, A.C.H.; Schelhaas, H.J.; Zwarts, M.J.

    2008-01-01

    Transcutaneous botulinum toxin injection in the salivary glands was introduced in 2000 as a new treatment for sialorrhoea in amyotrophic lateral sclerosis (ALS). We describe an ALS patient who developed serious complications of botulinum toxin treatment for sialorrhoea, and we review the relevant

  6. Myasthenia gravis with muscle specific kinase antibodies mimicking amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Huijbers, Maartje G; Niks, Erik H; Klooster, Rinse; de Visser, Marianne; Kuks, Jan B; Veldink, Jan H; Klarenbeek, Pim; Van Damme, Philip; de Baets, Marc H; van der Maarel, Silvère M; van den Berg, Leonard H; Verschuuren, Jan J

    Muscle-specific kinase (MuSK) myasthenia gravis (MG) is hallmarked by the predominant involvement of bulbar muscles and muscle atrophy. This might mimic amyotrophic lateral sclerosis (ALS) presenting with bulbar weakness. We encountered four cases of MuSK MG patients with an initial misdiagnosis of

  7. No association between Borrelia burgdorferi antibodies and amyotrophic lateral sclerosis in a case-control study

    NARCIS (Netherlands)

    Visser, A E; Verduyn Lunel, F M; Veldink, J H; van den Berg, L H

    BACKGROUND AND PURPOSE: Previous studies, mostly case reports and uncontrolled studies, provide a low level of evidence for the hypothesized link between Lyme disease and amyotrophic lateral sclerosis (ALS). In order to make evidence-based recommendations regarding testing for Borrelia burgdorferi

  8. Prognostic value of a decreased tongue strength for survival time in patients with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Alexander Geurts; J. Weikamp; J. Hendriks; J. Schelhaas; Bert de Swart

    2012-01-01

    Decreased tongue strength (TS) might herald bulbar involvement in patients with amyotrophic lateral sclerosis (ALS) well before dysarthria or dysphagia occur, and as such might be prognostic of short survival. The purpose of this study was to investigate the prognostic value of a decreased TS, in

  9. Prognostic value of decreased tongue strength on survival time in patients with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Weikamp, J.G.; Schelhaas, H.J.; Hendriks, J.C.M.; Swart, B.J.M. de; Geurts, A.C.H.

    2012-01-01

    Decreased tongue strength (TS) might herald bulbar involvement in patients with amyotrophic lateral sclerosis (ALS) well before dysarthria or dysphagia occur, and as such might be prognostic of short survival. The purpose of this study was to investigate the prognostic value of a decreased TS, in

  10. Increased IL-17, a Pathogenic Link between Hepatosplenic Schistosomiasis and Amyotrophic Lateral Sclerosis: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Oswald Moling

    2014-01-01

    Full Text Available The immune system protects the organism from foreign invaders and foreign substances and is involved in physiological functions that range from tissue repair to neurocognition. However, an excessive or dysregulated immune response can cause immunopathology and disease. A 39-year-old man was affected by severe hepatosplenic schistosomiasis mansoni and by amyotrophic lateral sclerosis. One question that arose was, whether there was a relation between the parasitic and the neurodegenerative disease. IL-17, a proinflammatory cytokine, is produced mainly by T helper-17 CD4 cells, a recently discovered new lineage of effector CD4 T cells. Experimental mouse models of schistosomiasis have shown that IL-17 is a key player in the immunopathology of schistosomiasis. There are also reports that suggest that IL-17 might have an important role in the pathogenesis of amyotrophic lateral sclerosis. It is hypothesized that the factors that might have led to increased IL-17 in the hepatosplenic schistosomiasis mansoni might also have contributed to the development of amyotrophic lateral sclerosis in the described patient. A multitude of environmental factors, including infections, xenobiotic substances, intestinal microbiota, and vitamin D deficiency, that are able to induce a proinflammatory immune response polarization, might favor the development of amyotrophic lateral sclerosis in predisposed individuals.

  11. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Es, Michael A.; van Vught, Paul Wj; Blauw, Hylke M.; Franke, Lude; Saris, Christiaan G. J.; Van Den Bosch, Ludo; de Jong, Sonja W.; de Jong, Vianney; Baas, Frank; van't Slot, Ruben; Lemmens, Robin; Schelhaas, Helenius J.; Birve, Anna; Sleegers, Kristel; Van Broeckhoven, Christine; Schymick, Jennifer C.; Traynor, Bryan J.; Wokke, John H. J.; Wijmenga, Cisca; Robberecht, Wim; Andersen, Peter M.; Veldink, Jan H.; Ophoff, Roel A.; van den Berg, Leonard H.

    We identified a SNP in the DPP6 gene that is consistently strongly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in different populations of European ancestry, with an overall P value of 5.04x10(-8) in 1,767 cases and 1,916 healthy controls and with an odds ratio of 1.30 (95%

  12. Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Gaastra, Benjamin; Shatunov, Aleksey; Pulit, Sara; Jones, Ashley R; Sproviero, William; Gillett, Alexandra; Chen, Zhongbo; Kirby, Janine; Fogh, Isabella; Powell, John F; Leigh, P Nigel; Morrison, Karen E; Shaw, Pamela J; Shaw, Christopher E; van den Berg, Leonard H; Veldink, Jan H; Lewis, Cathryn M; Al-Chalabi, Ammar

    2016-01-01

    Our objective was to identify whether rare genetic variation in amyotrophic lateral sclerosis (ALS) candidate survival genes modifies ALS survival. Candidate genes were selected based on evidence for modifying ALS survival. Each tail of the extreme 1.5% of survival was selected from the UK MND DNA

  13. Neurofilament and glial alterations in the cerebral cortex in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Troost, D.; Sillevis Smitt, P. A.; de Jong, J. M.; Swaab, D. F.

    1992-01-01

    According to the literature, only minor nonspecific histopathological lesions are present in the motor cortex in up to 90% of the amyotrophic lateral sclerosis (ALS) patients. These observations, however, have so far been based mainly on conventional staining techniques. An exception to this is the

  14. Deep learning predictions of survival based on MRI in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van der Burgh, Hannelore K|info:eu-repo/dai/nl/413641066; Schmidt, Ruben; Westeneng, Henk-Jan|info:eu-repo/dai/nl/413993663; de Reus, Marcel A|info:eu-repo/dai/nl/413970728; van den Berg, Leonard H|info:eu-repo/dai/nl/288255216; van den Heuvel, Martijn P|info:eu-repo/dai/nl/304820466

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease, with large variation in survival between patients. Currently, it remains rather difficult to predict survival based on clinical parameters alone. Here, we set out to use clinical characteristics in combination with MRI data

  15. Speech Intelligibility and Marital Communication in Amyotrophic Lateral Sclerosis: An Exploratory Study

    Science.gov (United States)

    Joubert, Karin; Bornman, Juan; Alant, Erna

    2011-01-01

    Amyotrophic lateral sclerosis (ALS), a rapidly progressive neuromuscular disease, has a devastating impact not only on individuals diagnosed with ALS but also their spouses. Speech intelligibility, often compromised as a result of dysarthria, affects the couple's ability to maintain effective, intimate communication. The purpose of this…

  16. Euthanasia and physician-assisted suicide among patients with amyotrophic lateral sclerosis in the Netherlands

    NARCIS (Netherlands)

    Veldink, Jan H.; Wokke, John H. J.; van der Wal, Gerrit; de Jong, J. M. B. Vianney; van den Berg, Leonard H.

    2002-01-01

    Amyotrophic lateral sclerosis (ALS) is a disease that causes progressive paralysis leading to respiratory failure. Patients with ALS may consider physician-assisted suicide. However, it is not known how many patients, if given the option, would actually decide to end their lives by

  17. A comprehensive analysis of rare genetic variation in amyotrophic lateral sclerosis in the UK.

    Science.gov (United States)

    Morgan, Sarah; Shatunov, Aleksey; Sproviero, William; Jones, Ashley R; Shoai, Maryam; Hughes, Deborah; Al Khleifat, Ahmad; Malaspina, Andrea; Morrison, Karen E; Shaw, Pamela J; Shaw, Christopher E; Sidle, Katie; Orrell, Richard W; Fratta, Pietro; Hardy, John; Pittman, Alan; Al-Chalabi, Ammar

    2017-06-01

    Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2. We found 11 patients (1%) carried more than one pathogenic variant (P = 0.001) consistent with an oligogenic basis of amyotrophic lateral sclerosis. These findings show that the genetic architecture of amyotrophic lateral sclerosis is complex and that variation in the regulatory regions of associated genes may be important in disease pathogenesis. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  18. Inclusions of amyotrophic lateral sclerosis-linked superoxide dismutase in ventral horns, liver, and kidney

    DEFF Research Database (Denmark)

    Jonsson, P.A.; Bergemalm, D.; Andersen, P.M.

    2008-01-01

    Mutant superoxide dismutases type 1 (SOD1s) cause amyotrophic lateral sclerosis by an unidentified toxic property. In a patient carrying the G127X truncation mutation, minute amounts of SOD1 were found in ventral horns using a mutant-specific antibody. Still, both absolute levels and ratios versus...

  19. Factor analysis of the Zarit Burden Interview in family caregivers of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Oh, Juyeon; Kim, Jung A

    2017-10-16

    The Zarit Burden Interview has been used in many studies to assess caregiver burden in family caregivers of patients with amyotrophic lateral sclerosis, but the factor structure of the Zarit Burden Interview in the caregivers of amyotrophic lateral sclerosis patients is unknown. The aim of this study was to explore the factor structure of the Zarit Burden Interview in family caregivers of amyotrophic lateral sclerosis patients using exploratory factor analysis. The exploratory factor analysis was performed using generalized least squares with oblique rotation in a sample of 202 family caregivers. Three factors had an eigenvalue greater than 1 and accounted for 60.33% of the total variance. The three factors were named as follows: (factor 1) "Social restrictions" (items 2, 3, and 10-15); (factor 2) "Self-criticism" (items 20-21); and (factor 3) "Anger and frustration" (items 1, 4-6, 9, and 16-19). The correlation between factors 1 and 3 was much higher (r = 0.79) than that between factors 1 and 2 (r = 0.14) or factors 2 and 3 (r = 0.15). The findings of this study enriched our understanding of several meaningful dimensions of the caregiving burden in caregivers of an amyotrophic lateral sclerosis population and provided opportunities for future intervention.

  20. Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume

    NARCIS (Netherlands)

    Raaphorst, J.; van Tol, M.J.; de Visser, M.; van der Kooi, A.J.; Majoie, C.B.; van den Berg, L.H.; Schmand, B.; Veltman, D.J.

    2015-01-01

    Background and purpose: Thirty per cent of amyotrophic lateral sclerosis (ALS) patients have non-motor symptoms, including executive and memory deficits. The in vivo anatomical basis of memory deficits in ALS has not been elucidated. In this observational study, brain atrophy in relation to memory

  1. Prose memory impairment in amyotrophic lateral sclerosis patients is related to hippocampus volume

    NARCIS (Netherlands)

    Raaphorst, J.; Tol, M.J. van; Visser, M de; Kooi, A.J. van der; Majoie, C.B.; Berg, L.H. van den; Schmand, B.; Veltman, D.J.

    2015-01-01

    BACKGROUND AND PURPOSE: Thirty per cent of amyotrophic lateral sclerosis (ALS) patients have non-motor symptoms, including executive and memory deficits. The in vivo anatomical basis of memory deficits in ALS has not been elucidated. In this observational study, brain atrophy in relation to memory

  2. Speech Movement Measures as Markers of Bulbar Disease in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Shellikeri, Sanjana; Green, Jordan R.; Kulkarni, Madhura; Rong, Panying; Martino, Rosemary; Zinman, Lorne; Yunusova, Yana

    2016-01-01

    Purpose: The goal of this study was to identify the effects of amyotrophic lateral sclerosis (ALS) on tongue and jaw control, both cross-sectionally and longitudinally. The data were examined in the context of their utility as a diagnostic marker of bulbar disease. Method: Tongue and jaw movements were recorded cross-sectionally (n = 33…

  3. Is There a Role for Exercise in the Management of Bulbar Dysfunction in Amyotrophic Lateral Sclerosis?

    Science.gov (United States)

    Plowman, Emily K.

    2015-01-01

    Purpose: The role of exercise in the management of people with amyotrophic lateral sclerosis (PALS) is controversial and currently unclear. The purpose of this review article is to review literature examining the impact of limb, respiratory, and oral motor exercise on function, disease progression, and survival in PALS and the transgenic ALS…

  4. 75 FR 35711 - Schedule for Rating Disabilities; Evaluation of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2010-06-23

    ... Sclerosis AGENCY: Department of Veterans Affairs. ACTION: Proposed rule. SUMMARY: The Department of Veterans... for amyotrophic lateral sclerosis (ALS) to provide a 100-percent evaluation for any veteran with... Sclerosis.'' Copies of comments received will be available for public inspection in the Office of Regulation...

  5. Methods of Communication at End of Life for the Person with Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Brownlee, Alisa; Bruening, Lisa M.

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results in loss of most motor functions by the time of death. Most persons with ALS experience a dysarthria that eventually renders oral/vocal communication unintelligible. This article reviews the communication needs of persons with ALS and the range of communication…

  6. Symptomatic treatments for amyotrophic lateral sclerosis/motor neuron disease.

    Science.gov (United States)

    Ng, Louisa; Khan, Fary; Young, Carolyn A; Galea, Mary

    2017-01-10

    Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited. To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND. We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND. We assessed the methodological quality of the included reviews using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the GRADE approach. We followed standard Cochrane study (review) selection and data extraction procedures. We reported findings narratively and in tables. We included nine Cochrane Systematic Reviews of interventions to treat symptoms in people with MND. Three were empty reviews with no included randomised controlled trials (RCTs); however, all three reported on non-RCT evidence and the remaining six included mostly one or two studies. We deemed all of the included reviews of high methodological quality. Drug therapy for painThere is no RCT evidence in a Cochrane Systematic Review exploring the efficacy of drug therapy for pain in MND. Treatment for crampsThere is evidence (13 RCTs, N = 4012) that for the treatment of cramps in MND, compared to placebo:- memantine and tetrahydrocannabinol (THC) are probably ineffective (moderate-quality evidence);- vitamin E may have little or no effect (low-quality evidence); and- the effects of L-threonine, gabapentin, xaliproden, riluzole, and baclofen are uncertain as the evidence is either very low quality or the trial specified the outcome but did not report numerical data.The review reported adverse effects of riluzole, but it is not clear whether other interventions had adverse effects. Treatment for spasticityIt is uncertain whether an endurance-based exercise programme improved spasticity or quality of life, measured at three months after the

  7. Imaging Findings Associated with Cognitive Performance in Primary Lateral Sclerosis and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Avner Meoded

    2013-08-01

    Full Text Available Introduction: Executive dysfunction occurs in many patients with amyotrophic lateral sclerosis (ALS, but it has not been well studied in primary lateral sclerosis (PLS. The aims of this study were to (1 compare cognitive function in PLS to that in ALS patients, (2 explore the relationship between performance on specific cognitive tests and diffusion tensor imaging (DTI metrics of white matter tracts and gray matter volumes, and (3 compare DTI metrics in patients with and without cognitive and behavioral changes. Methods: The Delis-Kaplan Executive Function System (D-KEFS, the Mattis Dementia Rating Scale (DRS-2, and other behavior and mood scales were administered to 25 ALS patients and 25 PLS patients. Seventeen of the PLS patients, 13 of the ALS patients, and 17 healthy controls underwent structural magnetic resonance imaging (MRI and DTI. Atlas-based analysis using MRI Studio software was used to measure fractional anisotropy, and axial and radial diffusivity of selected white matter tracts. Voxel-based morphometry was used to assess gray matter volumes. The relationship between diffusion properties of selected association and commissural white matter and performance on executive function and memory tests was explored using a linear regression model. Results: More ALS than PLS patients had abnormal scores on the DRS-2. DRS-2 and D-KEFS scores were related to DTI metrics in several long association tracts and the callosum. Reduced gray matter volumes in motor and perirolandic areas were not associated with cognitive scores. Conclusion: The changes in diffusion metrics of white matter long association tracts suggest that the loss of integrity of the networks connecting fronto-temporal areas to parietal and occipital areas contributes to cognitive impairment.

  8. Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study.

    Science.gov (United States)

    Al-Chalabi, Ammar; Calvo, Andrea; Chio, Adriano; Colville, Shuna; Ellis, Cathy M; Hardiman, Orla; Heverin, Mark; Howard, Robin S; Huisman, Mark H B; Keren, Noa; Leigh, P Nigel; Mazzini, Letizia; Mora, Gabriele; Orrell, Richard W; Rooney, James; Scott, Kirsten M; Scotton, William J; Seelen, Meinie; Shaw, Christopher E; Sidle, Katie S; Swingler, Robert; Tsuda, Miho; Veldink, Jan H; Visser, Anne E; van den Berg, Leonard H; Pearce, Neil

    2014-11-01

    Amyotrophic lateral sclerosis shares characteristics with some cancers, such as onset being more common in later life, progression usually being rapid, the disease affecting a particular cell type, and showing complex inheritance. We used a model originally applied to cancer epidemiology to investigate the hypothesis that amyotrophic lateral sclerosis is a multistep process. We generated incidence data by age and sex from amyotrophic lateral sclerosis population registers in Ireland (registration dates 1995-2012), the Netherlands (2006-12), Italy (1995-2004), Scotland (1989-98), and England (2002-09), and calculated age and sex-adjusted incidences for each register. We regressed the log of age-specific incidence against the log of age with least squares regression. We did the analyses within each register, and also did a combined analysis, adjusting for register. We identified 6274 cases of amyotrophic lateral sclerosis from a catchment population of about 34 million people. We noted a linear relationship between log incidence and log age in all five registers: England r(2)=0·95, Ireland r(2)=0·99, Italy r(2)=0·95, the Netherlands r(2)=0·99, and Scotland r(2)=0·97; overall r(2)=0·99. All five registers gave similar estimates of the linear slope ranging from 4·5 to 5·1, with overlapping confidence intervals. The combination of all five registers gave an overall slope of 4·8 (95% CI 4·5-5·0), with similar estimates for men (4·6, 4·3-4·9) and women (5·0, 4·5-5·5). A linear relationship between the log incidence and log age of onset of amyotrophic lateral sclerosis is consistent with a multistage model of disease. The slope estimate suggests that amyotrophic lateral sclerosis is a six-step process. Identification of these steps could lead to preventive and therapeutic avenues. UK Medical Research Council; UK Economic and Social Research Council; Ireland Health Research Board; The Netherlands Organisation for Health Research and Development (ZonMw); the

  9. MTHFSD and DDX58 are novel RNA-binding proteins abnormally regulated in amyotrophic lateral sclerosis.

    Science.gov (United States)

    MacNair, Laura; Xiao, Shangxi; Miletic, Denise; Ghani, Mahdi; Julien, Jean-Pierre; Keith, Julia; Zinman, Lorne; Rogaeva, Ekaterina; Robertson, Janice

    2016-01-01

    Tar DNA-binding protein 43 (TDP-43) is an RNA-binding protein normally localized to the nucleus of cells, where it elicits functions related to RNA metabolism such as transcriptional regulation and alternative splicing. In amyotrophic lateral sclerosis, TDP-43 is mislocalized from the nucleus to the cytoplasm of diseased motor neurons, forming ubiquitinated inclusions. Although mutations in the gene encoding TDP-43, TARDBP, are found in amyotrophic lateral sclerosis, these are rare. However, TDP-43 pathology is common to over 95% of amyotrophic lateral sclerosis cases, suggesting that abnormalities of TDP-43 play an active role in disease pathogenesis. It is our hypothesis that a loss of TDP-43 from the nucleus of affected motor neurons in amyotrophic lateral sclerosis will lead to changes in RNA processing and expression. Identifying these changes could uncover molecular pathways that underpin motor neuron degeneration. Here we have used translating ribosome affinity purification coupled with microarray analysis to identify the mRNAs being actively translated in motor neurons of mutant TDP-43(A315T) mice compared to age-matched non-transgenic littermates. No significant changes were found at 5 months (presymptomatic) of age, but at 10 months (symptomatic) the translational profile revealed significant changes in genes involved in RNA metabolic process, immune response and cell cycle regulation. Of 28 differentially expressed genes, seven had a ≥ 2-fold change; four were validated by immunofluorescence labelling of motor neurons in TDP-43(A315T) mice, and two of these were confirmed by immunohistochemistry in amyotrophic lateral sclerosis cases. Both of these identified genes, DDX58 and MTHFSD, are RNA-binding proteins, and we show that TDP-43 binds to their respective mRNAs and we identify MTHFSD as a novel component of stress granules. This discovery-based approach has for the first time revealed translational changes in motor neurons of a TDP-43 mouse model

  10. Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pettit, Lewis D; Bastin, Mark E; Smith, Colin; Bak, Thomas H; Gillingwater, Thomas H; Abrahams, Sharon

    2013-11-01

    Cognitive impairment in amyotrophic lateral sclerosis is characterized by deficits on tests of executive function; however, the contribution of abnormal processing speed is unknown. Methods are confounded by tasks that depend on motor speed in patients with physical disability. Structural and functional magnetic resonance imaging studies have revealed multi-system cerebral involvement, with evidence of reduced white matter volume and integrity in predominant frontotemporal regions. The current study has two aims. First, to investigate whether cognitive impairments in amyotrophic lateral sclerosis are due to executive dysfunction or slowed processing speed using methodology that accommodates motor disability. This is achieved using a dual-task paradigm and tasks that manipulate stimulus presentation times and do not rely on response motor speed. Second, to identify relationships between specific cognitive impairments and the integrity of distinct white matter tracts. Thirty patients with amyotrophic lateral sclerosis and 30 age- and education-matched control subjects were administered an experimental dual-task procedure that combined a visual inspection time task and digit recall. In addition, measures of executive function (including letter fluency) and processing speed (visual inspection time and rapid serial letter identification) were administered. Integrity of white matter tracts was determined using region of interest analyses of diffusion tensor magnetic resonance imaging data. Patients with amyotrophic lateral sclerosis did not show impairments on tests of processing speed, but executive deficits were revealed once visual inspection time was combined with digit recall (dual-task) and in letter fluency. In addition to the corticospinal tracts, significant differences in fractional anisotropy and mean diffusivity were found between groups in a number of prefrontal and temporal white matter tracts including the anterior cingulate, anterior thalamic radiation

  11. Widespread grey matter pathology dominates the longitudinal cerebral MRI and clinical landscape of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Menke, Ricarda A L; Körner, Sonja; Filippini, Nicola; Douaud, Gwenaëlle; Knight, Steven; Talbot, Kevin; Turner, Martin R

    2014-09-01

    Diagnosis, stratification and monitoring of disease progression in amyotrophic lateral sclerosis currently rely on clinical history and examination. The phenotypic heterogeneity of amyotrophic lateral sclerosis, including extramotor cognitive impairments is now well recognized. Candidate biomarkers have shown variable sensitivity and specificity, and studies have been mainly undertaken only cross-sectionally. Sixty patients with sporadic amyotrophic lateral sclerosis (without a family history of amyotrophic lateral sclerosis or dementia) underwent baseline multimodal magnetic resonance imaging at 3 T. Grey matter pathology was identified through analysis of T1-weighted images using voxel-based morphometry. White matter pathology was assessed using tract-based spatial statistics analysis of indices derived from diffusion tensor imaging. Cross-sectional analyses included group comparison with a group of healthy controls (n = 36) and correlations with clinical features, including regional disability, clinical upper motor neuron signs and cognitive impairment. Patients were offered 6-monthly follow-up MRI, and the last available scan was used for a separate longitudinal analysis (n = 27). In cross-sectional study, the core signature of white matter pathology was confirmed within the corticospinal tract and callosal body, and linked strongly to clinical upper motor neuron burden, but also to limb disability subscore and progression rate. Localized grey matter abnormalities were detected in a topographically appropriate region of the left motor cortex in relation to bulbar disability, and in Broca's area and its homologue in relation to verbal fluency. Longitudinal analysis revealed progressive and widespread changes in the grey matter, notably including the basal ganglia. In contrast there was limited white matter pathology progression, in keeping with a previously unrecognized limited change in individual clinical upper motor neuron scores, despite advancing disability

  12. Copper mediated neurological disorder: visions into amyotrophic lateral sclerosis, Alzheimer and Menkes disease.

    Science.gov (United States)

    Ahuja, Anami; Dev, Kapil; Tanwar, Ranjeet S; Selwal, Krishan K; Tyagi, Pankaj K

    2015-01-01

    Copper (Cu) is a vital redox dynamic metal that is possibly poisonous in superfluous. Metals can traditionally or intricately cause propagation in reactive oxygen species (ROS) accretion in cells and this may effect in programmed cell death. Accumulation of Cu causes necrosis that looks to be facilitated by DNA damage, followed by activation of P53. Cu dyshomeostasis has also been concerned in neurodegenerative disorders such as Alzheimer, Amyotrophic lateral sclerosis (ALS) or Menkes disease and is directly related to neurodegenerative syndrome that usually produces senile dementia. These mortal syndromes are closely related with an immense damage of neurons and synaptic failure in the brain. This review focuses on copper mediated neurological disorders with insights into amyotrophic lateral sclerosis, Alzheimer and Menkes disease. Copyright © 2014 Elsevier GmbH. All rights reserved.

  13. Calcium in the pathomechanism of amyotrophic lateral sclerosis - Taking center stage?

    Science.gov (United States)

    Patai, Roland; Nógrádi, Bernát; Engelhardt, József I; Siklós, László

    2017-02-19

    Amyotrophic lateral sclerosis is an incurable, relentlessly progressive disease primarily affecting motor neurons. The cause of the disease, except for the mutations identified in a small fraction of patients, is unknown. The major mechanisms contributing to the degeneration of motor neurons have already been disclosed and characterized, including excitotoxicity, oxidative stress, mitochondrial dysfunction, and immune/inflammatory processes. During the progression of the disease these toxic processes are not discrete, but each facilitates the deleterious effect of the other. However, due to their common reciprocal calcium dependence, calcium ions may act as a common denominator and through a positive feedback loop may combine the individual pathological processes into a unified escalating mechanism of neuronal destruction. This mini-review provides an overview of the mutual calcium dependence of the major toxic mechanisms associated with amyotrophic lateral sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Concomitant rheumatoid arthritis and amyotrophic lateral sclerosis: report of two new cases and review of literature.

    Science.gov (United States)

    Padovan, Melissa; Caniatti, Luisa Maria; Trotta, Francesco; Govoni, Marcello

    2011-06-01

    To describe a rare association between rheumatoid arthritis (RA) and amyotrophic lateral sclerosis (ALS). Two new cases of patients with RA who developed amyotrophic lateral sclerosis (ALS), one receiving anti-TNFα agents, were reported. Only other five cases of this rare association have been previously described in literature. The simultaneous presence of the two diseases represents a difficult diagnostic challenge because RA may mimic some musculoskeletal symptoms of ALS. There is no evidence in favor of a common pathophysiologic mechanism, and thus the possibility of a fortuitous association must be raised. A neurotoxic side effect of various drugs for RA treatment could be considered. Casual or causal association remains a difficult choice. The possibility of a coincidental association must be raised but neurologic side effects of TNFα blockers lead to discussion.

  15. Mesenchymal stem cell therapy for the treatment of amyotrophic lateral sclerosis: signals for hope?

    Science.gov (United States)

    Allers, Carolina; Jones, Janet A; Lasala, Gabriel P; Minguell, José J

    2014-01-01

    Based on the distinctive cellular, molecular and immunomodulatory traits of mesenchymal stem cells (MSC), it has been postulated that these cells may play a critical role in regenerative medicine. In addition to the participation of MSC in the repair of mesodermal-derived tissues (bone, cartilage), robust data have suggested that MSC may also play a reparative role in conditions involving damage of cells of ectodermal origin. The above content has been supported by the capability of MSC to differentiate into neuron-like cells as well as by a competence to generate a 'neuroprotective' environment. In turn, several preclinical studies have put forward the concept that MSC therapy may represent an option for the treatment of several neurological disorders and injuries, including amyotrophic lateral sclerosis. We expect that the above foundations, which have inspired this review, may result in the founding of an effective and/or palliative therapy for amyotrophic lateral sclerosis.

  16. Irradiation of salivary glands in the amyotrophic lateral sclerosis; Irradiation des glandes salivaires dans la sclerose laterale amyotrophique

    Energy Technology Data Exchange (ETDEWEB)

    Bourry, N.; Lapeyre, M.; Tortochaux, J.; Gilliot, O.; Achard, J.L.; Verrelle, P. [Centre Jean-Perrin, Dept. de Radiotherapie 63 - Clermont-Ferrand (France); Clavelou, P.; Rouvet, S. [CHU Gabriel-Montpied, Service de Neurologie, 63 - Clermont-Ferrand (France)

    2006-11-15

    The irradiation of salivary glands in the amyotrophic lateral sclerosis is efficient. A dose about 20 Gy in five seances delivered by electrons seems a correct compromise between efficiency and toxicity. (N.C.)

  17. Diffusion tensor imaging analysis of sequential spreading of disease in amyotrophic lateral sclerosis confirms patterns of TDP-43 pathology.

    Science.gov (United States)

    Kassubek, Jan; Müller, Hans-Peter; Del Tredici, Kelly; Brettschneider, Johannes; Pinkhardt, Elmar H; Lulé, Dorothée; Böhm, Sarah; Braak, Heiko; Ludolph, Albert C

    2014-06-01

    Diffusion tensor imaging can identify amyotrophic lateral sclerosis-associated patterns of brain alterations at the group level. Recently, a neuropathological staging system for amyotrophic lateral sclerosis has shown that amyotrophic lateral sclerosis may disseminate in a sequential regional pattern during four disease stages. The objective of the present study was to apply a new methodological diffusion tensor imaging-based approach to automatically analyse in vivo the fibre tracts that are prone to be involved at each neuropathological stage of amyotrophic lateral sclerosis. Two data samples, consisting of 130 diffusion tensor imaging data sets acquired at 1.5 T from 78 patients with amyotrophic lateral sclerosis and 52 control subjects; and 55 diffusion-tensor imaging data sets at 3.0 T from 33 patients with amyotrophic lateral sclerosis and 22 control subjects, were analysed by a tract of interest-based fibre tracking approach to analyse five tracts that become involved during the course of amyotrophic lateral sclerosis: the corticospinal tract (stage 1); the corticorubral and the corticopontine tracts (stage 2); the corticostriatal pathway (stage 3); the proximal portion of the perforant path (stage 4); and two reference pathways. The statistical analyses of tracts of interest showed differences between patients with amyotrophic lateral sclerosis and control subjects for all tracts. The significance level of the comparisons at the group level was lower, the higher the disease stage with corresponding involved fibre tracts. Both the clinical phenotype as assessed by the amyotrophic lateral sclerosis functional rating scale-revised and disease duration correlated significantly with the resulting staging scheme. In summary, the tract of interest-based technique allowed for individual analysis of predefined tract structures, thus making it possible to image in vivo the disease stages in amyotrophic lateral sclerosis. This approach can be used not only for

  18. Reduced isotope uptake restricted to the motor area in patients with amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Abe, K. (Dept. of Neurology, Osaka Univ. Medical School (Japan)); Yorifuji, S. (Dept. of Neurology, Osaka Univ. Medical School (Japan)); Nishikawa, Y. (Dept. of Neurology, Osaka Univ. Medical School (Japan))

    1993-01-01

    To study degeneration in the central nervous system in amyotrophic lateral sclerosis (ALS), we studied four patients using single photon emission tomography (SPECT) and magnetic resonance imaging (MRI). MRI demonstrated high intensity along the pyramidal tract on T2-weighted images in two. SPECT demonstrated reduced isotope uptake restricted to the motor area. While the cause of degeneration of the cortical neurons in the motor area is unknown, SPECT is useful for detecting the degeneration in patients with ALS. (orig.)

  19. Magnetic resonance findings in amyotrophic lateral sclerosis using a spin echo magnetization transfer sequence: preliminary report

    Directory of Open Access Journals (Sweden)

    ROCHA ANTÔNIO JOSÉ DA

    1999-01-01

    Full Text Available We present the magnetic resonance (MR findings of five patients with amyotrophic lateral sclerosis (ALS using a spin-echo sequence with an additional magnetization transfer (MT pulse on T1-weighted images (T1 SE/MT. These findings were absent in the control group and consisted of hyperintensity of the corticospinal tract. Moreover we discuss the principles and the use of this fast but simple MR technique in the diagnosis of ALS

  20. Agraphia in Bulbar-Onset Amyotrophic Lateral Sclerosis: Not Merely a Consequence of Dementia or Aphasia

    OpenAIRE

    Hiroo Ichikawa; Nobuyoshi Takahashi; Soutaro Hieda; Hideki Ohno; Mitsuru Kawamura

    2008-01-01

    The clinical significance and characteristics of writing errors in bulbar-onset amyotrophic lateral sclerosis (ALS) are not clear. We retrospectively investigated writing samples in 19 patients with bulbar-onset ALS without preceding extra-motor symptoms. Co-development of dementia and/or aphasia was also explored and single photon emission computed tomography (SPECT) images of the brain were reviewed. As a result, a high prevalence of writing errors (15 of the 19 patients) was found. Of note...

  1. State of the art and the dark side of amyotrophic lateral sclerosis

    OpenAIRE

    2010-01-01

    Amyotrophic lateral sclerosis (ALS) is a disorder that involves the degeneration of motor neurons, muscle atrophy, and paralysis. In a few familiar forms of ALS, mutations in the superoxide dismutase-1 (SOD1) gene have been held responsible for the degeneration of motor neurons. Nevertheless, after the discovery of the SOD1 mutations no consensus has emerged as to which cells, tissues and pathways are primarily implicated in the pathogenic events that lead to ALS. Ubiquitous overexpression of...

  2. The Use of Integrative Therapies in Patients with Amyotrophic Lateral Sclerosis in Shanghai, China

    OpenAIRE

    Weidong Pan; Xiangjun Chen; Jie Bao; Yu Bai; Hua Lu; Qiudong Wang; Yi Liu; Canxing Yuan; Wenwei Li; Zhenguo Liu; Jun Liu; Xuying Zhu; Baofeng Qin; Dingfang Cai; Hua Zhou

    2013-01-01

    Objective. To investigate the current use of integrative therapies (IT) in the treatment of patients with amyotrophic lateral sclerosis (ALS). Methods. A cross-sectional, multicenter clinical epidemiological survey was conducted in 12 hospitals in Shanghai. We investigated the type and frequency of IT use and determined whether the use of IT correlated with demographic, social, or disease-specific characteristics in our patient population. Results. A total of 231 (89.5%) of 258 patients with ...

  3. What are the roles of carers in decision-making for amyotrophic lateral sclerosis multidisciplinary care?

    OpenAIRE

    Hogden A; Greenfield D; Nugus P; Kiernan MC

    2013-01-01

    Anne Hogden,1 David Greenfield,1 Peter Nugus,1 Matthew C Kiernan21Centre for Clinical Governance Research, Australian Institute of Health Innovation, University of New South Wales, 2Prince of Wales Clinical School, University of New South Wales and Neuroscience Research Australia, Sydney, NSW, AustraliaPurpose: Family carers of patients with amyotrophic lateral sclerosis (ALS) are presumed to have frequent involvement in decision-making for symptom management and quality of life. To better un...

  4. LRP4 antibodies in serum and CSF from amyotrophic lateral sclerosis patients

    OpenAIRE

    Tzartos, John S; Zisimopoulou, Paraskevi; Rentzos, Michael; Karandreas, Nikos; Zouvelou, Vasiliki; Evangelakou, Panagiota; Tsonis, Anastasios; Thomaidis, Thomas; Lauria, Giuseppe; Andreetta, Francesca; Mantegazza, Renato; Tzartos, Socrates J

    2013-01-01

    Objective Amyotrophic lateral sclerosis (ALS) and myasthenia gravis (MG) are caused, respectively, by motor neuron degeneration and neuromuscular junction (NMJ) dysfunction. The membrane protein LRP4 is crucial in the development and function of motor neurons and NMJs and LRP4 autoantibodies have been recently detected in some MG patients. Because of the critical role in motor neuron function we searched for LRP4 antibodies in ALS patients. Methods We developed a cell-based assay and a radioi...

  5. Are Amyotrophic Lateral Sclerosis Caregivers at Higher Risk for Health Problems?

    Science.gov (United States)

    Pinho, Ana Catarina; Gonçalves, Edna

    2016-01-01

    Amyotrophic lateral sclerosis is a rare neurodegenerative disease affecting motor neurons. Patients present with progressive physical impairment, respiratory failure being the main cause of death. A significant portion of patients presents neurobehavioral problems as well. As severe impairment occurs, patients become highly dependent and in general, their families assume the role of primary caregivers, exposing them to stress and other potential causes of disease like insomnia, physical strain from patients' mobilization and changes on eating habits. The aim of this work is to understand if taking care of patients with amyotrophic lateral sclerosis increases disease and health problems on caregivers. Comprehensive review of the literature published on the electronic databases PubMed and Scopus between 2010 and 2014. Eighteen studies met the inclusion criteria. We found that amyotrophic lateral sclerosis caregivers have higher levels of burden, depression and anxiety with lower quality of life. This is associated to age and gender of caregivers, time spent caring, patients' disability and neurobehavioral changes. Higher sense of support and spirituality on family seem to promote wellbeing. On our work, we were able to understand that several factors have influenced caregivers' quality of life and affect their health. Besides, we could understand that the outcomes studied are related between themselves and, as seen in some of the studies, related to patients' quality of life itself. Consequently, it has become essential to adopt a holistic approach of these patients and their families, fighting the deteriorating risk factors and investing on health promoters. Despite the large body of research on family caregiving for amyotrophic lateral sclerosis patients, little has changed and the outcomes measured remain almost the same before and after 2010. The work indicates that caregivers have lower levels of health than the general population. Still additional research is

  6. Prevalence of potential sports?associated risk factors in Swiss amyotrophic lateral sclerosis patients

    OpenAIRE

    Feddermann?Demont, Nina; Junge, Astrid; Weber, Konrad P.; Weller, Michael; Dvo??k, Ji??; Tarnutzer, Alexander A.

    2017-01-01

    Abstract Objectives Amyotrophic lateral sclerosis (ALS) has been reported to occur with increased incidence amongst physically active people. The role of extrinsic risk factors as physical activity, head trauma and drug/pesticide?exposure in the pathophysiology of ALS and especially in the context of practising sports remains controversial. Materials and Methods We retrospectively studied exposure to extrinsic factors in 92 ALS patients in the presymptomatic stage. Metabolic equivalents (METs...

  7. An Overview of Potential Targets for Treating Amyotrophic Lateral Sclerosis and Huntington's Disease

    Science.gov (United States)

    de Paula, Caroline Zocatelli; Gonçalves, Bruno Daniel Correia; Vieira, Luciene Bruno

    2015-01-01

    Neurodegenerative diseases affect millions of people worldwide. Progressive damage or loss of neurons, neurodegeneration, has severe consequences on the mental and physical health of a patient. Despite all efforts by scientific community, there is currently no cure or manner to slow degeneration progression. We review some treatments that attempt to prevent the progress of some of major neurodegenerative diseases: Amyotrophic Lateral Sclerosis and Huntington's disease. PMID:26295035

  8. Amyotrophic Lateral Sclerosis Presenting Respiratory Failure as the Sole Initial Manifestation

    OpenAIRE

    Fuyuki Tateno; Ryuji Sakakibara; Kengo Kawashima; Masahiko Kishi; Yohei Tsuyusaki; Yosuke Aiba; Tsuyoshi Ogata

    2014-01-01

    It is rare that amyotrophic lateral sclerosis (ALS) presents with respiratory failure as the sole initial manifestation. A 72-year-old man with mild chronic obstructive pulmonary disease developed exertional dyspnea for 13 months. He then progressed to limb weakness that led to the diagnosis of ALS. Although rare, ALS can present with respiratory failure as the sole initial manifestation more than 1 year prior to limb weakness.

