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Sample records for multiple sclerosis amyotrophic

  1. 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

  2. Cross-diagnostic validity of the SF-36 physical functioning scale in patients with stroke, multiple sclerosis and amyotrophic lateral sclerosis: a study using Rasch analysis

    NARCIS (Netherlands)

    Dallmeijer, Annet J.; de Groot, Vincent; Roorda, Leo D.; Schepers, Vera P. M.; Lindeman, Eline; van den Berg, Leonard H.; Beelen, Anita; Dekker, Joost

    2007-01-01

    The aim of this study was to investigate unidimensionality and differential item functioning of the SF-36 physical functioning scale (PF10) in patients with various neurological disorders. Patients: Patients post-stroke (n = 198), with multiple sclerosis (n = 151) and amyotrophic lateral sclerosis

  3. Amyotrophic lateral sclerosis mimic syndromes.

    Science.gov (United States)

    Ghasemi, Majid

    2016-04-03

    Amyotrophic lateral sclerosis (ALS) misdiagnosis has many broad implications for the patient and the neurologist. Potentially curative treatments exist for certain ALS mimic syndromes, but delay in starting these therapies may have an unfavorable effect on outcome. Hence, it is important to exclude similar conditions. In this review, we discuss some of the important mimics of ALS.

  4. 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

  5. Clinical neurogenetics: amyotrophic lateral sclerosis.

    Science.gov (United States)

    Harms, Matthew B; Baloh, Robert H

    2013-11-01

    Our understanding of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, 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 as targets for therapeutic development. This article reviews our current understanding of the heritability of ALS and 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. 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

  7. Multiple sclerosis

    Science.gov (United States)

    ... indwelling catheter Osteoporosis or thinning of the bones Pressure sores Side effects of medicines used to treat the ... Daily bowel care program Multiple sclerosis - discharge Preventing pressure ulcers Swallowing problems Images Multiple sclerosis MRI of the ...

  8. 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.

  9. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [de

  10. 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...... cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might...

  11. 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

  12. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin sheath, the material that surrounds and protects your nerve cells. This damage slows down ...

  13. 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

  14. Quantitative muscle ultrasonography in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Arts, I.M.P.; Rooij, F.G. van; Overeem, S.; Pillen, S.; Janssen, H.M.; Schelhaas, H.J.; Zwarts, M.J.

    2008-01-01

    In this study, we examined whether quantitative muscle ultrasonography can detect structural muscle changes in early-stage amyotrophic lateral sclerosis (ALS). Bilateral transverse scans were made of five muscles or muscle groups (sternocleidomastoid, biceps brachii/brachialis, forearm flexor group,

  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. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  17. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  18. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  19. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  20. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  1. Multiple Sclerosis.

    Science.gov (United States)

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  2. 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.

  3. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  4. Deontological aspects of the amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    T. M. Alekseeva

    2017-01-01

    Full Text Available One of the significant problems in deontology is the degree of awareness of terminally ill patients regarding the diagnosis and prognosis of their disease. This topic is complex and relevant, it touches ethical and psychological, legal and medical aspects. The article discusses the positive and negative aspects of fully informing patients  with amyotrophic lateral sclerosis about the fatal diagnosis. There are 2  clinical cases reflecting different approaches of this complex issue: full awareness and concealment of the diagnosis.

  5. MR imaging of amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Oba, Hiroshi; Monzawa, Shuichi (Yamanashi Medical College, Nakakoma (Japan). Hospital); Araki, Tsutomu (and others)

    1992-04-01

    Magnetic resonance imaging (MR imaging) provides a sensitive method for mapping the normal and pathological distribution of iron in the brain. High field strength MR imaging (1.5 T) was used to evaluate eight patients with amyotrophic lateral sclerosis (ALS) and 49 neurological normal control patients. All eight ALS patients showed decreased signal intensity in the motor cortex on T2-weighted images, while only one of the normal control patients showed this finding. The results suggested that the decreased signal intensity in the motor cortex in ALS was caused by the deposition of iron in this area. (author).

  6. [Local demyelination in amyotrophic lateral sclerosis].

    Science.gov (United States)

    Kvirkvelia, N; Shakarishvili, R

    2013-02-01

    It is well known that the demyelination of peripheral nerves can be diffuse or local. Pathogenesis of acute or chronic inflamentary demyelination polyneurophathy is based on diffuse demyelination. Local demyelination occured by conduction block with electoneuromyographic (ENMG) researches. It is the main characteristic of multifocal motor neuropathy (MMN). Generally it is considered, that conduction block is not usual for amyotrophic lateral sclerosis (ALS). More over, its existance excludes this diagnosis. The article discribes 3 cases of ALS with conduction block verified with ENMG researches. Article also deals with pathogenetic mechanisms of conduction block in ALS and MMN. In addition it observes the issues of differential diagnosis between ALS and MMW.

  7. Axonal excitability properties in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2006-07-01

    To investigate axolemmal ion channel function in patients diagnosed with sporadic amyotrophic lateral sclerosis (ALS). A recently described threshold tracking protocol was implemented to measure multiple indices of axonal excitability in 26 ALS patients by stimulating the median motor nerve at the wrist. The excitability indices studied included: stimulus-response curve (SR); strength-duration time constant (tauSD); current/threshold relationship; threshold electrotonus to a 100 ms polarizing current; and recovery curves to a supramaximal stimulus. Compound muscle action potential (CMAP) amplitudes were significantly reduced in ALS patients (ALS, 2.84+/-1.17 mV; controls, 8.27+/-1.09 mV, P<0.0005) and the SR curves for both 0.2 and 1 ms pulse widths were shifted in a hyperpolarized direction. Threshold electrotonus revealed a greater threshold change to both depolarizing and hyperpolarizing conditioning stimuli, similar to the 'fanned out' appearance that occurs with membrane hyperpolarization. The tauSD was significantly increased in ALS patients (ALS, 0.50+/-0.03 ms; controls, 0.42+/-0.02 ms, P<0.05). The recovery cycle of excitability following a conditioning supramaximal stimulus revealed increased superexcitability in ALS patients (ALS, 29.63+/-1.25%; controls, 25.11+/-1.01%, P<0.01). Threshold tracking studies revealed changes indicative of widespread dysfunction in axonal ion channel conduction, including increased persistent Na+ channel conduction, and abnormalities of fast paranodal K+ and internodal slow K+ channel function, in ALS patients. An increase in persistent Na+ conductances coupled with reduction in K+ currents would predispose axons of ALS patients to generation of fasciculations and cramps. Axonal excitability studies may provide insight into mechanisms responsible for motor neuron loss in ALS.

  8. Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

    DEFF Research Database (Denmark)

    McLaughlin, Russell L; Schijven, Dick; van Rheenen, Wouter

    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...

  9. Genotyping of presenilin-1 polymorphism in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Panas, M; Karadima, G; Kalfakis, N; Psarrou, O; Floroskoufi, P; Kladi, A; Petersen, M B; Vassilopoulos, D

    2000-12-01

    The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis are not fully understood. Recent studies suggest that apoptosis is involved in the abnormal neural death that occurs in this devastating disease. Presenilin-1, a transmembrane protein, seems to be implicated in apoptosis. To determine whether presenilin-1 intron 8 polymorphism has an influence in the course of amyotrophic lateral sclerosis, we examined this polymorphism genotypes in a large group of patients (n = 72) with amyotrophic lateral sclerosis and in a random sample of 213 healthy individuals. The results showed a significant difference in genotype (P < 0.04) and allele (P < 0.03) distribution between patients controls. These results suggest a possible intervention of presenilin-1 in the pathogenesis of amyotrophic lateral sclerosis.

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

    Science.gov (United States)

    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

  11. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis

    OpenAIRE

    Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P.; Rogaeva, Ekaterina A.; St George-Hyslop, Peter H.; Bernardi, Giorgio; Kawarai, Toshitaka

    2010-01-01

    The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite ...

  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. SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis.