  9. <Poster>Cystatin C immunoreactivity and neuronal degeneration in amyotrophic lateral sclerosis

    OpenAIRE

    Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Wakabayashi, Koichi

    2010-01-01

    Cystatin C (CC), a cysteine protease inhibitor involved in protein degradation, is a marker of Buninabodies in lower motor neurons in amyotrophic lateral sclerosis (ALS). TDP-43-immunoreactive inclusions are alsohistological hallmark of ALS. However, immunohistochemical localization of CC in ALS motor neurons with or withoutinclusions is uncertain. Recently, we demonstrated that the majority of anterior horn cells showed moderate to intenseimmunoreactivity for CC in controls and that CC immun...

  10. An Overview of Potential Targets for Treating Amyotrophic Lateral Sclerosis and Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Caroline Zocatelli de Paula

    2015-01-01

    Full Text Available Neurodegenerative diseases affect millions of people worldwide. Progressive damage or loss of neurons, neurodegeneration, has severe consequences on the mental and physical health of a patient. Despite all efforts by scientific community, there is currently no cure or manner to slow degeneration progression. We review some treatments that attempt to prevent the progress of some of major neurodegenerative diseases: Amyotrophic Lateral Sclerosis and Huntington’s disease.

  11. Hypermetabolism is a deleterious prognostic factor in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jésus, P; Fayemendy, P; Nicol, M; Lautrette, G; Sourisseau, H; Preux, P-M; Desport, J-C; Marin, B; Couratier, P

    2018-01-01

    The aim of this study was to investigate patients with amyotrophic lateral sclerosis in order to determine their nutritional, neurological and respiratory parameters, and survival according to metabolic level. Nutritional assessment included resting energy expenditure (REE) measured by indirect calorimetry [hypermetabolism if REE variation (ΔREE) > 10%] and fat mass (FM) using impedancemetry. Neurological assessment included the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score. Survival analysis used the Kaplan-Meier method and multivariate Cox model. A total of 315 patients were analysed. Median age at diagnosis was 65.9 years and 55.2% of patients were hypermetabolic. With regard to the metabolic level (ΔREE: 20%), patients with ΔREE > 20% initially had a lower FM(29.7% vs. 32.1% in those with ΔREE ≤10%; P = 0.0054). During follow-up, the median slope of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised tended to worsen more in patients with ΔREE > 20% (-1.4 vs. -1.0 points/month in those with ΔREE ≤10%; P = 0.07). Overall median survival since diagnosis was 18.4 months. ΔREE > 20% tended to increase the risk of dying compared with ΔREE ≤10% (hazard ratio, 1.33; P = 0.055). In multivariate analysis, an increased REE:FM ratio was independently associated with death (hazard ratio, 1.005; P = 0.001). Hypermetabolism is present in more than half of patients with amyotrophic lateral sclerosis. It modifies the body composition at diagnosis, and patients with hypermetabolism >20% have a worse prognosis than those without hypermetabolism. © 2017 EAN.

  12. Amyotrophic Lateral Sclerosis Presenting Respiratory Failure as the Sole Initial Manifestation

    Directory of Open Access Journals (Sweden)

    Fuyuki Tateno

    2014-08-01

    Full Text Available It is rare that amyotrophic lateral sclerosis (ALS presents with respiratory failure as the sole initial manifestation. A 72-year-old man with mild chronic obstructive pulmonary disease developed exertional dyspnea for 13 months. He then progressed to limb weakness that led to the diagnosis of ALS. Although rare, ALS can present with respiratory failure as the sole initial manifestation more than 1 year prior to limb weakness.

  13. "Understanding my ALS". Experiences and reflections of persons with amyotrophic lateral sclerosis and relatives on participation in peer group rehabilitation.

    Science.gov (United States)

    Madsen, Louise Sofia; Jeppesen, Jørgen; Handberg, Charlotte

    2018-01-26

    The aim of this study was to gain insight into experiences and reflections of persons with amyotrophic lateral sclerosis and relatives concerning the peer group rehabilitation programme "More Life - Less Illness". This qualitative study used the Interpretive Description methodology with Symbolic Interactionism as the analytical framework. Eighteen programme participants representing persons with amyotrophic lateral sclerosis (n = 8) and relatives (n = 10) were included. Data consisted of individual interviews and participant observation. The analysis revealed two categorical themes, "Sense of Community Building" and "Understanding my ALS", which represented the participants' experiences and reflections on peer group rehabilitation. Through the analysis, it became apparent that "Sense of Community Building" gave rise to an increased and personalised understanding of amyotrophic lateral sclerosis among the participants. As a part of the continuous processing of the knowledge gained, "Facing Facts" and "Retaining Normality" appeared as subthemes regarding the participants' ability to live a less dependent and more meaningful life. This study of peer group rehabilitation for persons with amyotrophic lateral sclerosis and relatives indicates that programme participation leads to positive experiences in terms of living a shared meaningful life despite severe disability. The findings may guide practice to develop longitudinal peer group rehabilitation programmes with joint inclusion of persons with amyotrophic lateral sclerosis and relatives. Implications for Rehabilitation Peer group rehabilitation may facilitate an increased and personalised understanding of what it means to live with amyotrophic lateral sclerosis. A programme design with six months of sequential sessions enables a continuous processing of shared experiences and gained knowledge. Joint participation of persons with amyotrophic lateral sclerosis and their relatives supports both their internal

  14. Comment on the article titled "Increased Incidence of Amyotrophic Lateral Sclerosis in Polymyositis: A Nationwide Cohort Study".

    Science.gov (United States)

    Parperis, Konstantinos

    2017-10-03

    With interest, I read the recent article in Arthritis Care and Research titled "Increased Incidence of Amyotrophic Lateral Sclerosis in Polymyositis: A Nationwide Cohort Study" (1). Tseng at al (1) conducted a retrospective cohort study in Taiwan, exploring a link between amyotrophic lateral sclerosis (ALS) and polymyositis (PM). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Awake fi beroptic intubation of a patient with amyotrophic lateral sclerosis: case report

    Directory of Open Access Journals (Sweden)

    Elif Bakı

    2012-12-01

    Full Text Available Amyotrophic Lateral Sclerosis is a rapidly progressive disease from the fi fth to sixth decades of life causing degeneration and death of the upper and lower motor neurons and no effective treatment. The diagnosis isdependent on the clinical presentation and consistent electrodiagnostic studies. Progressive denervation affects the muscles, causing muscular weakness and atrophy, when the ventilation muscles are affected deathdue to respiratory failure occurs within a few years. We present the case of a 54 years old, 180 cm height and 94 kg weight male patient with amyotrophic lateral sclerosis who underwent surgical treatment of thyroidcancer. Fiberoptic intubation was orally performed providing spontaneus breathing. Propofol was applied after passing vocal cords. Anesthesia was maintained with sevofl orane (%2 and a mixture of oxygen and airunder volume controlled ventilation. Rocuronium was used 20 mg at the beginning of the surgery. At the end of surgery, he wasn’t extubated and transferred to anesthesia intensive care unit. He was extubated after tenhours and he was awaked perfectly. The patient was discharged from intensive care unit after 24 hours and from hospital after ten days. We reported that amyotrophic lateral sclerosis patient with limited mouth opening who underwent thyroid surgery, using awake intubation.

  16. Clinical outcomes and serum uric acid levels in elderly patients with amyotrophic lateral sclerosis aged ≥ 70 years.

    Science.gov (United States)

    Kataoka, Hiroshi; Kiriyama, Takao; Kobayashi, Yasuyo; Horikawa, Hirosei; Ueno, Satoshi

    2013-01-01

    Amyotrophic lateral sclerosis is a slowly progressive fetal neurodegenerative disease in which clinical phenotype and nutritional status are considered prognostic factors. Advanced age has also been reported to carry a poor prognosis in amyotrophic lateral sclerosis. The elderly population is expected to increase in Japan, as well as in other countries in the near future. Whether late-onset amyotrophic lateral sclerosis affects the average lifespan or survival of patients and the nutritional status was related to survival remains an open question. We studied the survival of elderly 34 patients with clinically definite amyotrophic lateral sclerosis aged ≥ 70 years and investigated serum triglycerides, cholesterol, LDL/HDL ratio, and glucose. Serum uric acid was examined. The average age at respiratory disorders or death as a whole was 77.5 ± 4.3 years. Survival did not differ significantly between different clinical phenotypes or between patients with and those without riluzole usage. Survival differed significantly between patients with and those without other complications. No biochemical parameter is correlated with outcome in this series, including elevated triglyceride or cholesterol levels and an increased LDL/HDL ratio. The survival correlated with the serum uric acid level (r = 0.407, p = 0.017). The onset of amyotrophic lateral sclerosis at ≥ 70 years of age might not be the key determinant of survival in patients with amyotrophic lateral sclerosis.

  17. Information-seeking Behavior and Information Needs in Patients With Amyotrophic Lateral Sclerosis: Analyzing an Online Patient Community.

    Science.gov (United States)

    Oh, Juyeon; Kim, Jung A

    2017-07-01

    A few studies have examined the specific informational needs of the population with amyotrophic lateral sclerosis. The aims of this study were to describe the information-seeking behavior and information needs of patients with amyotrophic lateral sclerosis and their families in Korea by analyzing messages from an online patient community. A total of 1047 messages from the question and answer forum of the "Lou Gehrig's Disease Network" (http://cafe.daum.net/alsfree) from January 2010 to September 2015 were collected. The word frequency, main questions, and asker of the messages were analyzed and coded. Terms such as "hospital," "mother," "father," "gastrostomy," and "ALS" were most frequently identified. The most commonly mentioned main topic was about disease-specific information, while the most frequent subcategory was symptoms or management of symptoms. Other prominent categories concerned information about treatment, rehabilitation, and the medical system. The people who wrote the questions were mostly the son/daughter of patients with amyotrophic lateral sclerosis. Patients with amyotrophic lateral sclerosis and their family members commonly obtained information by posting their inquiries online and have a variety of questions regarding amyotrophic lateral sclerosis in this study. The findings of this study can be used as a base of information for developing educational programs and resources for patients with amyotrophic lateral sclerosis and their families.

  18. [Respiratory disorders during sleep in amyotrophic lateral sclerosis].

    Science.gov (United States)

    Camu, W

    2001-11-01

    Amyotropic lateral sclerosis is a severe degenerative disease of the nervous system. Progressive death of central and peripheral motor neurons leads to rapidly extensive paralysis of the four limbs, the bulbar region and the respiratory system. Sleep respiratory disorders is a useful sign to follow in these patients. Apnea is generally central rather than obstructive. Hypoventilation, particularly during REM sleep has been reported and causes nocturnal desaturation. These patients also appear to have a disrupted sleep pattern with a longer phase I and a shorter total duration of sleep. These nocturnal respiratory disorders observed in amyotropic lateral sclerosis are similar to those observed in muscle diseases. Management must however be undertaken very early in these patients because outcome can be rapidly fatal after the development of significant desaturation. Nasal ventilation can improve not only quality of life but also life expectancy for these patients.

  19. Ciliary neurotrophic factor (CNTF) for amyotrophic lateral sclerosis/motor neuron disease.

    Science.gov (United States)

    Bongioanni, P; Reali, C; Sogos, V

    2004-01-01

    Amyotrophic lateral sclerosis, also known as motor neuron disease, is a fatal neuromuscular disease characterized by progressive muscle weakness resulting in paralysis, which might be treated with ciliary neurotrophic factor. The objective of this review was to examine the efficacy of ciliary neutrophic factor in amyotrophic lateral sclerosis. We searched the Cochrane Neuromuscular Disease Group trials register (searched June 2003) for randomized trials, MEDLINE (from January 1966 to October 2003) and EMBASE (from January 1980 to October 2003), checked the reference lists of papers identified and contacted the authors of studies identified to get additional unpublished results. We considered the following selection criteria: Types of studies: randomized controlled clinical trials; adults with a diagnosis of either probable or definite amyotrophic lateral sclerosis according to the El Escorial criteria; Types of interventions: treatment with ciliary neurotrophic factor for at least six months, in a placebo-controlled randomized format; Types of outcome measures Primary: survival; Secondary: muscle strength, respiratory function, changes in bulbar functions, changes in quality of life, proportion of patients with adverse side effects (such as cough, asthenia, nausea, anorexia, weight loss and increased salivation). We identified two randomized trials. The data were extracted and examined independently by the reviewers. Some missing data were obtained from investigators. Two trials, with a total population of 1,300 amyotrophic lateral sclerosis patients treated with subcutaneous injections of recombinant human ciliary neurotrophic factor, were examined in this review. The methodological quality of these trials was considered adequate. No significant difference was observed between ciliary neurotrophic factor and placebo groups for survival, the primary outcome measure. The relative risk was 1.07 (95% CI 0.81 to 1.41). No significant differences between the groups were

  20. Translation and validation of the amyotrophic lateral sclerosis severity scale (ALSSS)

    OpenAIRE

    Lima, Núbia Maria Freire Vieira; Guerra, Celise Cirelli; Teixeira, Luciane de Cássia; Silva, Luciano Bruno de Carvalho; Sordi, Marina di; Mourão, Lúcia; Nucci, Anamarli

    2009-01-01

    O objetivo do trabalho foi traduzir a Amyotrophic Lateral Sclerosis Severity Scale para o português, como Escala de gravidade da esclerose lateral amiotrófica (Egela), além de validar e estudar sua confiabilidade. A escala foi submetida à versão e retroversão por tradutores bilíngües e três fisioterapeutas treinaram para padronizar sua aplicação. Foram avaliados 22 pacientes (5 mulheres, 17 homens, média de idade 45,9 anos) pela Egela e pela medida de independência funcional (MIF); 11 foram e...

  1. Application of botulinum toxin to treat sialorrhea in amyotrophic lateral sclerosis patients: a literature review.

    Science.gov (United States)

    Oliveira, Ademar Francisco de; Silva, Gêssyca Adryene de Menezes; Almeida, Débora Milenna Xavier

    2016-01-01

    Amyotrophic lateral sclerosis is a progressive and fatal neurodegenerative disease characterized by the degeneration of motor neurons, which are the central nervous system cells that control voluntary muscle movements. The excessive salivation (sialorrhea) is present in approximately 50% of amyotrophic lateral sclerosis cases. Thus, some alternative therapeutic methods are sought, such as anticholinergic drugs and surgery. Recently the use of botulinum toxin applied at a midpoint of the salivary glands, often guided by ultrasound, have demonstrated positive results. The objective was to review the literature to demonstrate an alternative method to treatments of sialorrhea in patients with amyotrophic lateral sclerosis. In recent studies, the efficacy of botulinum toxin is confirmed, although new applications are required. Since the side effects are negligible, this is an alternative to treat amyotrophic lateral sclerosis, and other patients with diseases that present sialorrhea. RESUMO Esclerose lateral amiotrófica é uma doença neurodegenerativa progressiva e fatal, caracterizada pela degeneração dos neurônios motores, as células do sistema nervoso central que controlam os movimentos voluntários dos músculos. A salivação excessiva (sialorreia) está presente em cerca de 50% dos casos de esclerose lateral amiotrófica. Dessa forma, surgem medidas terapêuticas alternativas como drogas anticolinérgicas e cirurgia, e recentemente, o uso da toxina botulínica, aplicada em um ponto central das glândulas salivares, muitas vezes guiado por ultrassonografia, demostrou resultados positivos. Objetivou-se revisar a literatura no intuito de demonstrar um método alternativo aos tratamentos de sialorreia em pacientes com esclerose lateral amiotrófica. Em estudos recentes, a eficácia do tratamento com toxina botulínica foi confirmada e, mesmo requerendo novas aplicações, os efeitos colaterais são ínfimos. Ela surge então como alternativa não só ao

  2. Supportive care needs of patients with amyotrophic lateral sclerosis/motor neuron disease and their caregivers: A scoping review.

    Science.gov (United States)

    Oh, Juyeon; Kim, Jung A

    2017-12-01

    To identify the supportive care needs of amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers, categorise and summarise them into a Supportive Care Needs Framework and identify gaps in literature. Little is known about the supportive care needs of amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers, and this subject has not previously been systemically reviewed. Scoping review. We conducted a scoping review from the MEDLINE, EMBASE, CINAHL and Cochrane databases for the period January 2000-July 2016, using the following inclusion criteria: (i) written in English only, (ii) published in peer-reviewed journals, (iii) at least part of the research considered the supportive care needs perspective of amyotrophic lateral sclerosis/motor neuron disease patients or their caregivers and (iv) the population sample included patients of amyotrophic lateral sclerosis/motor neuron disease or their caregivers. Thirty-seven articles were included. Our review shows that amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers' supportive care needs were mentioned across all seven domains of the Supportive Care Needs Framework. Most common were practical needs (n = 24), followed by Informational needs (n = 19), Social needs (n = 18), Psychological needs (n = 16), Physical needs (n = 15), Emotional needs (n = 13) and Spiritual needs (n = 8). From the perspectives of amyotrophic lateral sclerosis/motor neuron disease patients and their caregivers, there is a significant need for more practical, social, informational, psychological, physical, emotional and spiritual support. The Supportive Care Needs Framework has potential utility in the development of patient-centred support services or healthcare policies and serves as an important base for further studies; especially, specific examples of each supportive care needs domain can guide in clinical settings when healthcare professionals

  3. System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice.

    Science.gov (United States)

    Mesci, Pinar; Zaïdi, Sakina; Lobsiger, Christian S; Millecamps, Stéphanie; Escartin, Carole; Seilhean, Danielle; Sato, Hideyo; Mallat, Michel; Boillée, Séverine

    2015-01-01

    Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression. However, microglial-derived neurotoxic factors still remain largely unidentified in amyotrophic lateral sclerosis. With excitotoxicity being a major mechanism proposed to cause motor neuron death in amyotrophic lateral sclerosis, our hypothesis was that excessive glutamate release by activated microglia through their system [Formula: see text] (a cystine/glutamate antiporter with the specific subunit xCT/Slc7a11) could contribute to neurodegeneration. Here we show that xCT expression is enriched in microglia compared to total mouse spinal cord and absent from motor neurons. Activated microglia induced xCT expression and during disease, xCT levels were increased in both spinal cord and isolated microglia from mutant SOD1 amyotrophic lateral sclerosis mice. Expression of xCT was also detectable in spinal cord post-mortem tissues of patients with amyotrophic lateral sclerosis and correlated with increased inflammation. Genetic deletion of xCT in mice demonstrated that activated microglia released glutamate mainly through system [Formula: see text]. Interestingly, xCT deletion also led to decreased production of specific microglial pro-inflammatory/neurotoxic factors including nitric oxide, TNFa and IL6, whereas expression of anti-inflammatory/neuroprotective markers such as Ym1/Chil3 were increased, indicating that xCT regulates microglial functions. In amyotrophic lateral sclerosis mice, xCT deletion surprisingly led to earlier symptom onset but, importantly, this was followed by a significantly slowed progressive disease phase, which resulted in more surviving motor neurons. These results are consistent with a deleterious contribution of microglial-derived glutamate during symptomatic

  4. A PET/CT approach to spinal cord metabolism in amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Marini, Cecilia [CNR Institute of Bioimages and Molecular Physiology, Milan, Section of Genoa (Italy); University of Genoa, Nuclear Medicine, IRCCS San Martino IST, and Depth of Health Science, Genoa (Italy); IRCCS AOU San Martino-IST, CNR Institute of Bioimages and Molecular Physiology, Section of Genoa, C/o Nuclear Medicine, Genoa (Italy); Cistaro, Angelina; Fania, Piercarlo [Positron Emission Tomography Centre IRMET, Affidea, Turin (Italy); Campi, Cristina; Perasso, Annalisa; Massone, Anna Maria [SPIN Institute, CNR, Genoa (Italy); Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Cammarosano, Stefania; Chio, Adriano [University of Turin, ALS Center, ' ' Rita Levi Montalcini' ' Department of Neuroscience, Turin (Italy); AUO Citta della Salute e della Scienza, Turin (Italy); Caponnetto, Claudia; Nobili, Flavio Mariano; Novi, Giovanni; Scialo, Carlo; Mancardi, Gianluigi [IRCCS San Martino IST, Department of Neuroscience, Genoa (Italy); DINOGMI University of Genoa, Genoa (Italy); Beltrametti, Mauro C. [University of Genoa, Department of Mathematics (DIMA), Genoa (Italy); Buschiazzo, Ambra; Pomposelli, Elena; Morbelli, Silvia; Sambuceti, Gianmario [University of Genoa, Nuclear Medicine, IRCCS San Martino IST, and Depth of Health Science, Genoa (Italy); Bagnara, Maria Claudia [IRCCS AOU San Martino-IST, Medical Physics unit, Genoa (Italy); Bruzzi, Paolo [IRCCS AOU San Martino-IST, Statistics and Epidemiology Unit, Genoa (Italy); Piana, Michele [SPIN Institute, CNR, Genoa (Italy); University of Genoa, Department of Mathematics (DIMA), Genoa (Italy)

    2016-10-15

    In amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms. A new computational three-dimensional method to extract the spinal cord from {sup 18}F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls. The algorithm identified the skeleton on the CT images by using an extension of the Hough transform and then extracted the spinal canal and the spinal cord. In these regions, {sup 18}F-FDG standardized uptake values were measured to estimate the metabolic activity of the spinal canal and cord. Measurements were performed in the cervical and dorsal spine and normalized to the corresponding value in the liver. Uptake of {sup 18}F-FDG in the spinal cord was significantly higher in patients than in controls (p < 0.05). By contrast, no significant differences were observed in spinal cord and spinal canal volumes between the two groups. {sup 18}F-FDG uptake was completely independent of age, gender, degree of functional impairment, disease duration and riluzole treatment. Kaplan-Meier analysis showed a higher mortality rate in patients with standardized uptake values above the fifth decile at the 3-year follow-up evaluation (log-rank test, p < 0.01). The independence of this value was confirmed by multivariate Cox analysis. Our computational three-dimensional method enabled the evaluation of spinal cord metabolism and volume and might represent a potential new window onto the pathophysiology of amyotrophic lateral sclerosis. (orig.)

  5. Prognostic Factors in Amyotrophic Lateral Sclerosis: A Population-Based Study.

    Science.gov (United States)

    Moura, Mirian Conceicao; Novaes, Maria Rita Carvalho Garbi; Eduardo, Emanoel Junio; Zago, Yuri S S P; Freitas, Ricardo Del Negro Barroso; Casulari, Luiz Augusto

    2015-01-01

    To determine the prognostic factors associated with survival in amyotrophic lateral sclerosis at diagnosis. This retrospective population-based study evaluated 218 patients treated with riluzole between 2005 and 2014 and described their clinical and demographic profiles after the analysis of clinical data and records from the mortality information system in the Federal District, Brazil. Cox multivariate regression analysis was conducted for the parameters found. The study sample consisted of 132 men and 86 women with a mean age at disease onset of 57.2±12.3 years; 77.6% of them were Caucasian. The mean periods between disease onset and diagnosis were 22.7 months among men and 23.5 months among women, and the mean survival periods were 45.7±47.0 months among men and 39.3±29.8 months among women. In addition, 80.3% patients presented non-bulbar-onset amyotrophic lateral sclerosis, and 19.7% presented bulbar-onset. Cox regression analysis indicated worse prognosis for body mass index (BMI) 75 years (RR: 12.47, 95% CI: 3.51-44.26), and bulbar-onset (RR: 4.56, 95% CI: 2.06-10.12). Electromyography did not confirm the diagnosis in 55.6% of the suspected cases and in 27.9% of the bulbar-onset cases. The factors associated with lower survival in amyotrophic lateral sclerosis were age >75 years, BMI <25 kg/m2, and bulbar-onset.

  6. An Investigation of Perspectives of Respite Admission Among People Living With Amyotrophic Lateral Sclerosis and the Hospitals That Support Them.

    Science.gov (United States)

    Nakai, Michiko; Narita, Yugo; Tomimoto, Hidekazu

    2017-07-01

    Amyotrophic lateral sclerosis is a progressive disease with rapid degeneration. Respite care is an essential service for improving the well-being of both patients with this disease and their family caregivers, but accessibility of respite services is limited. This study investigates perspectives on respite admission among people living with amyotrophic lateral sclerosis and the hospitals supporting them. We conducted semistructured interviews among 3 patients with amyotrophic lateral sclerosis and 12 family members, exploring demographic information and their awareness and experience of respite admission. We also interviewed 16 representatives from hospitals about awareness of and preparation for respite admission for patients with this disease, the role of regional networks for intractable diseases, and knowledge about communication support schemes. We found significant differences in the revised Amyotrophic Lateral Sclerosis Functional Rating Scale between patients who had and had not received respite admission. Qualitative analysis of the data indicated that respite admission was a contributory factor in continuing and stabilizing home care. Limited provision of social services and hospital care quality were barriers to respite admission. Respite admission was essential to continued home care for patients with amyotrophic lateral sclerosis. Severe-stage patients were eligible for respite admission. Its accessibility, however, was limited, especially for patients living in rural areas. Supporting hospitals had limited capacity to respond to patients' needs. Individualized care and communication were internal barriers to respite admission.

  7. Illness trajectories in patients with amyotrophic lateral sclerosis: How illness progression is related to life narratives and interpersonal relationships.

    Science.gov (United States)

    Cipolletta, Sabrina; Gammino, Giorgia Rosamaria; Palmieri, Arianna

    2017-12-01

    To identify illness trajectories in amyotrophic lateral sclerosis by analysing personal, social and functional dimensions related to amyotrophic lateral sclerosis progression. Previous studies have considered some psychological distinct variables that may moderate illness progression, but no research has combined an extensive qualitative understanding of amyotrophic lateral sclerosis patients' psychological characteristics and illness progression. A mixed-methods approach was used to combine quantitative and qualitative measures. Illness progression was assessed through a longitudinal design. Eighteen patients with amyotrophic lateral sclerosis attending a Neurology Department in northern Italy participated in the study. Semi-structured interviews to explore personal experience, and dependency grids to assess the distribution of dependency; ALSFRS-R and neuropsychological screening were, respectively, used to measure physical and cognitive impairment. To assess the progression of the disease, ALSFRS-R was re-administered after 8 months and mortality rate was considered. Data were analysed using the grounded theory approach. Illness progression changed according to the perception of the disease, the trust placed in medical care, self-construction and the distribution of dependency. Based on these categories, cases that had similar experiences were grouped, and four illness trajectories were identified: aggressiveness, threat, constriction and guilt. The findings suggest that it is possible to identify different illness trajectories in amyotrophic lateral sclerosis. Personalised intervention strategies may be construed based on the different trajectories identified. © 2017 John Wiley & Sons Ltd.

  8. Higher risk of complications in odynophagia-associated dysphagia in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Karen Fontes Luchesi

    2014-03-01

    Full Text Available Objective This investigation aimed to identify associated factors with dysphagia severity in amyotrophic lateral sclerosis (ALS. Method We performed a cross-sectional study of 49 patients with ALS. All patients underwent fiberoptic endoscopy evaluation of swallowing and answered a verbal questionnaire about swallowing complaints. The patients were divided into groups according to dysphagia severity. Results Among the factors analyzed, only odynophagia was associated with moderate or severe dysphagia. Conclusion Odynophagia was associated with moderate and severe dysphagia in ALS and suggests a high risk of pulmonary and nutritional complications.

  9. Evidence for a dopaminergic deficit in sporadic amyotrophic lateral sclerosis on positron emission scanning

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Hirohide; Snow, B.J.; Bhatt, M.H.; Peppard, R.; Eisen, A.; Calne, D.B. (Univ. of British Columbia, Vancouver (Canada))

    1993-10-23

    Although rare, the chronic neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and idiopathic parkinsonism coexist to a greater degree than expected by chance. This suggests that patients with ALS may have subclinical lesions of the nigrostriatal dopaminergic pathway. To study this hypothesis, the authors did positron emission tomography with 6-fluorodopa on 16 patients with sporadic ALS and without extrapyramidal disease, and compared the results with age-matched controls. They found a significant progressive fall in 6-fluorodopa uptake with time since diagnosis, and reduced dopaminergic function in 3 patients with ALS of long duration. This supports the hypothesis that ALS and IP may share pathogenesis, and, perhaps, etiology.

  10. CDC Grand Rounds: National Amyotrophic Lateral Sclerosis (ALS) Registry Impact, Challenges, and Future Directions.

    Science.gov (United States)

    Mehta, Paul; Horton, D Kevin; Kasarskis, Edward J; Tessaro, Ed; Eisenberg, M Shira; Laird, Susan; Iskander, John

    2017-12-22

    Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a rapidly progressive fatal neurologic disease. Currently, there is no cure for ALS and the available treatments only extend life by an average of a few months. The majority of ALS patients die within 2-5 years of diagnosis, though survival time varies depending on disease progression (1,2). For approximately 10% of patients, ALS is familial, meaning it and has a genetic component; the remaining 90% have sporadic ALS, where etiology is unknown, but might be linked to environmental factors such as chemical exposures (e.g., heavy metals, pesticides) and occupational history (3).

  11. Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy

    DEFF Research Database (Denmark)

    Gredal, O; Rosenbaum, S; Topp, S

    1997-01-01

    20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control...... subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard. The concentrations of Cho and Cr/PCr in both brain regions, as well as the concentration of NAA in the cerebellum, were unaltered in the MND patients compared with the controls. Only MND patients...

  12. Spatial clustering of amyotrophic lateral sclerosis in Finland at place of birth and place of death

    DEFF Research Database (Denmark)

    Sabel, Clive E.; Boyle, P. J.; Löytönen, M.

    2003-01-01

    -scan statistic, the authors examine whether there are significant clusters of the disease at both time of birth and time of death. Two significant, neighboring clusters were identified in southeast and south-central Finland at the time of death. A single significant cluster was identified in southeast Finland...... location at the time of death as the basis for cluster detection, rather than exploring clusters at other points in the life cycle. In this study, the authors examine 1,000 cases of amyotrophic lateral sclerosis distributed throughout Finland who died between June 1985 and December 1995. Using a spatial...

  13. Statins and amyotrophic lateral sclerosis--the level of evidence for an association.

    Science.gov (United States)

    Sørensen, H Toft; Lash, T L

    2009-12-01

    Myopathy is a known side effect of statins, but neurotoxicity is not. Two studies reported that statins and amyotrophic lateral sclerosis (ALS) appear together more than expected amongst adverse events in overlapping surveillance databases. A pooled analysis of clinical trials, many with short follow-up, showed no higher rate of ALS in the statins arms. In older age groups, statin use increased from approximately 5% in 1991 to approximately 40% in 1998 and then remained constant. There was no similar increase in ALS incidence. The initial signals of a strong association from drug surveillance systems should now be discounted, but not disregarded.

  14. Structural and Functional Analysis of Human SOD1 in Amyotrophic Lateral Sclerosis

    OpenAIRE

    Lorenna Giannini Alves Moreira; Livia Costa Pereira; Priscila Ramalho Drummond; Joelma Freire De Mesquita

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with familial inheritance (fALS) in 5% to 10% of cases; 25% of those are caused by mutations in the superoxide dismutase 1 (SOD1) protein. More than 100 mutations in the SOD1 gene have been associated with fALS, altering the geometry of the active site, protein folding and the interaction between monomers. We performed a functional analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in 124 fALS SOD1 mutan...

  15. Mutation analysis of PFN1 in familial amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Daoud, Hussein; Dobrzeniecka, Sylvia; Camu, William; Meininger, Vincent; Dupré, Nicolas; Dion, Patrick A; Rouleau, Guy A

    2013-04-01

    Mutations in the profilin 1 (PFN1) gene, encoding a member of the profilin family of small actin-binding proteins, have been recently reported in patients with familial amyotrophic lateral sclerosis (ALS). In this study we aimed to determine the prevalence of PFN1 mutations by sequencing the coding region of this gene in a cohort of 94 familial ALS patients from France and Quebec. No mutations were identified in our cohort suggesting that PFN1 gene mutations are a very rare cause of familial ALS among patients with predominantly European ancestry. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Neuroimmunity dynamics and the development of therapeutic strategies for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bowerman, Melissa; Vincent, Thierry; Scamps, Frédérique; Perrin, Florence E; Camu, William; Raoul, Cédric

    2013-11-19

    Amyotrophic lateral sclerosis (ALS) is a fatal paralytic disorder characterized by the progressive and selective loss of both upper and lower motoneurons. The neurodegenerative process is accompanied by a sustained inflammation in the brain and spinal cord. The neuron-immune interaction, implicating resident microglia of the central nervous system and blood-derived immune cells, is highly dynamic over the course of the disease. Here, we discuss the timely controlled neuroprotective and neurotoxic cues that are provided by the immune environment of motoneurons and their potential therapeutic applications for ALS.

  17. Tracheomegaly Secondary to Tracheotomy Tube Cuff in Amyotrophic Lateral Sclerosis: A Case Report.

    Science.gov (United States)

    Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

    2015-10-01

    Tracheomegaly has not been reported in amyotrophic lateral sclerosis (ALS). Herein, the authors report a case of tracheomegaly secondary to tracheotomy tube cuff in a patient with ALS. To our knowledge, this is the first report of an ALS patient with tracheomegaly and of tracheomegaly being associated with tracheotomy tube cuff and home tracheotomy mechanical ventilator.The clinician should consider the possibility of tracheomegaly in the differential diagnosis, if a patient with ALS develops repeat air leakage around the tracheotomy tube or rupture of tracheotomy tube cuff.

  18. Sense making and benefit finding among patients with amyotrophic lateral sclerosis and their primary caregivers.

    Science.gov (United States)

    Mock, Steven; Boerner, Kathrin

    2010-01-01

    The associations of sense making and benefit finding with depressive symptoms were examined among patient and caregiver pairs coping with Amyotrophic Lateral Sclerosis. Benefit finding, but not sense making, was associated with fewer depressive symptoms for both patients and caregivers. Patient and caregiver pairs where neither found benefit had more depressive symptoms compared to pairs where at least one member found benefit. Patients cited benefits related to relationships and caregivers were more likely to cite finding personal strength as a benefit. Results suggest situational constraints to making sense and on the kinds of benefit that can be found.

  19. Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Statland, Jeffrey M; Barohn, Richard J; McVey, April L; Katz, Jonathan S; Dimachkie, Mazen M

    2015-11-01

    When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Cronobacter sakazakii DNA Detection in Cerebrospinal Fluid of a Patient with Amyotrophic Lateral Sclerosis Mimic Syndrome

    Directory of Open Access Journals (Sweden)

    Marianna Piombo

    2015-12-01

    Full Text Available A 45-year-old male noticed progressive weakness of the right lower limb with gait disturbance. Over the following months, motor deficits worsened, spreading to the right upper limb. Electromyography showed active denervation in the upper and lower limb muscles. A diagnosis of amyotrophic lateral sclerosis (ALS was made. About 2 years after symptom onset, gradual improvement occurred. Cerebrospinal fluid analysis performed about 3 years after the beginning of symptoms identified Cronobacter sakazakii. Since no other possible causes were identified, we suggest that an almost completely reversible ALS-like syndrome had been triggered by Cronobacter infection in our immunocompetent patient.

  1. Brugada syndrome in a patient with amyotrophic lateral sclerosis: a case report.

    Science.gov (United States)

    Battineni, Anusha; Gummi, Rohit; Mullaguri, Naresh; Govindarajan, Raghav

    2017-07-14

    Amyotrophic lateral sclerosis is a fatal neuromuscular disorder characterized by progressive death of the upper and lower motor neurons in the central nervous system. Patients with this disease die mostly as a result of respiratory failure; however, owing to prolonged survival through assisted ventilation, cardiovascular causes are increasingly responsible for mortality. We report what is to the best of our knowledge the first case of type 2 Brugada syndrome causing ventricular tachyarrhythmia and cardiac arrest in a patient with upper limb onset amyotrophic lateral sclerosis. A 48-year-old Caucasian woman with a significant past medical history of papillary thyroid carcinoma status postresection, pulmonary embolism on anticoagulation, and a recent diagnosis of right upper limb-onset amyotrophic lateral sclerosis presented to the emergency department of our hospital with acute on chronic shortness of breath. On further evaluation, she was found to have hypoxic and hypercapnic respiratory failure and was placed on bilevel positive airway pressure ventilation. Her 12-lead electrocardiogram showed sinus rhythm with J-point elevation, saddle-shaped ST segment elevation, predominantly in V1 and V2 with no significant QTc prolongation. No troponin elevation was noted in her laboratory workup. Because she was unable to protect her airway, a decision was made to intubate her. After 1 minute of induction with etomidate and succinylcholine, she went into pulseless ventricular tachycardia and fibrillation requiring three cycles of cardiopulmonary resuscitation with high-quality chest compressions, three doses of epinephrine, and a loading dose of amiodarone prior to return of spontaneous circulation. She was further evaluated by cardiology services and was diagnosed with type 2 Brugada syndrome, for which she was started on quinidine. Her respiratory failure and the drugs she received for intubation likely caused her ventricular tachycardia to occur in conjunction with an

  2. Dietary Fiber and Amyotrophic Lateral Sclerosis: Results From 5 Large Cohort Studies

    OpenAIRE

    Fondell, Elinor; O'Reilly, Éilis J.; Fitzgerald, Kathryn C.; Falcone, Guido J.; Kolonel, Laurence N; Park, Yikyung; McCullough, Marjorie L.; Ascherio, Alberto

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a fast-progressing neurodegenerative disease with a median survival time from diagnosis of 1.5–3 years. The cause of ALS is unknown, but inflammation may play a role. Fiber has been shown to lower inflammatory markers, and a high fiber intake was associated with a lower risk of ALS in a case-control study; however, prospective studies are lacking. We explored the relation between dietary intake of fiber and the risk of ALS in 5 large prospective cohort s...

  3. Palliative Care Issues in Amyotrophic Lateral Sclerosis: An Evidenced-Based Review.

    Science.gov (United States)

    Karam, Chafic Y; Paganoni, Sabrina; Joyce, Nanette; Carter, Gregory T; Bedlack, Richard

    2016-02-01

    As palliative care physicians become increasingly involved in the care of patients with amyotrophic lateral sclerosis (ALS), they will be asked to provide guidance regarding the use of supplements, diet, exercise, and other common preventive medicine interventions. Moreover, palliative care physicians have a crucial role assisting patients with ALS in addressing health care decisions to maximize quality of life and cope with a rapidly disabling disease. It is therefore important for palliative care physicians to be familiar with commonly encountered palliative care issues in ALS. This article provides an evidenced-based review of palliative care options not usually addressed in national and international ALS guidelines. © The Author(s) 2014.

  4. Live monitoring of brain damage in the rat model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bataveljić, Danijela; Djogo, Nevena; Zupunski, Ljubica; Bajić, Aleksandar; Nicaise, Charles; Pochet, Roland; Bacić, Goran; Andjus, Pavle R

    2009-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurological disorder affecting upper and lower motoneurons. The transgenic ALS rat model (hSOD-1(G93A)) was used for magnetic resonance imaging (MRI) study using a low field wide bore magnet. T2-weighted hyperintensities were observed in the brainstem, rubrospinal tract and vagus motor nuclei with prominent lateral ventricle and cerebral aqueduct enlargements. These changes could be observed already in presymptomatic animals. T2*-weighted MRI with magnetically labeled antibodies (against CD4) revealed lymphocyte infiltration in the brainstem-midbrain region corresponding to the areas of dilated lateral ventricles. Confocal imaging revealed reactive astroglia in these areas. Thus, with the use of wide bore MRI new sites of neurodegeneration and inflammation were revealed in the hSOD-1(G93A) rat model.

  5. The Cyanobacteria Derived Toxin Beta-N-Methylamino-L-Alanine and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Elijah W. Stommel

    2010-12-01

    Full Text Available There is mounting evidence to suggest that environmental factors play a major role in the development of neurodegenerative diseases like ALS (Amyotrophic Lateral Sclerosis. The non-protein amino acid beta-N-methylamino-L-alanine (BMAA was first associated with the high incidence of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC in Guam, and has been implicated as a potential environmental factor in ALS, Alzheimer’s disease, and other neurodegenerative diseases. BMAA has a number of toxic effects on motor neurons including direct agonist action on NMDA and AMPA receptors, induction of oxidative stress, and depletion of glutathione. As a non-protein amino acid, there is also the strong possibility that BMAA could cause intraneuronal protein misfolding, the hallmark of neurodegeneration. While an animal model for BMAA-induced ALS is lacking, there is substantial evidence to support a link between this toxin and ALS. The ramifications of discovering an environmental trigger for ALS are enormous. In this article, we discuss the history, ecology, pharmacology and clinical ramifications of this ubiquitous, cyanobacteria-derived toxin.

  6. Linking amyotrophic lateral sclerosis and spinal muscular atrophy through RNA-transcriptome homeostasis: a genomics perspective.

    Science.gov (United States)

    Gama-Carvalho, Margarida; L Garcia-Vaquero, Marina; R Pinto, Francisco; Besse, Florence; Weis, Joachim; Voigt, Aaron; Schulz, Jörg B; De Las Rivas, Javier

    2017-04-01

    In this review, we present our most recent understanding of key biomolecular processes that underlie two motor neuron degenerative disorders, amyotrophic lateral sclerosis, and spinal muscular atrophy. We focus on the role of four multifunctional proteins involved in RNA metabolism (TDP-43, FUS, SMN, and Senataxin) that play a causal role in these diseases. Recent results have led to a novel scenario of intricate connections between these four proteins, bringing transcriptome homeostasis into the spotlight as a common theme in motor neuron degeneration. We review reported functional and physical interactions between these four proteins, highlighting their common association with nuclear bodies and small nuclear ribonucleoprotein particle biogenesis and function. We discuss how these interactions are turning out to be particularly relevant for the control of transcription and chromatin homeostasis, including the recent identification of an association between SMN and Senataxin required to ensure the resolution of DNA-RNA hybrid formation and proper termination by RNA polymerase II. These connections strongly support the existence of common pathways underlying the spinal muscular atrophy and amyotrophic lateral sclerosis phenotype. We also discuss the potential of genome-wide expression profiling, in particular RNA sequencing derived data, to contribute to unravelling the underlying mechanisms. We provide a review of publicly available datasets that have addressed both diseases using these approaches, and highlight the value of investing in cross-disease studies to promote our understanding of the pathways leading to neurodegeneration. © 2017 International Society for Neurochemistry.

  7. Mutant SOD1 inhibits ER-Golgi transport in amyotrophic lateral sclerosis.

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    Atkin, Julie D; Farg, Manal A; Soo, Kai Ying; Walker, Adam K; Halloran, Mark; Turner, Bradley J; Nagley, Phillip; Horne, Malcolm K

    2014-04-01

    Cu/Zn-superoxide dismutase is misfolded in familial and sporadic amyotrophic lateral sclerosis, but it is not clear how this triggers endoplasmic reticulum (ER) stress or other pathogenic processes. Here, we demonstrate that mutant SOD1 (mSOD1) is predominantly found in the cytoplasm in neuronal cells. Furthermore, we show that mSOD1 inhibits secretory protein transport from the ER to Golgi apparatus. ER-Golgi transport is linked to ER stress, Golgi fragmentation and axonal transport and we also show that inhibition of ER-Golgi trafficking preceded ER stress, Golgi fragmentation, protein aggregation and apoptosis in cells expressing mSOD1. Restoration of ER-Golgi transport by over-expression of coatomer coat protein II subunit Sar1 protected against inclusion formation and apoptosis, thus linking dysfunction in ER-Golgi transport to cellular pathology. These findings thus link several cellular events in amyotrophic lateral sclerosis into a single mechanism occurring early in mSOD1 expressing cells. © 2013 International Society for Neurochemistry.

  8. Amyotrophic lateral sclerosis progression and stability of brain-computer interface communication.

    Science.gov (United States)

    Silvoni, Stefano; Cavinato, Marianna; Volpato, Chiara; Ruf, Carolin A; Birbaumer, Niels; Piccione, Francesco

    2013-09-01

    Our objective was to investigate the relationship between brain-computer interface (BCI) communication skill and disease progression in amyotrophic lateral sclerosis (ALS). We sought also to assess stability of BCI communication performance over time and whether it is related to the progression of neurological impairment before entering the locked-in state. A three years follow-up, BCI evaluation in a group of ALS patients (n = 24) was conducted. For a variety of reasons only three patients completed the three years follow-up. BCI communication skill and disability level, using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, were assessed at admission and at each of the three follow-ups. Multiple non-parametric statistical methods were used to ensure reliability of the dependent variables: correlations, paired test and factor analysis of variance. Results demonstrated no significant relationship between BCI communication skill (BCI-CS) and disease evolution. The patients who performed the follow-up evaluations preserved their BCI-CS over time. Patients' age at admission correlated positively with the ability to achieve control over a BCI. In conclusion, disease evolution in ALS does not affect the ability to control a BCI for communication. BCI performance can be maintained in the different stages of the illness.

  9. The P413L chromogranin B variation in French patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blasco, Hélène; Corcia, Philippe; Veyrat-Durebex, Charlotte; Coutadeur, Cathleen; Fournier, Clémentine; Camu, William; Gordon, Paul; Praline, Julien; Andres, Christian R; Vourc'h, Patrick

    2011-05-01

    Chromogranins interact with mutant forms of superoxide dismutase 1 (SOD1) responsible for a portion of familial amyotrophic lateral sclerosis (ALS). A particular variation (P413L) in the chromogranin B gene, CHGB, has been recently associated with an earlier age at onset in both familial and sporadic ALS. The aim of our study was to evaluate the P413L chromogranin variation in French patients with sporadic amyotrophic lateral sclerosis. We developed a High Resolution DNA Melting (HRM) protocol to analyse the P413L variation in the CHGB gene in 540 French patients with sporadic ALS and 504 controls. The clinical characteristics of patients were analysed in relation to their genotype. Results showed that our study on a large cohort of French-Caucasian patients with SALS and controls failed to confirm an increased frequency of the 413L variant in SALS patients. This frequency was 5.3% in the SALS population and 5.5% in the control group. Moreover, we did not observe a previous observation of a difference of age at onset between T-allele carriers and non-carriers (median age of onset 60.4 vs. 62.0 years of age, respectively). Thus, our findings do not support the 413L variant of rs742710 as a risk factor for sporadic ALS in the French population.

  10. A Case of Morvan Syndrome Mimicking Amyotrophic Lateral Sclerosis With Frontotemporal Dementia.

    Science.gov (United States)

    Freund, Brin; Maddali, Manoj; Lloyd, Thomas E

    2016-06-01

    Morvan syndrome is a rare autoimmune/paraneoplastic disorder involving antibodies to the voltage-gated potassium channel complex. It is defined by subacute encephalopathy, neuromuscular hyperexcitability, dysautonomia, and sleep disturbance. It may present a diagnostic dilemma when trying to differentiate from amyotrophic lateral sclerosis with frontotemporal dementia. A 76-year-old man with a history of untreated prostate adenocarcinoma was evaluated for subacute cognitive decline, diffuse muscle cramps, and hyponatremia. MRI demonstrated atrophy most prominent in the frontal and temporal regions. Electromyography (EMG) demonstrated diffuse myokymia/neuromyotonia. Polysomnography lacked REM and N3 sleep. Paraneoplastic panel detected antibodies to voltage-gated potassium channel complex (CASPR2 subtype). It is difficult to differentiate between Morvan syndrome and amyotrophic lateral sclerosis with frontotemporal dementia with examination and neuroimaging alone. There may be a link between Morvan syndrome and prostate adenocarcinoma which could help with screening/diagnosis. The authors found that laboratory and neurophysiological tests are indispensable in diagnosing and treating Morvan syndrome.

  11. Nutritional assessment of amyotrophic lateral sclerosis in routine practice: value of weighing and bioelectrical impedance analysis.

    Science.gov (United States)

    Roubeau, Vincent; Blasco, Hélène; Maillot, François; Corcia, Philippe; Praline, Julien

    2015-04-01

    We evaluated clinical and bioelectrical impedance (BIA) parameters at the time of diagnosis and during follow-up and associated these parameters with survival in amyotrophic lateral sclerosis (ALS) patients. One hundred seventeen patients were enrolled and were evaluated prospectively every 3 months. All patients underwent at least 1 BIA-based assessment, and 73 underwent at least 2 assessments. Data regarding the site of onset, age at onset, weight, body mass index (BMI), amyotrophic lateral sclerosis functional rating scale score (ALSFRS), fat-free mass (FFM), fat mass (FM), and phase angle (PA) were collected. At the time of diagnosis, weight loss exceeding 5% of the premorbid weight and low PA were poor prognostic factors. During follow-up, a decrease of PA and FFM were associated with shorter survival, regardless of weight loss. These results confirm that BIA is useful to identify poor prognostic factors at the time of diagnosis and during follow-up and thus could be used to monitor patients during follow-up. Early identification of poor prognostic factors enables nutritional management and might improve patient survival. © 2014 Wiley Periodicals, Inc.

  12. Spatial Elucidation of Spinal Cord Lipid- and Metabolite- Regulations in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Hanrieder, Jörg; Ewing, Andrew G.

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressing disease of the central nervous system that is characterized by motor neuron degeneration in the brain stem and the spinal cord. We employed time of flight secondary ion mass spectrometry (ToF-SIMS) to profile spatial lipid- and metabolite- regulations in post mortem human spinal cord tissue from ALS patients to investigate chemical markers of ALS pathogenesis. ToF-SIMS scans and multivariate analysis of image and spectral data were performed on thoracic human spinal cord sections. Multivariate statistics of the image data allowed delineation of anatomical regions of interest based on their chemical identity. Spectral data extracted from these regions were compared using two different approaches for multivariate statistics, for investigating ALS related lipid and metabolite changes. The results show a significant decrease for cholesterol, triglycerides, and vitamin E in the ventral horn of ALS samples, which is presumably a consequence of motor neuron degeneration. Conversely, the biogenic mediator lipid lysophosphatidylcholine and its fragments were increased in ALS ventral spinal cord, pointing towards neuroinflammatory mechanisms associated with neuronal cell death. ToF-SIMS imaging is a promising approach for chemical histology and pathology for investigating the subcellular mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis.

  13. Structures of the G85R Variant of SOD1 in Familial Amyotrophic Lateral Sclerosis

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    Cao, Xiaohang; Antonyuk, Svetlana V.; Seetharaman, Sai V.; Whitson, Lisa J.; Taylor, Alexander B.; Holloway, Stephen P.; Strange, Richard W.; Doucette, Peter A.; Valentine, Joan Selverstone; Tiwari, Ashutosh; Hayward, Lawrence J.; Padua, Shelby; Cohlberg, Jeffrey A.; Hasnain, S. Samar; Hart, P. John (Texas-HSC); (Cal. State); (UMASS, MED); (UCLA); (Daresbury)

    2008-07-21

    Mutations in the gene encoding human copper-zinc superoxide dismutase (SOD1) cause a dominant form of the progressive neurodegenerative disease amyotrophic lateral sclerosis. Transgenic mice expressing the human G85R SOD1 variant develop paralytic symptoms concomitant with the appearance of SOD1-enriched proteinaceous inclusions in their neural tissues. The process(es) through which misfolding or aggregation of G85R SOD1 induces motor neuron toxicity is not understood. Here we present structures of the human G85R SOD1 variant determined by single crystal x-ray diffraction. Alterations in structure of the metal-binding loop elements relative to the wild type enzyme suggest a molecular basis for the metal ion deficiency of the G85R SOD1 protein observed in the central nervous system of transgenic mice and in purified recombinant G85R SOD1. These findings support the notion that metal-deficient and/or disulfide-reduced mutant SOD1 species contribute to toxicity in SOD1-linked amyotrophic lateral sclerosis.

  14. Correlation between functional independence and quality of life of patients with amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalia Priscilla Oliveira Silva

    2014-12-01

    Full Text Available Functional independence and quality of life are impacted by amyotrophic lateral sclerosis (ALS, a degenerative and progressive disease. The aim of this study was to investigate the functional independence and quality of life of patients with ALS in the municipality of Natal, Rio Grande do Norte state, Brazil. This is a cross-sectional observational study conducted with 24 patients. The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40/BR and the Functional Independence Measure (FIM were used as evaluation instruments. The data were analyzed through the Spearman’s correlation and Mann-Whitney tests. The individuals investigated presented modified functional dependence in the FIM, with mean of 64.9±20.5, and alteration in all areas of the ALSAQ-40/ BR. There was significant inverse correlation between FIM and the ALSAQ-40/BR areas of “Mobility” (p<0.01, “Activities of Daily Living (DLAs” (p<0.01, “Eating ability” (p=0.02, and “Communication” (p<0.01, but not in the domain of “Emotional Aspect”. Despite the reduced sample, all patients presented reduction in functional independence and quality of life. The use of these instruments may be a tool to assist the elaboration of intervention plans and interdisciplinary treatment, contributing to retard functional dependence and improve the quality of life of these patients.

  15. Etiogenic factors present in the cerebrospinal fluid from amyotrophic lateral sclerosis patients induce predominantly pro-inflammatory responses in microglia.

    Science.gov (United States)

    Mishra, Pooja-Shree; Vijayalakshmi, K; Nalini, A; Sathyaprabha, T N; Kramer, B W; Alladi, Phalguni Anand; Raju, T R

    2017-12-16

    Microglial cell-associated neuroinflammation is considered as a potential contributor to the pathophysiology of sporadic amyotrophic lateral sclerosis. However, the specific role of microglia in the disease pathogenesis remains to be elucidated. We studied the activation profiles of the microglial cultures exposed to the cerebrospinal fluid from these patients which recapitulates the neurodegeneration seen in sporadic amyotrophic lateral sclerosis. This was done by investigating the morphological and functional changes including the expression levels of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), TNF-α, IL-6, IFN-γ, IL-10, inducible nitric oxide synthase (iNOS), arginase, and trophic factors. We also studied the effect of chitotriosidase, the inflammatory protein found upregulated in the cerebrospinal fluid from amyotrophic lateral sclerosis patients, on these cultures. We report that the cerebrospinal fluid from amyotrophic lateral sclerosis patients could induce an early and potent response in the form of microglial activation, skewed primarily towards a pro-inflammatory profile. It was seen in the form of upregulation of the pro-inflammatory cytokines and factors including IL-6, TNF-α, iNOS, COX-2, and PGE2. Concomitantly, a downregulation of beneficial trophic factors and anti-inflammatory markers including VEGF, glial cell line-derived neurotrophic factor, and IFN-γ was seen. In addition, chitotriosidase-1 appeared to act specifically via the microglial cells. Our findings demonstrate that the cerebrospinal fluid from amyotrophic lateral sclerosis patients holds enough cues to induce microglial inflammatory processes as an early event, which may contribute to the neurodegeneration seen in the sporadic amyotrophic lateral sclerosis. These findings highlight the dynamic role of microglial cells in the pathogenesis of the disease, thus suggesting the need for a multidimensional and temporally guarded therapeutic approach targeting the inflammatory

  16. Amnesia in Frontotemporal Dementia with Amyotrophic Lateral Sclerosis, Masquerading Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    A. Yamanami-Irioka

    2011-10-01

    Full Text Available A 68-year-old man with a clinical diagnosis of Alzheimer’s disease (AD later developed amyotrophic lateral sclerosis (ALS, which was confirmed at autopsy at age 72 years. Because neuronal loss and AD-type pathologies (Braak stage II for neurofibrillary tangles were scant, TDP-43-positive intracytoplasmic inclusions in hippocampal dentate granular cells and in neurons in the subiculum and amygdala, even though small in amount, may represent the earliest lesions of ALS-related dementia and could be the cause of dementia in this patient. Although the persistent elevation of creatine kinase from the onset could be a pointer to the presence of motor involvement, more accurate characterization of dementia, which may differentiate ALS-related dementia and AD, is necessary.

  17. Acute deterioration of bulbar function after botulinum toxin treatment for sialorrhoea in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Meijer, Jan-Willem G; van Kuijk, Annet A; Geurts, Alexander C H; Schelhaas, H Jurgen; Zwarts, Machiel J

    2008-04-01

    Transcutaneous botulinum toxin injection in the salivary glands was introduced in 2000 as a new treatment for sialorrhoea in amyotrophic lateral sclerosis (ALS). We describe an ALS patient who developed serious complications of botulinum toxin treatment for sialorrhoea, and we review the relevant literature. A 64-yr-old woman with bulbar ALS for 6 mos was treated for disabling sialorrhoea. She had moderate dysphagia, but she was able to swallow. The submandibular and parotid glands were injected transcutaneously, under ultrasound guidance, with botulinum toxin (Dysport), 80 U on each side. Four days later, her bulbar function rapidly deteriorated, resulting in complete aphagia and anarthria on the fifth day. A PEG catheter was placed. Although according to the literature this treatment can be made safer by cautiously increasing the dosage and injecting the parotid glands first, BTX should not be the first-line treatment of sialorrhoea in ALS; comparative studies of BTX, amitryptiline, scopolamine, and radiation should be performed first.

  18. Spread Direction and Prognostic Factors in Limb-Onset Sporadic Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Hu, Fangfang; Jin, Jiaoting; Jia, Rui; Xiang, Li; Qi, Huaguang; Chen, Xin; Dang, Jingxia

    2016-01-01

    To investigate the spread direction and prognostic factors in limb-onset sporadic amyotrophic lateral sclerosis (sALS). Medical records of 128 patients with sALS were reviewed. Variables studied were age at symptom onset, gender, region and lateralization of onset, onset to diagnosis interval (ODI), progression direction, bulbar-involved, time from onset to bulbar-involved, ALSFRS-r, upper motor neuron (UMN) signs and progression rate. First, the horizontal and vertical directions are major spreading directions in limb-onset sALS. Second, in crossed and interposed groups, while ODI is shorter, the progression rate is faster and UMN signs are more pronounced (p spread directions in limb-onset sALS. Except for ALSFRS-r and ODI, bulbar-involved is an adverse factor for ALS progression, and progression rate is related to the time from onset symptoms to bulbar-involved. © 2016 S. Karger AG, Basel.

  19. Salivary glands radiotherapy to reduce sialorrhea in amyotrophic lateral sclerosis: dose and energy.

    Science.gov (United States)

    Bourry, N; Guy, N; Achard, J-L; Verrelle, P; Clavelou, P; Lapeyre, M

    2013-06-01

    This retrospective study evaluated the effectiveness of salivary gland radiotherapy for reducing sialorrhea in patients with amyotrophic lateral sclerosis (ALS). From August 2001 to February 2008, 21 patients with amyotrophic lateral sclerosis (six men, 15 women; mean age 61.2 years, range 39-81) received external beam radiotherapy for sialorrhea (evaluation by the ALS Functional Rating Scale). All patients had previously received pharmacological treatments with unsatisfactory results or side effects. The mean dose was 19.1Gy (range 3-48), delivered in five fractions (range 1-16) on 17 days (range 1-77). Eight patients received 3D-conformal and 13 received 2D-conformal radiotherapy. Clinical target volumes included the parotids and submandibular glands (18 patients), submandibular glands and one parotid (one patient), or parotids (two patients). Thirteen patients were treated with 5.5-6MV photons and eight were treated with 6-15MeV electrons. A satisfactory salivary response was defined as complete or partial improvement. The median follow up was 10.4 months (range 0.4-26). One patient was lost to follow up. A positive response was observed in 65% of patients during a mean of 7 months (range 1-23). Four patients (20%) treated with photons and no patients treated with electrons experienced acute toxicity. Half (50%) the patients treated with photons and 87.5% of patients treated with electrons responded positively (P=0.09). Positive responses were more common with a high total dose (≥16Gy; 78.6%) than a low total dose (amyotrophic lateral sclerosis. An adequate compromise between toxicity and efficiency was achieved with 3D-conformal radiotherapy delivered with electrons to parotids and submandibular glands in a total dose of 16Gy or more (mean: 20Gy in five fractions). Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  20. Reduced p75NTRexpression delays disease onset only in female mice of a transgenic model of familial amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Küst, B.M.; Brouwer, N.; Mantingh, I.J.; Boddeke, H.W.G.M.; Copray, J.C.V.M.

    2003-01-01

    hSOD1 (G93A) transgenic mice develop pathological changes similar to those in patients with familial amyotrophic lateral sclerosis (FALS). In particular, the progressive degeneration of motoneurons is charactered in this mouse model. One feature of stressed motoneurons in ALS and the hSOD1 mice is

  1. MUSCLE-FIBER CONDUCTION-VELOCITY IN AMYOTROPHIC-LATERAL-SCLEROSIS AND TRAUMATIC LESIONS OF THE PLEXUS BRACHIALIS

    NARCIS (Netherlands)

    VANDERHOEVEN, JH; ZWARTS, MJ; VANWEERDEN, TW

    1993-01-01

    Muscle fiber conduction velocity (MFCV) in biceps brachii was studied in traumatic brachial plexus lesions (16 patients) and amyotrophic lateral sclerosis (ALS) (22 patients) by means of an invasive (S-MFCV) and a surface (S-MFCV) method. After complete denervation an exponential decrease of the

  2. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M; McLaughlin, Russell L; Diekstra, Frank P; Pulit, Sara L; van der Spek, Rick A A; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H P; Koppers, Max; Blokhuis, Anna M; Sproviero, William; Jones, Ashley R; Kenna, Kevin P; van Eijk, Kristel R; Harschnitz, Oliver; Schellevis, Raymond D; Brands, William J; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E; Shaw, Pamela J; Hardy, John; Orrell, Richard W; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; Van Deerlin, Vivianna M; Trojanowski, John Q; Elman, Lauren; McCluskey, Leo; Basak, A Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A M; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M; van der Kooi, Anneke J; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E; Smith, Bradley N; Pansarasa, Orietta; Cereda, Cristina; Del Bo, Roberto; Comi, Giacomo P; D'Alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P; Fifita, Jennifer A; Nicholson, Garth A; Rowe, Dominic B; Pamphlett, Roger; Kiernan, Matthew C; Grosskreutz, Julian; Witte, Otto W; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A; Leigh, P Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C; Weishaupt, Jochen H; Robberecht, Wim; Van Damme, Philip; Franke, Lude; Pers, Tune H; Brown, Robert H; Glass, Jonathan D; Landers, John E; Hardiman, Orla; Andersen, Peter M; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R; Visscher, Peter M; de Bakker, Paul I W; van Es, Michael A; Pasterkamp, R Jeroen; Lewis, Cathryn M; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H; Veldink, Jan H

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  3. Genome-wide association analyses identify new risk variants and the genetic architecture of amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Rheenen, Wouter; Shatunov, Aleksey; Dekker, Annelot M.; McLaughlin, Russell L.; Diekstra, Frank P.; Pulit, Sara L.; van der Spek, Rick A. A.; Võsa, Urmo; de Jong, Simone; Robinson, Matthew R.; Yang, Jian; Fogh, Isabella; van Doormaal, Perry Tc; Tazelaar, Gijs H. P.; Koppers, Max; Blokhuis, Anna M.; Sproviero, William; Jones, Ashley R.; Kenna, Kevin P.; van Eijk, Kristel R.; Harschnitz, Oliver; Schellevis, Raymond D.; Brands, William J.; Medic, Jelena; Menelaou, Androniki; Vajda, Alice; Ticozzi, Nicola; Lin, Kuang; Rogelj, Boris; Vrabec, Katarina; Ravnik-Glavač, Metka; Koritnik, Blaž; Zidar, Janez; Leonardis, Lea; Grošelj, Leja Dolenc; Millecamps, Stéphanie; Salachas, François; Meininger, Vincent; de Carvalho, Mamede; Pinto, Susana; Mora, Jesus S.; Rojas-García, Ricardo; Polak, Meraida; Chandran, Siddharthan; Colville, Shuna; Swingler, Robert; Morrison, Karen E.; Shaw, Pamela J.; Hardy, John; Orrell, Richard W.; Pittman, Alan; Sidle, Katie; Fratta, Pietro; Malaspina, Andrea; Topp, Simon; Petri, Susanne; Abdulla, Susanne; Drepper, Carsten; Sendtner, Michael; Meyer, Thomas; Ophoff, Roel A.; Staats, Kim A.; Wiedau-Pazos, Martina; Lomen-Hoerth, Catherine; van Deerlin, Vivianna M.; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Basak, A. Nazli; Tunca, Ceren; Hamzeiy, Hamid; Parman, Yesim; Meitinger, Thomas; Lichtner, Peter; Radivojkov-Blagojevic, Milena; Andres, Christian R.; Maurel, Cindy; Bensimon, Gilbert; Landwehrmeyer, Bernhard; Brice, Alexis; Payan, Christine A. M.; Saker-Delye, Safaa; Dürr, Alexandra; Wood, Nicholas W.; Tittmann, Lukas; Lieb, Wolfgang; Franke, Andre; Rietschel, Marcella; Cichon, Sven; Nöthen, Markus M.; Amouyel, Philippe; Tzourio, Christophe; Dartigues, Jean-François; Uitterlinden, Andre G.; Rivadeneira, Fernando; Estrada, Karol; Hofman, Albert; Curtis, Charles; Blauw, Hylke M.; van der Kooi, Anneke J.; de Visser, Marianne; Goris, An; Weber, Markus; Shaw, Christopher E.; Smith, Bradley N.; Pansarasa, Orietta; Cereda, Cristina; del Bo, Roberto; Comi, Giacomo P.; D'alfonso, Sandra; Bertolin, Cinzia; Sorarù, Gianni; Mazzini, Letizia; Pensato, Viviana; Gellera, Cinzia; Tiloca, Cinzia; Ratti, Antonia; Calvo, Andrea; Moglia, Cristina; Brunetti, Maura; Arcuti, Simona; Capozzo, Rosa; Zecca, Chiara; Lunetta, Christian; Penco, Silvana; Riva, Nilo; Padovani, Alessandro; Filosto, Massimiliano; Muller, Bernard; Stuit, Robbert Jan; Blair, Ian; Zhang, Katharine; McCann, Emily P.; Fifita, Jennifer A.; Nicholson, Garth A.; Rowe, Dominic B.; Pamphlett, Roger; Kiernan, Matthew C.; Grosskreutz, Julian; Witte, Otto W.; Ringer, Thomas; Prell, Tino; Stubendorff, Beatrice; Kurth, Ingo; Hübner, Christian A.; Leigh, P. Nigel; Casale, Federico; Chio, Adriano; Beghi, Ettore; Pupillo, Elisabetta; Tortelli, Rosanna; Logroscino, Giancarlo; Powell, John; Ludolph, Albert C.; Weishaupt, Jochen H.; Robberecht, Wim; van Damme, Philip; Franke, Lude; Pers, Tune H.; Brown, Robert H.; Glass, Jonathan D.; Landers, John E.; Hardiman, Orla; Andersen, Peter M.; Corcia, Philippe; Vourc'h, Patrick; Silani, Vincenzo; Wray, Naomi R.; Visscher, Peter M.; de Bakker, Paul I. W.; van Es, Michael A.; Pasterkamp, R. Jeroen; Lewis, Cathryn M.; Breen, Gerome; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan H.

    2016-01-01

    To elucidate the genetic architecture of amyotrophic lateral sclerosis (ALS) and find associated loci, we assembled a custom imputation reference panel from whole-genome-sequenced patients with ALS and matched controls (n = 1,861). Through imputation and mixed-model association analysis in 12,577

  4. Evidence for neuronal localisation of enteroviral sequences in motor neurone disease/amyotrophic lateral sclerosis by in situ hybridization.

    Science.gov (United States)

    Woodall, C J; Graham, D I

    2004-01-01

    Sequences resembling those of human enterovirus type B sequences have been associated with motor neurone disease/amyotrophic lateral sclerosis. In a previous study we detected enteroviral sequences in spinal cord/brain stem from cases of motor neurone disease/amyotrophic lateral sclerosis, but not controls. Adjacent tissue sections to two of those strongly positive for these sequences by reverse-transcriptase polymerase chain reaction were analyzed by in situ hybridization with digoxigenin-labelled virus-specific antisense riboprobes. In one case, a female aged 83 showing 12 month rapid progressive disease, signal was specifically localized to cells identifiable as motor neurones of the anterior horn. In another case, a male aged 63 with a 60-month history of progressive muscle weakness, dysarthia, dyspnoea and increased tendon reflexes, signal was located to neurones in the gracile/cuneate nuclei of the brain stem tissue block that had been analyzed. This case showed loss of neurones in the anterior horn of the spinal cord by histopathologic examination which would account for clinical signs of motor neurone disease/amyotrophic lateral sclerosis. Dysfunction of the gracile/cuneate nuclei might have been masked by the paralytic disease. These structures are adjacent to the hypoglossal nuclei, and suggest either localised dissemination from hypoglossal nuclei or a possible route of dissemination of infection through the brainstem to the hypoglossal nuclei. These findings provide further evidence for the possible involvement of enteroviruses in motor neurone disease/amyotrophic lateral sclerosis.

  5. Evidence for neuronal localisation of enteroviral sequences in motor neurone disease/amyotrophic lateral sclerosis by in situ hybridization

    Directory of Open Access Journals (Sweden)

    CJ Woodall

    2009-06-01

    Full Text Available Sequences resembling those of human enterovirus type B sequences have been associated with motor neurone disease/ amyotrophic lateral sclerosis. In a previous study we detected enteroviral sequences in spinal cord/brain stem from cases of motor neurone disease/amyotrophic lateral sclerosis, but not controls. Adjacent tissue sections to two of those strongly positive for these sequences by reverse-transcriptase polymerase chain reaction were analyzed by in situ hybridization with digoxigenin-labelled virus-specific antisense riboprobes. In one case, a female aged 83 showing 12 month rapid progressive disease, signal was specifically localized to cells identifiable as motor neurones of the anterior horn. In another case, a male aged 63 with a 60-month history of progressive muscle weakness, dysarthia, dyspnoea and increased tendon reflexes, signal was located to neurones in the gracile/cuneate nuclei of the brain stem tissue block that had been analyzed. This case showed loss of neurones in the anterior horn of the spinal cord by histopathologic examination which would account for clinical signs of motor neurone disease/amyotrophic lateral sclerosis. Dysfunction of the gracile/cuneate nuclei might have been masked by the paralytic disease. These structures are adjacent to the hypoglossal nuclei, and suggest either localised dissemination from hypoglossal nuclei or a possible route of dissemination of infection through the brainstem to the hypoglossal nuclei. These findings provide further evidence for the possible involvement of enteroviruses in motor neurone disease/amyotrophic lateral sclerosis.

  6. The cortisol awakening response in amyotrophic lateral sclerosis is blunted and correlates with clinical status and depressive mood

    NARCIS (Netherlands)

    Roozendaal, Benno; Kim, Sungchul; Wolf, Oliver T.; Kim, Min Soo; Sung, Kang-Keyng; Lee, Sangkwan

    Considerable evidence indicates that amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease of the motor system, has an enormous impact on the patient's emotional and physical well-being. As previous findings indicated that particularly the rise in cortisol levels immediately

  7. Neuron-specific expression of mutant superoxide dismutase is sufficient to induce amyotrophic lateral sclerosis in transgenic mice

    NARCIS (Netherlands)

    Jaarsma, Dick; Teuling, Eva; Haasdijk, Elize D; De Zeeuw, Chris I; Hoogenraad, Casper C

    2008-01-01

    Mutations in superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS), an adult-onset progressive paralytic disease characterized by loss of motor neurons, and cause an ALS-like disease when expressed in mice. Recent data have suggested that motor neuron degeneration results from toxic

  8. IgG from amyotrophic lateral sclerosis affects tubular calcium channels of skeletal muscle.

    Science.gov (United States)

    Delbono, O; García, J; Appel, S H; Stefani, E

    1991-06-01

    Amyotrophic lateral sclerosis (ALS) is a devastating human disease of upper and lower motoneurons. We studied the action of the immunoglobulin G (IgG) from ALS and disease control patients on dihydropyridine (DHP)-sensitive Ca2+ channels in single mammalian skeletal muscle fibers with the double Vaseline gap technique. The peak of the Ca2+ current (ICa) and the charge movement were reduced when the fibers were incubated in ALS IgG. These effects were lost when the IgG was boiled or adsorbed with skeletal tubular membranes. ALS IgG reduced skeletal muscle ICa in a similar fashion as nifedipine; the ICa blockade was voltage dependent, and the associated charge movement was reduced. These observations suggest that IgG from ALS patients reacts with the skeletal muscle DHP-sensitive Ca2+ channels or some associated regulatory moiety.

  9. Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Sato, Kanako; Masutani, Yoshitaka; Watadani, Takeyuki; Nakata, Yasuhiro; Yoshida, Mariko; Abe, Osamu; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Bunkyo, Tokyo (Japan); Aoki, Shigeki [Juntendo University, Department of Radiology, Bunkyo, Tokyo (Japan); Iwata, Nobue K.; Terao, Yasuo; Tsuji, Shoji [University of Tokyo, Department of Neurology, Graduate School of Medicine, Bunkyo, Tokyo (Japan)

    2010-08-15

    The uncinate fasciculus (UF) consists of core fibers connecting the frontal and temporal lobes and is considered to be related to cognitive/behavioral function. Using diffusion tensor tractography, we quantitatively evaluated changes in fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the UF by tract-specific analysis to evaluate the damage of the UF in patients with amyotrophic lateral sclerosis (ALS). We obtained diffusion tensor images of 15 patients with ALS and 9 age-matched volunteers. Patients with ALS showed significantly lower mean FA (P = 0.029) compared with controls. No significant difference was seen in mean ADC. The results suggest that damage of the UF in patients with ALS can be quantitatively evaluated with FA. (orig.)

  10. Health and social care costs of managing amyotrophic lateral sclerosis (ALS): an Irish perspective.

    Science.gov (United States)

    Connolly, Sheelah; Heslin, Chloe; Mays, Iain; Corr, Bernie; Normand, Charles; Hardiman, Orla

    2015-03-01

    The aim of this study was to quantify the health and social care costs associated with managing amyotrophic lateral sclerosis (ALS) in Ireland. Resource use of a representative group of deceased ALS patients attending a multidisciplinary ALS clinic was identified from a retrospective chart review and telephone interview with the main caregiver. Unit cost estimates were applied to each resource to identify the cost per patient. Cost drivers were identified using multivariate linear regression. Results showed that from time of diagnosis to death, the cost per month was €1795, 21% of which was attributable to costs associated with the multidisciplinary clinic, 72% to community based care and 7% to aids and appliances. Higher monthly cost was associated with shorter survival and use of gastrostomy and non-invasive ventilation. In conclusion, ALS imposes a significant cost burden on the health services. More work is required to quantify the costs in other sectors, including informal care and productivity losses.

  11. Mechanisms of Neuroprotection by Protein Disulphide Isomerase in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Adam K. Walker

    2011-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a devastating neurodegenerative disease characterised by the progressive loss of motor neurons, leading to paralysis and death within several years of onset. Although protein misfolding is a key feature of ALS, the upstream triggers of disease remain elusive. Recently, endoplasmic reticulum (ER stress was identified as an early and central feature in ALS disease models as well as in human patient tissues, indicating that ER stress could be an important process in disease pathogenesis. One important chaperone induced by ER stress is protein disulphide isomerase (PDI, which is both upregulated and posttranslationally inhibited by S-nitrosylation in ALS. In this paper, we present evidence from studies of genetics, model organisms, and patient tissues which indicate an active role for PDI and ER stress in ALS disease processes.

  12. Skeletal Muscle Remodelling as a Function of Disease Progression in Amyotrophic Lateral Sclerosis

    DEFF Research Database (Denmark)

    Jensen, L; Jørgensen, L H; Bech, R D

    2016-01-01

    Muscle weakness is considered the pivotal sign of amyotrophic lateral sclerosis (ALS). Knowledge about the skeletal muscle degeneration/regeneration process and the myogenic potential is limited in ALS patients. Therefore, we investigate these processes in a time course perspective by analysing...... skeletal muscle biopsies from ALS patients collected before and after a 12-week period of normal daily activities and compare these with healthy age-matched control tissue. We do this by evaluating mRNA and protein (immunohistochemical) markers of regeneration, neurodegeneration, myogenesis, cell cycle...... regulation, and inflammation. Our results show morphological changes indicative of active denervation and reinnervation and an increase in small atrophic fibres. We demonstrate differences between ALS and controls in pathways controlling skeletal muscle homeostasis, cytoskeletal and regenerative markers...

  13. An early history of Japanese amyotrophic lateral sclerosis (ALS) and the current significance.

    Science.gov (United States)

    Abe, Koji

    2017-04-28

    The present review focuses an early history of Japanese amyotrophic lateral sclerosis (ALS) and the current significance in comparison to previously known and newly found reports on Japanese ALS. After a preliminary case report of ALS by Masamichi Hirai on 1890, 2 completed reports were simultaneously published within 2 weeks of 1891 by Momojiro Nakamura and Zenjiro Inoue, followed by Eikichi Watanabe's report on 1892. After Shonosuke Hasegawa's and Hiroshi Kawahara's case reports on 1894-1896, Aihiko Sata first reported an autopsy case of ALS on 1897. The great contribution of Kinnosuke Miura was also introduced for the naming and pathogenesis in the early stage of ALS history in Japan during 1893-1911.

  14. Cardiac Failure as an Unusual Presentation in a Patient with History of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Mohammad Hasan Namazi

    2014-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most well-known form of motor neuron diseases in which both upper and lower motor neurons are involved in this disease. We presented an unusual case of ALS whom had presented with chief complaint of dyspnea. Cardiac failure was diagnosed at the final stage of the ALS disease. The pathogenetic mechanism leading to an elevated occurrence of cardiomyopathy in ALS is not comprehensible. Dilated cardiomyopathy has been explained in some previous studies. Based on the collected data, it was hypothesized that cardiomyopathy is underdiagnosed in the ALS population, probably because symptoms are masqueraded as a result of the patients’ disability. It was suggested that in all motor neuron diseases a serial cardiological evaluation should be executed, including annual echocardiography.

  15. Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits

    Energy Technology Data Exchange (ETDEWEB)

    Hecht, M.J.; Neundoerfer, B. [University of Erlangen-Nurenberg, Department of Neurology, Erlangen (Germany); Fellner, C.; Fellner, F.A. [University of Erlangen-Nurenberg, Institute of Diagnostic Radiology, Erlangen (Germany); Landes-Nervenklinik Wagner-Jauregg, Institute of Radiology, Linz (Austria); Schmid, A. [University of Erlangen-Nurenberg, Institute of Diagnostic Radiology, Erlangen (Germany)

    2005-11-01

    Signal shortening of the motor cortex in T2-weighted MR images is a frequent finding in patients with amyotrophic lateral sclerosis (ALS). The cause of signal shortening in ALS is unknown, although iron deposits have been suggested. To test this hypothesis, we acquired T2*-weighted gradient-echo (GRE) MR images in addition to T2-weighted turbo spin-echo in 69 patients with ALS. Signal shortening in T2-weighted images was found in 31 patients. In T2*-weighted GRE images, only three patients had signal shortening. One patient with additional bifrontal haemorrhage had frontal but no motor cortex signal shortening. Iron deposits do not cause cortical signal shortening in patients with ALS predominantly. Other factors are presumably more important in the generation of cortical T2 shortening in ALS. (orig.)