    Science.gov (United States)

    Orlacchio, Antonio; Babalini, Carla; Borreca, Antonella; Patrono, Clarice; Massa, Roberto; Basaran, Sarenur; Munhoz, Renato P; Rogaeva, Ekaterina A; St George-Hyslop, Peter H; Bernardi, Giorgio; Kawarai, Toshitaka

    2010-02-01

    The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.

  14. 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.

  15. MR imaging appearance of amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Carvlin, M.J.; Fielding, R.; Rajan, S.S.; Muraki, A.; Manz, G.; Schellinger, D.; Hackney, D.B.

    1989-01-01

    The authors have investigated fresh (normal) and fixed (histologically proven amyotrophic lateral sclerosis [ALS]) cord specimens using high-resolution MR techniques in order to document, accurately and noninvasively, the internal structure of the spinal cord. Short TR/TE (500/27 [repetition time/echo time, msec]) and long TR/TE (2,00/54) spin-echo images were obtained in the axial, sagittal, and coronal planes at 4.7 T (Varian), with inplane resolution of either 85 x 150 or 40 x 50 μm, section thickness of 0.8-1.5 mm. In the ALS cords, the bilateral degeneration of corticospinal tracts was well visualized as areas of high signal intensity on both short TR/TE and long TR/TE images

  16. 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

  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. [Neurophysiological investigations in amyotrophic lateral sclerosis].

    Science.gov (United States)

    Camdessanché, Jean-Philippe; Lenglet, Timothée

    2014-05-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative disease which prognosis is poor. Early diagnosis permits to set up immediately adapted treatment and cares. Available diagnostic criteria are based on the detection of both the central and peripheral motor neuron injury in bulbar, cervical, thoracic and lumbar regions. Electromyographic study is the key tool to identify peripheral motor neuron involvement. Conduction velocities are systematically performed to rule out differential diagnosis. Needle examination records abnormal activities at rest and looks for neurogenic pattern during muscle contraction. Motor unit potentials morphology is modified primary to recruitment. Motor evoked potentials remain the test of choice to identify impairment of central motor neurons. For the monitoring of ALS patients, the MUNE technique (motor unit number estimation) seems the most interesting. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  19. 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.

  20. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Stephanie R Shepheard

    Full Text Available Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (p<0.001 than 12 controls (2.6±0.2 ng/mg creatinine and 19 patients with other neurological disease (Parkinson's disease and Multiple Sclerosis; 4.1±0.2 ng/mg creatinine. Pilot data of disease progression rates in 14 MND patients indicates that p75NTR(ECD levels were significantly higher (p = 0.0041 in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1(G93A mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  1. 76 FR 78823 - Schedule for Rating Disabilities; Evaluation of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2011-12-20

    ...; Evaluation of Amyotrophic Lateral Sclerosis AGENCY: Department of Veterans Affairs. ACTION: Final rule... revising the disability evaluation criterion provided for amyotrophic lateral sclerosis (ALS) to provide an...) a proposed rule that would revise the evaluation criterion for amyotrophic lateral sclerosis (ALS...

  2. 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... under this section: (1) If there is affirmative evidence that amyotrophic lateral sclerosis was not...

  3. Fatigue and Multiple Sclerosis

    Science.gov (United States)

    ... to navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... of MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  4. Altered cortical communication in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Blain-Moraes, Stefanie; Mashour, George A; Lee, Heonsoo; Huggins, Jane E; Lee, Uncheol

    2013-05-24

    Amyotrophic lateral sclerosis (ALS) is a disorder associated primarily with the degeneration of the motor system. More recently, functional connectivity studies have demonstrated potentially adaptive changes in ALS brain organization, but disease-related changes in cortical communication remain unknown. We recruited individuals with ALS and age-matched controls to operate a brain-computer interface while electroencephalography was recorded over three sessions. Using normalized symbolic transfer entropy, we measured directed functional connectivity from frontal to parietal (feedback connectivity) and parietal to frontal (feedforward connectivity) regions. Feedback connectivity was not significantly different between groups, but feedforward connectivity was significantly higher in individuals with ALS. This result was consistent across a broad electroencephalographic spectrum (4-35 Hz), and in theta, alpha and beta frequency bands. Feedback connectivity has been associated with conscious state and was found to be independent of ALS symptom severity in this study, which may have significant implications for the detection of consciousness in individuals with advanced ALS. We suggest that increases in feedforward connectivity represent a compensatory response to the ALS-related loss of input such that sensory stimuli have sufficient strength to cross the threshold necessary for conscious processing in the global neuronal workspace. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. 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

  6. 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

  7. The cortical signature of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Federica Agosta

    Full Text Available The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74. Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03. Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

  8. The cortical signature of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Agosta, Federica; Valsasina, Paola; Riva, Nilo; Copetti, Massimiliano; Messina, Maria Josè; Prelle, Alessandro; Comi, Giancarlo; Filippi, Massimo

    2012-01-01

    The aim of this study was to explore the pattern of regional cortical thickness in patients with non-familial amyotrophic lateral sclerosis (ALS) and to investigate whether cortical thinning is associated with disease progression rate. Cortical thickness analysis was performed in 44 ALS patients and 26 healthy controls. Group differences in cortical thickness and the age-by-group effects were assessed using vertex-by-vertex and multivariate linear models. The discriminatory ability of MRI variables in distinguishing patients from controls was estimated using the Concordance Statistics (C-statistic) within logistic regression analyses. Correlations between cortical thickness measures and disease progression rate were tested using the Pearson coefficient. Relative to controls, ALS patients showed a bilateral cortical thinning of the primary motor, prefrontal and ventral frontal cortices, cingulate gyrus, insula, superior and inferior temporal and parietal regions, and medial and lateral occipital areas. There was a significant age-by-group effect in the sensorimotor cortices bilaterally, suggesting a stronger association between age and cortical thinning in ALS patients compared to controls. The mean cortical thickness of the sensorimotor cortices distinguished patients with ALS from controls (C-statistic ≥ 0.74). Cortical thinning of the left sensorimotor cortices was related to a faster clinical progression (r = -0.33, p = 0.03). Cortical thickness measurements allowed the detection and quantification of motor and extramotor involvement in patients with ALS. Cortical thinning of the precentral gyrus might offer a marker of upper motor neuron involvement and disease progression.

  9. 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

  10. Amyotrophic lateral sclerosis: sonographic evaluation of dysphagia.

    Science.gov (United States)

    Tamburrini, S; Solazzo, A; Sagnelli, A; Del Vecchio, L; Reginelli, A; Monsorrò, M; Grassi, R

    2010-08-01

    The authors sought to determine the role of video ultrasonography (VUS) in the diagnostic assessment of dysphagia in patients with amyotrophic lateral sclerosis (ALS). Nine patients underwent simultaneous static and dynamic VUS examination and videofluoroscopy (VFS) of swallowing. At the static phase, VUS showed 5/9 patients had lingual atrophy. Abnormal bolus position was observed in 6/9 patients at VUS and 3/9 at VFS. Both techniques identified an inability to keep the bolus in the oral cavity in 4/9 patients. At the dynamic phase, reduced lingual movement was observed in 5/9 patients at VUS and 2/9 at VFS. Disorganised tongue movement was seen in 3/9 patients at VUS and in 2/9 at VFS. Fragmented swallowing was only visualised at VUS. Stagnation of ingested material was never visualised at VUS, whereas it was clearly depicted in 2/9 patients at VFS. VUS can be integrated into the diagnostic protocol for evaluating swallowing in patients with ALS, as it has higher sensitivity than VFS in assessing the dynamic factors that represent the early signs of dysphagia.