  16. Coping strategies and psychological distress in caregivers of patients with Amyotrophic Lateral Sclerosis (ALS).

    Science.gov (United States)

    Siciliano, Mattia; Santangelo, Gabriella; Trojsi, Francesca; Di Somma, Carmela; Patrone, Manila; Femiano, Cinzia; Monsurrò, Maria Rosaria; Trojano, Luigi; Tedeschi, Gioacchino

    2017-08-01

    Amyotrophic lateral sclerosis (ALS) causes distress in caregivers. The present study aims to examine the association between coping strategies and psychological distress in caregivers of ALS patients. Coping strategies were assessed in 96 ALS informal caregivers by means of the Coping Inventory for Stressful Situations. Data about caregivers' demographic characteristics, levels of burden, depression and anxiety (psychological distress) were also gathered by standardised questionnaires. Patients' clinical, cognitive and behavioural disturbances were evaluated by ALS specific assessment tools. Sequential logistic regression analysis showed that emotion-oriented coping strategy was significantly associated with high levels of depressive (p ALS caregivers. These findings suggest that interventions aimed at reducing utilisation of maladaptive coping strategies may improve well-being in ALS caregivers, and, possibly, management of symptoms in ALS patients.

  17. Comparison of psychosocial factors between patients with benign fasciculations and those with amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Rana Sandeep

    2009-01-01

    Full Text Available In this retrospective study, we compared the initial presentation of patients who were eventually diagnosed with either benign fasciculations (BF or amyotrophic lateral sclerosis (ALS. We found a significantly higher number of patients with BF reporting a past history of psychiatric symptoms, life stressors, and concurrent psychosomatic symptoms. There was no difference between the two groups in patient report of current anxiety or depression symptoms. These findings support our hypothesis that BF are a manifestation of psychological distress due to somatization and that reviewing psychosocial history is important when patients are being evaluated for fasciculations. Patients seeking medical attention for fasciculations and who do not report a history of underlying psychiatric or psychosomatic disorders should be followed closely as fasciculations have been reported to be a presenting feature of ALS.

  18. [Amyotrophic lateral sclerosis and cognition disorders. Neuropsychological study of a population of 26 patients].

    Science.gov (United States)

    Dary-Auriol, M; Ingrand, P; Bonnaud, V; Dumas, P; Neau, J P; Gil, R

    1997-05-01

    Typical amyotrophic lateral sclerosis (ALS) is described as a motoneuron disease which spared cognitive functions. Recent studies reported cognitive impairement associated with classical ALS. Gallasi and al. (1985) detect subtle cognitive impairement sparing memory in a population of 22 patients affected with sporadic motoneuron disease. Iwasaki and al. (1990) finds lower scores, including memory tests. Our study evaluated 26 patients compared with 26 control subjects with neurospychological tests (rapid evaluation of cognitive function fluency, Weschler adult intelligence scale, Wisconsin cards, Rey scheme, memory tests - Luria -, trail making, visual retentional test of Benton Violon Seyll test). All the neuropsychological tests were significantly lower for the patients group. The cognitive impairement is global: memory and frontal functions were not spared and this impairement is also subtle. It may easily go undetected without tests. We cannot isolate a cortical or subcortical profile of the deterioration.

  19. Protein aggregation and protein instability govern familial amyotrophic lateral sclerosis patient survival.

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2008-07-01

    Full Text Available The nature of the "toxic gain of function" that results from amyotrophic lateral sclerosis (ALS-, Parkinson-, and Alzheimer-related mutations is a matter of debate. As a result no adequate model of any neurodegenerative disease etiology exists. We demonstrate that two synergistic properties, namely, increased protein aggregation propensity (increased likelihood that an unfolded protein will aggregate and decreased protein stability (increased likelihood that a protein will unfold, are central to ALS etiology. Taken together these properties account for 69% of the variability in mutant Cu/Zn-superoxide-dismutase-linked familial ALS patient survival times. Aggregation is a concentration-dependent process, and spinal cord motor neurons have higher concentrations of Cu/Zn-superoxide dismutase than the surrounding cells. Protein aggregation therefore is expected to contribute to the selective vulnerability of motor neurons in familial ALS.

  20. Mountain Ginseng Pharmacopuncture Treatment on Three Amyotrophic Lateral Sclerosis Patients -Case Report-

    Directory of Open Access Journals (Sweden)

    Ryu Young-jin

    2010-12-01

    Full Text Available Objectives : The objective of this study is to report the change of progress in symptoms and various scales after treated with Mountain Ginseng Pharmacopuncture(MGP on the patients of Amyotrophic Lateral Sclerosis(ALS. Methods : The three ALS patients who treated with MGP, were checked the change of progress by ALS Functional Rating Scale(ALSFRS, ALS Severity Score(ALSSS, grasping power on both arms and circumference of both thighs and calves. Results : After MGP treatment on three ALS patients, first case did not grow worse during MGP treated whereas she got worse rapidly during none treated period . Second case did not grow worse during treated period and third case got worse in progress by slow degrees despite of MGP treatment. Conclusions : Although MGP could not control the progress of ALS completely, MGP may help the improving of quality of life(QOL in ALS patients and have the effect of delayed ALS progression.

  1. CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs

    Directory of Open Access Journals (Sweden)

    Lixia Wang

    2017-04-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs from fibroblasts of familial ALS patients bearing SOD1 +/A272C and FUS +/G1566A mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq analysis of motor neurons derived from SOD1 +/A272C and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.

  2. Participation restrictions in ambulatory amyotrophic lateral sclerosis patients: Physical and psychological factors.

    Science.gov (United States)

    Van Groenestijn, Annerieke C; Schröder, Carin D; Kruitwagen-Van Reenen, Esther T; Van Den Berg, Leonard H; Visser-Meily, Johanna M A

    2017-11-01

    The aim of this study was to assess the prevalence of participation restrictions in ambulatory patients with amyotrophic lateral sclerosis (ALS) and to identify physical and psychological contributory factors. In this cross-sectional study, self-reported participation restrictions of 72 ambulatory ALS patients were assessed using the social health status dimension (SIPSOC) of the Sickness Impact Profile (SIP-68). Associations between SIPSOC and physical functioning, psychological factors, and demographic factors were analyzed using hierarchical regression analyses. Ninety-two percent of the patients reported participation restrictions; 54.9% could be explained by physical functioning; psychological factors accounted for 8.1% of the variance. Lung capacity, functional mobility, fatigue, and helplessness were independently associated with participation restrictions. Ambulatory ALS patients have participation restrictions, which may be influenced if early ALS care is directed toward lung capacity, functional mobility, fatigue, and feelings of helplessness. Muscle Nerve 56: 912-918, 2017. © 2017 Wiley Periodicals, Inc.

  3. Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2017-08-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease that affects upper motor neurons (MNs comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease.

  4. Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

    Directory of Open Access Journals (Sweden)

    Sabrina Giacoppo

    2016-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic ap-proaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.

  5. Preservation of the nucleus X-pelvic floor motosystem in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Schrøder, H D; Reske-Nielsen, E

    1984-01-01

    were observed in Onuf's nucleus X, not even in 8 cases in which other caudal motoneuron nuclei presented a severe loss of neurons. The striated sphincters proper demonstrated no signs of neurogenic atrophy in contrast to muscles in the limbs. The bulbo- and ischiocavernosus muscles, also supposedly......Fourteen cases of amyotrophic lateral sclerosis (ALS) were investigated neuropathologically, emphazising the sacral spinal cord which contains Onuf's nucleus X. The nucleus innervates the pelvic sphincters. In two cases, small striated pelvic muscles were studied. No changes characteristic of ALS...... innervated by Onuf's nucleus, were without pathological changes. Moreover, the latter two muscles were found to have a composition very similar to that of the sphincters. This indicates that a characteristic morphology of the nucleus X-innervated muscles exists. A review of the clinical records of all...

  6. Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

    Science.gov (United States)

    Liu, Jia; Wang, Fei

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects upper motor neurons (MNs) comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease. PMID:28871262

  7. Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Lee, Jong-Min; Tan, Vanessa; Lovejoy, David; Braidy, Nady; Rowe, Dominic B; Brew, Bruce J; Guillemin, Gilles J

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by a progressive degeneration of central and peripheral motor neurons, leading to the atrophy of voluntary muscles. It has been previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in ALS. In particular, the neuroactive intermediate, quinolinic acid (QUIN) has been shown to accumulate with a concomitant decrease in other neuroprotective and immunomodulatory KP metabolites. Furthermore, multiple biochemical phenomena associated with QUIN cytotoxicity are present in ALS, suggesting that QUIN may play a substantial role in the pathogenesis of ALS. This review highlights the potential roles of QUIN in ALS, and explores KP modulation as a therapeutic candidate in ALS. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Effects of lumbar sympathetic ganglion block for a patient with amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Kitoh, Takeshi; Kobayashi, Koichi; Ina, Hiroaki; Ofusa, Yukihiro; Otagiri, Tetsutaro; Tanaka, Satoshi; Ono, Koichi

    2006-01-01

    A 59-year-old man with amyotrophic lateral sclerosis (ALS) received lumbar epidural and sympathetic ganglion blocks to increase regional blood flow and improve his clinical symptoms. After a lumbar epidural block (0.5% mepivacaine), the skin temperature of his affected lower extremities rose by 7.0 degrees C and became close to that of the intact side, and the distance he was able to walk with his cane increased from 2 to 8 m. The clinical effects produced by the lumbar sympathetic ganglion block (99.5% alcohol) were sustained for approximately 8 weeks after the first block and for approximately 6 weeks after the second block. There were no particular adverse effects or complications associated with these nerve block procedures. Epidural and sympathetic ganglion blocks for an ALS patient, albeit their effects are of a transient nature, may improve related clinical symptoms, and were thought to play a contributory role in improving our patient's quality of life.

  9. Interdisciplinary palliative care, including massage, in treatment of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blatzheim, Kendra

    2009-10-01

    Amyotrophic lateral sclerosis (ALS) is a progressive fatal neurological disease that affects approximately 20,000 Americans. Symptoms include muscle weakness, fatigue, twitching, atrophy, spasticity, pain, oropharyngeal dysfunction, pseudobulbar affect, weight loss, and respiratory impairment. Death occurs within 3-5 yr after onset of symptoms, with diagnosis taking from 11 to 17.5 months. The only FDA-approved drug for ALS is Riluzole, which only increases the life expectancy by a few months. All other treatments for ALS provide symptom management to improve the patient's quality of life. An interdisciplinary palliative care team for the ALS patient helps to reduce the stress that the illness places on families. Massage can be a useful adjunctive treatment for spasticity and pain when medication side effects are unwanted. A holistic interdisciplinary palliative care team supports both the patient and the family improving their quality of life.

  10. Stem cells: comprehensive treatments for amyotrophic lateral sclerosis in conjunction with growth factor delivery.

    Science.gov (United States)

    Lunn, J Simon; Hefferan, Michael P; Marsala, Martin; Feldman, Eva L

    2009-06-01

    Amyotrophic lateral sclerosis (ALS) is characterized by loss of both upper and lower motor neurons. ALS progression is complex and likely due to cellular dysfunction at multiple levels, including mitochondrial dysfunction, glutamate excitotoxicity, oxidative stress, axonal dysfunction, reactive astrocytosis, and mutant superoxide dismutase expression, therefore, treatment must provide neuronal protection from multiple insults. A significant amount of ALS research focuses on growth factor-based therapies. Growth factors including insulin-like growth factor-I, vascular endothelial growth factor, brain-derived neurotrophic factor, and glial-derived neurotrophic factor exhibit robust neuroprotective effects on motor neurons in ALS models. Issues concerning growth factor delivery, stability and unwanted side effects slow the transfer of these treatments to human ALS patients. Stem cells represent a new therapeutic approach offering both cellular replacement and trophic support for the existing population. Combination therapy consisting of stem cells expressing beneficial growth factors may provide a comprehensive treatment for ALS.

  11. A review of experimental research on herbal compounds in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhang, Xue; Hong, Yan-Long; Xu, De-Sheng; Feng, Yi; Zhao, Li-Jie; Ruan, Ke-Feng; Yang, Xiu-Juan

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease worldwide, leading to progressive muscle atrophy and paralysis. The limited success of conventional treatment for ALS has prompted investigations into complementary and alternative therapies. Herbal remedies provide good prospects of ALS prevention and treatment, with advantages such as multiple targets, multiple links, and few side effects. Studies in vitro and in vivo have shown that herbs have a great potential for treatment of ALS, with therapeutic effects against oxidative stress, excitatory amino acid toxicity, neuroinflammation, and calcium cytotoxicity. Active monomers or ingredients extracted from herbs are considered promising candidates for ALS. Therefore, we review recent experimental research on monomers and compounds isolated from herbal remedies for preventing and treating ALS. Copyright © 2013 John Wiley & Sons, Ltd.

  12. Riluzole use during pregnancy in a patient with amyotrophic lateral sclerosis: a case report.

    Science.gov (United States)

    Kawamichi, Y; Makino, Y; Matsuda, Y; Miyazaki, K; Uchiyama, S; Ohta, H

    2010-01-01

    Pregnancy with amyotrophic lateral sclerosis (ALS) is rare and generally considered dangerous. Riluzole is the only drug approved for use in ALS, but the effect on maternal and fetal health is unknown. We describe the case of an ALS patient taking riluzole throughout pregnancy. A 34-year old Japanese woman, who had been diagnosed with probable ALS 4 years earlier, visited our hospital for abdominal distension, without knowing that she was pregnant. The patient had been taking riluzole for 2 years, inclusive of her gestational months, and we decided to continue administration of the medication. The patient delivered a normal female infant transvaginally at 38 weeks gestation. The patient's neurological status was stable 1 year after delivery and the baby had developed normally. We found that, in this case, riluzole did not cause any side-effects to the pregnant woman or her fetus.

  13. Analysis of the SORT1 gene in familial amyotrophic lateral sclerosis.

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    Belzil, Véronique V; André-Guimont, Catherine; Atallah, Marie-Renée; Daoud, Hussein; Dupré, Nicolas; Bouchard, Jean-Pierre; Camu, William; Dion, Patrick A; Rouleau, Guy A

    2012-08-01

    Substantial efforts have been deployed in the past decade to identify the genetic causes of amyotrophic lateral sclerosis (ALS), and we hypothesized here that mutations in SORT1 or aberrant SORT1 splicing reduce progranulin level and promote neurodegeneration. We sequenced the coding exons of SORT1 in a cohort of 112 unrelated individuals with familial ALS. We also tested for aberrant SORT1 splicing by RT-PCR using RNA samples from cell lines expressing six different ALS-associated TARDBP mutations. We identified one unique missense and two unique silent mutations in our cohort. None are predicted to have functional effects. No aberrant SORT1 splicing event was observed. SORT1 mutations are not a common cause of familial ALS, and the influence of TARDBP mutations on SORT1 splicing still needs to be clarified. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis

    Science.gov (United States)

    Ono, S.; Yamauchi, M.

    1992-01-01

    Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross-links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS.

  15. Predictive genetic testing for amyotrophic lateral sclerosis and frontotemporal dementia: genetic counselling considerations.

    Science.gov (United States)

    Crook, Ashley; Williams, Kelly; Adams, Lorel; Blair, Ian; Rowe, Dominic B

    2017-11-01

    Once a gene mutation that is causal of amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD) is identified in a family, relatives may decide to undergo predictive genetic testing to determine whether they are at risk of developing disease. Recent advances in gene discovery have led to a pressing need to better understand the implications of predictive genetic testing. Here we review the uptake of genetic counselling, predictive and reproductive testing, and the factors that impact the decision to undergo testing, for consideration in clinical practice. The literature suggests that the factors impacting the decision to undergo testing are complex due to the nature of these diseases, absence of available preventative medical treatment and variable age of onset in mutation carriers. Gaining further insight into the decision-making process and the impact of testing is critical as we seek to develop best-practice guidelines for predictive testing for familial ALS and FTD.

  16. Epidemiology of amyotrophic lateral sclerosis patients in a centre in Buenos Aires

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    Mariela Bettini

    2011-12-01

    Full Text Available Sporadic amyotrophic lateral sclerosis (sALS is considered a multifactorial disease with genetic and environmental factors causing motor neuron degeneration. OBJECTIVE: To describe the epidemiological and occupational characteristics of patients with sALS who attended the Ramos Mejía Hospital at Buenos Aires, Argentina. METHOD: We analyzed the medical records of sALS patients diagnosed between 2001 and 2008. All occupations were coded according to the International Standard Classification of Occupation (ISCO. RESULTS: 187 patients were assessed, 38.5% were women and 61.5% men. Mean age at diagnosis was 55 years. 16% of them came from rural areas; 68% of the studied population had no health insurance. 40% were employed in elementary occupations, 19 were technicians and 8 handicraftsmen. CONCLUSION: The most represented profession was elementary occupation. A large proportion of patients came from rural areas, which might suggest an increased risk of environmental exposure to an unknown agent in those regions.

  17. Shortcomings in the Current Amyotrophic Lateral Sclerosis Trials and Potential Solutions for Improvement

    Science.gov (United States)

    Katyal, Nakul; Govindarajan, Raghav

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials. In this review, we have outlined the possible reasons for failure of ALS clinical trials, addressed the factors limiting timely diagnosis, and suggested possible solutions for future considerations for each of the shortcomings. PMID:29033893

  18. Widespread Structural and Functional Connectivity Changes in Amyotrophic Lateral Sclerosis: Insights from Advanced Neuroimaging Research

    Science.gov (United States)

    Trojsi, Francesca; Monsurrò, Maria Rosaria; Esposito, Fabrizio; Tedeschi, Gioacchino

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease principally affecting motor neurons. Besides motor symptoms, a subset of patients develop cognitive disturbances or even frontotemporal dementia (FTD), indicating that ALS may also involve extramotor brain regions. Both neuropathological and neuroimaging findings have provided further insight on the widespread effect of the neurodegeneration on brain connectivity and the underlying neurobiology of motor neurons degeneration. However, associated effects on motor and extramotor brain networks are largely unknown. Particularly, neuropathological findings suggest that ALS not only affects the frontotemporal network but rather is part of a wide clinicopathological spectrum of brain disorders known as TAR-DNA binding protein 43 (TDP-43) proteinopathies. This paper reviews the current state of knowledge concerning the neuropsychological and neuropathological sequelae of TDP-43 proteinopathies, with special focus on the neuroimaging findings associated with cognitive change in ALS. PMID:22720174

  19. Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam

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    Perl, D.P.; Gajdusek, D.C.; Garruto, R.M.; Yanagihara, R.T.; Gibbs, C.J.

    1982-09-10

    Scanning electron microscopy with energy-dispersive x-ray spectrometry was used to analyze the elemental content of neurofibrillary tangle (NFT)-bearing and NFT-free neurons within the Sommer's sector (H1 region) of the hippocampus in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia and in neurologically normal controls. Preliminary data indicate prominent accumulation of aluminum within the nuclear region and perikaryal cytoplasm of NFT-bearing hippocampal neurons, regardless of the underlying neurological diagnosis. These findings further extend the association between intraneuronal aluminum and NFT formation and support the hypothesis that environmental factors are related to the neurodegenerative changes seen in the Chamorro population.

  20. Shortcomings in the Current Amyotrophic Lateral Sclerosis Trials and Potential Solutions for Improvement

    Directory of Open Access Journals (Sweden)

    Nakul Katyal

    2017-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials. In this review, we have outlined the possible reasons for failure of ALS clinical trials, addressed the factors limiting timely diagnosis, and suggested possible solutions for future considerations for each of the shortcomings.

  1. Shortcomings in the Current Amyotrophic Lateral Sclerosis Trials and Potential Solutions for Improvement.

    Science.gov (United States)

    Katyal, Nakul; Govindarajan, Raghav

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a clinically progressive neurodegenerative syndrome predominantly affecting motor neurons and their associated tracts. Riluzole and edaravone are the only FDA certified drugs for treating ALS. Over the past two decades, almost all clinical trials aiming to develop a successful therapeutic strategy for this disease have failed. Genetic complexity, inadequate animal models, poor clinical trial design, lack of sensitive biomarkers, and diagnostic delays are some of the potential reasons limiting any significant development in ALS clinical trials. In this review, we have outlined the possible reasons for failure of ALS clinical trials, addressed the factors limiting timely diagnosis, and suggested possible solutions for future considerations for each of the shortcomings.

  2. Electrical Impedance Myography (EIM) in the Evaluation of the Tongue Musculature in Amyotrophic Lateral Sclerosis (ALS)

    Science.gov (United States)

    Shellikeri, Sanjana; Yunusova, Yana; Green, Jordan R.; Pattee, Gary L.; Berry, James D.; Rutkove, Seward B.; Zinman, Lorne

    2015-01-01

    Introduction Electrical impedance myography (EIM) quantifies muscle health and is used as a biomarker of muscle abnormalities in neurogenic and myopathic diseases. EIM has yet to be evaluated in the tongue musculature in people with amyotrophic lateral sclerosis (ALS), who often show clinical bulbar signs. Methods The lingual musculature of 19 subjects with motor neuron disease and 21 of normal participants were assessed using EIM, strength and endurance testing, and clinical observation. Results Tongue musculature in the ALS group was characterized by significantly smaller phase (Ph) and larger resistance (R) when compared to the healthy cohort. Ph and tongue endurance were correlated in the ALS group. Discussion EIM of tongue musculature could distinguish people with ALS from healthy controls. The demonstrated relationship between tongue function and Ph supports further testing of EIM of the tongue as a potential biomarker in ALS. PMID:25580728

  3. Attention and P300-based BCI performance in people with amyotrophic lateral sclerosis

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    Angela eRiccio

    2013-11-01

    Full Text Available The purpose of this study was to investigate the support of attentional and memory processes in controlling a P300-based brain-computer interface (BCI in people suffering from amyotrophic lateral sclerosis (ALS. Eight people with ALS performed two behavioural tasks: i a rapid serial visual presentation (RSVP task, screening the temporal filtering capacity and the speed of the update of the attentive filter, and ii a change detection task, screening the memory capacity and the spatial filtering capacity. The participants were also asked to perform a P300-based BCI spelling task. By using correlation and regression analyses, we found that only the temporal filtering capacity in the RSVP task was a predictor of both the P300-based BCI accuracy and of the amplitude of the P300 elicited performing the BCI task. We concluded that the ability to keep the attentional filter active during the selection of a target influences performance in BCI control.

  4. Meditation training for people with amyotrophic lateral sclerosis and their caregivers.

    Science.gov (United States)

    Pagnini, Francesco; Di Credico, Chiara; Gatto, Ramona; Fabiani, Viviana; Rossi, Gabriella; Lunetta, Christian; Marconi, Anna; Fossati, Federica; Castelnuovo, Gianluca; Tagliaferri, Aurora; Banfi, Paolo; Corbo, Massimo; Sansone, Valeria; Molinari, Enrico; Amadei, Gherardo

    2014-04-01

    Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that is clinically characterized by progressive weakness leading to death by respiratory insufficiency, usually within three years. Although the patient's intellect and personality usually remain unimpaired, as the disease progresses, the patient becomes immobile, develops wasting, and speech becomes impaired, often resulting in social isolation and a high degree of psychological suffering. Mindfulness meditation has proven to be effective technique for reducing distress in many chronic diseases. However, to date, no study has investigated the effect of mindfulness meditation on patients with ALS. A mindfulness meditation training program for ALS patients needs to consider the particularities of ALS symptoms, including the loss of muscular functions and difficulties in respiration, together with the subsequent emotional impairments. With these caveats in mind, a modified protocol, based on original mindfulness meditation interventions, has been created specifically for the ALS population. This article describes the protocol and preliminary results.

  5. Fine-Tuning ER Stress Signal Transducers to Treat Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Medinas, Danilo B; González, Jose V; Falcon, Paulina; Hetz, Claudio

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motoneurons and paralysis. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting disturbances in motoneuron proteostasis. Endoplasmic reticulum (ER) stress has emerged as an early pathogenic event underlying motoneuron vulnerability and denervation in ALS. Maintenance of ER proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). Inositol-requiring enzyme 1 (IRE1) is an ER-located kinase and endoribonuclease that operates as a major ER stress transducer, mediating the establishment of adaptive and pro-apoptotic programs. Here we discuss current evidence supporting the role of ER stress in motoneuron demise in ALS and build the rational to target IRE1 to ameliorate neurodegeneration.

  6. Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials

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    Syed I. Khalid

    2017-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing.

  7. Fine-Tuning ER Stress Signal Transducers to Treat Amyotrophic Lateral Sclerosis

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    Danilo B. Medinas

    2017-07-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by the progressive loss of motoneurons and paralysis. The mechanisms underlying neuronal degeneration in ALS are starting to be elucidated, highlighting disturbances in motoneuron proteostasis. Endoplasmic reticulum (ER stress has emerged as an early pathogenic event underlying motoneuron vulnerability and denervation in ALS. Maintenance of ER proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR. Inositol-requiring enzyme 1 (IRE1 is an ER-located kinase and endoribonuclease that operates as a major ER stress transducer, mediating the establishment of adaptive and pro-apoptotic programs. Here we discuss current evidence supporting the role of ER stress in motoneuron demise in ALS and build the rational to target IRE1 to ameliorate neurodegeneration.

  8. Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis

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    Julianne Aebischer

    2013-01-01

    Full Text Available While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS. ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75NTR signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.

  9. Recognition of amyotrophic lateral sclerosis disease using factorial hidden Markov model.

    Science.gov (United States)

    Khorasani, Abed; Daliri, Mohammad Reza; Pooyan, Mohammad

    2016-02-01

    Amyotrophic lateral sclerosis (ALS) is a common disease among neurological disorders that can change the pattern of gait in human. One of the effective methods for recognition and analysis of gait patterns in ALS patients is utilizing stride interval time series. With proper preprocessing for removing unwanted artifacts from the raw stride interval times and then extracting meaningful features from these data, the factorial hidden Markov model (FHMM) was used to distinguish ALS patients from healthy subjects. The results of classification accuracy evaluated using the leave-one-out (LOO) cross-validation algorithm showed that the FHMM method provides better recognition of ALS and healthy subjects compared to standard HMM. Moreover, comparing our method with a state-of-the art method named least square support vector machine (LS-SVM) showed the efficiency of the FHMM in distinguishing ALS subjects from healthy ones.

  10. Onset and spreading patterns of upper and lower motor neuron symptoms in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Körner, Sonja; Kollewe, Katja; Fahlbusch, Marion; Zapf, Antonia; Dengler, Reinhard; Krampfl, Klaus; Petri, Susanne

    2011-05-01

    The potential linkage between upper (UMN) and lower motor neuron (LMN) involvement in amyotrophic lateral sclerosis (ALS) has not yet been fully elucidated. There is ongoing discussion as to whether ALS is primarily a disease of UMNs or LMNs. We performed a retrospective analysis of 189 ALS patients from our ALS outpatient database to investigate the different spreading patterns of UMN and LMN affection in disease progression in relation to the onset region. The body region with the highest UMN involvement at onset in general also had the highest frequency of LMN signs and vice versa. This is in line with the hypothesis of a focal onset of disease, which then spreads to adjacent areas. However, there was a great variation between ALS phenotypes. These observations support the hypothesis of focal damage of a localized group of motor neurons, which then spreads to adjacent motor neurons. Copyright © 2010 Wiley Periodicals, Inc.

  11. Retraction: DNAJC6 variants in Parkinson's disease and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jiang, Teng; Zhang, Ying-Dong; Tan, Lan; Yu, Jin-Tai

    2016-04-04

    The above Letter to the Editor from Annals of Neurology, published online as an Accepted Article on 4th April 2016 on Wiley Online Library (wileyonlinelibrary.com), has been withdrawn at the request of the authors with agreement from the journal editor, Clifford B. Saper, and Wiley Periodicals, Inc. The withdrawal has been agreed due to an acknowledgement from the authors that they inappropriately implied that material from the PD Gene and ALS Gene public databases and a figure from the Max Planck Society for the Advancement of Science was their own work. Reference Jiang, T., Zhang, Y-D., Tan, L., and Yu, J-T (2016) DNAJC6 variants in Parkinson's disease and amyotrophic lateral sclerosis. Ann Neurol. doi: 10.1002/ana.24658. © 2016 American Neurological Association.

  12. Golgi Fragmentation in Amyotrophic Lateral Sclerosis, an Overview of Possible Triggers and Consequences

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    Vinod eSundaramoorthy

    2015-10-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is an invariably fatal neurodegenerative disorder, which specifically targets motor neurons in the brain, brain stem and spinal cord. Whilst the etiology of ALS remains unknown, fragmentation of the Golgi apparatus is detected in ALS patient motor neurons and in animal/cellular disease models. The Golgi is a highly dynamic organelle that acts as a dispatching station for the vesicular transport of secretory/transmembrane proteins. It also mediates autophagy and maintains endoplasmic reticulum (ER and axonal homeostasis. Both the trigger for Golgi fragmentation and the functional consequences of a fragmented Golgi apparatus in ALS remain unclear. However recent evidence has highlighted defects in vesicular trafficking as a pathogenic mechanism in ALS. This review summarises the evidence describing Golgi fragmentation in ALS, with possible links to other disease processes including cellular trafficking, ER stress, defective autophagy and axonal degeneration.

  13. Transcranial magnetic stimulation and BDNF plasma levels in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Angelucci, Francesco; Oliviero, Antonio; Pilato, Fabio; Saturno, Eleonora; Dileone, Michele; Versace, Viviana; Musumeci, Gabriella; Batocchi, Anna P; Tonali, Pietro A; Di Lazzaro, Vincenzo

    2004-03-22

    Low- and high-frequency repetitive transcranial magnetic stimulation (rTMS) of the motor cortex results in lasting changes of excitatory neurotransmission. We investigated the effects of suprathreshold 1 Hz rTMS on brain derived neurotrophic factor (BDNF) plasma levels in 10 healthy subjects and effects of either 1 Hz or 20 Hz rTMS in four amyotrophic lateral sclerosis (ALS) patients. BDNF levels were progressively decreased by 1 Hz rTMS in healthy subjects; there was no effect of 1 Hz rTMS on BDNF plasma levels in ALS patients, an effect probably due to the loss of motor cortex pyramidal cells. High frequency rTMS determined a transitory decrease in BDNF plasma levels. Cumulatively these findings suggest that rTMS might influence the BDNF production by interfering with neuronal activity.

  14. Riluzole 5 mg/mL oral suspension: for optimized drug delivery in amyotrophic lateral sclerosis

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    Dyer AM

    2016-12-01

    Full Text Available Ann Margaret Dyer, Alan Smith PharmaSci Consulting Limited, Nottingham, UK Abstract: The aim of the present work is to extensively evaluate the pharmaceutical attributes of currently available riluzole presentations. The article describes the limitations and risks associated with the administration of crushed tablets, including the potential for inaccurate dosing and reduced rate of absorption when riluzole is administered with high-fat foods, and the advantages that a recently approved innovative oral liquid form of riluzole confers on amyotrophic lateral sclerosis (ALS patients. The article further evaluates the patented and innovative controlled flocculation technology used in the pseudoplastic suspension formulation to reduce the oral anesthesia seen with crushed tablets, resulting in optimized drug delivery for riluzole. Riluzole is the only drug licensed for treating ALS, which is the most common form of motor neurone disease and a highly devastating neurodegenerative condition. The licensed indication is to extend life or the time to mechanical ventilation. Until recently, riluzole was only available as an oral tablet dosage form in the UK; however, an innovative oral liquid form, Teglutik® 5 mg/mL oral suspension, is now available. An oral liquid formulation provides an important therapeutic option for patients with ALS, >80% of who may become unable to swallow solid oral dosage forms due to disease-related dysphagia. Prior to the launch of riluzole oral suspension, the only way for many patients to continue to take riluzole as their disease progressed was through crushed tablets. A novel suspension formulation enables more accurate dosing and consistent ongoing administration of riluzole. There are clear and important advantages such as enhanced patient compliance compared with crushed tablets administered with food or via an enteral feeding tube and the potential for an improved therapeutic outcome and enhanced quality of life for

  15. Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome and use of hospital facilities.

    Science.gov (United States)

    Chiò, A; Bottacchi, E; Buffa, C; Mutani, R; Mora, G

    2006-08-01

    To evaluate the effects of tertiary centres for amyotrophic lateral sclerosis (ALS) on ALS outcome and the use of hospital facilities. The study was based on the data of an epidemiological, prospective, population-based register on ALS (Piemonte and Valle d'Aosta Register for amyotrophic lateral sclerosis, PARALS). The 221 patients recruited between 1995 and 1996 were prospectively followed up for outcome and use of hospital-based services. In all, 97 patients were followed up by tertiary ALS centres and 124 by general neurological clinics. Patients followed up by tertiary ALS centres were found to be 4 years younger and underwent percutaneous endoscopic gastronomy and non-invasive positive-pressure ventilation more often. Patients followed up by tertiary ALS centres were found to have a considerably longer median survival time (1080 v 775 days), even when stratifying by age, site of onset and respiratory function at diagnosis. In Cox multivariate analysis, attending a tertiary ALS centre was observed to be an independent positive prognostic factor. Moreover, patients attending a tertiary ALS centre were admitted to hospital less often (1.2 v 3.3) and were more frequently admitted for planned interventions. Conversely, patients followed up by general neurological clinics were more frequently admitted for acute events. Also, the hospital stay was considerably shorter for patients attending tertiary ALS centres (5.8 v 12.4 days). Improved survival was seen in patients with ALS attending tertiary ALS centres, independently from all other known prognostic factors, possibly through a better implementation of supportive treatments. Moreover, because of these centres, the hospitalisation rate was markedly reduced, thus offering a cost-effective service to patients with ALS and to the community as a whole.

  16. Structural and functional analysis of human SOD1 in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Moreira, Lorenna Giannini Alves; Pereira, Livia Costa; Drummond, Priscila Ramalho; De Mesquita, Joelma Freire

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with familial inheritance (fALS) in 5% to 10% of cases; 25% of those are caused by mutations in the superoxide dismutase 1 (SOD1) protein. More than 100 mutations in the SOD1 gene have been associated with fALS, altering the geometry of the active site, protein folding and the interaction between monomers. We performed a functional analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in 124 fALS SOD1 mutants. Eleven different algorithms were used to estimate the functional impact of the replacement of one amino acid on protein structure: SNPs&GO, PolyPhen-2, SNAP, PMUT, Sift, PhD-SNP, nsSNPAnalyzer, TANGO, WALTZ, LIMBO and FoldX. For the structural analysis, theoretical models of 124 SNPs of SOD1 were created by comparative modeling using the MHOLline workflow, which includes Modeller and Procheck. Models were aligned with the native protein by the TM-align algorithm. A human-curated database was developed using the server side include in Java, JMOL. The results of this functional analysis indicate that the majority of the 124 natural mutants are harmful to the protein structure and thus corroborate the correlation between the reported mutations and fALS. In the structural analysis, all models showed conformational changes when compared to wild-type SOD1, and the degree of structural alignment varied between them. The SOD1 database converge structural and functional analyses of SOD1; it is a vast resource for the molecular analysis of amyotrophic lateral sclerosis, which allows the user to expand his knowledge on the molecular basis of the disease. The SOD1 database is available at http://bioinfogroup.com/database.

  17. Structural and functional analysis of human SOD1 in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Lorenna Giannini Alves Moreira

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease with familial inheritance (fALS in 5% to 10% of cases; 25% of those are caused by mutations in the superoxide dismutase 1 (SOD1 protein. More than 100 mutations in the SOD1 gene have been associated with fALS, altering the geometry of the active site, protein folding and the interaction between monomers. We performed a functional analysis of non-synonymous single nucleotide polymorphisms (nsSNPs in 124 fALS SOD1 mutants. Eleven different algorithms were used to estimate the functional impact of the replacement of one amino acid on protein structure: SNPs&GO, PolyPhen-2, SNAP, PMUT, Sift, PhD-SNP, nsSNPAnalyzer, TANGO, WALTZ, LIMBO and FoldX. For the structural analysis, theoretical models of 124 SNPs of SOD1 were created by comparative modeling using the MHOLline workflow, which includes Modeller and Procheck. Models were aligned with the native protein by the TM-align algorithm. A human-curated database was developed using the server side include in Java, JMOL. The results of this functional analysis indicate that the majority of the 124 natural mutants are harmful to the protein structure and thus corroborate the correlation between the reported mutations and fALS. In the structural analysis, all models showed conformational changes when compared to wild-type SOD1, and the degree of structural alignment varied between them. The SOD1 database converge structural and functional analyses of SOD1; it is a vast resource for the molecular analysis of amyotrophic lateral sclerosis, which allows the user to expand his knowledge on the molecular basis of the disease. The SOD1 database is available at http://bioinfogroup.com/database.

  18. Vitamin D deficiency and its supplementation in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Karam, Chafic; Barrett, Matthew J; Imperato, Theresa; MacGowan, Daniel J L; Scelsa, Stephen

    2013-11-01

    We studied 25-hydroxyvitamin D (vitamin D) levels in patients with amyotrophic lateral sclerosis (ALS) and the effect of vitamin D supplementation. Vitamin D levels were checked in 37 consecutive patients with ALS. Demographic data, vitamin D supplementation, change in Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score, and side effects from vitamin D were noted over a 9 month follow-up period. ALSFRS-R scores were compared between patients who took vitamin D and those who did not. The median age was 55 years and median time since symptom onset was 61 months. The mean vitamin D level was 22.3 ng/mL (normal range, 30-80 ng/mL). Eighty-one percent of patients had a vitamin D level lower than 30 ng/mL and 43% had a vitamin D level lower than 20 ng/mL. Twenty patients took 2000 international units of vitamin D daily. After adjustment for age and baseline vitamin D levels in a linear regression model, the ALSFRS-R score decline was smaller in patients taking vitamin D at 9 months (p=0.02) but was not significantly different at 3 or 6 months. Median vitamin D levels rose from 18.5 to 31.0 ng/mL at 6 months in the group taking vitamin D. No side effects secondary to vitamin D supplementation were reported. Vitamin D supplementation at 2000 international units daily was safe over a period of 9 months and may have a beneficial effect on ALSFRS-R scores. Further studies are warranted to determine whether there is a benefit in vitamin D supplementation for all ALS patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Depression and anxiety in individuals with amyotrophic lateral sclerosis: a systematic review.

    Science.gov (United States)

    Carvalho, Tatiana Lins; de Almeida, Lilian Maria Sanguinett; Lorega, Camila Maria Araújo; Barata, Mirella Francyne Oliveira; Ferreira, Maria Lúcia Brito; de Brito-Marques, Paulo Roberto; Correia, Carolina da Cunha

    2016-01-01

    Studies assessing symptoms of depression and anxiety in individuals with amyotrophic lateral sclerosis (ALS) have reported contradictory results. The objective of this systematic review is to identify the prevalence of these mood disorders in the literature. We searched the PubMed, HighWire, MEDLINE, SciELO, LILACS and ScienceDirect databases. Literature was selected for review in two stages, according to eligibility criteria. The first stage involved searching databases and checking titles and abstracts. The second step consisted of reading complete articles and excluding those that did not meet the inclusion criteria. The inclusion criteria were articles written in Portuguese, English or Spanish, published in the last five years and involving people with ALS diagnosed according to the El Escorial criteria. The database searches returned a total of 1,135 titles and abstracts and then 1,117 of these were excluded. Eighteen articles were selected for review. The 12-item Amyotrophic Lateral Sclerosis Depression Inventory (ADI-12) was the only instrument designed specifically to assess depression in ALS, but it was only used in three studies. No instruments specifically designed for anxiety in ALS were used. A large number of studies found presence and slight increase of anxiety disorders. There was considerable large variation in the results related to depressive disorders, ranging from moderate depression to an absence of symptoms. Patients with ALS may exhibit symptoms of depression and anxiety at different levels, but there is a need for studies using specific instruments with larger samples in order to ascertain the prevalence of symptoms in ALS and the factors associated with it.

  20. Specific Physical Exercise Improves Energetic Metabolism in the Skeletal Muscle of Amyotrophic-Lateral- Sclerosis Mice

    Science.gov (United States)

    Desseille, Céline; Deforges, Séverine; Biondi, Olivier; Houdebine, Léo; D’amico, Domenico; Lamazière, Antonin; Caradeuc, Cédric; Bertho, Gildas; Bruneteau, Gaëlle; Weill, Laure; Bastin, Jean; Djouadi, Fatima; Salachas, François; Lopes, Philippe; Chanoine, Christophe; Massaad, Charbel; Charbonnier, Frédéric

    2017-01-01

    Amyotrophic Lateral Sclerosis is an adult-onset neurodegenerative disease characterized by the specific loss of motor neurons, leading to muscle paralysis and death. Although the cellular mechanisms underlying amyotrophic lateral sclerosis (ALS)-induced toxicity for motor neurons remain poorly understood, growing evidence suggest a defective energetic metabolism in skeletal muscles participating in ALS-induced motor neuron death ultimately destabilizing neuromuscular junctions. In the present study, we report that a specific exercise paradigm, based on a high intensity and amplitude swimming exercise, significantly improves glucose metabolism in ALS mice. Using physiological tests and a biophysics approach based on nuclear magnetic resonance (NMR), we unexpectedly found that SOD1(G93A) ALS mice suffered from severe glucose intolerance, which was counteracted by high intensity swimming but not moderate intensity running exercise. Furthermore, swimming exercise restored the highly ALS-sensitive tibialis muscle through an autophagy-linked mechanism involving the expression of key glucose transporters and metabolic enzymes, including GLUT4 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Importantly, GLUT4 and GAPDH expression defects were also found in muscles from ALS patients. Moreover, we report that swimming exercise induced a triglyceride accumulation in ALS tibialis, likely resulting from an increase in the expression levels of lipid transporters and biosynthesis enzymes, notably DGAT1 and related proteins. All these data provide the first molecular basis for the differential effects of specific exercise type and intensity in ALS, calling for the use of physical exercise as an appropriate intervention to alleviate symptoms in this debilitating disease. PMID:29104532

  1. Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis survival.

    Directory of Open Access Journals (Sweden)

    John D Beard

    Full Text Available Military veterans may have higher rates of amyotrophic lateral sclerosis (ALS mortality than non-veterans. Few studies, with sparse exposure information and mixed results, have studied relationships between military-related factors and ALS survival. We evaluated associations between military-related factors and ALS survival among U.S. military veteran cases.We followed 616 medical record-confirmed cases from enrollment (2005-2010 in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study until death or July 25, 2013, whichever came first. We ascertained vital status information from several sources within the Department of Veterans Affairs. We obtained information regarding military service, deployments, and 39 related exposures via standardized telephone interviews. We used Cox proportional hazards regression models to estimate hazard ratios (HRs and 95% confidence intervals. We adjusted for potential confounding and missing covariate data biases via inverse probability weights. We also used inverse probability weights to adjust for potential selection bias among a case group that included a disproportionate number of long-term survivors at enrollment.We observed 446 deaths during 24,267 person-months of follow-up (median follow-up: 28 months. Survival was shorter for cases who served before 1950, were deployed to World War II, or mixed and applied burning agents, with HRs between 1.58 and 2.57. Longer survival was associated with exposure to: paint, solvents, or petrochemical substances; local food not provided by the Armed Forces; or burning agents or Agent Orange in the field with HRs between 0.56 and 0.73.Although most military-related factors were not associated with survival, associations we observed with shorter survival are potentially important because of the large number of military veterans.

  2. Noninvasive ventilation in amyotrophic lateral sclerosis: effects on sleep quality and quality of life.

    Science.gov (United States)

    Vandoorne, Eva; Vrijsen, Bart; Belge, Catharina; Testelmans, Dries; Buyse, Bertien

    2016-12-01

    Little is known about the effects of noninvasive ventilation (NIV) on sleep quality in amyotrophic lateral sclerosis (ALS). We aim to evaluate the long-term effects of NIV on sleep quality and quality of life in patients with ALS. In this prospective observational study, 13 ALS patients were followed for one year after initiating NIV. We evaluated sleep quality, quality of life and functional status with several questionnaires: Epworth sleepiness Scale (ESS), Pittsburg sleep quality index (PSQI), Short Form 36 Health Questionnaire (SF-36), McGill Quality of Life questionnaire (McGillQoL) and revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores (ALSFRS-R). Median and interquartile range (IQR) at the start of NIV was 59 (53-65) years. The ALSFRS-R at start was 30 (24-37) (median, IQR), with three patients having severe bulbar impairment (ALSFRS-R-bulbar ≤ 9). The PaCO2 at start of NIV treatment was 48 (43-52) mmHg (median, IQR). During the one-year follow-up period, a significant decrease in the ALSFRS-R was observed. The impact of NIV in a short term (1 month) revealed a statistically significant decrease in ESS, decrease in total PSQI and of four PSQI subscales and improvement of almost all subscales of the McGill questionnaire. Long-term analyses (9 months to 1 year) revealed that amelioration in ESS and total PSQI was sustained. We conclude that accurately titrated NIV in ALS patients can stabilize sleep quality and quality of life for at least one year, despite significant disease progression.

  3. A prospective study of quality of life in amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Jakobsson Larsson, B; Ozanne, A G; Nordin, K; Nygren, I

    2017-12-01

    The aim of this prospective and longitudinal study was to describe individual quality of life in patients with amyotrophic lateral sclerosis (ALS) and its correlations with physical function and emotional well-being from diagnosis and over time. Thirty-six patients were included in the study. Individual quality of life was measured with the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), illness severity was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), and emotional distress was measured using the Hospital Anxiety and Depression Scale (HADS). Data were collected from diagnosis and thereafter, every six months for a period of two years. Twelve patients completed the 24-month follow-up. Family, friends and own physical health were important for overall quality of life, from diagnosis and during the disease progression. Most patients had good quality of life, which remained stable, despite changed physical functions. Several patients scored above the cut-off score for doubtful and clinical anxiety and depression early on after diagnosis, and there was a significant decrease in anxiety over time. Soon after diagnosis, there was a correlation between depression and quality of life. The family, social relations and own physical health are important for overall quality of life in patients with ALS. Thus, supporting the family and facilitating so that patients can continue to stay in contact with friends are important aspects during the disease. Conducting an early screening for depression can be important for preventing decreased quality of life. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chen, Xueping; Chen, Yongping; Wei, Qianqian; Ou, Ruwei; Cao, Bei; Zhao, Bi; Shang, Hui-Fang

    2016-09-15

    The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS). Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA. Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %. Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

  5. Diffusion tensor tractography analysis of the corpus callosum fibers in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kim, Jee-Eun; Oh, Jungsu S; Sung, Jung-Joon; Lee, Kwang-Woo; Song, In Chan; Hong, Yoon-Ho

    2014-07-01

    Involvement of the corpus callosum (CC) is reported to be a consistent feature of amyotrophic lateral sclerosis (ALS). We examined the CC pathology using diffusion tensor tractography analysis to identify precisely which fiber bundles are involved in ALS. Diffusion tensor imaging was performed in 14 sporadic ALS patients and 16 age-matched healthy controls. Whole brain tractography was performed using the multiple-region of interest (ROI) approach, and CC fiber bundles were extracted in two ways based on functional and structural relevance: (i) cortical ROI selection based on Brodmann areas (BAs), and (ii) the sulcal-gyral pattern of cortical gray matter using FreeSurfer software, respectively. The mean fractional anisotropy (FA) values of the CC fibers interconnecting the primary motor (BA4), supplementary motor (BA6), and dorsolateral prefrontal cortex (BA9/46) were significantly lower in ALS patients than in controls, whereas those of the primary sensory cortex (BA1, BA2, BA3), Broca's area (BA44/45), and the orbitofrontal cortex (BA11/47) did not differ significantly between the two groups. The FreeSurfer ROI approach revealed a very similar pattern of abnormalities. In addition, a significant correlation was found between the mean FA value of the CC fibers interconnecting the primary motor area and disease severity, as assessed using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale, and the clinical extent of upper motor neuron signs. Our findings suggest that there is some degree of selectivity or a gradient in the CC pathology in ALS. The CC fibers interconnecting the primary motor and dorsolateral prefrontal cortices may be preferentially involved in ALS.

  6. Noninvasive Ventilation Improves Sleep in Amyotrophic Lateral Sclerosis: A Prospective Polysomnographic Study

    Science.gov (United States)

    Vrijsen, Bart; Buyse, Bertien; Belge, Catharina; Robberecht, Wim; Van Damme, Philip; Decramer, Marc; Testelmans, Dries

    2015-01-01

    Study Objective: To evaluate the effects of noninvasive ventilation (NIV) on sleep in patients with amyotrophic lateral sclerosis (ALS) after meticulous titration with polysomnography (PSG). Methods: In this prospective observational study, 24 ALS patients were admitted to the sleep laboratory during 4 nights for in-hospital NIV titration with PSG and nocturnal capnography. Questionnaires were used to assess subjective sleep quality and quality of life (QoL). Patients were readmitted after one month. Results: In the total group, slow wave sleep and REM sleep increased and the arousal-awakening index improved. The group without bulbar involvement (non-bulbar) showed the same improvements, together with an increase in sleep efficiency. Nocturnal oxygen and carbon dioxide levels improved in the total and non-bulbar group. Except for oxygen saturation during REM sleep, no improvement in respiratory function or sleep structure was found in bulbar patients. However, these patients showed less room for improvement. Patient-reported outcomes showed improvement in sleep quality and QoL for the total and non-bulbar group, while bulbar patients only reported improvements in very few subscores. Conclusions: This study shows an improvement of sleep architecture, carbon dioxide, and nocturnal oxygen saturation at the end of NIV titration and after one month of NIV in ALS patients. More studies are needed to identify the appropriate time to start NIV in bulbar patients. Our results suggest that accurate titration of NIV by PSG improves sleep quality. Commentary: A commentary on this article appears in this issue on page 511. Citation: Vrijsen B, Buyse B, Belge C, Robberecht W, Van Damme P, Decramer M, Testelmans D. Noninvasive ventilation improves sleep in amyotrophic lateral sclerosis: a prospective polysomnographic study. J Clin Sleep Med 2015;11(5):559–566. PMID:25766713

  7. Specific Physical Exercise Improves Energetic Metabolism in the Skeletal Muscle of Amyotrophic-Lateral- Sclerosis Mice

    Directory of Open Access Journals (Sweden)

    Céline Desseille

    2017-10-01

    Full Text Available Amyotrophic Lateral Sclerosis is an adult-onset neurodegenerative disease characterized by the specific loss of motor neurons, leading to muscle paralysis and death. Although the cellular mechanisms underlying amyotrophic lateral sclerosis (ALS-induced toxicity for motor neurons remain poorly understood, growing evidence suggest a defective energetic metabolism in skeletal muscles participating in ALS-induced motor neuron death ultimately destabilizing neuromuscular junctions. In the present study, we report that a specific exercise paradigm, based on a high intensity and amplitude swimming exercise, significantly improves glucose metabolism in ALS mice. Using physiological tests and a biophysics approach based on nuclear magnetic resonance (NMR, we unexpectedly found that SOD1(G93A ALS mice suffered from severe glucose intolerance, which was counteracted by high intensity swimming but not moderate intensity running exercise. Furthermore, swimming exercise restored the highly ALS-sensitive tibialis muscle through an autophagy-linked mechanism involving the expression of key glucose transporters and metabolic enzymes, including GLUT4 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH. Importantly, GLUT4 and GAPDH expression defects were also found in muscles from ALS patients. Moreover, we report that swimming exercise induced a triglyceride accumulation in ALS tibialis, likely resulting from an increase in the expression levels of lipid transporters and biosynthesis enzymes, notably DGAT1 and related proteins. All these data provide the first molecular basis for the differential effects of specific exercise type and intensity in ALS, calling for the use of physical exercise as an appropriate intervention to alleviate symptoms in this debilitating disease.

  8. Patients' self-perceived burden, caregivers' burden and quality of life for amyotrophic lateral sclerosis patients: a cross-sectional study.

    Science.gov (United States)

    Geng, Dan; Ou, RuWei; Miao, XiaoHui; Zhao, LiHong; Wei, QianQian; Chen, XuePing; Liang, Yan; Shang, HuiFang; Yang, Rong

    2017-10-01

    This study surveys the quality of life of amyotrophic lateral sclerosis patients and the factors associated with amyotrophic lateral sclerosis patients' self-perceived burden and their caregivers' burden. Burdens of patients with amyotrophic lateral sclerosis and their caregivers in Chinese population are largely unknown. A cross-sectional study was conducted among 81 pairs of amyotrophic lateral sclerosis patients and their caregivers. Amyotrophic lateral sclerosis patients' self-perceived burden and caregivers' burden were assessed by the Self-Perceived Burden Scale and Zarit-Burden Interview, respectively. Quality of life of amyotrophic lateral sclerosis patients was measured using the World Health Organization Quality of Life-Bref. The amyotrophic lateral sclerosis Functional Rating Scale-Revised questionnaire was used to estimate patients' physical function. Both patients and caregivers reported a mild to moderate burden. The World Health Organization quality of life-Bref scores were decreased in respondents with lower amyotrophic lateral sclerosis Functional Rating Scale-Revised, higher Self-Perceived Burden Scale and higher Zarit-Burden Interview scores. Self-Perceived Burden Scale scores were associated with patients' knowledge of amyotrophic lateral sclerosis, respiratory function and female sex. Zarit-Burden Interview scores were associated with caregivers' age, patients' motor function and out-of-pocket payment. With increase in amyotrophic lateral sclerosis patients' self-perceived burden and caregivers' burden, quality of life of amyotrophic lateral sclerosis patients decreased. Female patients, who had known more about the disease, and those with severe respiratory dysfunction were subject to higher self-perceived burden. Older caregivers and caregivers of patients with severe motor dysfunction and more out-of-pocket payment experienced more care burdens. Our study suggests that paying more attention to female amyotrophic lateral sclerosis patients

  9. Value of 18fluorodeoxyglucose-positron-emission tomography in amyotrophic lateral sclerosis: a prospective study.

    Science.gov (United States)

    Van Laere, Koen; Vanhee, Annelies; Verschueren, Jolien; De Coster, Liesbeth; Driesen, An; Dupont, Patrick; Robberecht, Wim; Van Damme, Philip

    2014-05-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder primarily affecting the motor system, with extramotor involvement to a variable extent. Biomarkers for early differential diagnosis and prognosis are needed. An autosomal dominant hexanucleotide (GGGGCC) expansion in the noncoding region of the chromosome 9 open reading frame 72 (C9orf72) gene is the most frequent genetic cause of ALS, but its metabolic pattern has not been studied systematically. To evaluate the use of 18fluorodeoxyglucose-positron-emission tomography as a marker of ALS pathology and investigate whether a specific metabolic signature is present in patients with C9orf72 mutations. In total, 81 patients with a suspected diagnosis of ALS at University Hospital Leuven were prospectively investigated. All underwent detailed neurological examination and electrodiagnostic and genetic testing for the major known genetic causes of ALS (C9orf72, SOD1, TARDBP, and FUS). A diagnosis of ALS was made in 70 of 81 patients. Of these, 11 were C9orf72 positive and 59 were C9orf72 negative. In 7 patients, the diagnosis of primary lateral sclerosis was made; 4 patients had progressive muscular atrophy. A screened healthy control population was used for comparison. Positron-emission tomographic data were spatially normalized and analyzed using a predefined volume of interest and a voxel-based analysis (SPM8). Discriminant analysis was done both volume of interest based and voxel based using a support vector machine approach. Compared with control participants, 18fluorodeoxyglucose-positron-emission tomography showed perirolandic and variable prefrontal hypometabolism in most patients. Patients with primary lateral sclerosis showed a similar pattern. Patients with C9orf72-positive ALS had discrete relative hypometabolism in the thalamus and posterior cingulate compared with those with C9orf72-negative ALS. A posteriori-corrected discriminant analysis was able to correctly classify 95% of ALS cases and

  10. A Potential Biomarker in Amyotrophic Lateral Sclerosis: Can Assessment of Brain Iron Deposition with SWI and Corticospinal Tract Degeneration with DTI Help?

    Science.gov (United States)

    Sheelakumari, R; Madhusoodanan, M; Radhakrishnan, A; Ranjith, G; Thomas, B

    2016-02-01

    Iron-mediated oxidative stress plays a pivotal role in the pathogenesis of amyotrophic lateral sclerosis. This study aimed to assess iron deposition qualitatively and quantitatively by using SWI and microstructural changes in the corticospinal tract by using DTI in patients with amyotrophic lateral sclerosis. Seventeen patients with amyotrophic lateral sclerosis and 15 age- and sex-matched controls underwent brain MR imaging with SWI and DTI. SWI was analyzed for both signal-intensity scoring and quantitative estimation of iron deposition in the anterior and posterior banks of the motor and sensory cortices and deep gray nuclei. The diffusion measurements along the corticospinal tract at the level of pons and medulla were obtained by ROI analysis. Patients with amyotrophic lateral sclerosis showed reduced signal-intensity grades in the posterior bank of the motor cortex bilaterally. Quantitative analysis confirmed significantly higher iron content in the posterior bank of the motor cortex in patients with amyotrophic lateral sclerosis. In contrast, no significant differences were noted for the anterior bank of the motor cortex, anterior and posterior banks of the sensory cortex, and deep nuclei. Receiver operating characteristic comparison showed a cutoff of 35μg Fe/g of tissue with an area under the curve of 0.78 (P = .008) for the posterior bank of the motor cortex in discriminating patients with amyotrophic lateral sclerosis from controls. Fractional anisotropy was lower in the pyramidal tracts of patients with amyotrophic lateral sclerosis at the pons and medulla on either side, along with higher directionally averaged mean diffusivity values. The combination of SWI and DTI revealed an area under the curve of 0.784 for differentiating patients with amyotrophic lateral sclerosis from controls. Measurements of motor cortex iron deposition and diffusion tensor parameters of the corticospinal tract may be useful biomarkers for the diagnosis of clinically suspected

  11. Altered cortical activation during action observation in amyotrophic lateral sclerosis patients: a parametric functional MRI study

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    Li, Haiqing; Li, Yuxin; Yin, Bo; Tang, Weijun; Yu, Xiangrong; Geng, Daoying [Huashan Hospital, Department of Radiology, Fudan University, Shanghai (China); Chen, Yan [Fudan University, Department of Neurology, Huashan Hospital, Shanghai (China); Huang, Weiyuan [People' s Hospital of Hainan Province, Department of Radiology, Haikou, Hainan Province (China); Zhang, Biyun [Nanjing University of Traditional Chinese Medicine, Department of radiotherapy, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2015-09-15

    To investigate functional cerebral abnormalities in patients with amyotrophic lateral sclerosis (ALS) using functional magnetic resonance imaging (fMRI) during action observation. Thirty patients with ALS and 30 matched healthy controls underwent fMRI with an experimental paradigm while observing a video of repetitive flexion-extension of the fingers at three frequency levels or three complexity levels, alternated with periods of a static hand. A parametric analysis was applied to determine the effects of each of the two factors. Action observation activated similar neural networks as the research on execution of action in the ALS patients and healthy subjects in several brain regions related to the mirror-neuron system (MNS). In the ALS patients, in particular, the dorsal lateral premotor cortex (dPMC), inferior parietal gyrus (IPG), and SMA, were more activated compared with the activation in the controls. Increased activation within the primary motor cortex (M1), dPMC, inferior frontal gyrus (IFG), and superior parietal gyrus (SPG) mainly correlated with hand movement frequency/complexity in the videos in the patients compared with controls. The findings indicated an ongoing compensatory process occurring within the higher order motor-processing system of ALS patients, likely to overcome the loss of function. (orig.)

  12. Concordance between site of onset and limb dominance in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Turner, M R; Wicks, P; Brownstein, C A; Massagli, M P; Toronjo, M; Talbot, K; Al-Chalabi, A

    2011-08-01

    Focality of onset of amyotrophic lateral sclerosis (ALS) is not understood. Attempts to implicate physical exercise in the aetiology of ALS have provided inconsistent results. If physical use of a limb were important in defining the site of onset, then handedness might be expected to influence the side of upper limb-onset disease and footedness likewise in lower limb-onset ALS. ALS patients registered with an internet-based support site were invited to complete an online questionnaire concerning site of onset of symptoms and their dominant hand and foot. A binomial test of proportions was used to investigate the null hypothesis that handedness and footedness do not influence side of onset in upper and lower limb-onset ALS, respectively. 343 ALS patients with limb-onset disease were studied. For upper limb-onset patients, there was concordance for side of onset and handedness (64%; pside of onset and footedness was absent. The frequency of left handedness was commensurate with that found in the general population. These results are potentially consistent with the hypothesis that exercise influences pathogenesis in ALS since routine physical demands on the upper limb are heavily influenced by limb dominance, whereas in the lower limbs the commonest function is standing or locomotion, which uses both legs equally. However, there may also be an inherent cortical vulnerability underlying upper limb-onset laterality, possibly influenced by changes in neuronal connectivity and cortical excitability in relation to handedness and reflected by the "split hand" phenomenon consistently observed in ALS.

  13. Eye tracking communication devices in amyotrophic lateral sclerosis: impact on disability and quality of life.

    Science.gov (United States)

    Caligari, Marco; Godi, Marco; Guglielmetti, Simone; Franchignoni, Franco; Nardone, Antonio

    2013-12-01

    People with amyotrophic lateral sclerosis (PwALS) show progressive loss of voluntary muscle strength. In advanced disease, motor and phonatory impairments seriously hinder the patient's interpersonal communication. High-tech devices such as eye tracking communication devices (ETCDs) are used to aid communication in the later stages of ALS. We sought to evaluate the effect of ETCDs on patient disability, quality of life (QoL), and user satisfaction, in a group of 35 regular ETCD users in late-stage ALS with tetraplegia and anarthria. The following scales were administered: 1) the Individually Prioritized Problem Assessment (IPPA) scale, in three conditions: without device, with ETCD and, when applicable, with an Eye Transfer (ETRAN) board; 2) the Psychosocial Impact of Assistive Devices Scale (PIADS); and 3) the Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST 2.0). With ETRAN, IPPA showed an increase in communicative abilities with respect to the condition without device, but ETCD produced a further significant increase. PIADS evidenced a large increase of QoL, and QUEST 2.0 showed high user satisfaction with ETCD use. In conclusion, ETCDs should be considered in late-stage ALS with tetraplegia and anarthria, since in these patients they can reduce communication disability and improve QoL.

  14. Oral motor functions, speech and communication before a definitive diagnosis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Makkonen, Tanja; Korpijaakko-Huuhka, Anna-Maija; Ruottinen, Hanna; Puhto, Riitta; Hollo, Kirsi; Ylinen, Aarne; Palmio, Johanna

    2016-01-01

    The aim of this study was to explore the cranial nerve symptoms, speech disorders and communicative effectiveness of Finnish patients with diagnosed or possible amyotrophic lateral sclerosis (ALS) at their first assessment by a speech-language pathologist. The group studied consisted of 30 participants who had clinical signs of bulbar deterioration at the beginning of the study. They underwent a thorough clinical speech and communication examination. The cranial nerve symptoms and ability to communicate were compared in 14 participants with probable or definitive ALS and in 16 participants with suspected or possible ALS. The initial type of ALS was also assessed. More deterioration in soft palate function was found in participants with possible ALS than with diagnosed ALS. Likewise, a slower speech rate combined with more severe dysarthria was observed in possible ALS. In both groups, there was some deterioration in communicative effectiveness. In the possible ALS group the diagnostic delay was longer and speech therapy intervention actualized later. The participants with ALS showed multidimensional decline in communication at their first visit to the speech-language pathologist, but impairments and activity limitations were more severe in suspected or possible ALS. The majority of persons with bulbar-onset ALS in this study were in the latter diagnostic group. This suggests that they are more susceptible to delayed diagnosis and delayed speech therapy assessment. It is important to start speech therapy intervention during the diagnostic processes particularly if the person already shows bulbar symptoms. Copyright © 2016. Published by Elsevier Inc.

  15. Treatment for spasticity in amyotrophic lateral sclerosis/motor neuron disease.

    Science.gov (United States)

    Ashworth, Nigel L; Satkunam, L E; Deforge, Dan

    2012-02-15

    Spasticity commonly affects patients with motor neuron disease. It is likely to contribute to worsening muscle dysfunction, increased difficulty with activities of daily living and deteriorating quality of life. This is an update of a review first published in 2003 and previously updated in 2005 and 2008. The objective of this review is to systematically review treatments for spasticity in amyotrophic lateral sclerosis, also known as motor neuron disease. We searched the Cochrane Neuromuscular Disease Group Specialized Register (4 July 2011), CENTRAL (2011, Issue 2), MEDLINE (January 1966 to July 2011), EMBASE (January 1980 to July 2011 ), CINAHL Plus (January 1937 to July 2011), AMED (January 1985 to July 2011) and LILACS (January 1982 to July 2011 ). We reviewed the bibliographies of the randomized controlled trials identified, and contacted authors and experts in the field. We included quasi-randomized or randomized controlled trials of participants with probable or definite amyotrophic lateral sclerosis according to the El Escorial diagnostic criteria (or a revised version) or the Airlie House revision. We would have included trials of physical therapy, modalities, prescription medications, non-prescription medications, chemical neurolysis, surgical interventions, and alternative therapies. Our primary outcome measure was reduction in spasticity at three months or greater as measured by the Ashworth (or modified Ashworth) spasticity scale. Our secondary outcome measures were: validated measures based on history, physical examination, physiological measures, measures of function, measures of quality of life, all adverse events, and measures of cost. Two authors independently screened the abstracts of potential trials retrieved from the searches. Two authors extracted the data. We also contacted the author of the paper and obtained information not available in the published article. All three authors assessed the methodological quality of all included trials

  16. Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study.

    Science.gov (United States)

    Kioumourtzoglou, Marianthi-Anna; Rotem, Ran S; Seals, Ryan M; Gredal, Ole; Hansen, Johnni; Weisskopf, Marc G

    2015-08-01

    Although prior studies have suggested a role of cardiometabolic health on pathogenesis of amyotrophic lateral sclerosis (ALS), the association with diabetes mellitus has not been widely examined. Amyotrophic lateral sclerosis is the most common motor neuron disorder. Several vascular risk factors have been associated with decreased risk for ALS. Although diabetes is also a risk factor for vascular disease, the few studies of diabetes and ALS have been inconsistent. To examine the association between diabetes and obesity, each identified through International Statistical Classification of Diseases, Eighth or Tenth Revision codes in a hospital registry, and ALS using data from the Danish National Registers. Population-based nested case-control study of 3650 Danish residents diagnosed as having ALS between January 1, 1982, and December 31, 2009, and 365,000 controls (100 for each ALS case) matched on age and sex. The analysis was conducted in September and October 2014. Adjusted odds ratio for ALS associated with diabetes or obesity diagnoses at least 3 years prior to the ALS diagnosis date. When considering diabetes and our obesity indicator together, the estimated odds ratio for ALS was 0.61 (95% CI, 0.46-0.80) for diabetes and 0.81 (95% CI, 0.57-1.16) for obesity. We observed no effect modification on the association with diabetes by sex. We did find a significant modification by age at ALS diagnosis and age at first mention of diabetes in the hospital registers. The protective association was stronger with increasing age at ALS diagnosis (P = .01), and the odds ratio for first mention of diabetes was 1.66 (95% CI, 0.85-3.21) before age 40 years but 0.52 (95% CI, 0.39-0.70) for older ages. These results are consistent with different associations for type 1 vs type 2 diabetes. In this Danish nationwide study to investigate the association between diabetes and ALS diagnosis, our findings are in agreement with previous reports of a protective association between

  17. Amyotrophic lateral sclerosis (ALS): three letters that change the people's life. For ever.

    Science.gov (United States)

    Oliveira, Acary Souza Bulle; Pereira, Roberto Dias Batista

    2009-09-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting the motor nervous system. It causes progressive and cumulative physical disabilities in patients, and leads to eventual death due to respiratory muscle failure. The disease is diverse in its presentation, course, and progression. We do not yet fully understand the cause or causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. Currently, we rely on a multidisciplinary approach to symptomatically manage and care for patients who have ALS. Although amyotrophic lateral sclerosis and its variants are readily recognized by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. Prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with Riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. In this review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. Multiple problems require a multidisciplinary approach including aggressive symptomatic management, rehabilitation to maintain motor function, nutritional support (enteric feeding, gastrostomy), respiratory support (non invasive home ventilation, invasive ventilation, tracheotomy), augmentative communication devices, palliative care, psychological support for both patients and families (because family members so often play a central role in management and care), communication between the care team, the patient and his or her family, and recognition of

  18. Esclerose lateral amiotrófica e neurossífilis Amyotrophic lateral sclerosis and neurosyphilis. A case report

    Directory of Open Access Journals (Sweden)

    Eliova Zukerman

    1973-09-01

    Full Text Available É relatado um caso clínico de esclerose lateral amiotrófica (ELA, caracterizado por amiotrofias extensas na cintura escapular e membros superiores, associadas a exaltação dos reflexos osteotendinosos nos membros inferiores, com sinal de Rossolimo bilateral e sinal Babinski esboçado a esquerda, sem distúrbios sensitivos ou esfinterianos, em mulher de 51 anos de idade e com história progressiva de um ano. O exame de líquido cefalorraqueano permitiu o diagnóstico de neurossífilis parenquimatosa. Chamando a atenção para a raridade dessa associação, os AA. discutem o papel da neuro-lues como fator causal da síndrome de ELA, concluindo por uma provável relação de causa e efeito no caso descrito, por ter havido estabilização do quadro sintomatológico após terapêutica penicilínica.A clinic case of amyotrophic lateral sclerosis (ALS in a 51 years old woman is reported. The patient exhibited signs of pyramidal system and anterior motor neuron involvement. The cerebrospinal fluid examinations showed clear cut indications of parenchymatous neurosyphilis. Attention is called to the rarity of the association above mentioned. The role of neurosyphilis as an atiological factor of ALS is discussed. The authors conclude that in the case described there is a close relationship between the two entities.

  19. Distribution of Arsenic, Manganese, and Selenium in the Human Brain in Chronic Renal Insufficiency, Parkinsons Disease and Amyotrophic Lateral Sclerosis

    DEFF Research Database (Denmark)

    Larsen, N. A.; Pakkenberg, H.; Damsgaard, Else

    1981-01-01

    The concentrations of arsenic, manganese and selenium/g wet tissue weight were determined in samples from 24 areas of the human brain from 3 patients with chronic renal insufficiency, 2 with Parkinson's disease and 1 with amyotrophic lateral sclerosis. The concentrations of the 3 elements were...... determined for each sample by neutron activation analysis with radiochemical separation. Overall arsenic concentrations were about 2.5 times higher in patients with chronic renal failure than in controls, and lower than normal in the patients with Parkinson's disease and amyotrophic lateral sclerosis....... There were no obvious differences in the overall concentrations of manganese and selenium from one group to another. Even multivariate data analysis by the SIMCA method failed to reveal any significant difference in the distribution pattern of manganese and selenium in Parkinson's disease compared to normal...

  20. Immunohistochemical localization of group I and II metabotropic glutamate receptors in control and amyotrophic lateral sclerosis human spinal cord: upregulation in reactive astrocytes

    NARCIS (Netherlands)

    Aronica, E.; Catania, M. V.; Geurts, J.; Yankaya, B.; Troost, D.

    2001-01-01

    Excitotoxicity, which is mediated by the excessive activation of glutamate receptors, has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). There is substantial information about the distribution and function of ionotropic glutamate receptors in the spinal cord, although

  1. Atypical Initial Presentation of Painful Muscle Cramps in a Patient with Amyotrophic Lateral Sclerosis: A Case Report and Brief Review of the Literature.

    Science.gov (United States)

    Kuzel, Aaron R; Lodhi, Muhammad Uzair; Syed, Intekhab Askari; Rahim, Mustafa

    2017-11-10

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized clinically by progressive muscle weakness that can occur proximally or distally in either the upper or lower extremities. It includes both upper motor neuron signs (spasticity, hyperreflexia, clonus, and Babinski sign) and lower motor neuron signs (atrophy, weakness, and muscle fasciculation). Initial presentation of progressively painful muscle cramps should lead the physician to screen for other signs of amyotrophic lateral sclerosis. We report the case of a 51-year-old male, who presented with dull muscle cramps in the right upper shoulder and arm. After a careful history and physical exam, it was found that patient had both upper and lower motor neuron signs; therefore, a diagnosis of amyotrophic lateral sclerosis was made. Amyotrophic lateral sclerosis should strongly be considered in the differential diagnosis of patients presenting with an atypical initial presentation of progressively painful muscle cramps.

  2. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis†

    OpenAIRE

    Cheroni, Cristina; Marino, Marianna; Tortarolo, Massimo; Veglianese, Pietro; De Biasi, Silvia; Fontana, Elena; Zuccarello, Laura Vitellaro; Maynard, Christa J.; Dantuma, Nico P; Bendotti, Caterina

    2008-01-01

    In familial and sporadic amyotrophic lateral sclerosis (ALS) and in rodent models of the disease, alterations in the ubiquitin-proteasome system (UPS) may be responsible for the accumulation of potentially harmful ubiquitinated proteins, leading to motor neuron death. In the spinal cord of transgenic mice expressing the familial ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we found a decrease in constitutive proteasome subunits during disease progression, as assessed by re...

  3. The use of P300-based BCIs in amyotrophic lateral sclerosis : from augmentative and alternative communication to cognitive assessment

    OpenAIRE

    Cipresso, P; L. Carelli; Solca, F; Meazzi, D.; Meriggi, P.; Poletti, B.; Lulè, D.; Ludolph, A.C.; Silani, V; Riva, G.

    2012-01-01

    The use of augmentative and alternative communication (AAC) tools in patients with amyotrophic lateral sclerosis (ALS), as effective means to compensate for the progressive loss of verbal and gestural communication, has been deeply investigated in the recent literature. The development of advanced AAC systems, such as eye-tracking (ET) and brain-computer interface (BCI) devices, allowed to bypass the important motor difficulties present in ALS patients. In particular, BCIs could be used in mo...

  4. Engaging in patient decision-making in multidisciplinary care for amyotrophic lateral sclerosis: the views of health professionals

    OpenAIRE

    Hogden A; Greenfield D; Nugus P; Kiernan MC

    2012-01-01

    Anne Hogden,1 David Greenfield,1 Peter Nugus,1 Matthew C Kiernan21Centre for Clinical Governance Research, Australian Institute of Health Innovation, University of New South Wales, 2Prince of Wales Clinical School, University of New South Wales, and Neuroscience Research Australia, Sydney, New South Wales, AustraliaBackground: The aim of this study was to explore clinician perspectives on patient decision-making in multidisciplinary care for amyotrophic lateral sclerosis (ALS), in an attempt ...

  5. Disease-related changes in the cerebrospinal fluid metabolome in amyotrophic lateral sclerosis detected by GC/TOFMS.

    Directory of Open Access Journals (Sweden)

    Anna Wuolikainen

    2011-04-01

    Full Text Available The changes in the cerebrospinal fluid (CSF metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF.Using gas chromatography coupled to mass spectrometry (GC/TOFMS and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls.The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS without superoxide dismutase-1 gene (SOD1 mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar.Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease.

  6. Disease-related changes in the cerebrospinal fluid metabolome in amyotrophic lateral sclerosis detected by GC/TOFMS.

    Science.gov (United States)

    Wuolikainen, Anna; Moritz, Thomas; Marklund, Stefan L; Antti, Henrik; Andersen, Peter Munch

    2011-04-04

    The changes in the cerebrospinal fluid (CSF) metabolome associated with the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) are poorly understood and earlier smaller studies have shown conflicting results. The metabolomic methodology is suitable for screening large cohorts of samples. Global metabolomics can be used for detecting changes of metabolite concentrations in samples of fluids such as CSF. Using gas chromatography coupled to mass spectrometry (GC/TOFMS) and multivariate statistical modeling, we simultaneously studied the metabolome signature of ∼120 small metabolites in the CSF of patients with ALS, stratified according to hereditary disposition and clinical subtypes of ALS in relation to controls. The study is the first to report data validated over two sub-sets of ALS vs. control patients for a large set of metabolites analyzed by GC/TOFMS. We find that patients with sporadic amyotrophic lateral sclerosis (SALS) have a heterogeneous metabolite signature in the cerebrospinal fluid, in some patients being almost identical to controls. However, familial amyotrophic lateral sclerosis (FALS) without superoxide dismutase-1 gene (SOD1) mutation is less heterogeneous than SALS. The metabolome of the cerebrospinal fluid of 17 ALS patients with a SOD1 gene mutation was found to form a separate homogeneous group. Analysis of metabolites revealed that glutamate and glutamine were reduced, in particular in patients with a familial predisposition. There are significant differences in the metabolite profile and composition among patients with FALS, SALS and patients carrying a mutation in the SOD1 gene suggesting that the neurodegenerative process in different subtypes of ALS may be partially dissimilar. Patients with a genetic predisposition to amyotrophic lateral sclerosis have a more distinct and homogeneous signature than patients with a sporadic disease.

  7. Lack of unique neuropathology in amyotrophic lateral sclerosis associated with p.K54E angiogenin (ANG) mutation.

    Science.gov (United States)

    Kirby, J; Highley, J R; Cox, L; Goodall, E F; Hewitt, C; Hartley, J A; Hollinger, H C; Fox, M; Ince, P G; McDermott, C J; Shaw, P J

    2013-08-01

    Five to 10% of cases of amyotrophic lateral sclerosis are familial, with the most common genetic causes being mutations in the C9ORF72, SOD1, TARDBP and FUS genes. Mutations in the angiogenin gene, ANG, have been identified in both familial and sporadic patients in several populations within Europe and North America. The aim of this study was to establish the incidence of ANG mutations in a large cohort of 517 patients from Northern England and establish the neuropathology associated with these cases. The single exon ANG gene was amplified, sequenced and analysed for mutations. Pathological examination of brain, spinal cord and skeletal muscle included conventional histology and immunohistochemistry. Mutation screening identified a single sporadic amyotrophic lateral sclerosis case with a p.K54E mutation, which is absent from 278 neurologically normal control samples. The clinical presentation was of limb onset amyotrophic lateral sclerosis, with rapid disease progression and no evidence of cognitive impairment. Neuropathological examination established the presence of characteristic ubiquitinated and TDP-43-positive neuronal and glial inclusions, but no abnormality in the distribution of angiogenin protein. There is only one previous report describing the neuropathology in a single case with a p.K17I ANG mutation which highlighted the presence of eosinophilic neuronal intranuclear inclusions in the hippocampus. The absence of this feature in the present case indicates that patients with ANG mutations do not always have pathological changes distinguishable from those of sporadic amyotrophic lateral sclerosis. © 2012 The Authors. Neuropathology and Applied Neurobiology © 2012 British Neuropathological Society.