  11. Respiratory exercise in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Pinto, Susana; Swash, Michael; de Carvalho, Mamede

    2012-01-01

    We have evaluated the potential role of respiratory exercise by implementing specific inspiratory muscle training in a selected population of early-affected amyotrophic lateral sclerosis (ALS) patients. We studied 26 patients with ALS with normal respiratory function using two groups of patients in a parallel, control-group, randomized, delayed-start design. Patients in the first group (G1) started the active inspiratory exercise programme at entry and were followed for eight months, while the second group (G2) of patients followed a placebo exercise programme for the first four months and then active exercise for the second four-month period. The primary outcome measure was the ALSFRS. Respiratory tests, neurophysiological measurements, fatigue and quality of life scales were secondary outcomes. Analysis of covariance was used to compare changes between and within groups. Results showed that there was no significant difference between the two patient groups. Within-group analysis suggested that inspiratory exercise promotes a transient improvement in the respiratory subscore and in the maximal voluntary ventilation, peak expiratory flow, and sniff inspiratory pressure. In conclusion, there was no clear positive or negative outcome of the respiratory exercise protocol we have proposed, but we cannot rule out a minor positive effect. Exercise regimes merit more detailed clinical evaluation in ALS.

  12. Use of Sugammadex in a Patient with Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Kelsaka, Ebru; Karakaya, Deniz; Zengin, Eyüp Cağatayn

    2013-01-01

    Objective To report on general anesthesia management in amyotrophic lateral sclerosis. Case Presentation and Intervention A 47-year-old man presented with fracture of the humerus. The patient was diagnosed with amyotrophic lateral sclerosis. General anesthesia was induced with propofol, rocuronium and remifentanil. After uneventful surgical repair, TOF (train-of-four) ratio reached >0.90 at the end of operation. However, muscle strength and tidal volume were inadequate. After sugammadex 2 mg kg−1 i.v. was given, the patient was extubated 120 s later. Conclusion This case highlights that rocuronium and sugammadex can be used safely in patients with amyotrophic lateral sclerosis undergoing surgery with general anesthesia. PMID:23075763

  13. 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

  14. Amyotrophic Lateral Sclerosis (ALS and Adenosine Receptors

    Directory of Open Access Journals (Sweden)

    Ana M. Sebastião

    2018-04-01

    Full Text Available In the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS. Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early symptomatic stages that mirror those in advanced disease stages. Information starts to emerge pointing toward a beneficial role of A2A receptors (A2AR, most probably at early disease states, and a detrimental role of caffeine, in clear contrast with what occurs in other neurodegenerative diseases. However, some evidence also exists on a beneficial action of A2AR antagonists. It may happen that there are time windows where A2AR prove beneficial and others where their blockade is required. Furthermore, the same changes may not occur simultaneously at the different synapses. In line with this, it is not fully understood if ALS is a dying back disease or if it propagates in a centrifugal way. It thus seems crucial to understand how motor neuron dysfunction occurs, how adenosine receptors are involved in those dysfunctions and whether the early changes in purinergic signaling are compensatory or triggers for the disease. Getting this information is crucial before starting the design of purinergic based strategies to halt or delay disease progression.

  15. [Clinical polymorphism of amyotrophic lateral sclerosis].

    Science.gov (United States)

    Kovrazhkina, E A; Razinskaya, O D; Gubsky, L V

    To clarify clinical polymorphism of amyotrophic lateral sclerosis (ALS). The study was based on records of a hospital personalized register. Ninety-four patients, aged from 25 to 81 years, diagnosed with ALS according to El Escorial criteria were included. Electromyography and, if necessary, transcranial magnetic stimulation and magnetic-resonance tomography were used to confirm the diagnosis. Disease progression was assessed with the ARSFRS. Age at disease onset, progression rate and duration of survival of patients, rare symptoms of ALS ('extramotor'), time for palliative care (gastrostomy, non-invasive and invasive lung ventilation) and provision of the care to the patient, family history were recorded in a specially designed questionnaire. Most of the patients had sporadic ALS, only two familial cases were identified. Spinal onset ALS was found in 66.0% of the patients, bulbar onset in 29.8%, diffuse onset (spinal and bulbar motor neurons were affected simultaneously) in 4.2%. Moderate ALS progression was observed in 42.6% of the patients, mean time till death was 3.0±1.2 years. A slow progression was found in patients with cervical, low back and bulbar onset. A rapid and even 'momentary' type of progression was in diffuse and breast onset. An extremely slow progression with the long-term hospital treatment and survival >5 years was found in 9.7%. Rare ALS symptoms were represented by specific cognitive and psychological impairments, a type of frontal/temporal dysfunction, but only 5 (5.3%) patients were diagnosed with ALS-dementia. Signs of pathological muscle fatigue (myasthenic syndrome) were identified in 18 (19.1%), extrapyramidal disorders in 5 (5.3%), coordination disorders in 4 (4.3%), pain in 12 (12.8%), sensory symptoms in 5 (5.3%) of the patients. ALS is a multisystemic neurodegeneration disease though the progressive motor neuron death determines the fatal outcome.

  16. 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.

  17. Nutritional intervention for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Morassutti, I; Giometto, M; Baruffi, C; Marcon, M L; Michieletto, S; Giometto, B; Spinella, N; Paccagnella, A

    2012-09-01

    The aim of the study was to assess the consequences of early and systematic nutritional intervention on the clinical conditions of amyotrophic lateral sclerosis (ALS) patients and on the opportunity to maintain a good nutritional status for as long as possible. Thirty-three subjects with ALS. Protocol Group: 12 subjects (9 M and 3 F) monitored according to a precise nutritional intervention protocol. 21 subjects (10 M and 11 F) monitored before applying the protocol. Data recorded at the time of initial assessment were compared and expressed as the mean ± standard deviation for the Protocol Group vs. the BMI (kg/m2) 23.6 ± 4.1 vs. 21.6 ± 3.5; weight loss as a percentage of usual weight 6.6 ± 7.9 vs. 16.3 ± 8.8 (P=0.003). At six months: weight loss as a percentage of usual weight 4.9 ± 6.2 vs. 16.9 ± 10.2 (P=0.002). At 12 months: weight loss as a percentage of usual weight 7.3 ± 7.1 vs. 17.5 ± 11.1 (P=0.03). At the first follow-up visit, fewer patients in the Protocol Group were receiving enteral nutrition (25%) than patients in the CONTROL GROUP (60%). At six-month follow-up visit: 30% vs. 68%. Standard enteral nutrition formulas were used. One year after initial assessment, the mortality rate was 17% for the Protocol Group, whereas it was 24% at six months and 33% after one year for the CONTROL GROUP. If patients are treated before any significant weight loss occurs, early and specific nutritional intervention allows good nutritional status to be maintained for a longer period; if artificial nutrition is required, standard diets are able to ensure adequate clinical results.

  18. 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.

    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

  19. 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...

  20. 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…

  1. 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

  2. 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

  3. Caregiver burden in amyotrophic lateral sclerosis : A systematic review

    NARCIS (Netherlands)

    de Wit, Jessica; Bakker, Leonhard A; van Groenestijn, Annerieke C; van den Berg, Leonard H; Schröder, Carin D; Visser-Meily, Johanna Ma; Beelen, Anita

    BACKGROUND: Informal caregivers of patients with amyotrophic lateral sclerosis experience increased levels of caregiver burden as the disease progresses. Insight in the factors related to caregiver burden is needed in order to develop supportive interventions. AIM: To evaluate the evidence on

  4. 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.

  5. 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

  6. 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.

  7. Amyotrophic Lateral Sclerosis and Organ Donation: Is There Risk of Disease Transmission?

    OpenAIRE

    Holmes, Brandon B.; Diamond, Marc I.

    2012-01-01

    A new protocol suggests that patients with amyotrophic lateral sclerosis (ALS) are a viable source of tissue for organ transplantation. However, multiple lines of evidence suggest that many neurodegenerative diseases, including ALS, might progress due to transcellular propagation of protein aggregation among neurons. Transmission of the disease state from donor to host thus may be possible under the permissive circumstances of graft transplantation. We argue for careful patient selection and ...

  8. Fisetin Exerts Antioxidant and Neuroprotective Effects in Multiple Mutant hSOD1 Models of Amyotrophic Lateral Sclerosis by Activating ERK.