  8. TDP-43 expression in mouse models of amyotrophic lateral sclerosis and spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Ansorge Olaf

    2008-10-01

    Full Text Available Abstract Background Redistribution of nuclear TAR DNA binding protein 43 (TDP-43 to the cytoplasm and ubiquitinated inclusions of spinal motor neurons and glial cells is characteristic of amyotrophic lateral sclerosis (ALS pathology. Recent evidence suggests that TDP-43 pathology is common to sporadic ALS and familial ALS without SOD1 mutation, but not SOD1-related fALS cases. Furthermore, it remains unclear whether TDP-43 abnormalities occur in non-ALS forms of motor neuron disease. Here, we characterise TDP-43 localisation, expression levels and post-translational modifications in mouse models of ALS and spinal muscular atrophy (SMA. Results TDP-43 mislocalisation to ubiquitinated inclusions or cytoplasm was notably lacking in anterior horn cells from transgenic mutant SOD1G93A mice. In addition, abnormally phosphorylated or truncated TDP-43 species were not detected in fractionated ALS mouse spinal cord or brain. Despite partial colocalisation of TDP-43 with SMN, depletion of SMN- and coilin-positive Cajal bodies in motor neurons of affected SMA mice did not alter nuclear TDP-43 distribution, expression or biochemistry in spinal cords. Conclusion These results emphasise that TDP-43 pathology characteristic of human sporadic ALS is not a core component of the neurodegenerative mechanisms caused by SOD1 mutation or SMN deficiency in mouse models of ALS and SMA, respectively.

  9. A cognitive brain-computer interface for patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Hohmann, M R; Fomina, T; Jayaram, V; Widmann, N; Förster, C; Just, J; Synofzik, M; Schölkopf, B; Schöls, L; Grosse-Wentrup, M

    2016-01-01

    Brain-computer interfaces (BCIs) are often based on the control of sensorimotor processes, yet sensorimotor processes are impaired in patients suffering from amyotrophic lateral sclerosis (ALS). We devised a new paradigm that targets higher-level cognitive processes to transmit information from the user to the BCI. We instructed five ALS patients and twelve healthy subjects to either activate self-referential memories or to focus on a process without mnemonic content while recording a high-density electroencephalogram (EEG). Both tasks are designed to modulate activity in the default mode network (DMN) without involving sensorimotor pathways. We find that the two tasks can be distinguished after only one experimental session from the average of the combined bandpower modulations in the theta- (4-7Hz) and alpha-range (8-13Hz), with an average accuracy of 62.5% and 60.8% for healthy subjects and ALS patients, respectively. The spatial weights of the decoding algorithm show a preference for the parietal area, consistent with modulation of neural activity in primary nodes of the DMN. © 2016 Elsevier B.V. All rights reserved.

  10. Characterizing the complexity of spontaneous motor unit patterns of amyotrophic lateral sclerosis using approximate entropy

    Science.gov (United States)

    Zhou, Ping; Barkhaus, Paul E.; Zhang, Xu; Zev Rymer, William

    2011-10-01

    This paper presents a novel application of the approximate entropy (ApEn) measurement for characterizing spontaneous motor unit activity of amyotrophic lateral sclerosis (ALS) patients. High-density surface electromyography (EMG) was used to record spontaneous motor unit activity bilaterally from the thenar muscles of nine ALS subjects. Three distinct patterns of spontaneous motor unit activity (sporadic spikes, tonic spikes and high-frequency repetitive spikes) were observed. For each pattern, complexity was characterized by calculating the ApEn values of the representative signal segments. A sliding window over each segment was also introduced to quantify the dynamic changes in complexity for the different spontaneous motor unit patterns. We found that the ApEn values for the sporadic spikes were the highest, while those of the high-frequency repetitive spikes were the lowest. There is a significant difference in mean ApEn values between two arbitrary groups of the three spontaneous motor unit patterns (P < 0.001). The dynamic ApEn curve from the sliding window analysis is capable of tracking variations in EMG activity, thus providing a vivid, distinctive description for different patterns of spontaneous motor unit action potentials in terms of their complexity. These findings expand the existing knowledge of spontaneous motor unit activity in ALS beyond what was previously obtained using conventional linear methods such as firing rate or inter-spike interval statistics.

  11. Adeno Associated Viral Vector Delivered RNAi for Gene Therapy of SOD1 Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Stoica, Lorelei; Sena-Esteves, Miguel

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease caused by progressive loss of upper and lower motor neurons. Mutations in superoxide dismutase 1 (SOD1) are a leading cause of ALS, responsible for up to 20% of familial cases. Although the exact mechanism by which mutant SOD1 causes disease remains unknown, multiple studies have shown that reduction of the mutant species leads to delayed disease onset and extension of lifespan of animal models. This makes SOD1 an ideal target for gene therapy coupling adeno associated virus vector (AAV) gene delivery with RNAi molecules. In this review we summarize the studies done thus far attempting to decrease SOD1 gene expression, using AAV vectors as delivery tools, and RNAi as therapeutic molecules. Current hurdles to be overcome, such as the need for widespread gene delivery through the entire central nervous system (CNS), are discussed. Continued efforts to improve current AAV delivery methods and capsids will accelerate the application of these therapeutics to the clinic.

  12. Lack of an association between attention-deficit/hyperactivity disorder (ADHD) and amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Ebel, Leonie; Petri, Susanne; Krauss, Joachim K; Dengler, Reinhard; de Zwaan, Martina

    2018-02-15

    Lulé, Ludolph, and Ludolph (2008) hypothesized that there may be a pathophysiological link between attention-deficit/hyperactivity disorder (ADHD) and amyotrophic lateral sclerosis (ALS). They summarized common clinical features, specifically enhanced physical and psychological activity, which have been described typically for ADHD patients and also as common personality traits before disease onset in patients with ALS. We assessed the lifetime prevalence rate of ADHD in 104 patients with ALS using valid self-report instruments for ADHD symptoms in childhood (WURS-k) and adulthood (ADHD-SB). Results were compared with a population-based sample (n=2069) and with patients with Parkinson's disease (PD, n=52) using regression analyses and adjusting for sociodemographic differences. Physical activity was assessed by the 21-item exercise dependency scale (EDS-21). ALS patients reported a lower prevalence of childhood ADHD compared to the general population. Both clinical groups reported significantly lower scores on the WURS-k scale and the attention deficit subscale of the ADHD-SB. The EDS-21 showed significantly longer exercise times in ALS and PD patients. We could not show that ADHD is more common in ALS patients. However, our results revealed shared personality traits in ALS and PD with lower rates of premorbid attention deficit symptoms and increased physical activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Magnetic resonance imaging and {sup 1}H-magnetic resonance spectroscopy in amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Sarchielli, P.; Gallai, V. [Neurological Clinic, Policlinico Monte Luce, Perugia (Italy); Pelliccioli, G.P.; Chiarini, P. [Dept. of Neuroradiology, Azienda Ospedaliera, Perugia (Italy); Tarducci, R.; Presciutti, O.; Gobbi, G. [Dept. of Medical Physics, Azienda Ospedaliera, Perugia (Italy)

    2001-03-01

    We aimed to increase confidence in the combined use of MRI and proton MR spectroscopy ({sup 1}H-MRS) in diagnosis of amyotrophic lateral sclerosis (ALS). We investigated 12 patients with ALS, seven definite and five probable, taking into account clinical measures of motor neuron function. On T2-weighted images we found high signal in the corticospinal tract in six and low signal in the primary motor cortex in seven of the 12 patients. Atrophy of the precentral gyrus was apparent in all the patients apart from one with probable ALS. Absolute quantification of cerebral metabolites using {sup 1}H-MRS demonstrated a significantly lower mean concentration of N-acetylaspartate (NAA) in the precentral gyrus of patients with probable and definite ALS (8.5 {+-} 0.62) than in control subjects (10.4 {+-} 0.71; P < 0.001). NAA concentration in primary motor cortex correlated with Norris scale scores (r = 0.30; P < 0.0001) but not with the ALS Functional Rating Scale score or disease duration. Significantly lower levels of NAA were detected in patients with low signal in the motor cortex than in those without (P < 0.01). Mean choline (Cho) and creatine (Cr) values did not differ between patients with ALS and controls. (orig.)

  14. Toenail mercury levels are associated with amyotrophic lateral sclerosis (ALS) risk.

    Science.gov (United States)

    Andrew, Angeline S; Chen, Celia Y; Caller, Tracie A; Tandan, Rup; Henegan, Patricia L; Jackson, Brian P; Hall, Brenda P; Bradley, Walter G; Stommel, Elijah W

    2018-01-04

    Mercury is a neurotoxic metal that is potentially a risk factor for amyotrophic lateral sclerosis (ALS). Consumption of methylmercury contaminated fish is the primary source of U.S. population exposure to mercury. We used inductively coupled plasma mass spectrometry to measure levels of mercury in toenail samples from ALS patients (n=46) and from controls (n=66), as a biomarker of mercury exposure. ALS patients had higher toenail mercury levels (OR 2.49 95%CI 1.18-5.80, P=0.024) compared to controls, adjusted for age and gender. We also estimated the amount of mercury consumed from finfish and shellfish and found toenail mercury levels elevated overall among ALS patients and controls in the top quartile for consumption (P=0.018). Biomarker data show ALS associated with increased with mercury levels, which were related to estimated methylmercury intake via fish. Replication of these associations in additional populations is warranted. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

  15. A seeded propagation of Cu,Zn-superoxide dismutase aggregates in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Mariko eOgawa

    2014-03-01

    Full Text Available Abnormal accumulation of protein inclusions in motor neurons has been known as a major pathological change in amyotrophic lateral sclerosis (ALS. Increasing numbers of proteins including mutant Cu,Zn-superoxide dismutase (SOD1 have been identified as constituents of pathological inclusions in a form of insoluble fibrillar aggregates. Notably, protein fibrillar aggregates exhibit a self-perpetuating property, which can convert a soluble native protein into insoluble fibrillar aggregates. Such seeding reaction of protein fibrils can accelerate the aggregation significantly and would contribute to the spread of inclusion pathologies from an affected cell to its neighboring cells in neurodegenerative diseases. In ALS, a pathological change first occurs at the site of disease onset and then propagates throughout the affected tissues in a time-dependent manner; therefore, it can be assumed that seeded aggregation may be the key factor of disease progression in ALS. In this mini review, we will briefly summarize recent studies on possible roles of a seeded aggregation of SOD1 in pathomechanism of ALS.

  16. New ALS-Related Genes Expand the Spectrum Paradigm of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Sabatelli, Mario; Marangi, Giuseppe; Conte, Amelia; Tasca, Giorgio; Zollino, Marcella; Lattante, Serena

    2016-03-01

    Amyotrophic Lateral Sclerosis (ALS) is characterized by the degeneration of upper and lower motor neurons. Clinical heterogeneity is a well-recognized feature of the disease as age of onset, site of onset and the duration of the disease can vary greatly among patients. A number of genes have been identified and associated to familial and sporadic forms of ALS but the majority of cases remains still unexplained. Recent breakthrough discoveries have demonstrated that clinical manifestations associated with ALS-related genes are not circumscribed to motor neurons involvement. In this view, ALS appears to be linked to different conditions over a continuum or spectrum in which overlapping phenotypes may be identified. In this review, we aim to examine the increasing number of spectra, including ALS/Frontotemporal Dementia and ALS/Myopathies spectra. Considering all these neurodegenerative disorders as different phenotypes of the same spectrum can help to identify common pathological pathways and consequently new therapeutic targets in these incurable diseases. © 2016 International Society of Neuropathology.

  17. An inactivating mutation in the SOD 1 gene causes familial amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Pramatarova, A.; Rouleau, G.A. [Montreal General Hospital Research Institute (Canada); Goto, J. [Univ. of Tokyo (Japan)] [and others

    1994-09-01

    Amyotrophic lateral sclerosis (ALS) is characterized by highly selective death of large motor neurons in the cerebral cortex and spinal cord. The familial form of ALS (FALS) accounts for approximately 10% of the cases and is transmitted in an autosomal dominant manner. Recently the defective gene causing chromosome 21-linked FALS was shown to be the Cu/Zn superoxide dismutase (SOD 1). However, the precise mechanism of neurotoxicity seen in FALS with SOD 1 mutations is still unknown. Until now all SOD 1 mutations reported were single base pair substitutions (missense). We have identified a nonsense mutation in exon 5 of the SOD 1 gene in a FALS kindred. This two base pair deletion provokes a frameshift and a predicted premature truncation of the protein. The region affected has a very important structural and functional role: it contains part of the active loop and is involved in dimer contact. We would predict that the loss of these structures would impair the functioning of the enzyme.

  18. [A amyotrophic lateral sclerosis (ALS) 4 family misdiagnosed as hereditary spastic paraplegia-a case report].

    Science.gov (United States)

    Taniguchi, Takaki; Hokezu, Youichi; Okada, Takashi; Ishibashi, Masato; Hashiguchi, Akihiro; Matsuura, Eiji; Takashima, Hiroshi

    2017-11-25

    We report a 44 years old man with slowly progressive muscular atrophy of the extremities for over 30 years. He experienced difficulty in walking in his 10's and was diagnosed as hereditary spastic paraplegia (HSP) in his 20's. And then, muscle atrophy of the extremities slowly progressed especially in his distal muscles. Sensory axonal neuropathy was detected with sural nerve biopsy. His father and uncle have been diagnosed as HSP in their early days. His father noticed weakness of his leg in his 20's. He lost motor function of the leg in his 60's. In addition, marked disturbance of thermal sensation, vibration, and sense of position were found by physical examination. Our genetic study detected senataxin (SETX) gene mutation (c.8C>T,p.T3I) in the blood of those two patients, and they had been identified as family cases of amyotrophic lateral sclerosis (ALS) 4. As clinical symptoms of ALS4 would be similar to those of HSP at the onset, we suggest considering ALS4 in seeing patients with HSP without gene diagnosis.

  19. Phenotypic differences of amyotrophic lateral sclerosis (ALS) in China and Germany.

    Science.gov (United States)

    Rosenbohm, Angela; Liu, Mingsheng; Nagel, Gabriele; Peter, Raphael S; Cui, Bo; Li, Xiaoguang; Kassubek, Jan; Rothenbacher, Dietrich; Lulé, Dorothée; Cui, Liying; Ludolph, Albert C

    2018-02-01

    The aim of this study is to explore phenotypical differences of amyotrophic lateral sclerosis (ALS) between two cohorts from Germany and China. Registry-based studies of ALS were conducted in South-West Germany from 2010 to 2014 and an ALS clinic in Beijing from 2013 to 2016, respectively. Demographic and clinical features of 663 German and 276 Chinese ALS patients were collected and compared. Mean age-at-onset was higher in German than in Chinese ALS patients [66.6 years (95% CI 65.7, 67.5) vs. 53.2 years (95% CI 52.0, 54.5)]. Age distribution of ALS patients peaked around 70-74 years in Germany and 50-54 years in China. Bulbar onset was more prevalent among German than among Chinese patients (35.9 vs. 22.8%). Diagnostic delay was higher in the Chinese than in the German study sample (12 vs. 5 months). Cognitive deficits were more pronounced in the Chinese cohort. Both cohorts differed in smoking habits, prevalence of diabetes and in body mass index (BMI). The apparent discrepancies between German and Chinese ALS patients (age at onset, gender distribution, bulbar forms, cognitive dysfunction, risk factors) reveal a quite different clinical phenotype in China, maybe due to socioeconomic status, environmental factors or genetic background. The observed differences in phenotype need to be pursued by further epidemiological studies on environmental and genetic risk factors.

  20. MRI of paraventricular white matter lesions in amyotrophic lateral sclerosis. Analysis by diffusion-weighted images

    Energy Technology Data Exchange (ETDEWEB)

    Segawa, Fuminori; Kinoshita, Masao (Toho Univ., Tokyo (Japan). Ohashi Hospital); Kishibayashi, Jun; Kamada, Kazuhiko; Sunohara, Nobuhiko

    1994-09-01

    Magnetic resonance images in some cases of amyotrophic lateral sclerosis (ALS) revealed abnormal signals in both the paraventriculer white matter and in the posterior limbs of the internal capsule. We examined T[sub 2]- and diffusion-weighted MR images of these lesions in 18 cases of ALS. There were symmetrical high-signal areas in the posterior limbs of the internal capsule in all of the cases. The high-signal areas in the internal capsule corresponded to the pyramidal tracts in the anatomical atlas by Talairach. In 5 of the cases of ALS, T[sub 2]-weighted MR images showed discrete paraventricular white matter lesions as well. The mean age of the ALS patients with paraventricular white matter lesions was higher than that of the ALS patients without such lesions. Proton densities calculated from the conventional MR images were higher in both the capsular and paraventricular lesions. The diffusion coefficients perpendicular to the pyramidal tract in the internal capsular lesions were within the normal range, where as the diffusion coefficients in the paraventricular lesions were increased in all directions. Thus, diffusion anisotropy was lost in the paraventricular lesions. These findings are similar to those observed in the white matter lesions of cerebro-vascular origin. As a result, the pathology of the paraventricular lesions in ALS was confirmed to be different from that of the internal capsular lesions. (author).

  1. A muscle ultrasound score in the diagnosis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tsuji, Yukiko; Noto, Yu-Ichi; Shiga, Kensuke; Teramukai, Satoshi; Nakagawa, Masanori; Mizuno, Toshiki

    2017-06-01

    The aims of this study are to elucidate the frequencies and distribution of fasciculations using muscle ultrasound in patients with amyotrophic lateral sclerosis (ALS) and those with other conditions mimicking ALS, and subsequently to develop a novel fasciculation score for the diagnosis of ALS. Ultrasound of 21 muscles was performed to detect fasciculations in 36 consecutive patients suspected of having ALS. We developed a fasciculation ultrasound score that indicated the number of muscles with fasciculations in statistically selected muscles. A total of 525 muscles in 25 ALS patients and 231 in 11 non-ALS patients were analysed. Using relative operating characteristic and multivariate logistic regression analysis, we selected the trapezius, deltoid, biceps brachii, abductor pollicis brevis, abdominal, vastus lateralis, vastus medialis, biceps femoris, and gastrocnemius muscles for the fasciculation ultrasound score. The mean scores were higher in the ALS group than those in the non-ALS group (5.3±0.5vs. 0.3±0.7) (mean±SD); pALS patients from non-ALS patients. The fasciculation ultrasound score can be a simple and useful diagnostic marker of ALS. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  2. Amyotrophic lateral sclerosis: analysis of ALS cases in a predominantly admixed population of Ecuador.

    Science.gov (United States)

    Bucheli, Miriam; Andino, Andres; Montalvo, Mayra; Cruz, Jose; Atassi, Nazem; Berry, James; Salameh, Johnny

    2014-03-01

    Recent studies suggest amyotrophic lateral sclerosis (ALS) prevalence, incidence, and age of onset are heterogeneous across populations. These include studies from South America (SA) where lower prevalence, earlier onset, and reduced survival time of ALS are reported. However, the scarcity of epidemiological and clinical data confounds effective comparison. To investigate ALS incidence in the predominantly admixed population of Ecuador, we analyzed patient data. We analyzed case data from two major hospitals. To confirm diagnosis, we evaluated clinical and EMG examinations in a cohort of patients. For 2000-2012, we found 116 patients with ALS diagnosis in the two hospitals. Crude incidence was 0.2-0.6 per 100,000. Median age of onset was 54.3 (+ 15.06 SD). Clinical re-evaluation found misdiagnosis in three cases in the cohort. In conclusion, ALS incidence in the Ecuadorian hospital population is in accord with rates reported in recent studies for other admixed populations, and lower than that in the United States and Europe. Our study found that appropriate EMG administration and interpretation for the purposes of supporting a diagnosis of ALS with current consensus guidelines prevent adequate use of this test as an essential tool in the evaluation and diagnosis of ALS. Training for required standardization in Ecuador is recommended.

  3. Amyotrophic lateral sclerosis - frontotemporal spectrum disorder (ALS-FTSD): Revised diagnostic criteria.

    Science.gov (United States)

    Strong, Michael J; Abrahams, Sharon; Goldstein, Laura H; Woolley, Susan; Mclaughlin, Paula; Snowden, Julie; Mioshi, Eneida; Roberts-South, Angie; Benatar, Michael; HortobáGyi, Tibor; Rosenfeld, Jeffrey; Silani, Vincenzo; Ince, Paul G; Turner, Martin R

    2017-05-01

    This article presents the revised consensus criteria for the diagnosis of frontotemporal dysfunction in amyotrophic lateral sclerosis (ALS) based on an international research workshop on frontotemporal dementia (FTD) and ALS held in London, Canada in June 2015. Since the publication of the Strong criteria, there have been considerable advances in the understanding of the neuropsychological profile of patients with ALS. Not only is the breadth and depth of neuropsychological findings broader than previously recognised - - including deficits in social cognition and language - but mixed deficits may also occur. Evidence now shows that the neuropsychological deficits in ALS are extremely heterogeneous, affecting over 50% of persons with ALS. When present, these deficits significantly and adversely impact patient survival. It is the recognition of this clinical heterogeneity in association with neuroimaging, genetic and neuropathological advances that has led to the current re-conceptualisation that neuropsychological deficits in ALS fall along a spectrum. These revised consensus criteria expand upon those of 2009 and embrace the concept of the frontotemporal spectrum disorder of ALS (ALS-FTSD).

  4. Split hand index and ulnar to median ratio in Hirayama disease and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kalita, Jayantee; Kumar, Surendra; Misra, Usha K; Neyaz, Zafar

    2017-11-01

    We report the relative usefulness of split hand index (SHI) and ulnar to median (UM) ratio in Hirayama disease (HD) and amyotrophic lateral sclerosis (ALS). The patients with HD, ALS and matched controls were subjected to evaluation of UM ratio and SHI. Compound muscle action potentials (CMAPs) were recorded from abductor digit minimi (ADM) and first dorsal interosseous (FDI) by stimulating ulnar nerve at the wrist, and abductor pollicis brevis (APB) by stimulating median nerve at the wrist. UM ratio (ADM/APB) and SHI (APB × FDI/ADM) were calculated, and compared. Sensitivity and specificity of SHI and UM ratio in HD and ALS were calculated. Twenty-six HD and 31 ALS patients were included. Twenty-six matched controls for HD and 20 for ALS were also evaluated. The APB amplitude was significantly lower in ALS compared to HD (6.89 ± 2.0 mv vs. 2.13 ± 1.27 mv, p = 0.01). UM ratio ALS. UM ratio had a poor specificity for ALS (18.9%) and SHI for HD (34%). UM ratio is more sensitive and specific for HD and SHI for ALS patients.

  5. Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS).

    Science.gov (United States)

    Kuczmarski, Thomas; Stommel, Elijah W; Riley, Kristen; Tandan, Rup; Chaudhry, Vinay; Clawson, Lora; Caller, Tracie A; Henegan, Patricia L; Facciponte, Dominic N; Bradley, Walter G; Andrew, Angeline S

    2017-08-01

    A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of 'antineoplastic agents' and 'immunosuppressants'. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case-control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients. A history of chemotherapy treatment was significantly associated with a decreased ALS risk (OR 0.46, 95% CI 0.22-0.89, P = 0.026). We did not observe an association between risk of ALS and immunosuppressant therapy use (OR 0.78, 95% CI 0.50-1.02, P = 0.23). Analyses were adjusted for age, gender, and smoking. Our results support the prior report for chemotherapy treatment and lead to further discussion of the underlying mechanism.

  6. Early-onset alopecia and amyotrophic lateral sclerosis: a cohort study.

    Science.gov (United States)

    Fondell, Elinor; Fitzgerald, Kathryn C; Falcone, Guido J; O'Reilly, Eilis J; Ascherio, Alberto

    2013-10-01

    A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46-81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992-2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation.

  7. The Folding process of Human Profilin-1, a novel protein associated with familial amyotrophic lateral sclerosis.

    Science.gov (United States)

    Del Poggetto, Edoardo; Chiti, Fabrizio; Bemporad, Francesco

    2015-07-31

    Human profilin-1 is a novel protein associated with a recently discovered form of familial amyotrophic lateral sclerosis. This urges the characterization of possible conformational states, different from the fully folded state, potentially able to initiate self-assembly. Under native conditions, profilin-1 is monomeric and possesses a well-defined secondary and tertiary structure. When incubated at low pH or with high urea concentrations, profilin-1 remains monomeric but populates unfolded states exhibiting larger hydrodynamic radius and disordered structure, as assessed by dynamic light scattering, far-UV circular dichroism and intrinsic fluorescence. Refolding from the urea-unfolded state was studied at equilibrium and in real-time using a stopped-flow apparatus. The results obtained with intrinsic fluorescence and circular dichroism indicate a single phase without significant changes of the corresponding signals before the major refolding transition. However, such a transition is preceded by a burst phase with an observed increase of ANS fluorescence, which indicates the conversion into a transiently populated collapsed state possessing solvent-exposed hydrophobic clusters. Kinetic analysis reveals that such state has a conformational stability comparable to that of the fully unfolded state. To our knowledge, profilin-1 is the first example of an amyloid-related protein where folding occurs in the absence of thermodynamically stable partially folded states.

  8. Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel.

    Science.gov (United States)

    Weil, Clara; Zach, Neta; Rishoni, Shay; Shalev, Varda; Chodick, Gabriel

    2016-01-01

    Globally, the annual incidence and prevalence of amyotrophic lateral sclerosis (ALS) are estimated at 1.9 and 4.5 per 100,000 population, respectively. This study is aimed at describing the epidemiology of ALS in Israel in a real-world setting. A retrospective study was performed using the databases of Maccabi Healthcare Services (MHS), a 2-million-member health maintenance organization in Israel. The study included all MHS adults diagnosed with ALS between 1997 and 2013. In 2013, characteristics of ALS patients were compared to those of age-sex-matched patients without ALS. Survival after ALS diagnosis was assessed until death and until tracheostomy or death (follow-up through 2014). In 2013 (n = 158), the prevalence of ALS was 8.1 per 100,000 population in MHS. In 1997-2013, a total of 375 ALS patients were diagnosed, corresponding to an average annual incidence of 1.8 per 100,000 population in MHS. The median survival from diagnosis to death was 3.5 years (95% CI 2.9-4.1), with approximately 28% surviving at least 10 years. Median tracheostomy-free survival was 2.5 years (95% CI 2.1-2.9). Results suggest that there is a relatively high prevalence of ALS in Israel. Further research is needed to investigate factors that may contribute to the survival of patients with ALS in Israel. © 2016 S. Karger AG, Basel.

  9. Predicting Early Bulbar Decline in Amyotrophic Lateral Sclerosis: A Speech Subsystem Approach

    Science.gov (United States)

    2015-01-01

    Purpose. To develop a predictive model of speech loss in persons with amyotrophic lateral sclerosis (ALS) based on measures of respiratory, phonatory, articulatory, and resonatory functions that were selected using a data-mining approach. Method. Physiologic speech subsystem (respiratory, phonatory, articulatory, and resonatory) functions were evaluated longitudinally in 66 individuals with ALS using multiple instrumentation approaches including acoustic, aerodynamic, nasometeric, and kinematic. The instrumental measures of the subsystem functions were subjected to a principal component analysis and linear mixed effects models to derive a set of comprehensive predictors of bulbar dysfunction. These subsystem predictors were subjected to a Kaplan-Meier analysis to estimate the time until speech loss. Results. For a majority of participants, speech subsystem decline was detectible prior to declines in speech intelligibility and speaking rate. Among all subsystems, the articulatory and phonatory predictors were most responsive to early bulbar deterioration; and the resonatory and respiratory predictors were as responsive to bulbar decline as was speaking rate. Conclusions. The articulatory and phonatory predictors are sensitive indicators of early bulbar decline due to ALS, which has implications for predicting disease onset and progression and clinical management of ALS. PMID:26136624

  10. Coping with amyotrophic lateral sclerosis; from diagnosis and during disease progression.

    Science.gov (United States)

    Jakobsson Larsson, Birgitta; Nordin, Karin; Nygren, Ingela

    2016-02-15

    To evaluate coping strategies among patients with Amyotrophic lateral sclerosis starting with diagnosis and during the disease progression, as well as investigate changes and correlations between coping strategies, emotional well-being and physical function. A total of 36 patients participated in the study. The patients filled out the Hospital Anxiety and Depression Scale and the Motor Neuron Disease Coping Scale. Physical function was measured using the revised ALS functional rating scale. Data were collected regularly from diagnosis and over a two years period. As a way to cope with the disease patients relied on both problem focused and emotional focused strategies. The use of coping strategies remained stable. Both physical disabilities and emotional well-being was related to some coping strategies, with some variation during the disease progression. Moreover, some coping strategies were related to symptoms of anxiety and depression. Irrespective of whether the coping strategies affect the emotional well-being or vice versa, the results show the importance of early and continuous evaluation of coping and emotional well-being to ease the emotional distress and provide support to the patient so that he/she can cope with the disease during the disease progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; Scionti, Domenico; Diomede, Francesca; Grassi, Gianpaolo; Pollastro, Federica; Piattelli, Adriano; Cocco, Lucio; Bramanti, Placido; Mazzon, Emanuela; Trubiani, Oriana

    2017-04-01

    Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), etc., at in vitro level. Cannabidiol, a non-psychotrophic cannabinoid, has been demonstrated as a potent anti-inflammatory and neuroprotective agent in neurological preclinical models. In the present study, we investigated the modulatory role of cannabidiol on genes associated with ALS using human gingiva-derived mesenchymal stromal cells (hGMSCs) as an in vitro model system. Next generation transcriptomic sequencing analysis demonstrated considerable modifications in the expression of genes connected with ALS pathology, oxidative stress, mitochondrial dysfunction, and excitotoxicity in hGMSCs treated with cannabidiol. Our results suggest the efficacy of cannabidiol to delineate the unknown molecular pathways, which may underlie ALS pathology at an early stage using hGMSCs as a compelling in vitro system. J. Cell. Biochem. 118: 819-828, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  12. Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases

    Directory of Open Access Journals (Sweden)

    Asako Otomo

    2012-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a heterogeneous group of incurable motor neuron diseases (MNDs characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative genes for ALS/MNDs have been identified and their underlying pathogenesis, including oxidative stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction, neural inflammation, protein misfolding and accumulation, dysfunctional intracellular trafficking, abnormal RNA processing, and noncell-autonomous damage, has begun to emerge. It is currently believed that a complex interplay of multiple toxicity pathways is implicated in disease onset and progression. Among such mechanisms, ones that are associated with disturbances of protein homeostasis, the ubiquitin-proteasome system and autophagy, have recently been highlighted. Although it remains to be determined whether disease-associated protein aggregates have a toxic or protective role in the pathogenesis, the formation of them results from the imbalance between generation and degradation of misfolded proteins within neuronal cells. In this paper, we focus on the autophagy-lysosomal and endocytic degradation systems and implication of their dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway could be a major target for the development of therapeutic agents for ALS/MNDs.

  13. Molecular Mechanisms in Amyotrophic Lateral Sclerosis: The Role of Angiogenin, a Secreted RNase

    Directory of Open Access Journals (Sweden)

    Isabela M. Aparicio-Erriu

    2012-11-01

    Full Text Available Amyotrophic lateral sclerosis is a fatal neurodegenerative disease caused by the loss of motoneurons. The precise molecular and cellular basis for neuronal death is not yet well established, but the contemporary view is that it is a culmination of multiple aberrant biological processes. Among the proposed mechanisms of motoneuron degeneration, alterations in the homeostasis of RNA binding proteins (RBP and the consequent changes in RNA metabolism have received attention recently.The ribonuclease, angiogenin was one of the first RBPs associated with familial and sporadic ALS. It is enriched in motoneurons under physiological conditions, and is required for motoneuron survival under stress conditions. Furthermore, delivery of angiogenin protects cultured motoneurons against stress-induced injury, and significantly increases the survival of motoneurons in SODG93A mice. In this overview on the role of angiogenin in RNA metabolism and in the control of motoneuron survival, we discuss potential pathogenic mechanisms of angiogenin dysfunction relevant to ALS and other neurodegenerative disorders. We also discuss recent evidence demonstrating that angiogenin secreted from stressed motoneurons may alter RNA metabolism in astrocytes.

  14. EMG-force relation in the first dorsal interosseous muscle of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jahanmiri-Nezhad, Faezeh; Hu, Xiaogang; Suresh, Nina L; Rymer, William Z; Zhou, Ping

    2014-01-01

    The relationship between surface electromyography (EMG) and muscle force is essential to assess muscle function and its deficits. However, few studies have explored the EMG-force relation in patients with amyotrophic lateral sclerosis (ALS). The purpose of this study was to examine the EMG-force relation in ALS subjects and its alteration in comparison with healthy control subjects. Surface EMG and force signals were recorded while 10 ALS and 10 age-matched healthy control subjects produced isometric voluntary contractions in the first dorsal interosseous (FDI) muscle over the full range of activation. A linear fit of the EMG-force relation was evaluated through the normalized root mean square error (RMSE) between the experimental and predicted EMG amplitudes. The EMG-force relation was compared between the ALS and the healthy control subjects. With a linear fit, the normalized RMSE between the experimental and predicted EMG amplitudes was 9.6 ± 3.6% for the healthy control subjects and 12.3 ± 8.0% for the ALS subjects. The slope of the linear fit was 2.9 ± 2.2 μVN-1 for the ALS subjects and was significantly shallower (p 0.05). A linear fit can be used to well describe the EMG-force relation for the FDI muscle of both ALS and healthy control subjects. A variety of processes may work together in ALS that can adversely affect the EMG-force relation.

  15. Retinoids and motor neuron disease: Potential role in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Riancho, Javier; Berciano, Maria T; Ruiz-Soto, Maria; Berciano, Jose; Landreth, Gary; Lafarga, Miguel

    2016-01-15

    Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MN). This fatal disease is characterized by progressive muscular atrophy and unfortunately it does not have an effective treatment. Although a small proportion of ALS cases have a familiar origin, the vast majority of them are thought to have a sporadic origin. Although the pathogenesis of ALS has not been fully elucidated, various disorders in different cellular functions such as gene expression, protein metabolism, axonal transport and glial cell disorders have been linked to MN degeneration. Among them, proteostasis is one of the best studied. Retinoids are vitamin A-derived substances that play a crucial role in embryogenesis, development, programmed cell death and other cellular functions. Retinoid agonists behave as transcription factors throughout the activation of the nuclear retinoid receptors. Several reports in the literature suggest that retinoids are involved in proteostasis regulation, by modulating its two major pathways, the ubiquitin-proteasome system and the autophagy-lysosome response. Additionally, there are some evidences for a role of retinoids themselves, in ALS pathogenesis. In this review, we discuss the importance of proteostasis disruption as a trigger for MN degeneration and the capability of retinoids to modulate it, as well as the potential therapeutic role of retinoids as a new therapy in ALS. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Is exposure to cyanobacteria an environmental risk factor for amyotrophic lateral sclerosis and other neurodegenerative diseases?

    Science.gov (United States)

    Bradley, Walter G.; Borenstein, Amy R.; Nelson, Lorene M.; Codd, Geoffrey A.; Rosen, Barry H.; Stommel, Elijah W.; Cox, Paul Alan

    2013-01-01

    There is a broad scientific consensus that amyotrophic lateral sclerosis (ALS) is caused by gene-environment interactions. Mutations in genes underlying familial ALS (fALS) have been discovered in only 5–10% of the total population of ALS patients. Relatively little attention has been paid to environmental and lifestyle factors that may trigger the cascade of motor neuron death leading to the syndrome of ALS, although exposure to chemicals including lead and pesticides, and to agricultural environments, smoking, certain sports, and trauma have all been identified with an increased risk of ALS. There is a need for research to quantify the relative roles of each of the identified risk factors for ALS. Recent evidence has strengthened the theory that chronic environmental exposure to the neurotoxic amino acid β-N-methylamino-L-alanine (BMAA) produced by cyanobacteria may be an environmental risk factor for ALS. Here we describe methods that may be used to assess exposure to cyanobacteria, and hence potentially to BMAA, namely an epidemiologic questionnaire and direct and indirect methods for estimating the cyanobacterial load in ecosystems. Rigorous epidemiologic studies could determine the risks associated with exposure to cyanobacteria, and if combined with genetic analysis of ALS cases and controls could reveal etiologically important gene-environment interactions in genetically vulnerable individuals.

  17. The role of D-amino acids in amyotrophic lateral sclerosis pathogenesis: a review.

    Science.gov (United States)

    Paul, Praveen; de Belleroche, Jacqueline

    2012-11-01

    A potential role for D-amino acids in motor neuron disease/amyotrophic lateral sclerosis (ALS) is emerging. D-Serine, which is an activator/co-agonist at the N-methyl-D-aspartate glutamate receptor subtype, is elevated both in spinal cord from sporadic cases of ALS and in an animal model of ALS. Furthermore, we have shown that a mutation in D-amino acid oxidase (DAO), an enzyme strongly localized to spinal cord motor neurons and brain stem motor nuclei, is associated with familial ALS. DAO plays an important role in regulating levels of D-serine, and its function is impaired by the presence of this mutation and this may contribute to the pathogenic process in ALS. In sporadic ALS cases, elevated D-serine may arise from induction of serine racemase, its synthetic enzyme, caused by cell stress and inflammatory processes thought to contribute to disease progression. Both these abnormalities in D-serine metabolism lead to an increase in synaptic D-serine which may contribute to disease pathogenesis.

  18. Covert visuospatial attention orienting in a brain-computer interface for amyotrophic lateral sclerosis patients.

    Science.gov (United States)

    Marchetti, Mauro; Piccione, Francesco; Silvoni, Stefano; Gamberini, Luciano; Priftis, Konstantinos

    2013-06-01

    Brain-computer interfaces (BCIs) allow people to control devices by translating brain signals into commands. BCIs represent a concrete solution with regard to communication and motor control disabilities of patients with amyotrophic lateral sclerosis (ALS). Most of the BCIs rely on visual interfaces in which patients must move their eyes to achieve efficient BCI control. This fact represents a limitation of BCI use in ALS patients who are in the final stages of the disease. We aimed to improve visual interfaces for ALS patients to control the movement of a cursor on a monitor by orienting their covert visuospatial attention (i.e., orienting without eye movements). A total of 10 ALS patients with different levels of impairment used 2 new visual interfaces in an event-related potential (ERP)-based BCI. In the first interface, they were required to use exogenous visuospatial attention orienting (VAO), whereas in the second interface, they were required to use endogenous VAO. . ALS patients were able to use the 2 interfaces for controlling the ERP-based BCI system in real time. Nevertheless, better target classification and information transfer rate were associated with the interface that was based on endogenous VAO. ALS patients can exploit their covert VAO to control a BCI that does not require eye movements. The implementation of endogenous VAO in the design of covert visuospatial attention-based interfaces seems to be suitable for designing more ergonomic and efficient BCIs for ALS patients with impaired eye movements.

  19. The Balloon-Based Manometry Evaluation of Swallowing in Patients with Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Jerzy Tomik

    2017-03-01

    Full Text Available The aim of the study was to analyse the disturbances of the oro-pharyngeal swallowing phase of dysphagia in amyotrophic lateral sclerosis (ALS patients with the use of specific manometric measurements and to evaluate their plausible association with the duration of the disease. Seventeen patients with ALS were evaluated with manometric examinations of the oral and pharyngeal part of the gastrointestinal tract. Tests were carried out by using the oesophageal balloon-based method with four balloon transducers located 5 cm away from each other. The following manometric parameters were analysed: the base of tongue contraction (BTC and the upper oesophageal sphincter pressure (UESP, and the hypopharyngeal suction pump (HSP as well as the oro-pharyngeal, pharyngeal and hypopharyngeal transit time and average pharyngeal bolus velocity (oropharyngeal transit time (OTT, pharyngeal transit time (PTT, hypopharyngeal transit time (HTT and average pharyngeal bolus velocity (APBV, respectively. Manomatric examinations during swallowing in patients with ALS showed significant weakness of BTC, a decrease of HSP and a decrease of the velocity of bolus transit inside the pharynx which were particularly marked between the first and the third examination. Manometric examinations of the oro-pharyngeal part of the gastrointestinal tract are useful and supportive methods in the analysis of swallowing disturbances in ALS patients.

  20. Characterization of intercostal muscle pathology in canine degenerative myelopathy: a disease model for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Morgan, Brandie R; Coates, Joan R; Johnson, Gayle C; Bujnak, Alyssa C; Katz, Martin L

    2013-12-01

    Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset neuromuscular disorder called degenerative myelopathy (DM) that has many similarities to amyotrophic lateral sclerosis (ALS). Both disorders are characterized by widespread progressive declines in motor functions, accompanied by atrophic changes in the descending spinal cord tracts. Some forms of ALS are also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a result of respiratory failure from severe functional impairment of respiratory muscles. The mechanisms that lead to this loss of function are not known. Dogs with DM are euthanized at all stages of disease progression, providing an opportunity to characterize the onset and progression of any pathological changes in the respiratory muscles that may precede respiratory failure. To characterize such potential disease-related pathology, we evaluated intercostal muscles from Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM disease progression. DM was found to result in intercostal muscle atrophy, fibrosis, increased variability in muscle fiber size and shape, and alteration in muscle fiber type composition. This pathology was not accompanied by retraction of the motor neuron terminals from the muscle acetylcholine receptor complexes, suggesting that the muscle atrophy did not result from physical denervation. These findings provide a better understanding of the mechanisms that likely lead to respiratory failure in at least some forms of ALS and will be useful in the development and evaluation of potential therapeutic interventions using the DM model. Copyright © 2013 Wiley Periodicals, Inc.

  1. Evidence-based evaluation of therapeutic measures for amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    JIA Hua

    2012-06-01

    Full Text Available Objective To evaluate the therapeutic efficacy and side effects of various treatments for amyotrophic lateral sclerosis (ALS in order to formulate the best therapeutic regimen. Methods ALS, Riluzole, Gabapentin, Lamotrigine, neurotrophic factor, antioxidant and free radical scavenger gene therapy, neural stem cell treatment, treatment were appointed as retrieval words. MEDLINE, Cochrane Library, Wanfang Database for Scientific Journals in China and Chinese National Knowledge Infrastructure (CNKI for Scientific Journals Database were used for retrieval. Related clinical guidelines, systematic reviews, randomised controlled trials, controlled clinical trials and case-observation studies were collected following the corresponding inclusion criteria and exclusion criteria and evaluated by Jadad Scale to judge the authenticity and reliability of the conclusion. Manual searching was also used. Results After screening, 39 related articals were selected as follow: 4 systematic reviews, 18 randomised controlled trials, 11 controlled clinical trials, and 6 case-observation studies. Twenty-seven articals were of high quality (according to Jadad Scale, 11 with score 4, 13 with score 5, and 3 with score 7, while 12 were of low quality with score 3. According to the evaluation of therapeutic efficacy and side effects of various therapies, it is suggested that: 1 The Riluzole is the only drug approved by American FDA, lacking of more effective treatments. 2 When the patients' condition is not relieved, medicine-combined therapies and symptomatic treatments should be used. Conclusion Evidence-based medicine can provide best clinical evidence on ALS treatment.

  2. Functional contribution of the transcription factor ATF4 to the pathogenesis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Matus, Soledad; Lopez, Estefanía; Valenzuela, Vicente; Nassif, Melissa; Hetz, Claudio

    2013-01-01

    Endoplasmic reticulum (ER) stress represents an early pathological event in amyotrophic lateral sclerosis (ALS). ATF4 is a key ER stress transcription factor that plays a role in both adaptation to stress and the activation of apoptosis. Here we investigated the contribution of ATF4 to ALS. ATF4 deficiency reduced the rate of birth of SOD1(G86R) transgenic mice. The fraction of ATF4(-/-)-SOD1(G85R) transgenic mice that were born are more resistant to develop ALS, leading to delayed disease onset and prolonged life span. ATF4 deficiency completely attenuated the induction of pro-apoptotic genes, including BIM and CHOP, and also led to quantitative changes in the ER protein homeostasis network. Unexpectedly, ATF4 deficiency enhanced mutant SOD1 aggregation at the end stage of the disease. Studies in the motoneuron cell line NSC34 demonstrated that knocking down ATF4 enhances mutant SOD1 aggregation possibly due to alteration in the redox status of the cell. Our results support a functional role of ATF4 in ALS, offering a novel target for disease intervention.

  3. Association between estimated total daily energy expenditure and stage of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Lee, Jihye; Baek, Heejoon; Kim, Seung Hyun; Park, Yongsoon

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and nutritional status is one of the major prognostic factors of ALS. The aim of this study was to investigate the relationship between total daily energy expenditure (TDEE) and progression of disease in ALS patients, as well as sex differences in TDEE. Patients with ALS (N = 370) were diagnosed according to El Escorial criteria and categorized into stage 2, 3, or 4 using a clinical staging system. TDEEs were calculated by summing resting energy expenditure (REE) and physical activity. REE was calculated using equations of Harris-Benedict or Mifflin St. Jeor, and physical activity was calculated using the ALS Functional Rating Scale-Revised, a physical activity coefficient, or adding 30% of REE. TDEE significantly decreased with progression of ALS stage and did not vary by sex. Actual energy intake was lower than TDEE in patients in all stages and lowest in patients with stage 3 ALS. Comparing TDEEs 1 to 5, TDEE 2 decreased with progression of ALS stage and was similar to the average TDEE. The present study suggests that TDEE decreases with progression of ALS, and patients consume insufficient energy compared with required intake at all stages, particularly at stage 3, suggesting that nutrition support should be started at least before stage 3. Additionally, among the five equations for TDEE, TDEE 2 could be the best for evaluating the nutritional status of patients with ALS. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Aggregation of FET Proteins as a Pathological Change in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Furukawa, Yoshiaki; Tokuda, Eiichi

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease that is characterized by the formation of abnormal inclusions in neurons. While the pathomechanism of ALS remains obscure, a number of proteins have been identified in the inclusion bodies, and the pathological roles of RNA-binding proteins have been increasingly emphasized. Among those, the FET proteins (FUS, EWSR1, TAF15) were recently identified as RNA-binding proteins in pathological inclusions of ALS and other neurodegenerative diseases; moreover, mutations in the genes encoding the FET proteins were found to be associated with familial forms of ALS. FET proteins are normally localized in the nucleus, but the introduction of pathogenic mutations in FET proteins leads to their abnormal redistribution to the cytoplasm, where they form aggregates. While further investigation will be required to understand the intracellular factors controlling the aggregation propensities of FET proteins, they are thought to lose their physiological functions and become toxic through their misfolding/aggregation. Here, we will briefly review recent advances of our understanding of the physiological functions and aggregation behavior of FET proteins in vivo as well as in vitro.

  5. Protein Quality Control and the Amyotrophic Lateral Sclerosis/Frontotemporal Dementia Continuum

    Science.gov (United States)

    Shahheydari, Hamideh; Ragagnin, Audrey; Walker, Adam K.; Toth, Reka P.; Vidal, Marta; Jagaraj, Cyril J.; Perri, Emma R.; Konopka, Anna; Sultana, Jessica M.; Atkin, Julie D.

    2017-01-01

    Protein homeostasis, or proteostasis, has an important regulatory role in cellular function. Protein quality control mechanisms, including protein folding and protein degradation processes, have a crucial function in post-mitotic neurons. Cellular protein quality control relies on multiple strategies, including molecular chaperones, autophagy, the ubiquitin proteasome system, endoplasmic reticulum (ER)-associated degradation (ERAD) and the formation of stress granules (SGs), to regulate proteostasis. Neurodegenerative diseases are characterized by the presence of misfolded protein aggregates, implying that protein quality control mechanisms are dysfunctional in these conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that are now recognized to overlap clinically and pathologically, forming a continuous disease spectrum. In this review article, we detail the evidence for dysregulation of protein quality control mechanisms across the whole ALS-FTD continuum, by discussing the major proteins implicated in ALS and/or FTD. We also discuss possible ways in which protein quality mechanisms could be targeted therapeutically in these disorders and highlight promising protein quality control-based therapeutics for clinical trials. PMID:28539871

  6. Modafinil to treat fatigue in amyotrophic lateral sclerosis: an open label pilot study.

    Science.gov (United States)

    Carter, Gregory T; Weiss, Michael D; Lou, Jau-Shin; Jensen, Mark P; Abresch, R Ted; Martin, Tara K; Hecht, Thomas W; Han, Jay J; Weydt, Patrick; Kraft, George H

    2005-01-01

    An open label trial of modafinil was conducted to determine whether it would be tolerated and effective in treating fatigue for people with amyotrophic lateral sclerosis (ALS). Fifteen patients with ALS were treated for two weeks with either 200 mg or 400 mg of modafinil. Reported side effects of the medication were mild and included diarrhea, headache, nervousness, and insomnia. Side effects did not result in any study dropouts. Following treatment, mean scores on the Fatigue Severity Scale (FSS) decreased from 51.3 (SD 9.2) to 42.8 (SD 10.2). On the Epworth Sleepiness Scale (ESS), mean scores decreased from 8.2 (SD 2.0) to 4.5 (SD 2.4). Reductions in both the FSS and the ESS were significant at p < 0.001. Mean scores on the self-report version of the Functional Independence Measure (FIM-SR) increased from 115.2 (SD 5.6) to 118.1 (SD 5.4), with p < 0.01. This pilot study suggests that modafinil is well-tolerated and may reduce symptoms of fatigue in ALS. Further blinded, controlled studies of modafinil in larger numbers of ALS patients are warranted.

  7. Symmetric temporal abnormalities on MR imaging in amyotrophic lateral sclerosis with dementia.

    Science.gov (United States)

    Mori, H; Yagishita, A; Takeda, T; Mizutani, T

    2007-09-01

    Our aim was to clarify imaging findings of amyotrophic lateral sclerosis with dementia (ALSD). T2-weighted MR images (T2WI) of 3 patients with ALSD (2 men, 1 woman; 58-71 years of age) and 21 patients with ALS without dementia (12 men, 9 women; 46-74 years of age) were examined for frontotemporal lobar atrophy and signal-intensity alterations in the white matter of the anterior temporal lobes, corticospinal tracts (CST), and precentral gyri and in precentral cortices. The brain of one of the patients with ALSD was examined at autopsy. All patients with ALSD showed bilateral frontotemporal atrophy mostly with temporal lobe dominance. In the ALSD group, T2WI demonstrated hyperintensity in the subcortical white matter on the medial side of the anterior temporal lobes, whereas in the group without dementia, none showed this imaging finding. MR images demonstrated no abnormal signal-intensity changes in CST in the internal capsule or the brain stem in the ALSD group. In the group without dementia, 6 patients (28.6%) showed this imaging finding. In neuropathologic examinations of the brain of 1 patient with ALSD, myelin-stained sections of the brain demonstrated loss of myelin in the subcortical white matter on the medial side of the anterior temporal white matter. A symmetric pattern of frontotemporal atrophy and anteromedial subcortical hyperintensities in the temporal lobes on T2WI could be characteristic of ALSD.

  8. The use of integrative therapies in patients with amyotrophic lateral sclerosis in shanghai, china.

    Science.gov (United States)

    Pan, Weidong; Chen, Xiangjun; Bao, Jie; Bai, Yu; Lu, Hua; Wang, Qiudong; Liu, Yi; Yuan, Canxing; Li, Wenwei; Liu, Zhenguo; Liu, Jun; Zhu, Xuying; Qin, Baofeng; Cai, Dingfang; Zhou, Hua

    2013-01-01

    Objective. To investigate the current use of integrative therapies (IT) in the treatment of patients with amyotrophic lateral sclerosis (ALS). Methods. A cross-sectional, multicenter clinical epidemiological survey was conducted in 12 hospitals in Shanghai. We investigated the type and frequency of IT use and determined whether the use of IT correlated with demographic, social, or disease-specific characteristics in our patient population. Results. A total of 231 (89.5%) of 258 patients with ALS were eligible for the study and 229 (99% of all) of 231 reported the use of at least one IT for the treatment of ALS. Vitamins and Chinese herb decoctions, Chinese herb compounds, massage therapy, and acupuncture were the 5 most commonly used therapies. There was a strong association between education level, income, and use of IT. A household income of more than 75,000 RMB ($49,995) correlated with multiple IT use, and married patients used IT more often than single individuals. The main reasons for using IT were to treat weakness and fatigue, muscle atrophy, the development of ALS, depression, insomnia, limb pain or numbness, and side effects associated with Riluzole. Conclusion. The use of IT is common in patients with ALS in Shanghai. Vitamins and TCM are the most used additional therapies and the widespread and largely unexamined use of IT for ALS requires more attention.

  9. Survey of current enteral nutrition practices in treatment of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhang, May; Hubbard, Jane; Rudnicki, Stacy A; Johansen, Carolyn S; Dalton, Kate; Heiman-Patterson, Terry; Forshew, Dalles A; Wills, Anne-Marie

    2013-02-01

    Enteral nutrition (EN) is commonly prescribed for dysphagia and weight loss in amyotrophic lateral sclerosis (ALS), but there are currently no ALS-specific EN guidelines. We aimed to survey current practices prescribing EN to ALS patients. An online survey was distributed using list servers administered by the Academy of Nutrition and Dietetics (AND), Muscular Dystrophy Association (MDA), and ALS Association (ALSA). A total of 148 dietitians, nurses, and physicians participated in the survey, of whom 50% were dietitians and 68% were associated with an ALS clinic. Only 47% of respondents reported their patients to be fully compliant with EN recommendations. Side effects (fullness, diarrhea, constipation, and bloating) were the most important reason for patient noncompliance, followed by dependence on caregivers. By contrast, only 3% of providers rated depression/hopelessness as the most important reason for noncompliance. Half of those surveyed reported that more than 25% of patients continued to lose weight after starting EN. Our survey results show a high frequency of gastrointestinal side effects and weight loss in ALS patients receiving EN. These findings may be limited by sampling error and non-response bias. Prospective studies are needed to help establish EN guidelines for ALS.

  10. Anaesthesia for ophthalmologic surgical procedures in a patient with advanced amyotrophic lateral sclerosis: a case report.

    Science.gov (United States)

    Kowalik, Maciej M; Smiatacz, Tomasz; Pajuro, Robert; Skowroński, Roman; Trocha, Hanna; Nyka, Walenty; Raczyńska, Krystyna; Wujtewicz, Maria

    2008-11-20

    Anaesthesia procedures for surgical interventions in patients with amyotrophic lateral sclerosis (ALS) are not commonly found in clinical practice, and often have special considerations that must be taken into account in treatment planning. As a result, these procedures are rarely subject to publication, rendering it difficult for the anaesthesiologists to find useful and reliable information on this topic. ALS also presents a contraindication to the use of nondepolarising neuromuscular blocking drugs during general anaesthesia. In the case presented here, a 52-year old, White man, the progression of the disease to tetraparesis and respiratory failure, in addition to having the patient on chronic mechanical ventilation support, provided additional challenges to the handling team. The maturation of cataracts severely impaired communication with the patient, and surgical treatment of the cataract presented the only means to save communication. Such interventions are generally performed under local anaesthesia with the advice of the attending anaesthesiologist. However, in this case the patients' announcements during the operation would be unreadable to the advising anaesthesiologist. Here, the authors share experiences from a successfully applied combination of topical and general anaesthesia for two cataract operations and a vitrectomy. This was tolerated well by the patient, and without any side-effects. The applied treatment resulted in a substantial improvement of the vision and allowed communication to be maintained with the patient.

  11. Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Miyazaki, Kazunori; Ohta, Yasuyuki; Nagai, Makiko; Morimoto, Nobutoshi; Kurata, Tomoko; Takehisa, Yasushi; Ikeda, Yoshio; Matsuura, Tohru; Abe, Koji

    2011-05-01

    Recent reports suggest that functional or structural defect of vascular components are implicated in amyotrophic lateral sclerosis (ALS) pathology. In the present study, we examined a possible change of the neurovascular unit consisting of endothelium (PCAM-1), tight junction (occludin), and basement membrane (collagen IV) in relation to a possible activation of MMP-9 in ALS patients and ALS model mice. We found that the damage in the neurovascular unit was more prominent in the outer side and preferentially in the anterior horn of ALS model mice. This damage occurred prior to motor neuron degeneration and was accompanied by MMP-9 up-regulation. We also found the dissociation between the PCAM-1-positive endothelium and GFAP-positive astrocyte foot processes in both humans and the animal model of ALS. The present results indicate that perivascular damage precedes the sequential changes of the disease, which are held in common between humans and the animal model of ALS, suggesting that the neurovascular unit is a potential target for therapeutic intervention in ALS. Copyright © 2011 Wiley-Liss, Inc.

  12. Dexpramipexole, the R(+) enantiomer of pramipexole, for the potential treatment of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Cheah, Benjamin C; Kiernan, Matthew C

    2010-12-01

    Dexpramipexole (KNS-760704), the R(+) enantiomer of pramipexole, is under development by Knopp Neurosciences and Biogen Idec as a potential neuroprotective therapy for amyotrophic lateral sclerosis (ALS), a universally fatal neurodegenerative disease. Pramipexole, exclusively the S(-) enantiomer, is a non-ergot dopaminergic autoreceptor agonist that is currently marketed for use in the treatment of Parkinson's disease and restless legs syndrome. Pramipexole has been proposed to exert a broad spectrum of neuroprotective properties, primarily through antioxidant effects, inhibiting apoptotic enzymes and preserving mitochondrial structure and activity. More recent work has suggested that pramipexole possesses anti-excitotoxic properties, raising the possibility of beneficial effects in patients with ALS. However, pramipexole has high intrinsic dopaminergic receptor activity and, consequently, dose-limiting side effects, including orthostatic hypotension and hallucination, are frequent. Dexpramipexole exhibits significantly lower affinity for dopaminergic receptors, thereby making it unlikely to be associated with dopaminergic side effects. In clinical trials to date, dexpramipexole has been safe and well tolerated at doses up to 67-fold higher than the maximum recommended daily dose of pramipexole in patients with Parkinson's disease, and has demonstrated signs of neuroprotective benefit. This report summarizes the chemical and pharmacological properties of dexpramipexole and describes the potential utility of the drug in the pharmaceutical development pipeline.

  13. ALSoD: A user-friendly online bioinformatics tool for amyotrophic lateral sclerosis genetics.

    Science.gov (United States)

    Abel, Olubunmi; Powell, John F; Andersen, Peter M; Al-Chalabi, Ammar

    2012-09-01

    Amyotrophic lateral sclerosis (ALS) is the commonest adult onset motor neuron disease, with a peak age of onset in the seventh decade. With advances in genetic technology, there is an enormous increase in the volume of genetic data produced, and a corresponding need for storage, analysis, and interpretation, particularly as our understanding of the relationships between genotype and phenotype mature. Here, we present a system to enable this in the form of the ALS Online Database (ALSoD at http://alsod.iop.kcl.ac.uk), a freely available database that has been transformed from a single gene storage facility recording mutations in the SOD1 gene to a multigene ALS bioinformatics repository and analytical instrument combining genotype, phenotype, and geographical information with associated analysis tools. These include a comparison tool to evaluate genes side by side or jointly with user configurable features, a pathogenicity prediction tool using a combination of computational approaches to distinguish variants with nonfunctional characteristics from disease-associated mutations with more dangerous consequences, and a credibility tool to enable ALS researchers to objectively assess the evidence for gene causation in ALS. Furthermore, integration of external tools, systems for feedback, annotation by users, and two-way links to collaborators hosting complementary databases further enhance the functionality of ALSoD. © 2012 Wiley Periodicals, Inc.

  14. Differential histone deacetylase mRNA expression patterns in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Janssen, Claas; Schmalbach, Sonja; Boeselt, Sebastian; Sarlette, Alexander; Dengler, Reinhard; Petri, Susanne

    2010-06-01

    Histone deacetylases (HDACs) are important regulators of gene expression and cell differentiation. The HDAC inhibitors have recently been considered as potential novel neuroprotective drugs for the treatment of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). A major limitation, however, lies in the broad spectrum of action of currently available HDAC inhibitors that may cause a variety of toxic side effects. The mRNA expression levels of the HDAC isoforms HDACs 1 to 11 have previously been characterized in rat brain but have not been studied in human tissue. Using in situ hybridization histochemistry and immunohistochemistry we assessed the distribution and expression levels of HDACs 1to 11 in postmortem ALS and control brain and spinal cord specimens (n = 6 cases each) to determine alterations in the mRNA expression pattern that could provide a basis for disease-specific therapies. We found a reduction of HDAC 11 mRNA and increased HDAC 2 levels in ALS brain and spinal cord compared with controls. A more precise knowledge of the disease-related expression pattern could lead to the development of more specific pharmacotherapeutic approaches.

  15. The Use of Integrative Therapies in Patients with Amyotrophic Lateral Sclerosis in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Weidong Pan

    2013-01-01

    Full Text Available Objective. To investigate the current use of integrative therapies (IT in the treatment of patients with amyotrophic lateral sclerosis (ALS. Methods. A cross-sectional, multicenter clinical epidemiological survey was conducted in 12 hospitals in Shanghai. We investigated the type and frequency of IT use and determined whether the use of IT correlated with demographic, social, or disease-specific characteristics in our patient population. Results. A total of 231 (89.5% of 258 patients with ALS were eligible for the study and 229 (99% of all of 231 reported the use of at least one IT for the treatment of ALS. Vitamins and Chinese herb decoctions, Chinese herb compounds, massage therapy, and acupuncture were the 5 most commonly used therapies. There was a strong association between education level, income, and use of IT. A household income of more than 75,000 RMB ($49,995 correlated with multiple IT use, and married patients used IT more often than single individuals. The main reasons for using IT were to treat weakness and fatigue, muscle atrophy, the development of ALS, depression, insomnia, limb pain or numbness, and side effects associated with Riluzole. Conclusion. The use of IT is common in patients with ALS in Shanghai. Vitamins and TCM are the most used additional therapies and the widespread and largely unexamined use of IT for ALS requires more attention.

  16. Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation.

    Science.gov (United States)

    Faravelli, Irene; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Zanetta, Chiara; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

    2014-09-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by degeneration of upper and lower motor neurons. There are currently no clinically impactful treatments for this disorder. Death occurs 3-5 years after diagnosis, usually due to respiratory failure. ALS pathogenesis seems to involve several pathological mechanisms (i.e., oxidative stress, inflammation, and loss of the glial neurotrophic support, glutamate toxicity) with different contributions from environmental and genetic factors. This multifaceted combination highlights the concept that an effective therapeutic approach should counteract simultaneously different aspects: stem cell therapies are able to maintain or rescue motor neuron function and modulate toxicity in the central nervous system (CNS) at the same time, eventually representing the most comprehensive therapeutic approach for ALS. To achieve an effective cell-mediated therapy suitable for clinical applications, several issues must be addressed, including the identification of the most performing cell source, a feasible administration protocol, and the definition of therapeutic mechanisms. The method of cell delivery represents a major issue in developing cell-mediated approaches since the cells, to be effective, need to be spread across the CNS, targeting both lower and upper motor neurons. On the other hand, there is the need to define a strategy that could provide a whole distribution without being too invasive or burdened by side effects. Here, we review the recent advances regarding the therapeutic potential of stem cells for ALS with a focus on the minimally invasive strategies that could facilitate an extensive translation to their clinical application.

  17. Agraphia in Bulbar-Onset Amyotrophic Lateral Sclerosis: Not Merely a Consequence of Dementia or Aphasia

    Directory of Open Access Journals (Sweden)

    Hiroo Ichikawa

    2008-01-01

    Full Text Available The clinical significance and characteristics of writing errors in bulbar-onset amyotrophic lateral sclerosis (ALS are not clear. We retrospectively investigated writing samples in 19 patients with bulbar-onset ALS without preceding extra-motor symptoms. Co-development of dementia and/or aphasia was also explored and single photon emission computed tomography (SPECT images of the brain were reviewed. As a result, a high prevalence of writing errors (15 of the 19 patients was found. Of note were isolated writing errors with neither dementia nor aphasia verified in 2 patients whose dysarthria was mild enough to evaluate spoken language. The remaining 13 patients also showed agraphia, but either dysarthria was too severe to evaluate aphasia or frontotemporal dementia (FTD-like features co-existed. Of these patients, one who initially lacked dementia subsequently developed FTD-like features. The frequent writing errors were omission or substitution of kana letters and syntactic errors. SPECT images showed bilateral or left-side dominant hypoperfusion in the frontotemporal lobes as a consistent feature. These results show that patients with bulbar-onset ALS frequently exhibit agraphic writing errors and that these are not merely consequences of dementia or aphasia. However, these writing errors may indicate the involvement of frontotemporal language-related areas beyond the primary motor cortex.

  18. Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.

    Science.gov (United States)

    Meininger, Vincent; Bensimon, Gilbert; Bradley, Walter R; Brooks, Benjamin; Douillet, Patrice; Eisen, Andrew A; Lacomblez, Lucette; Leigh, P Nigel; Robberecht, Wim

    2004-06-01

    Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive and fatal motor neuron disease. We carried out two randomized, double-blind, placebo-controlled, multi-centre, multi-national studies with xaliproden (a drug with neurotrophic effect) to assess drug efficacy and safety at two doses. Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1 (n=867); or to the same regimen with addition of riluzole 50 mg bid background therapy in Study 2 (n=1210 patients). The two primary endpoints were defined as: 1. Time to death, tracheostomy, or permanent assisted ventilation (DTP), and 2. Time to vital capacity (VC)side effects were largely associated with the serotonergic properties of xaliproden. An effect of xaliproden on functional parameters, especially VC, was noted. Although this effect did not reach statistical significance, xaliproden had a small effect on clinically noteworthy aspects of disease progression in ALS.

  19. Agraphia in bulbar-onset amyotrophic lateral sclerosis: not merely a consequence of dementia or aphasia.

    Science.gov (United States)

    Ichikawa, Hiroo; Takahashi, Nobuyoshi; Hieda, Soutaro; Ohno, Hideki; Kawamura, Mitsuru

    2008-01-01

    The clinical significance and characteristics of writing errors in bulbar-onset amyotrophic lateral sclerosis (ALS) are not clear. We retrospectively investigated writing samples in 19 patients with bulbar-onset ALS without preceding extra-motor symptoms. Co-development of dementia and/or aphasia was also explored and single photon emission computed tomography (SPECT) images of the brain were reviewed. As a result, a high prevalence of writing errors (15 of the 19 patients) was found. Of note were isolated writing errors with neither dementia nor aphasia verified in 2 patients whose dysarthria was mild enough to evaluate spoken language. The remaining 13 patients also showed agraphia, but either dysarthria was too severe to evaluate aphasia or frontotemporal dementia (FTD)-like features co-existed. Of these patients, one who initially lacked dementia subsequently developed FTD-like features. The frequent writing errors were omission or substitution of kana letters and syntactic errors. SPECT images showed bilateral or left-side dominant hypoperfusion in the frontotemporal lobes as a consistent feature. These results show that patients with bulbar-onset ALS frequently exhibit agraphic writing errors and that these are not merely consequences of dementia or aphasia. However, these writing errors may indicate the involvement of frontotemporal language-related areas beyond the primary motor cortex.

  20. State of the art and the dark side of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Musarò, Antonio

    2010-05-26

    Amyotrophic lateral sclerosis (ALS) is a disorder that involves the degeneration of motor neurons, muscle atrophy, and paralysis. In a few familiar forms of ALS, mutations in the superoxide dismutase-1 (SOD1) gene have been held responsible for the degeneration of motor neurons. Nevertheless, after the discovery of the SOD1 mutations no consensus has emerged as to which cells, tissues and pathways are primarily implicated in the pathogenic events that lead to ALS. Ubiquitous overexpression of mutant SOD1 in transgenic animals recapitulates the pathological features of ALS. However, the toxicity of mutant SOD1 is not necessarily limited to the central nervous system. Views about ALS pathogenesis are now enriched by the recent discovery of mutations in a pair of DNA/RNA-binding proteins called TDP-43 and FUS/TLS as causes of familial and sporadic forms of ALS. Although the steps that lead to the pathological state are well defined, several fundamental issues are still controversial: are the motor neurons the first direct targets of ALS; and what is the contribution of non-neuronal cells, if any, to the pathogenesis of ALS? The state of the art of ALS pathogenesis and the open questions are discussed in this review.

  1. Recombinant human granulocyte-colony stimulating factor administration for treating amyotrophic lateral sclerosis: A pilot study.

    Science.gov (United States)

    Nefussy, Beatrice; Artamonov, Irena; Deutsch, Varda; Naparstek, Ela; Nagler, Arnon; Drory, Vivian E

    2010-01-01

    Granulocyte-colony stimulating factor (G-CSF) is used to mobilize CD34+ haematopoietic stem cells from the bone marrow to the peripheral blood. We proposed to use cell subsets induced by G-CSF to slow down disease progression in patients with amyotrophic lateral sclerosis (ALS). Patients with definite or probable ALS were assigned in a double-blind manner to receive G-CSF or placebo every three months for a year. The primary outcome measure was the functional decline, measured by the revised ALS Functional Rating Scale, Revised (ALSFRS-R) score. Secondary outcome measures included vital capacity, manual muscle strength, compound muscle action potential amplitudes, neurophysiological index, and McGill single item quality of life score (QoL). Thirty-nine patients were enrolled. Seventeen patients who received G-CSF and 18 who received placebo were evaluated. G-CSF was effective in mobilizing CD34+ to blood. The outcome measures used showed no statistically significant benefit, although there was a trend of slowing disease progression following two G-CSF treatments, as shown by lower slopes of ALSFRS-R and QoL in the first six treatment months. The treatment had no major side-effects. G-CSF administration in ALS patients caused successful mobilization of autologous bone marrow cells, but was not effective in slowing down disease deterioration.

  2. Spatial profiling of the corticospinal tract in amyotrophic lateral sclerosis using diffusion tensor imaging.

    Science.gov (United States)

    Wong, John C T; Concha, Luis; Beaulieu, Christian; Johnston, Wendy; Allen, Peter S; Kalra, Sanjay

    2007-07-01

    Diffusion tensor imaging (DTI) was used as a noninvasive method to evaluate the anatomy of the corticospinal tract (CST) and the pattern of its degeneration in amyotrophic lateral sclerosis (ALS). Fourteen patients with ALS and 15 healthy controls underwent DTI. Parameters reflecting coherence of diffusion (fractional anisotropy, FA), bulk diffusion (apparent diffusion coefficient, ADC), and directionality of diffusion (eigenvalues) parallel to (lambda( parallel)) or perpendicular to (lambda( perpendicular)) fiber tracts were measured along the intracranial course of the CST. FA and lambda( parallel) increased, and ADC and lambda( perpendicular) decreased progressively from the corona radiata to the cerebral peduncle in all subjects. The most abnormal finding in patients with ALS was reduced FA in the cerebral peduncle contralateral to the side of the body with the most severe upper motor neuron signs. lambda( parallel) was increased in the corona radiata. Internal capsule FA correlated positively with symptom duration, and cerebral peduncle ADC positively with the Ashworth spasticity score. There is a spatial dependency of diffusion parameters along the CST in healthy individuals. Evidence of intracranial CST degeneration in ALS was found with distinct diffusion changes in the rostral and caudal regions.

  3. [Assessing frontal lobe function in patients with amyotrophic lateral sclerosis by frontal assessment battery].

    Science.gov (United States)

    Terada, Tatsuhiro; Obi, Tomokazu; Miyajima, Hiroaki; Mizoguchi, Kouichi

    2010-06-01

    Frontal Assessment Battery (FAB) is short neuropsychological battery for the bed side screening of frontal lobe function. Several studies have indicated that frontal lobe dysfunction is the main neuropsychological feature in Amyotrophic lateral sclerosis (ALS). We examined frontal lobe function in patients with ALS and in age-matched normal subjects by using the FAB. We examined 24 patients with sporadic ALS aged 66.0 +/- 10.1 years, with a mean disease duration of 2.0 +/- 0.7 years, a Mini-Mental State Examination score of > or = 24, a normal self-rating depression score, no dyspnea, and no or only slight disturbances in speech, cutting food, and handling utensils on the ALS Functional Rating Scale. Total FAB score, similarity score, and lexical fluency score were significantly lower in ALS patients. Total FAB score did not correlate with age, disease duration, ALS Functional Rating Scale, spirometry, or blood gas analyses. These results suggest frontal lobe dysfunction in ALS patients.

  4. Neuroimaging to Investigate Multisystem Involvement and Provide Biomarkers in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Pierre-François Pradat

    2014-01-01

    Full Text Available Neuroimaging allows investigating the extent of neurological systems degeneration in amyotrophic lateral sclerosis (ALS. Advanced MRI methods can detect changes related to the degeneration of upper motor neurons but have also demonstrated the participation of other systems such as the sensory system or basal ganglia, demonstrating in vivo that ALS is a multisystem disorder. Structural and functional imaging also allows studying dysfunction of brain areas associated with cognitive signs. From a biomarker perspective, numerous studies using diffusion tensor imaging showed a decrease of fractional anisotropy in the intracranial portion of the corticospinal tract but its diagnostic value at the individual level remains limited. A multiparametric approach will be required to use MRI in the diagnostic workup of ALS. A promising avenue is the new methodological developments of spinal cord imaging that has the advantage to investigate the two motor system components that are involved in ALS, that is, the lower and upper motor neuron. For all neuroimaging modalities, due to the intrinsic heterogeneity of ALS, larger pooled banks of images with standardized image acquisition and analysis procedures are needed. In this paper, we will review the main findings obtained with MRI, PET, SPECT, and nuclear magnetic resonance spectroscopy in ALS.

  5. Beta-2 microglobulin is important for disease progression in a murine model for amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Kim A Staats

    2013-12-01

    Full Text Available Beta-2 microglobulin (beta2m is an essential component of the major histocompatibility complex (MHC class I proteins and in the nervous system beta2m is predominantly expressed in motor neurons. As beta2m can promote nerve regeneration, we investigated its potential role in amyotrophic lateral sclerosis (ALS by investigating its expression level as well as the effect of genetically removing beta2m on the disease process in mutant SOD1G93A mice, a model of ALS. We observed a strong upregulation of beta2m in motor neurons during the disease process and ubiquitous removal of beta2m dramatically shortens the disease duration indicating that beta2m plays an essential and positive role during the disease process. We hypothesize that beta2m contributes to plasticity that is essential for muscle reinnervation. Absence of this plasticity will lead to faster muscle denervation and counteracting this process could be a relevant therapeutic target.

  6. Physician perceptions about living organ donation in patients with Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Ansari, S; Bromberg, M B; Gibson, S B

    2017-09-01

    Patients with Amyotrophic Lateral Sclerosis (ALS) have expressed desire to become living organ donors but are unable to do so with current organ donation policies. Our objective is to assess ALS patient's interest in organ donation, and perceived concerns of this practice by ALS neurologists. An electronic survey was administered to ALS neurologists across the United States regarding living organ donation in ALS patients prior to respiratory failure. 52 complete responses were received from 121 invites. 67% (35/52) of neurologists expressed no concerns about living organ donation in ALS patients, and 33% had concerns. The concerns related to respiratory failure, anesthesia exposure and renal dysfunction. With their concerns addressed, 71% of neurologists reported that they would endorse living organ donation. 49% of neurologists reported being asked by a patient for information regarding living organ donation. ALS neurologists felt that 22.8% of ALS patients (median 19%) would be interested in learning more about organ donation, while only 6% of neurologists broach this subject with their patients. Our results indicate that 1 in every 4 ALS patients may be interested in exploring options for living organ donation, and this topic is not routinely addressed by ALS clinics. These results indicate an unexplored area of patient interest. To honor a patient's wishes to donate, the transplant community will have to accommodate living organ donation from terminally ill patients, and address neurologist concerns. Such a practice could benefit two groups of patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. UBQLN2 mutations are rare in French and French-Canadian amyotrophic lateral sclerosis.

    Science.gov (United States)

    Daoud, Hussein; Suhail, Hamid; Szuto, Anna; Camu, William; Salachas, Francois; Meininger, Vincent; Bouchard, Jean-Pierre; Dupré, Nicolas; Dion, Patrick A; Rouleau, Guy A

    2012-09-01

    Mutations in the UBQLN2 gene, which encodes a member of the ubiquitin-like protein family (ubiquilin-2), have been recently identified in patients with dominant X-linked amyotrophic lateral sclerosis (ALS) and ALS with dementia. We report here the sequencing of the UBQLN2 gene in 590 ALS patients of French and French-Canadian ancestry. We identified two novel missense mutations (p.S155N and p.P189T) in two individuals with sporadic ALS. Bioinformatic analysis predicts that these missense mutations affect the normal protein's function. Importantly, these findings further highlight the importance of the proline residues located in the conserved domains of the ubiquilin-2 protein, suggesting that mutations affecting these residues are particularly relevant to the development of ALS. Our findings further support a causative role of the UBQLN2 gene in the pathogenesis of ALS and suggest that UBQLN2 mutations are rare in the French and French-Canadian population. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Vitamin D confers protection to motoneurons and is a prognostic factor of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Camu, William; Tremblier, Boris; Plassot, Carine; Alphandery, Sébastien; Salsac, Céline; Pageot, Nicolas; Juntas-Morales, Raul; Scamps, Frédérique; Daures, Jean-Pierre; Raoul, Cédric

    2014-05-01

    Amyotrophic lateral sclerosis (ALS) is an incurable paralytic disorder primarily typified by the selective and progressive degeneration of motoneurons in the brain and spinal cord. ALS causes muscle wasting and atrophy, resulting eventually in respiratory failure and death within 3-5 years of diagnosis. Vitamin D is a potent secosteroid hormone with diverse biological functions that include protection against neuronal damage. The detrimental consequences of vitamin D dietary deficiency have been documented in other neurodegenerative diseases. However, the protective effect of vitamin D on motoneuron and the influence of its levels on disease course remains elusive. Here we found that the biologically active form of vitamin D significantly potentiated the effect of neurotrophic factors and prevented motoneurons from a Fas-induced death, while electrophysiological properties of motoneurons were not affected. In ALS patients, we report that a severe vitamin D deficiency accelerates by 4 times the rate of decline and were associated with a marked shorter life expectancy. Our findings support a neuroprotective function of vitamin D on motoneurons and propose vitamin D as a reliable prognostic factor of ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. A Novel Locus for Familial Amyotrophic Lateral Sclerosis, on Chromosome 18q

    Science.gov (United States)

    Hand, Collette K.; Khoris, Jawad; Salachas, François; Gros-Louis, François; Lopes, Ana Amélia Simões; Mayeux-Portas, Veronique; Brown, Jr., Robert H.; Meininger, Vincent; Camu, William; Rouleau, Guy A.