    Science.gov (United States)

    Wang, T H; Wang, S Y; Wang, X D; Jiang, H Q; Yang, Y Q; Wang, Y; Cheng, J L; Zhang, C T; Liang, W W; Feng, H L

    2018-05-21

    Oxidative stress exhibits a central role in the course of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease commonly found to include a copper/zinc superoxide dismutase (SOD1) gene mutation. Fisetin, a natural antioxidant, has shown benefits in varied neurodegenerative diseases. The possible effect of fisetin in ALS has not been clarified as of yet. We investigated whether fisetin affected mutant hSOD1 ALS models. Three different hSOD1-related mutant models were used: Drosophila expressing mutant hSOD1 G85R , hSOD1 G93A NSC34 cells, and transgenic mice. Fisetin treatment provided neuroprotection as demonstrated by an improved survival rate, attenuated motor impairment, reduced ROS damage and regulated redox homeostasis compared with those in controls. Furthermore, fisetin increased the expression of phosphorylated ERK and upregulated antioxidant factors, which were reversed by MEK/ERK inhibition. Finally, fisetin reduced the levels of both mutant and wild-type hSOD1 in vivo and in vitro, as well as the levels of detergent-insoluble hSOD1 proteins. The results indicate that fisetin protects cells from ROS damage and improves the pathological behaviors caused by oxidative stress in disease models related to SOD1 gene mutations probably by activating ERK, thereby providing a potential treatment for ALS. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Frontal assessment battery and frontal atrophy in amyotrophic lateral sclerosis

    OpenAIRE

    Terada, Tatsuhiro; Miyata, Jun; Obi, Tomokazu; Kubota, Manabu; Yoshizumi, Miho; Yamazaki, Kinya; Mizoguchi, Kouichi; Murai, Toshiya

    2017-01-01

    Abstract Objectives To determine the potential utility of the frontal assessment battery (FAB) in assessing cognitive impairments in amyotrophic lateral sclerosis (ALS), we investigated the association between the FAB score and regional gray matter volume, and ascertained whether the regional brain alterations related to cognitive impairments occur in relatively mild stage of ALS. Materials and Methods Twenty?four ALS patients with a Mini?Mental State Examination score of >23, a normal score ...

  10. MRI and SPECT findings in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Ukada, F.; Sawada, H.; Seriu, N.; Shindou, K.; Nishitani, N.; Kameyama, M.

    1992-01-01

    MRI was performed in 21 patients and single photon emission computed tomography (SPECT) with N-isopropyl-p- 123 I iodoamphetamine in 16 patients, to visualize upper motor neurone lesions in amyotrophic lateral sclerosis. T2-weighted MRI revealed high signal along the course of the pyramidal tract in the internal capsule and cerebral peduncle in 4 of 21 patients. SPECT images were normal in 4 patients, but uptake was reduced in the cerebral cortex that includes the motor area in 11. (orig.)

  11. Noninvasive ventilation reduces energy expenditure in amyotrophic lateral sclerosis

    OpenAIRE

    Georges , Marjolaine; Morélot-Panzini , Capucine; Similowski , Thomas; Gonzalez-Bermejo , Jesus

    2014-01-01

    International audience; BackgroundAmyotrophic lateral sclerosis (ALS) leads to chronic respiratory failure. Diaphragmatic dysfunction, a major driver of dyspnea and mortality, is associated with a shift of the burden of ventilation to extradiaphragmatic inspiratory muscles, including neck muscles. Besides, energy expenditure is often abnormally high in ALS, and this is associated with a negative prognostic value. We hypothesized that noninvasive ventilation (NIV) would relieve inspiratory nec...

  12. Cortical Thinning and Clinical Heterogeneity in Amyotrophic Lateral Sclerosis

    OpenAIRE

    Mezzapesa, Domenico Maria; D?Errico, Eustachio; Tortelli, Rosanna; Distaso, Eugenio; Cortese, Rosa; Tursi, Marianna; Federico, Francesco; Zoccolella, Stefano; Logroscino, Giancarlo; Dicuonzo, Franca; Simone, Isabella Laura

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients in...

  13. Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis

    OpenAIRE

    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 und...

  14. Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

    OpenAIRE

    Nardo, Giovanni; Pozzi, Silvia; Pignataro, Mauro; Lauranzano, Eliana; Spano, Giorgia; Garbelli, Silvia; Mantovani, Stefania; Marinou, Kalliopi; Papetti, Laura; Monteforte, Marta; Torri, Valter; Paris, Luca; Bazzoni, Gianfranco; Lunetta, Christian; Corbo, Massimo

    2011-01-01

    Background 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. Methodology/Principal Findings We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel...

  15. 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...

  16. Neuroimaging of multimodal sensory stimulation in Amyotrophic Lateral Sclerosis (ALS)

    OpenAIRE

    Lulé , Dorothée; Diekmann , Volker; Müller , Hans-Peter; Kassubek , Jan; Ludolph , Albert C; Birbaumer , Niels

    2010-01-01

    Abstract Aim: Structural and functional imaging techniques were combined to investigate sensory system function in amyotrophic lateral sclerosis (ALS). Methods: Functional magnetic resonance imaging (fMRI) was used to investigate cortical activity during visual, auditory, and somato-sensory stimulation in fourteen ALS patients and eighteen control subjects. Changes in amplitude, latency and duration of the BOLD response were modelled. Furthermore, diffusion tensor imaging was ...

  17. 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

  18. 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.

  19. Multiple sclerosis research

    International Nuclear Information System (INIS)

    Battaglia, M.A.

    1990-01-01

    This volume proceedings contains four contributions which are in INIS scope, dealing with MRI and SPECT in the diagnosis of multiple sclerosis and assessment of disease activity. (H.W.). refs.; figs.; tabs

  20. Rehabilitation and multiple sclerosis

    DEFF Research Database (Denmark)

    Dalgas, Ulrik

    2011-01-01

    In a chronic and disabling disease like multiple sclerosis, rehabilitation becomes of major importance in the preservation of physical, psychological and social functioning. Approximately 80% of patients have multiple sclerosis for more than 35 years and most will develop disability at some point......, a paradigm shift is taking place and it is now increasingly acknowledged that exercise therapy is both safe and beneficial. Robot-assisted training is also attracting attention in multiple sclerosis rehabilitation. Several sophisticated commercial robots exist, but so far the number of scientific studies...... promising. This drug has been shown to improve walking ability in some patients with multiple sclerosis, associated with a reduction of patients' self-reported ambulatory disability. Rehabilitation strategies involving these different approaches, or combinations of them, may be of great use in improving...

  1. Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems.

    Directory of Open Access Journals (Sweden)

    Mireia Herrando-Grabulosa

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology, we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.

  2. Predicting functional decline and survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ong, Mei-Lyn; Tan, Pei Fang; Holbrook, Joanna D

    2017-01-01

    Better predictors of amyotrophic lateral sclerosis disease course could enable smaller and more targeted clinical trials. Partially to address this aim, the Prize for Life foundation collected de-identified records from amyotrophic lateral sclerosis sufferers who participated in clinical trials of investigational drugs and made them available to researchers in the PRO-ACT database. In this study, time series data from PRO-ACT subjects were fitted to exponential models. Binary classes for decline in the total score of amyotrophic lateral sclerosis functional rating scale revised (ALSFRS-R) (fast/slow progression) and survival (high/low death risk) were derived. Data was segregated into training and test sets via cross validation. Learning algorithms were applied to the demographic, clinical and laboratory parameters in the training set to predict ALSFRS-R decline and the derived fast/slow progression and high/low death risk categories. The performance of predictive models was assessed by cross-validation in the test set using Receiver Operator Curves and root mean squared errors. A model created using a boosting algorithm containing the decline in four parameters (weight, alkaline phosphatase, albumin and creatine kinase) post baseline, was able to predict functional decline class (fast or slow) with fair accuracy (AUC = 0.82). However similar approaches to build a predictive model for decline class by baseline subject characteristics were not successful. In contrast, baseline values of total bilirubin, gamma glutamyltransferase, urine specific gravity and ALSFRS-R item score-climbing stairs were sufficient to predict survival class. Using combinations of small numbers of variables it was possible to predict classes of functional decline and survival across the 1-2 year timeframe available in PRO-ACT. These findings may have utility for design of future ALS clinical trials.

  3. Respiratory therapies for amyotrophic lateral sclerosis: a primer.

    Science.gov (United States)

    Gruis, Kirsten L; Lechtzin, Noah

    2012-09-01

    Respiratory complications are a common cause of morbidity and mortality in amyotrophic lateral sclerosis (ALS). Treatment of respiratory insufficiency with noninvasive ventilation (NIV) improves ALS patients' quality of life and survival. Evidence-based practice guidelines for the management of ALS patients recommend treatment of respiratory insufficiency with NIV as well as consideration of insufflation/exsufflation to improve clearance of airway secretions. Despite these recommendations respiratory therapies remain underused. In this review we provide a practical guide for the clinician to prescribe and manage respiratory therapies for the patient with ALS. Copyright © 2012 Wiley Periodicals, Inc.

  4. Multiple Sclerosis and Vitamin D

    Science.gov (United States)

    ... Editors David C. Spencer, MD Steven Karceski, MD Multiple sclerosis and vitamin D Andrew J. Solomon, MD WHAT ... caused by improper immune responses (autoimmune diseases), including multiple sclerosis (MS). A recent Patient Page in Neurology provided ...

  5. 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

    2018-01-01

    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 SOD1 G93A 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 SOD1 G93A 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.

  6. “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

  7. [Differential diagnosis and atypical subsets of amyotrophic lateral sclerosis].

    Science.gov (United States)

    Pradat, P-F; Bruneteau, G

    2006-06-01

    Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons. In the absence of any validated biological marker, the diagnosis of ALS depends upon recognition of characteristic symptoms and signs together with supportive electrophysiological findings. The diagnosis of ALS is easy to recognize in its fully developed form but during the early stages both false positive and false negative diagnoses are common. In clinical practice, diagnostic difficulties mostly arise with patients who present either with only upper motor neuron, or with only lower motor neuron signs. It may be difficult to distinguish ALS with clinically predominant lower motor neuron involvement from alternative diagnoses including spinal atrophies of adult onset, Kennedy's disease, inclusion body myositis and motor neuropathies with conduction blocks. The diagnosis of ALS related syndromes (progressive muscular atrophy, primary lateral sclerosis and progressive bulbar palsy) requires the elimination of alternate diagnoses. This paper reviews the main characteristics of diseases mimicking ALS and the atypical subsets of ALS.

  8. Seizures in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus; Uyttenboogaart, Maarten; Polman, Susan; De Keyser, Jacques

    Seizures have long been recognized to be part of the disease spectrum of multiple sclerosis (MS). While they occur in only a minority of patients with MS, epileptic seizures can have serious consequences. The treatment of MS can be epileptogenic, and antiepileptic treatment can conversely worsen the

  9. Zinc in multiple sclerosis

    DEFF Research Database (Denmark)

    Bredholt, Mikkel; Fredriksen, Jette Lautrup

    2016-01-01

    In the last 35 years, zinc (Zn) has been examined for its potential role in the disease multiple sclerosis (MS). This review gives an overview of the possible role of Zn in the pathogenesis of MS as well as a meta-analysis of studies having measured Zn in serum or plasma in patients with MS...

  10. Vaccines and multiple sclerosis

    DEFF Research Database (Denmark)

    Frederiksen, J. L.; Topsøe Mailand, M.

    2017-01-01

    An association between certain vaccinations and onset or relapse of multiple sclerosis (MS) has been debated. Based on PubMed, we made a thorough literature review and included all relevant studies, 51 on MS and 15 on optic neuritis (ON). Case studies were excluded. With the exception of a live...

  11. Vaccines and multiple sclerosis

    DEFF Research Database (Denmark)

    Mailand, Mia Topsøe; Frederiksen, Jette Lautrup

    2017-01-01

    on the database PubMed. The study found no change in risk of developing multiple sclerosis (MS) after vaccination against hepatitis B virus, human papillomavirus, seasonal influenza, measles–mumps–rubella, variola, tetanus, Bacillus Calmette-Guérin (BCG), polio, or diphtheria. No change in risk of relapse...

  12. Lead content of neuromuscular tissue in amyotrophic lateral sclerosis: case report and other considerations

    Energy Technology Data Exchange (ETDEWEB)

    Petkau, A; Sawatzky, A; Hillier, C R; Hoogstraten, J

    1974-10-01

    In a case of amyotrophic lateral sclerosis in which occupational history and laboratory evidence indicated that exposure to lead had occurred, it was found at necropsy that in nerve, spinal cord, and cardiac and skeletal muscle tissues the lead content was abnormally high. Significantly elevated levels of lead were also found however, in nerve, spinal cord and muscle tissue in other cases of amyotrophic lateral sclerosis that had not been exposed to lead during life. A reassessment of the role of lead in amyotrophic lateral sclerosis is indicated. (CIS Abstract Vol. 2)

  13. 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.

  14. 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.

  15. Amyotrophic lateral sclerosis and organ donation: is there risk of disease transmission?

    Science.gov (United States)

    Holmes, Brandon B; Diamond, Marc I

    2012-12-01

    A new protocol suggests that patients with amyotrophic lateral sclerosis (ALS) are a viable source of tissue for organ transplantation. However, multiple lines of evidence suggest that many neurodegenerative diseases, including ALS, might progress due to transcellular propagation of protein aggregation among neurons. Transmission of the disease state from donor to host thus may be possible under the permissive circumstances of graft transplantation. We argue for careful patient selection and close longitudinal follow-up of recipients when harvesting organs from individuals with neurodegenerative disease, especially dominantly inherited forms. Copyright © 2012 American Neurological Association.

  16. Outcomes research in amyotrophic lateral sclerosis: lessons learned from the amyotrophic lateral sclerosis clinical assessment, research, and education database.

    Science.gov (United States)

    Miller, Robert G; Anderson, Fred; Brooks, Benjamin Rix; Mitsumoto, Hiroshi; Bradley, Walter G; Ringel, Steven P

    2009-01-01

    To examine the care of patients with ALS following the publication of the standardized recommendations for the management of patients with amyotrophic lateral sclerosis (ALS) published in 1999 by the American Academy of Neurology. Specific aspects of ALS patient management have been evaluated serially using a national Amyotrophic Lateral Sclerosis Clinical Assessment, Research, and Education (ALS CARE) database to encourage compliance with these recommendations and to assure continuing quality improvement. The most recent analysis of 5,600 patients shows interesting epidemiological observations and treatment trends. Proper management of many ALS symptoms has increased substantially since the first publication of the guidelines, and awareness of pseudobulbar affect has increased. Other recommendations are underutilized: Only 9% undergo percutaneous endoscopic gastrostomy, although this procedure was recommended in 22% of patients; and noninvasive positive pressure ventilation was used by only 21% of patients despite being associated with improved 5-year survival rates. This observational database has been a useful tool in monitoring compliance with the standard of care for patients with ALS and may have resulted in greater adherence to guidelines.

  17. Increased expression of Myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients

    KAUST Repository

    Conti, Antonio; Riva, Nilo; Pesca, Mariasabina Sabina; Iannaccone, Sandro; Cannistraci, Carlo; Corbo, Massimo; Previtali, Stefano Carlo; Quattrini, Angelo; Alessio, Massimo

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a severe and fatal neurodegenerative disease of still unknown pathogenesis. Recent findings suggest that the skeletal muscle may play an active pathogenetic role. To investigate ALS's pathogenesis and to seek

  18. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis.

    NARCIS (Netherlands)

    Oey, P.L.; Vos, P.E.; Wieneke, G.H.; Wokke, J.H.J.; Blankestijn, P.J.; Karemaker, J.M.