    2002-01-01

    Amyotrophic lateral sclerosis (ALS) is an adult-onset degenerative disorder characterized by the death of motor neurons in the cortex, brain stem, and spinal cord. Despite intensive research the basic pathophysiology of ALS remains unclear. Although most cases are sporadic, ∼10% of ALS cases are familial (FALS). Mutations in the Cu/Zn superoxide dismutase (SOD1) gene cause ∼20% of FALS. The gene(s) responsible for the remaining 80% of FALS remain to be found. Using a large European kindred without SOD1 mutation and with classic autosomal dominant adult-onset ALS, we have identified a novel locus by performing a genome scan and linkage analysis. The maximum LOD score is 4.5 at recombination fraction 0.0, for polymorphism D18S39. Haplotype analysis has identified a 7.5-cM, 8-Mb region of chromosome 18q21, flanked by markers D18S846 and D18S1109, as a novel FALS locus. PMID:11706389

  10. Mutations of the ANG gene in French patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Paubel, Agathe; Violette, Jeremy; Amy, Maïté; Praline, Julien; Meininger, Vincent; Camu, William; Corcia, Philippe; Andres, Christian R; Vourc'h, Patrick

    2008-10-01

    Mutations in the angiogenin gene, ANG, have been associated recently with familial and sporadic forms of amyotrophic lateral sclerosis (ALS). However, the cellular and molecular mechanisms that link ANG, a multidomain protein, to ALS are still unknown. To assess the frequency of ANG gene mutations in 855 French patients with sporadic ALS. We analyzed by direct sequencing the full coding region of the ANG gene in a cohort of French patients with sporadic ALS. The clinical characteristics of patients carrying ANG mutations are detailed. French ALS Study Group. Patients A total of 855 patients with sporadic ALS. Results of genetic analyses. We observed a previously identified mutation (pI46V) in 2 patients with ALS without a known family link and found a novel mutation (pR121H) in 1 patient who developed ALS with rapid progression. We did not observe an association between patients with ALS and the rs11701 polymorphism, as previously reported in certain ALS populations of other ethnic origins. Overall, our findings support the implication of ANG gene mutations as a rare but widespread cause of ALS.

  11. Study of the HFE gene common polymorphisms in French patients with sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Praline, Julien; Blasco, Hélène; Vourc'h, Patrick; Rat, Valérian; Gendrot, Chantal; Camu, William; Andres, Christian R

    2012-06-15

    Our objective was to investigate whether the C282Y (p.Cys 282 Tyr) and H63D (p. His 63 Asp) HFE polymorphisms were associated with sporadic amyotrophic lateral sclerosis (SALS) in the French population. We searched for a relation of HFE polymorphisms with the clinical characteristics of the disease. The HFE polymorphisms were studied in 824 patients with SALS and 583 controls. We compared the frequency of the polymorphisms between SALS and controls groups by univariate and multivariate statistics, taking into account gender, site, age-at-onset and survival. We did not observe significant difference in the frequency of H63D polymorphism between SALS and control group. We observed a significant difference for C282Y between patients and controls with a low frequency of the Y allele in patients (3.2%) compared to our control group (5.9%). Disease duration, distribution of gender, site-of-onset, age-at-onset did not differ between groups taking into account genotypes of each polymorphism. Our results in this large cohort of ALS patients indicate that H63D polymorphism is not associated with SALS in the French population. This conclusion does not exclude a weak effect of the HFE gene polymorphisms in certain ALS populations, or an effect of other rare HFE gene variants. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations.

    Science.gov (United States)

    Corcia, P; Valdmanis, P; Millecamps, S; Lionnet, C; Blasco, H; Mouzat, K; Daoud, H; Belzil, V; Morales, R; Pageot, N; Danel-Brunaud, V; Vandenberghe, N; Pradat, P F; Couratier, P; Salachas, F; Lumbroso, S; Rouleau, G A; Meininger, V; Camu, W

    2012-05-08

    To describe the phenotype and phenotype-genotype correlations in patients with amyotrophic lateral sclerosis (ALS) with TARDBP gene mutations. French TARDBP+ patients with ALS (n = 28) were compared first to 3 cohorts: 737 sporadic ALS (SALS), 192 nonmutated familial ALS (FALS), and 58 SOD1 + FALS, and then to 117 TARDBP+ cases from the literature. Genotype-phenotype correlations were studied for the most frequent TARDBP mutations. In TARDBP+ patients, onset was earlier (p = 0.0003), upper limb (UL) onset was predominant (p = 0.002), and duration was longer (p = 0.0001) than in patients with SALS. TARDBP+ and SOD1+ groups had the longest duration but diverged for site of onset: 64.3% UL onset for TARDBP+ and 74.1% on lower limbs for SOD1+ (p < 0.0001). The clinical characteristics of our 28 patients were similar to the 117 cases from the literature. In Caucasians, 51.3% of had UL onset, while 58.8% of Asians had bulbar onset (p = 0.02). The type of mutation influenced survival (p < 0.0001), and the G298S1, lying in the TARDBP super rich glycine-residue domain, was associated with the worst survival (27 months). Differences in phenotype between the groups as well as the differential influence of TARBDP mutations on survival may help physicians in ALS management and allow refining the strategy of genetic diagnosis.

  13. Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis.

    Science.gov (United States)

    Millecamps, Stéphanie; Corcia, Philippe; Cazeneuve, Cécile; Boillée, Séverine; Seilhean, Danielle; Danel-Brunaud, Véronique; Vandenberghe, Nadia; Pradat, Pierre-François; Le Forestier, Nadine; Lacomblez, Lucette; Bruneteau, Gaëlle; Camu, William; Brice, Alexis; Meininger, Vincent; LeGuern, Eric; Salachas, François

    2012-04-01

    Mutations in UBQLN2 encoding ubiquilin-2 have recently been identified in families with dominant X-linked juvenile and adult-onset amyotrophic lateral sclerosis (ALS) and ALS/dementia. Ubiquilin-2 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients. All the previously reported UBQLN2 mutations were localized in 1 of the 12 PXX domains of ubiquilin-2 protein. We sequenced UBQLN2 in 130 French patients with familial ALS (FALS) and absence of male-to-male transmission and the PXX domain in 240 more patients with sporadic ALS (SALS). We identified, at the heterozygote state, the c.1500_1508delCATAGGCCC, p.Gly502_Ile504del, in 1 affected woman. This deletion presumably leads to the in-frame deletion of 1 PXX repeat in the protein. This variant did not segregate with the disease in the corresponding family and was also detected in 1/380 control subject. Our results suggest that UBQLN2 gene mutations are rare in French ALS. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Single-photon emission computed tomographic findings and motor neuron signs in amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Terao, Shin-ichi; Sobue, Gen; Higashi, Naoki; Takahashi, Masahiko; Suga, Hidemichi; Mitsuma, Terunori [Aichi Medical Univ., Nagakute (Japan)

    1995-03-01

    {sup 123}I-amphetamine-single photon emission computed tomography (SPECT) was performed on 16 patients with amyotrophic lateral sclerosis (ALS) to investigate the correlation between regional cerebral blood flow (rCBF) and upper motor neuron signs. Significant decreased blood flow less than 2 SDs below the mean of controls was observed in the frontal lobe in 4 patients (25%) and in the frontoparietal lobe including the cortical motor area in 4 patients, respectively. The severity of extermity muscular weakness was significantly correlate with decrease in blood flow through the frontal lobe (p<0.05) and through the frontoparietal lobe (p<0.001). A significant correlation was also noted to exist between the severity of bulbar paralysis and decrease in blood flow through the frontoparietal lobe. No correlation, however, was observed between rCBF and severity of spasticity, presence or absence of Babinski`s sign and the duration of illness. Although muscular weakness in the limbs and bulbar paralysis are not pure upper motor neuron signs, the observed reduction in blood flow through the frontal or frontoparietal lobes appears to reflect extensive progression of functional or organic lesions of cortical neurons including the motor area. (author).

  15. Euthanasia and physician-assisted suicide in amyotrophic lateral sclerosis: a prospective study.

    Science.gov (United States)

    Maessen, Maud; Veldink, Jan H; Onwuteaka-Philipsen, Bregje D; Hendricks, Henk T; Schelhaas, Helenius J; Grupstra, Hepke F; van der Wal, Gerrit; van den Berg, Leonard H

    2014-10-01

    The objective of this study is to determine if quality of care, symptoms of depression, disease characteristics and quality of life of patients with amyotrophic lateral sclerosis (ALS) are related to requesting euthanasia or physician-assisted suicide (EAS) and dying due to EAS. Therefore, 102 ALS patients filled out structured questionnaires every 3 months until death and the results were correlated with EAS. Thirty-one percent of the patients requested EAS, 69% of whom eventually died as a result of EAS (22% of all patients). Ten percent died during continuous deep sedation; only one of them had explicitly requested death to be hastened. Of the patients who requested EAS, 86% considered the health care to be good or excellent, 16% felt depressed, 45% experienced loss of dignity and 42% feared choking. These percentages do not differ from the number of patients who did not explicitly request EAS. The frequency of consultations of professional caregivers and availability of appliances was similar in both groups. Our findings do not support continuous deep sedation being used as a substitute for EAS. In this prospective study, no evidence was found for a relation between EAS and the quality and quantity of care received, quality of life and symptoms of depression in patients with ALS. Our study does not support the notion that unmet palliative care needs are related to EAS.

  16. Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS

    Directory of Open Access Journals (Sweden)

    Timur A. Mavlyutov

    2015-01-01

    Full Text Available Amyotrophic Lateral Sclerosis (ALS is a neurodegenerative disease affecting spinal cord motoneurons (MN with an associative connection to Frontotemporal Lobar Dementia (FTLD. The endoplasmic reticulum (ER bound Sigma-1 Receptor (S1R chaperone protein localizes to specialized ER cisternae within 10 nm of the plasma membrane in spinal cord ventral horn cholinergic post synaptic C-terminals. Removal of the S1R gene in the Superoxide Dismutase-1 (SOD-1 mouse model of ALS exacerbated the neurodegenerative condition and resulted in a significantly reduced longevity when compared to the SOD-1/S1R wild type (WT mouse. The proposed amelioration of the ALS phenotype by the S1R is likely due to a “brake” on excitation of the MN as evidenced by a reduction in action potential generation in the MN of the WT when compared to the S1R KO mouse MN. Although the precise signal transduction pathway(s regulated by the S1R in the MN has/have not been elucidated at present, it is likely that direct or indirect functional interactions occur between the S1R in the ER cisternae with voltage gated potassium channels and/or with muscarinic M2 receptor signaling in the post synaptic plasma membrane. Possible mechanisms for regulation of MN excitability by S1R are discussed.

  17. End of life decisions in amyotrophic lateral sclerosis: a cross-cultural perspective.

    Science.gov (United States)

    Smyth, A; Riedl, M; Kimura, R; Olick, R; Siegler, M

    1997-10-01

    In an era where life-sustaining technology offers physicians unprecedented powers to prolong survival in terminal illness, the question of how end of life decisions are made has become a major subject of study and debate. Amyotrophic lateral sclerosis (ALS) is a disease in which physical ability declines while mental capacity most often remains intact. Since most patients with ALS die of respiratory failure, a distinguishing feature of this disease is whether a patient is offered and accepts a chance to go on long-term mechanical ventilation. This unusual feature makes ALS a compelling model for studying end of life decisions in different countries. This paper reviews the literature and presents preliminary data on how end of life decisions in ALS are made in the US, Great Britain, and Japan. We address this issue by examining how cultural differences in truth-telling and informed consent, societal differences in attitudes toward the use of artificial life support, and legal differences in the role and status of advance directives in each country influenced decisions in the following three groups of patients: (1) the mentally competent; (2) mentally incompetent patients who previously completed advance directives when competent; and (3) mentally incompetent patients who have not provided advance guidance about their wishes.

  18. End-of-life management in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Connolly, Sheelah; Galvin, Miriam; Hardiman, Orla

    2015-04-01

    Most health-care professionals are trained to promote and maintain life and often have difficulty when faced with the often rapid decline and death of people with terminal illnesses such as amyotrophic lateral sclerosis (ALS). By contrast, data suggest that early and open discussion of end-of-life issues with patients and families allows time for reflection and planning, can obviate the introduction of unwanted interventions or procedures, can provide reassurance, and can alleviate fear. Patients' perspectives regarding end-of-life interventions and use of technologies might differ from those of the health professionals involved in their care, and health-care professionals should recognise this and respect the patient's autonomy. Advance care directives can preserve autonomy, but their legal validity and use varies between countries. Clinical management of the end of life should aim to maximise quality of life of both the patient and caregiver and, when possible, incorporate appropriate palliation of distressing physical, psychosocial, and existential distress. Training of health-care professionals should include the development of communication skills that help to sensitively manage the inevitability of death. The emotional burden for health-care professionals caring for people with terminal neurological disease should be recognised, with structures and procedures developed to address compassion, fatigue, and the moral and ethical challenges related to providing end-of-life care. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Epigenetic differences between monozygotic twins discordant for amyotrophic lateral sclerosis (ALS) provide clues to disease pathogenesis.

    Science.gov (United States)

    Young, Paul E; Kum Jew, Stephen; Buckland, Michael E; Pamphlett, Roger; Suter, Catherine M

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating late-onset neurodegenerative disorder in which only a small proportion of patients carry an identifiable causative genetic lesion. Despite high heritability estimates, a genetic etiology for most sporadic ALS remains elusive. Here we report the epigenetic profiling of five monozygotic twin pairs discordant for ALS, four with classic ALS and one with the progressive muscular atrophy ALS variant, in whom previous whole genome sequencing failed to uncover a genetic basis for their disease discordance. By studying cytosine methylation patterns in peripheral blood DNA we identified thousands of large between-twin differences at individual CpGs. While the specific sites of differences were mostly idiosyncratic to a twin pair, a proportion involving GABA signalling were common to all ALS individuals. For both idiosyncratic and common sites the differences occurred within genes and pathways related to neurobiological functions or dysfunctions, some of particular relevance to ALS such as glutamate metabolism and the Golgi apparatus. All four classic ALS patients were epigenetically older than their unaffected co-twins, suggesting accelerated aging in multiple tissues in this disease. In conclusion, widespread changes in methylation patterns were found in ALS-affected co-twins, consistent with an epigenetic contribution to disease. These DNA methylation findings could be used to develop blood-based ALS biomarkers, gain insights into disease pathogenesis, and provide a reference for future large-scale ALS epigenetic studies.

  20. Positron emission tomography in amyotrophic lateral sclerosis: Towards targeting of molecular pathological hallmarks

    Energy Technology Data Exchange (ETDEWEB)

    Willekens, Stefanie M.A.; Weehaeghe, Donatienne van [University Hospitals Leuven and KU Leuven, Division of Nuclear Medicine, Department of Imaging and Pathology, Leuven (Belgium); Damme, Philip van [University Hospitals Leuven, Department of Neurology, Leuven (Belgium); KU Leuven, Department of Neurosciences, Experimental Neurology, Leuven (Belgium); Leuven Research Institute for Neuroscience and Disease (LIND), Leuven (Belgium); VIB, Vesalius Research Center, Laboratory of Neurobiology, Leuven (Belgium); Laere, Koen van [University Hospitals Leuven and KU Leuven, Division of Nuclear Medicine, Department of Imaging and Pathology, Leuven (Belgium); Leuven Research Institute for Neuroscience and Disease (LIND), Leuven (Belgium)

    2017-03-15

    During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD). Radionuclide imaging, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), form an attractive approach to quantitatively monitor the ongoing neurodegenerative processes. Although [{sup 18}F]-FDG has been recently proposed as a potential biomarker for ALS, active targeting of the underlying pathologic molecular processes is likely to unravel further valuable disease information and may help to decipher the pathogenesis of ALS. In this review, we provide an overview of radiotracers that have already been applied in ALS and discuss possible novel targets for in vivo imaging of various pathogenic processes underlying ALS onset and progression. (orig.)

  1. A(aLS: Ammonia-induced amyotrophic lateral sclerosis [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Bhavin Parekh

    2015-05-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a dreadful, devastating and incurable motor neuron disease. Aetiologically, it is a multigenic, multifactorial and multiorgan disease. Despite intense research, ALS pathology remains unexplained. Following extensive literature review, this paper posits a new integrative explanation. This framework proposes that ammonia neurotoxicity is a main player in ALS pathogenesis. According to this explanation, a combination of impaired ammonia removal— mainly because of impaired hepatic urea cycle dysfunction—and increased ammoniagenesis— mainly because of impaired glycolytic metabolism in fast twitch skeletal muscle—causes chronic hyperammonia in ALS. In the absence of neuroprotective calcium binding proteins (calbindin, calreticulin and parvalbumin, elevated ammonia—a neurotoxin—damages motor neurons. Ammonia-induced motor neuron damage occurs through multiple mechanisms such as macroautophagy-endolysosomal impairment, endoplasmic reticulum (ER stress, CDK5 activation, oxidative/nitrosative stress, neuronal hyperexcitability and neuroinflammation. Furthermore, the regional pattern of calcium binding proteins’ loss, owing to either ER stress and/or impaired oxidative metabolism, determines clinical variability of ALS. Most importantly, this new framework can be generalised to explain other neurodegenerative disorders such as Huntington’s disease and Parkinsonism.

  2. MRI of the intracranial corticospinal tracts in amyotrophic and primary lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Peretti-Viton, P.; Brunel, H.; Daniel, C.; Salazard, B.; Salamon, G. [Dept. of Neuroradiology, Hopital de la Timone, Marseille (France); Azulay, J.P.; Trefouret, S.; Pouget, J.; Serratrice, G. [Dept. of Neurology and Neuromuscular Diseases, Hopital de la Timone, Marseille (France); Viton, J.M. [Dept. of Physical Medicine and Rehabilitation, Hopital de la Timone, Marseille (France); Flori, A. [Medical Informatics Dept., Hopital Nord, Marseille (France)

    1999-10-01

    Our aim was to investigate the corticospinal tracts (CST) in motor neurone disease, using MRI, and to correlate findings with clinical data. We studied 31 patients with amyotrophic (ALS) and eight with primary lateral sclerosis (PLS). The signal from the CST was classified into four grades on T2-weighted images, and compared to T2-weighted images of 37 age-matched control subjects. No abnormalities were seen in the CST on T1-weighted images and were rarely evident on proton-density weighting. Variable high signal in the CST was found on T2-weighted images in 35 patients, and in 29 control subjects. Our grades 0 and 1 were more frequent in control subjects, grades 2 and 3 more frequent in patients. We found no correlation between the high signal and clinical data, including the duration of the illness. We therefore conclude that this technique is neither sensitive nor specific except in grade 3 which is quite specific for ALS. In half the patients we found atrophy of the superior parietal gyrus, which merits further study. (orig.)

  3. Adducin at the Neuromuscular Junction in Amyotrophic Lateral Sclerosis: Hanging on for Dear Life

    Directory of Open Access Journals (Sweden)

    Charles eKrieger

    2016-01-01

    Full Text Available The neurological dysfunction in amyotrophic lateral sclerosis (ALS/motor neurone disease (MND is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules linking the pre- and post-synaptic components of the neuromuscular junction (NMJ are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts. By controlling the levels of synaptic proteins, adducin can de-stabilize synaptic contacts. Interestingly, elevated levels of phosphorylated adducin have been reported in ALS patients and in a mouse model of the disease. Adducin is regulated by phosphorylation through protein kinase C (PKC, some isoforms of which exhibit Ca2+-dependence, raising the possibility that changes in intracellular Ca2+ might alter PKC activation and secondarily influence adducin phosphorylation. Furthermore, adducin has interactions with the alpha subunit of the Na+/K+-ATPase. Thus, the phosphorylation of adducin may secondarily influence synaptic stability at the NMJ and so influence pre- and post-synaptic integrity at the NMJ in ALS.

  4. Morphological abnormalities in mitochondria of the skin of patients with sporadic amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Gabriel E. Rodríguez

    2012-01-01

    Full Text Available OBJECTIVES: Mitochondrial dysfunction has been reported in the central nervous system, hepatocytes and peripheral blood lymphocytes from patients with sporadic amyotrophic lateral sclerosis (SALS. However, the status of skin mitochondria has not been reported, in spite of the fact that SALS patients present skin abnormalities. The objective of the present study was to compare mitochondrial ultrastructural parameters in keratinocytes from patients with SALS and healthy controls. METHODS: Our study was based on the analysis of 112 skin mitochondria from 5 SALS patients and 99 organelles from 4 control subjects by electron microscopy. RESULTS: Computerized image analysis showed that mitochondrial major axis length, area and perimeter of the organelle were significantly smaller in SALS respect of healthy control subjects. Morphologically, SALS mitochondria presented cristolysis and breakage of the outer membrane. CONCLUSIONS: Mitochondrial dysfunction in the skin may possibly reflect changes occurring in mitochondria of the central nervous system. The analysis of mitochondrial morphology in this tissue may be of value to follow disease progression and, eventually, the effectiveness of current therapies for SALS.

  5. Early-Onset Alopecia and Amyotrophic Lateral Sclerosis: A Cohort Study

    Science.gov (United States)

    Fondell, Elinor; Fitzgerald, Kathryn C.; Falcone, Guido J.; O'Reilly, Éilis J.; Ascherio, Alberto

    2013-01-01

    A recent meta-analysis of 7 genome-wide association studies on early balding (alopecia) revealed single nucleotide polymorphism variants in the region of the amyotrophic lateral sclerosis (ALS) gene TAR DNA-binding protein 43 (TARDBP/TDP-43). We therefore explored the association of early-onset alopecia and ALS in the Health Professionals Follow-up Study, a large cohort of 51,529 US men. In 1992, the participants (then aged 46–81 years) were asked to report their hair line pattern at age 45 years. During the follow-up period (1992–2008), 42 men were diagnosed with ALS. Of those, 13 had reported no alopecia, 18 had reported moderate alopecia, and 11 had reported extensive alopecia at age 45 years. Those who reported extensive alopecia had an almost 3-fold increased risk of ALS compared with those who reported no alopecia (relative risk = 2.74, 95% confidence interval: 1.23, 6.13). Furthermore, we observed a linear trend of increased risk of ALS with increasing level of balding at age 45 years (Ptrend = 0.02). In conclusion, men with early-onset alopecia seem to have a higher risk of ALS. The mechanisms underlying this association deserve further investigation. PMID:23942216

  6. Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons

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    Brian J. Wainger

    2014-04-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1, C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1+/+ stem cell line do not display the hyperexcitability phenotype. SOD1A4V/+ ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons can reveal disease-related mechanisms and identify therapeutic candidates.

  7. Osteopathic Manual Treatment for Amyotrophic Lateral Sclerosis: A Feasibility Pilot Study

    Science.gov (United States)

    Maggiani, Alberto; Tremolizzo, Lucio; Valentina, Andrea Della; Mapelli, Laurent; Sosio, Silvia; Milano, Valeria; Bianchi, Manuel; Badi, Francesco; Lavazza, Carolina; Grandini, Marco; Corna, Giovanni; Prometti, Paola; Lunetta, Christian; Riva, Nilo; Ferri, Alessandra; Lanfranconi, Francesca

    2016-01-01

    Background: Current interventions in amyotrophic lateral sclerosis (ALS) are focused on supporting quality of life (QoL) and easing pain with a multidisciplinary approach. Objective: Primary aim of this pilot work assessed feasibility, safety, tolerability and satisfaction of osteopathic manual treatment (OMT) in 14 ALS outpatients. Methods: Patients were randomized according to an initial single-blind design (12 weeks, T0-T1), in order to receive OMT (weekly for 4 weeks, and fortnightly for the following 8 weeks) versus usual-care (n=7 each group), followed by an OMT open period (T1-T2, once a week for 8 weeks, n=10). Secondary aims included blind osteopathic assessment of somatic dysfunctions (SD) for goal attainment scale (GAS) calculation, Brief Pain Inventory-short form and McGill QoL-16 items. Results: OMT was demonstrated feasible and safe and patients displayed high satisfaction (T1-VAS=8.34 ± 0.46; T2-VAS=8.52 ± 0.60). Considering secondary aims no significant differences emerged. Finally, at study entry (T0), a cervico-dorsal SD was found in 78% of ALS patients versus 28% of healthy matched controls (p<0.01). Conclusion: OMT was found feasible, safe and satisfactory in ALS. The lack of secondary aim differences can be due to the limited sample size. OMT could be an interesting option to explore in ALS. PMID:27651843

  8. Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols

    Directory of Open Access Journals (Sweden)

    Anne Vejux

    2018-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism. In various neurodegenerative diseases, such as Alzheimer’s disease or multiple sclerosis, the involvement of lipids is increasingly suggested based on lipid metabolism modifications. With regard to ALS, research has also focused on the possible involvement of lipids. Lipid involvement was suggested for clinical arguments where changes in cholesterol and LDL/HDL levels were reported with, however, differences in positivity between studies. Since lipids are involved in the membrane structure and certain signaling pathways, it may be considered to look for oxysterols, mainly 25-hydroxycholesterol and its metabolites involved in immune response, or phytosterols to find suitable biomarkers for this pathology.

  9. Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Riancho, J; Gonzalo, I; Ruiz-Soto, M; Berciano, J

    2016-02-04

    Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  10. The role of SIGMAR1 gene mutation and mitochondrial dysfunction in amyotrophic lateral sclerosis

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    Kohji Fukunaga

    2015-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS patients exhibit diverse pathologies such as endoplasmic reticulum (ER stress and mitochondrial dysfunction in motor neurons. Five to ten percent of patients have familial ALS, a form of the disease caused by mutations in ALS-related genes, while sporadic forms of the disease occur in 90–95% of patients. Recently, it was reported that familial ALS patients exhibit a missense mutation in SIGMAR1 (c.304G > C, which encodes sigma-1 receptor (Sig-1R, substituting glutamine for glutamic acid at amino acid residue 102 (p.E102Q. Expression of that mutant Sig-1RE102Q protein reduces mitochondrial ATP production, inhibits proteasome activity and causes mitochondrial injury, aggravating ER stress-induced neuronal death in neuro2A cells. In this issue, we discuss mechanisms underlying mitochondrial impairment seen in ALS motor neurons and propose that therapies that protect mitochondria might improve the quality of life (QOL of ALS patients and should be considered for clinical trials.

  11. Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records.

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    Paik, Hyojung; Chung, Ah-Young; Park, Hae-Chul; Park, Rae Woong; Suk, Kyoungho; Kim, Jihyun; Kim, Hyosil; Lee, KiYoung; Butte, Atul J

    2015-03-05

    Prediction of new disease indications for approved drugs by computational methods has been based largely on the genomics signatures of drugs and diseases. We propose a method for drug repositioning that uses the clinical signatures extracted from over 13 years of electronic medical records from a tertiary hospital, including >9.4 M laboratory tests from >530,000 patients, in addition to diverse genomics signatures. Cross-validation using over 17,000 known drug-disease associations shows this approach outperforms various predictive models based on genomics signatures and a well-known "guilt-by-association" method. Interestingly, the prediction suggests that terbutaline sulfate, which is widely used for asthma, is a promising candidate for amyotrophic lateral sclerosis for which there are few therapeutic options. In vivo tests using zebrafish models found that terbutaline sulfate prevents defects in axons and neuromuscular junction degeneration in a dose-dependent manner. A therapeutic potential of terbutaline sulfate was also observed when axonal and neuromuscular junction degeneration have already occurred in zebrafish model. Cotreatment with a β2-adrenergic receptor antagonist, butoxamine, suggests that the effect of terbutaline is mediated by activation of β2-adrenergic receptors.

  12. Predicting Early Bulbar Decline in Amyotrophic Lateral Sclerosis: A Speech Subsystem Approach

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    Panying Rong

    2015-01-01

    Full Text Available Purpose. To develop a predictive model of speech loss in persons with amyotrophic lateral sclerosis (ALS based on measures of respiratory, phonatory, articulatory, and resonatory functions that were selected using a data-mining approach. Method. Physiologic speech subsystem (respiratory, phonatory, articulatory, and resonatory functions were evaluated longitudinally in 66 individuals with ALS using multiple instrumentation approaches including acoustic, aerodynamic, nasometeric, and kinematic. The instrumental measures of the subsystem functions were subjected to a principal component analysis and linear mixed effects models to derive a set of comprehensive predictors of bulbar dysfunction. These subsystem predictors were subjected to a Kaplan-Meier analysis to estimate the time until speech loss. Results. For a majority of participants, speech subsystem decline was detectible prior to declines in speech intelligibility and speaking rate. Among all subsystems, the articulatory and phonatory predictors were most responsive to early bulbar deterioration; and the resonatory and respiratory predictors were as responsive to bulbar decline as was speaking rate. Conclusions. The articulatory and phonatory predictors are sensitive indicators of early bulbar decline due to ALS, which has implications for predicting disease onset and progression and clinical management of ALS.

  13. Initial gene vector dosing for studying symptomatology of amyotrophic lateral sclerosis in non-human primates.

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    Jackson, Kasey L; Dayton, Robert D; Fisher-Perkins, Jeanne M; Didier, Peter J; Baker, Kate C; Weimer, Maria; Gutierrez, Amparo; Cain, Cooper D; Mathis, J Michael; Gitcho, Michael A; Bunnell, Bruce A; Klein, Ronald L

    2015-04-01

    Most amyotrophic lateral sclerosis (ALS) research has focused on mice, but there are distinct differences in the functional neuroanatomy of the corticospinal pathway in primates vs. rodents. A non-human primate model may be more sensitive and more predictive for therapeutic efficacy. Rhesus macaques received recombinant adeno-associated virus (AAV9) encoding either the ALS-related pathological protein TDP-43 or a green fluorescent protein (GFP) control by intravenous administration. Motor function and electromyography were assessed over a nine-month expression interval followed by post-mortem analyses. Recombinant TDP-43 or GFP was stably expressed long term. Although the TDP-43 subjects did not manifest severe paralysis and atrophy, there were trends of a partial disease state in the TDP-43 subjects relative to the control. These data indicate that a higher gene vector dose will likely be necessary for more robust effects, yet augur that a relevant primate model is feasible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. TDP-43 in the hypoglossal nucleus identifies amyotrophic lateral sclerosis in behavioral variant frontotemporal dementia.

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    Halliday, Glenda M; Kiernan, Matthew C; Kril, Jillian J; Mito, Remika; Masuda-Suzukake, Masami; Hasegawa, Masato; McCann, Heather; Bartley, Lauren; Dobson-Stone, Carol; Kwok, John B J; Hornberger, Michael; Hodges, John R; Tan, Rachel H

    2016-07-15

    The hypoglossal nucleus was recently identified as a key brain region in which the presence of TDP-43 pathology could accurately discriminate TDP-43 proteinopathy cases with clinical amyotrophic lateral sclerosis (ALS). The objective of the present study was to assess the hypoglossal nucleus in behavioral variant frontotemporal dementia (bvFTD), and determine whether TDP-43 in this region is associated with clinical ALS. Twenty-nine cases with neuropathological FTLD-TDP and clinical bvFTD that had not been previously assessed for hypoglossal TDP-43 pathology were included in this study. Of these 29 cases, 41% (n=12) had a dual diagnosis of bvFTD-ALS at presentation, all 100% (n=12) of which demonstrated hypoglossal TDP-43 pathology. Of the 59% (n=17) cohort that presented with pure bvFTD, 35% (n=6) were identified with hypoglossal TDP-43 pathology. Review of the case files of all pure bvFTD cases revealed evidence of possible or probable ALS in 5 of the 6 hypoglossal-positive cases (83%) towards the end of disease, and this was absent from all cases without such pathology. In conclusion, the present study validates grading the presence of TDP-43 in the hypoglossal nucleus for the pathological identification of bvFTD cases with clinical ALS, and extends this to include the identification of cases with possible ALS at end-stage. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  15. Molecular Taxonomy of Sporadic Amyotrophic Lateral Sclerosis Using Disease-Associated Genes

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    Sebastiano Cavallaro

    2017-04-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Despite intensive research, the origin and progression of ALS remain largely unknown, suggesting that the traditional clinical diagnosis and treatment strategies might not be adequate to completely capture the molecular complexity underlying the disease. In our previous work, comprehensive genomic profiling of 41 motor cortex samples enabled to discriminate control from sporadic ALS patients and segregated these latter into two distinct subgroups, each associated with different deregulated genes and pathways. Interestingly, some deregulated genes in sporadic ALS were previously associated with familiar ALS, indicating shared pathogenic mechanisms between the two forms of disease. In this, we performed cluster analysis on the same whole-genome expression profiles using a restricted (203 subset of genes extensively implicated in monogenic forms of ALS. Surprisingly, this short and unbiased gene list was sufficiently representative to allow the accurate separation of SALS patients from controls and the stratification of SALS patients into two molecularly distinct subgroups. Overall, our findings support the existence of a molecular taxonomy for ALS and represent a further step toward the establishment of a molecular-based diagnosis and patient-tailored therapies.

  16. Association between depression and survival in Chinese amyotrophic lateral sclerosis patients.

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    Wei, Qianqian; Zheng, Zhenzhen; Guo, Xiaoyan; Ou, Ruwei; Chen, Xueping; Huang, Rui; Yang, Jing; Shang, Huifang

    2016-04-01

    To determine the prevalence of depression, to identify correlated factors for depression, and to explore the impact on the progression or survival of amyotrophic lateral sclerosis (ALS) by depression in a Chinese population. A total of 166 ALS patients were recruited. Diagnosis of depression disorders and the severity of depression were established by using the fourth diagnostic and statistical manual of mental disorders, Hamilton Depression Rating Scale-24 items (HDRS-24) and Beck Depression Inventory (BDI). Major depression was found in 15 patients (9.6 %). The multiple regression analysis showed that a lower ALS Functional Rating Scale-Revised (ALSFRS-R) score was correlated with increasing HDRS scores and BDI scores (P = 0.018 and P = 0.012). No significant difference in the median survival time between ALS patients with and without depression was revealed by Kaplan-Meier analysis (log-rank P = 0.282). Cox hazard model showed that the presence of depression in ALS was unrelated to the survival, while the severity of depression in ALS was correlated with the survival. The presence and severity of depression in ALS did not correlate with the progression of ALS. Major depression in ALS is uncommon. Depression evaluation should be given to ALS patients, especially those with lower ALSFRS-R score. The severity of depression may be associated with the survival; however, depression does not worse the progression of ALS.

  17. Survival and Cause of Death among a Cohort of Confirmed Amyotrophic Lateral Sclerosis Cases.

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    Susan T Paulukonis

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disorder. Estimates of survival from disease onset range from 20 to 48 months and have been generated using clinical populations or death records alone.Data on a cohort of ALS cases diagnosed between 2009-2011 were collected as part of the Los Angeles and San Francisco Bay Area Metropolitan ALS Surveillance projects; death records 2009-2013 were linked to these confirmed cases to determine survival post diagnosis and factors associated with survival time.There were 618 cases identified and 283 of these died during the follow up time period. Median age at death was 64.3 years, and median survival time post-diagnosis was 2.6 years. Age at diagnosis and year of diagnosis were predictors of survival time in adjusted models; those diagnosed at age 80 or older had shorter survival than those diagnosed at age 50 or younger. Most (92% had ALS noted as a cause of death.Survival post-diagnosis may be improved compared with previous reports. Age at diagnosis continues to be the strongest predictor of prognosis; recall case reporting bias may play a role in estimates of survival time.

  18. Evaluation of dysphagia at the initial diagnosis of amyotrophic lateral sclerosis.

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    Murono, Shigeyuki; Hamaguchi, Tsuyoshi; Yoshida, Hiroshi; Nakanishi, Yosuke; Tsuji, Akira; Endo, Kazuhira; Kondo, Satoru; Wakisaka, Naohiro; Yamada, Masahito; Yoshizaki, Tomokazu

    2015-06-01

    Dysphagia eventually occurs in amyotrophic lateral sclerosis (ALS). Swallowing in patients with ALS at their initial diagnosis was evaluated using videofluoroscopy (VF). Nineteen consecutive patients with ALS, 14 with bulbar symptoms, and 5 without them, underwent VF. Fourteen physiologic components, 6 oral and 8 pharyngeal components, were assessed during the examination. Significantly poorer scores were observed in three of the 6 oral components and 3 of the 8 pharyngeal components in patients with bulbar symptoms. Furthermore, bolus transport from the oral cavity to pharynx, pharyngeal constriction, oral residue and pharyngeal residue were impaired in patients even without bulbar symptoms. On the other hand, pharyngoesophageal segment opening was preserved in patients even with bulbar symptoms. Bolus transport and initiation of pharyngeal swallow were correlated with the swallowing category of the ALS severity scale. Defining types of impairment in patients with or without bulbar symptoms is useful for evaluating dysphagia in this disease. Although VF showed impairment of oral and pharyngeal phases of swallowing, the oral phase affected the eating habit in ALS at the initial diagnosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Climatic factors associated with amyotrophic lateral sclerosis: a spatial analysis from Taiwan

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    Ching-Piao Tsai

    2013-11-01

    Full Text Available Few studies have assessed the spatial association of amyotrophic lateral sclerosis (ALS incidence in the world. The aim of this study was to identify the association of climatic factors and ALS incidence in Taiwan. A total of 1,434 subjects with the primary diagnosis of ALS between years 1997 and 2008 were identified in the national health insurance research database. The diagnosis was also verified by the national health insurance programme, which had issued and providing them with “serious disabling disease (SDD certificates”. Local indicators of spatial association were employed to investigate spatial clustering of agestandardised incidence ratios in the townships of the study area. Spatial regression was utilised to reveal any association of annual average climatic factors and ALS incidence for the 12-year study period. The climatic factors included the annual average time of sunlight exposure, average temperature, maximum temperature, minimum temperature, atmospheric pressure, rainfall, relative humidity and wind speed with spatial autocorrelation controlled. Significant correlations were only found for exposure to sunlight and rainfall and it was similar in both genders. The annual average of the former was found to be negatively correlated with ALS, while the latter was positively correlated with ALS incidence. While accepting that ALS is most probably multifactorial, it was concluded that sunlight deprivation and/or rainfall are associated to some degree with ALS incidence in Taiwan.

  20. Infection of the central nervous system, sepsis and amyotrophic lateral sclerosis.

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    Fang Fang

    Full Text Available Severe infections may lead to chronic inflammation in the central nervous system (CNS which may in turn play a role in the etiopathogenesis of amyotrophic lateral sclerosis (ALS. The relentless progression and invasive supportive treatments of ALS may on the other hand induce severe infections among ALS patients.The present study included 4,004 ALS patients identified from the Swedish Patient Register during 1991-2007 and 20,020 age and sex matched general population controls. Conditional logistic regression was used to estimate the odds ratios (ORs of ALS given a previous hospitalization for CNS infection or sepsis. Cox models were used to estimate the hazard ratios (HRs of hospitalization for CNS infection or sepsis after ALS diagnosis. Overall, previous CNS infection (OR: 1.3, 95% confidence interval [CI]: 0.8, 2.4 or sepsis (OR: 1.2, 95% CI: 0.9, 1.6 was not associated with ALS risk. However, compared to ALS free individuals, ALS cases were more likely to be hospitalized for sepsis after diagnosis (HR: 2.6, 95% CI: 1.9, 3.5. We did not observe a higher risk of CNS infection after ALS diagnosis.Our results suggest that acute and severe infections unlikely contribute to the development of ALS; however, ALS patients are at a higher risk of sepsis after diagnosis, compared to ALS free individuals.