    2002-01-01

    The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

  19. Subtle involvement of the sympathetic nervous system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Oey, P. Liam; Vos, Pieter E.; Wieneke, George H.; Wokke, John H. J.; Blankestijn, Peter J.; Karemaker, John M.

    2002-01-01

    The literature on the involvement of the autonomic nervous system (ANS) in amyotrophic lateral sclerosis (ALS) is conflicting. We therefore investigated several aspects of autonomic function, namely muscle sympathetic nerve activity (MSNA), blood pressure, cardiac function (electrocardiogram; ECG),

  20. 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

  1. Chronic progressive multiple sclerosis

    International Nuclear Information System (INIS)

    Buffoli, A.; Micheletti, E.; Capra, R.; Mattioli, F.; Marciano', N.

    1991-01-01

    A long-lasting immunological suppression action seems to be produced by total lymphoid irradiation; some authors emphasize the favorable effect of this treatment on chronic progressive multiple sclerosis. In order to evaluate the actual role of TLI, 6 patients affected with chronic progressive multiple sclerosis were submitted to TLI with shaped and personalized fields at the Istituto del Radio, University of Brescia, Italy. The total dose delivered was 19.8 Gy in 4 weeks, 1.8 Gy/day, 5d/w; a week elapsed between the first and the second irradiation course. Disability according to Kurtzke scale was evaluated, together with blood lymphocyte count and irradiation side-effects, over a mean follow-up period of 20.8 months (range: 13-24). Our findings indicate that: a) disease progression was not markedly reduced by TLI; b) steroid hormones responsivity was restored after irradiation, and c) side-effects were mild and tolerable

  2. Suicide and multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E N; Stenager, Egon; Koch-Henriksen, N

    1992-01-01

    In a nationwide investigation the risk of death by suicide for patients with multiple sclerosis (MS) was assessed using records kept at the Danish Multiple Sclerosis Registry (DMSR) and the Danish National Register of Cause of Death. The investigation covers all MS patients registered with DSMR...... with an onset of the disease within the period 1953-85, or for whom MS was diagnosed in the same period. Fifty three of the 5525 cases in the onset cohort group committed suicide. Using the figures from the population death statistics by adjustment to number of subjects, duration of observation, sex, age......, and calendar year at the start of observation, the expected number of suicides was calculated to be nearly 29. The cumulative lifetime risk of suicide from onset of MS, using an actuarial method of calculation, was 1.95%. The standard mortality ratio (SMR) of suicide in MS was 1.83. It was highest for males...

  3. Treatment of Multiple Sclerosis

    OpenAIRE

    Bošnjak-Pašić, Marija; Vidrih, Branka; Miškov, Snježana; Demarin, Vida

    2009-01-01

    Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system, characterized by multifocal inflammatory destruction of myelin, axonal damage and loss of oligodendrocytes. The disease is carried through two stages: inflammatory and degenerative. The most common form of disease in approximately 85% of the cases is RRMS (relapsing-remitting form). The treatment of MS is divided into: treatment of the acute phase of illness, prevention of new relapses and di...

  4. Midkine and multiple sclerosis

    OpenAIRE

    Takeuchi, Hideyuki

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4+CD25+FoxP3+ regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the d...

  5. Racing against the clock: recognizing, differentiating, diagnosing, and referring the amyotrophic lateral sclerosis patient.

    Science.gov (United States)

    Shook, Steven J; Pioro, Erik P

    2009-01-01

    Recognition of the early symptoms and signs in amyotrophic lateral sclerosis, exclusion of alternative diagnoses, and referral to a tertiary center can have a significant positive impact on the lives of patients and their caregivers. This article provides the most current amyotrophic lateral sclerosis criteria, as well as helpful clinical clues to the diagnosis. An approach to laboratory testing, electrodiagnostic testing, and imaging to exclude diseases that mimic ALS also are discussed, as are atypical presentations that can confound timely diagnosis.

  6. Rehabilitation in multiple sclerosis.

    Science.gov (United States)

    Kubsik-Gidlewska, Anna M; Klimkiewicz, Paulina; Klimkiewicz, Robert; Janczewska, Katarzyna; Woldańska-Okońska, Marta

    2017-07-01

    The aim of the study is to present a strategy of rehabilitation in multiple sclerosis on the basis of the latest developments in the field of physiotherapy. The publications on the problem discuss a wide range of methods of physiotherapy that can be used in order to reduce the degree of disability and alleviate the symptoms associated with the disease. The complexity of the disease, the difficulty in determining the appropriate treatment and a wide range of symptoms require a comprehensive approach to the patient, which would include both pharmacology and neurorehabilitation. Rehabilitation, which includes psychotherapy and symptomatic therapy, is regarded nowadays as the best form of treatment for multiple sclerosis. An indepth diagnostic assessment of functional status and prognosis should be carried out before the start of the rehabilitation process. The prognosis should take into account the mental state, the neurological status and the awareness of the patient. The kinesiotherapy program in multiple sclerosis is based on a gradation of physiotherapy which assumes a gradual transition from basic movements to more complex ones till global functions are obtained. The most appropriate form of treatment is functional rehabilitation combined with physical procedures. Recent reports indicate the need for aerobic training to be included in the rehabilitation program. The introduction of physical activities, regardless of the severity of the disease, will reduce the negative effects of akinesia, and thus increase the functional capabilities of all body systems.

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

    Directory of Open Access Journals (Sweden)

    Chiara Crespi

    Full Text Available 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.

  8. 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.

  9. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shepheard, Stephanie R; Chataway, Tim; Schultz, David W; Rush, Robert A; Rogers, Mary-Louise

    2014-01-01

    Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A) mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (pneurotrophin receptor p75 was also readily detected in SOD1(G93A) mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  10. 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.

  11. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Daoud, H; Valdmanis, P N; Kabashi, E; Dion, P; Dupré, N; Camu, W; Meininger, V; Rouleau, G A

    2009-02-01

    Mutations in the TARDBP gene, which encodes the TAR DNA binding protein (TDP-43), have been described in individuals with familial and sporadic amyotrophic lateral sclerosis (ALS). We screened the TARDBP gene in 285 French sporadic ALS patients to assess the frequency of TARDBP mutations in ALS. Six individuals had potentially deleterious mutations of which three were novel including a Y374X truncating mutation and P363A and A382P missense mutations. This suggests that TARDBP mutations may predispose to ALS in approximately 2% of the individuals followed in this study. Our findings, combined with those from other collections, brings the total number of mutations in unrelated ALS patients to 17, further suggesting that mutations in the TARDBP gene have an important role in the pathogenesis of ALS.

  12. RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Stéphane Mathis

    2018-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

  13. RNA-Targeted Therapies and Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Mathis, Stéphane; Le Masson, Gwendal

    2018-01-15

    Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS. As in spinal muscular atrophy, RNA-targeted therapies have been proposed as potential strategies for treating this neurodegenerative disorder. Successes achieved in various animal models of ALS have proven that RNA therapies are both safe and effective. With careful consideration of the applicability of such therapies in humans, it is possible to anticipate ongoing in vivo research and clinical trial development of RNA therapies for treating ALS.

  14. Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

    Science.gov (United States)

    Carlesi, Cecilia; Pasquali, Livia; Piazza, Selina; Lo Gerfo, Annalisa; Caldarazzo Ienco, Elena; Alessi, Rosaria; Fornai, Francesco; Siciliano, Gabriele

    2011-03-01

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis. Here we review some of the recent progress in promoting therapeutic strategies for neurodegeneration.

  15. Is erythropoietin gene a modifier factor in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Ghezzi, Serena; Del Bo, Roberto; Scarlato, Marina; Nardini, Martina; Carlesi, Cecilia; Prelle, Alessandro; Corti, Stefania; Mancuso, Michelangelo; Briani, Chiara; Siciliano, Gabriele; Murri, Luigi; Bresolin, Nereo; Comi, Giacomo Pietro

    2009-05-01

    To investigate the role of erythropoietin (EPO) as genetic determinant in the susceptibility to sporadic amyotrophic lateral sclerosis (SALS). We sequenced a 259-bp region spanning the 3'hypoxia-responsive element of the EPO gene in 222 Italian SALS patients and 204 healthy subjects, matched for age and ethnic origin. No potentially causative variation was detected in SALS subjects; in addition, two polymorphic variants (namely C3434T and G3544T) showed the same genotype and haplotype frequencies in patients and controls. Conversely, a weak but significant association between G3544T and age of disease onset was observed (p=0.04). Overall, our data argue against the hypothesis of EPO as a genetic risk factor for motor neuron dysfunction, at least in Italian population. However, further studies on larger cohort of patients are needed to confirm the evidence of EPO gene as modifier factor.

  16. Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors.

    Science.gov (United States)

    Gargiulo Monachelli, G; Meyer, M; Rodríguez, G E; Garay, L I; Sica, R E P; De Nicola, A F; González Deniselle, M C

    2011-01-01

    Negative prognostic factors in amyotrophic lateral sclerosis include advanced age, shorter time from disease onset to diagnosis, bulbar onset and rapid progression rate. To compare progesterone (PROG) and cortisol serum levels in patients and controls and ascertain its relationship to prognostic factors and survival. We assessed serum hormonal levels in 27 patients and 21 controls. Both hormones were 1.4-fold higher in patients. PROG showed a negative correlation with age, positive correlation with survival and positive trend with time to diagnosis. Increased PROG was observed in spinal onset and slow progression patients. No correlation was demonstrated with cortisol. Increased hormonal levels in patients are probably due to hypothalamic-pituitary-adrenal axis activation. Nevertheless, in this preliminary report only PROG correlated positively with factors predicting better prognosis and survival. We hypothesize endogenous PROG and cortisol may be engaged in differential roles, the former possibly involved in a neuroprotective response. © 2010 John Wiley & Sons A/S.

  17. Amyotrophic lateral sclerosis or not: Keys for the diagnosis.

    Science.gov (United States)

    Lenglet, T; Camdessanché, J-P

    2017-05-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease (MND) which prognosis is poor. Early diagnosis permit to set up immediately adapted treatment and cares. Available diagnostic criteria are based on the detection of both central and peripheral motor neuron injury in bulbar, cervical, thoracic and lumbar regions. Electrodiagnostic (EDX) tests are the key tools to identify peripheral motor neuron involvement. Needle examination records abnormal activities at rest, and looks for neurogenic pattern during muscle contraction. Motor unit potentials morphology is modified primary to recruitment. Motor evoked potentials remain the test of choice to identify impairment of central motor neurons. In the absence of diagnostic biomarker of ALS and among essential investigations of suspected MND, a careful clinical and neurophysiological work-up is essential to rule out the differential diagnosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Tefera, Tesfaye W; Tan, Kah Ni; McDonald, Tanya S; Borges, Karin

    2017-06-01

    This review summarises the recent findings on metabolic treatments for epilepsy and Amyotrophic Lateral Sclerosis (ALS) in honour of Professor Ursula Sonnewald. The metabolic impairments in rodent models of these disorders as well as affected patients are being discussed. In both epilepsy and ALS, there are defects in glucose uptake and reduced tricarboxylic acid (TCA) cycling, at least in part due to reduced amounts of C4 TCA cycle intermediates. In addition there are impairments in glycolysis in ALS. A reduction in glucose uptake can be addressed by providing the brain with alternative fuels, such as ketones or medium-chain triglycerides. As anaplerotic fuels, such as the triglyceride of heptanoate, triheptanoin, refill the TCA cycle C4/C5 intermediate pool that is deficient, they are ideal to boost TCA cycling and thus the oxidative metabolism of all fuels.

  19. 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

  20. 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.

  1. CSF glial markers correlate with survival in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Süssmuth, S D; Sperfeld, A D; Hinz, A; Brettschneider, J; Endruhn, S; Ludolph, A C; Tumani, H

    2010-03-23

    In neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), CSF biomarkers are increasingly studied to evaluate their relevance for differential diagnosis, disease progression, and understanding of pathophysiologic processes. To identify a biomarker profile of neuronal and glial CSF proteins to discriminate ALS from other motor neuron diseases (MND) and to assess whether baseline levels of CSF measures in ALS are associated with the course of the disease. A total of 122 consecutive subjects with MND were included in this cross-sectional study (ALS, n = 75; lower motor neuron syndrome, n = 39; upper motor neuron diseases, n = 8). Clinical follow-up included 76 patients. We determined baseline levels of protein tau and astroglial S100beta in CSF and microglial sCD14 in CSF and serum in relation to diagnosis, duration of disease, and survival. CSF tau was significantly elevated in ALS and upper motor neuron diseases as compared to lower motor neuron diseases and controls. CSF S100beta levels were significantly lower in lower motor neuron diseases as compared to other MND. CSF concentrations of S100beta and sCD14 correlated with the survival time in patients with ALS. In motor neuron diseases, CSF tau elevation indicates the degeneration of upper motor neurons, while S100 beta and sCD14 may indicate the activation of CNS glial cells. Because S100beta and sCD14 concentrations correlate with survival in amyotrophic lateral sclerosis (ALS), we suppose that the combination of both markers may be useful to obtain prognostic information in patients with ALS.

  2. Interferon Treatment of Multiple Sclerosis

    OpenAIRE

    Alajbegovic, Azra; Deljo, Dervis; Alajbegovic, Salem; Djelilovic-Vranic, Jasminka; Todorovic, Ljubica; Tiric-Campara, Merita

    2012-01-01

    Introduction: In the treatment of Multiple Sclerosis (MS) differ: treatment of relapse, treatment slow the progression of the disease (immunomodulators and immunosuppression), and symptomatic treatment. The aim: The aim of this study is to analyze the application of interferon therapy in the treatment of MS-E: Process the disease, patients with multiple sclerosis who have passed the commission for multiple sclerosis at the Neurology Clinic of Clinical Center of Sarajevo University as a refere...

  3. Vascular comorbidities in multiple sclerosis

    DEFF Research Database (Denmark)

    Thormann, Anja; Magyari, Melinda; Koch-Henriksen, Nils

    2016-01-01

    To investigate the occurrence of vascular comorbidities before and after the clinical onset of multiple sclerosis. In this combined case-control and cohort study, all Danish born citizens with onset of multiple sclerosis 1980-2005 were identified from the Danish Multiple Sclerosis Registry...... and randomly matched with controls regarding year of birth, gender, and municipality on January 1st in the year of multiple sclerosis (MS) onset (index date). Individual-level information on comorbidities was obtained from several independent nationwide registries and linked to the study population by unique...

  4. Substantial Early, But Nonprogressive Neuronal Loss in Multiple Sclerosis (MS) Spinal Cord

    NARCIS (Netherlands)

    Schirmer, Lucas; Albert, Monika; Buss, Armin; Schulz-Schaeffer, Walter J.; Antel, Jack P.; Brueck, Wolfgang; Stadelmann, Christine

    2009-01-01

    Research in multiple sclerosis (MS) has recently been focusing on the extent of neuroaxonal damage and its contribution to disease outcome. In the present Study, we examined spinal cord tissue from 30 clinically well-characterized MS patients. MS, amyotrophic lateral sclerosis (ALS), and control

  5. Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Angelov, D N; Waibel, S; Guntinas-Lichius, O; Lenzen, M; Neiss, W F; Tomov, T L; Yoles, E; Kipnis, J; Schori, H; Reuter, A; Ludolph, A; Schwartz, M

    2003-04-15

    Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions. In acute degeneration after facial nerve axotomy, the number of surviving motor neurons was almost two times higher in Cop-1-vaccinated mice than in nonvaccinated mice, or in mice injected with PBS emulsified in complete Freund's adjuvant (P amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 +/- 7 days (n = 15) to 263 +/- 8 days (n = 14; P sclerosis. The protocol for non-autoimmune neurodegenerative diseases such as amyotrophic lateral sclerosis, remains to be established by future studies.

  6. High-Resolution 7T MR Imaging of the Motor Cortex in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Cosottini, M; Donatelli, G; Costagli, M; Caldarazzo Ienco, E; Frosini, D; Pesaresi, I; Biagi, L; Siciliano, G; Tosetti, M

    2016-03-01

    Amyotrophic lateral sclerosis is a progressive motor neuron disorder that involves degeneration of both upper and lower motor neurons. In patients with amyotrophic lateral sclerosis, pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of iron and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of iron-related signal changes in the primary motor cortex of patients with amyotrophic lateral sclerosis as possible in vivo biomarkers of upper motor neuron impairment. Twenty-two patients with definite amyotrophic lateral sclerosis and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in patients and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. Ultra-high field MR imaging revealed atrophy and signal hypointensity in the deep layers of the primary motor cortex of patients with amyotrophic lateral sclerosis with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with upper motor neuron impairment (r = -0.47; P amyotrophic lateral sclerosis. Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of upper motor neuron impairment in patients with amyotrophic lateral sclerosis. © 2016 by American Journal of Neuroradiology.

  7. Vaccines in Multiple Sclerosis.

    Science.gov (United States)

    Williamson, Eric M L; Chahin, Salim; Berger, Joseph R

    2016-04-01

    Vaccinations help prevent communicable disease. To be valuable, a vaccine's ability to prevent disease must exceed the risk of adverse effects from administration. Many vaccines present no risk of infection as they are comprised of killed or non-infectious components while other vaccines consist of live attenuated microorganisms which carry a potential risk of infection-particularly, in patients with compromised immunity. There are several unique considerations with respect to vaccination in the multiple sclerosis (MS) population. First, there has been concern that vaccination may trigger or aggravate the disease. Second, disease-modifying therapies (DMTs) employed in the treatment of MS may increase the risk of infectious complications from vaccines or alter their efficacy. Lastly, in some cases, vaccination strategies may be part of the treatment paradigm in attempts to avoid complications of therapy.

  8. Multiple sclerosis and suicide.

    Science.gov (United States)

    Feinstein, Anthony; Pavisian, Bennis

    2017-06-01

    Mortality rates are elevated in people with multiple sclerosis (MS) relative to the general population. There is, however, some uncertainty whether suicide contributes to this. Epidemiological data suggest that the standardized mortality ratio (SMR) for suicide in MS is approximately twice that of the general population with younger males in the first few years following diagnosis most at risk. Rates of suicidal intent, a potential harbinger of more self-destructive behavior, are also elevated, but the frequency with which intent is followed by suicide is not known. Depression, severity of depression, social isolation, and alcohol abuse are associated with thoughts of suicide. The variables linked with suicide and suicidal intent are therefore well defined and should be readily available from routine clinical inquiry. While vigilance on the part of clinicians is required, particularly in the context of high-risk patients, it is also recognized that prevention is dependent on full disclosure of intent.

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

    Science.gov (United States)

    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.

  10. 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.

  11. 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

    2017-01-09

    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.

  12. 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.

  13. Impaired Perception of Emotional Expression in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Oh, Seong Il; Oh, Ki Wook; Kim, Hee Jin; Park, Jin Seok; Kim, Seung Hyun

    2016-07-01

    The increasing recognition that deficits in social emotions occur in amyotrophic lateral sclerosis (ALS) is helping to explain the spectrum of neuropsychological dysfunctions, thus supporting the view of ALS as a multisystem disorder involving neuropsychological deficits as well as motor deficits. The aim of this study was to characterize the emotion perception abilities of Korean patients with ALS based on the recognition of facial expressions. Twenty-four patients with ALS and 24 age- and sex-matched healthy controls completed neuropsychological tests and facial emotion recognition tasks [ChaeLee Korean Facial Expressions of Emotions (ChaeLee-E)]. The ChaeLee-E test includes facial expressions for seven emotions: happiness, sadness, anger, disgust, fear, surprise, and neutral. The ability to perceive facial emotions was significantly worse among ALS patients performed than among healthy controls [65.2±18.0% vs. 77.1±6.6% (mean±SD), p=0.009]. Eight of the 24 patients (33%) scored below the 5th percentile score of controls for recognizing facial emotions. Emotion perception deficits occur in Korean ALS patients, particularly regarding facial expressions of emotion. These findings expand the spectrum of cognitive and behavioral dysfunction associated with ALS into emotion processing dysfunction.

  14. Dynamic markers of altered gait rhythm in amyotrophic lateral sclerosis

    Science.gov (United States)

    Hausdorff, J. M.; Lertratanakul, A.; Cudkowicz, M. E.; Peterson, A. L.; Kaliton, D.; Goldberger, A. L.

    2000-01-01

    Amyotrophic lateral sclerosis (ALS) is a disorder marked by loss of motoneurons. We hypothesized that subjects with ALS would have an altered gait rhythm, with an increase in both the magnitude of the stride-to-stride fluctuations and perturbations in the fluctuation dynamics. To test for this locomotor instability, we quantitatively compared the gait rhythm of subjects with ALS with that of normal controls and with that of subjects with Parkinson's disease (PD) and Huntington's disease (HD), pathologies of the basal ganglia. Subjects walked for 5 min at their usual pace wearing an ankle-worn recorder that enabled determination of the duration of each stride and of stride-to-stride fluctuations. We found that the gait of patients with ALS is less steady and more temporally disorganized compared with that of healthy controls. In addition, advanced ALS, HD, and PD were associated with certain common, as well as apparently distinct, features of altered stride dynamics. Thus stride-to-stride control of gait rhythm is apparently compromised with ALS. Moreover, a matrix of markers based on gait dynamics may be useful in characterizing certain pathologies of motor control and, possibly, in quantitatively monitoring disease progression and evaluating therapeutic interventions.

  15. Exposing asymmetric gray matter vulnerability in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    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.

  16. [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.

  17. [Pyramidal syndrome in lateral amyotrophic sclerosis: clinico-morphological analysis].

    Science.gov (United States)

    Musaeva, L S; Zavalishin, I A; Gulevskaia, T S

    2003-01-01

    Retrospective clinical analysis with a special focus on pyramidal syndrome expression in the disease course as well as morphological study of brain and spinal structures in all levels of cortical-spinal projection (from brain motor cortex to spinal lumbar segments) have been conducted for 11 section cases of lateral amyotrophic sclerosis (LAS), sporadic type. Two groups of patients were studied: with pronounced pyramidal syndrome (spasticity, hyperreflexia, etc)--7 cases and with some signs of pyramidal deficiency (anisoreflexia, stability of peritoneal reflexes)--4 cases. Pyramidal syndrome in LAS is considered as an emergence of current neurodegenerative process, embracing a significant part of upper motor neurons of both precentral convolution and its axons along the whole length of cerebrospinal axis in the form of cytoplasmic inclusions and axonal spheroids. A presence of pathomorphological changes in other upper segmental structures of motor control reveals their role in pyramidal deficiency. Comparative analysis showed that expression of pyramidal syndrome signs and its correlation to atrophic paresis appearances is specifically determined by the severity of upper and lower motor neurons lesions. With regard to morphological changes in CNS structures, the peculiarities of some pyramidal syndrome appearances in LAS are analyzed.

  18. The epidemiology of amyotrophic lateral sclerosis in Reggio Emilia, Italy.

    Science.gov (United States)

    Bonvicini, Francesca; Vinceti, Marco; Marcello, Norina; Rodolfi, Rossella; Rinaldi, Manuela

    2008-12-01

    Incidence and mortality rates of amyotrophic lateral sclerosis (ALS) vary between countries, and in some studies appear to increase over time. We performed a study to assess ALS incidence in a northern Italy area over a 10-year period. We identified the new cases of probable or definite ALS diagnosed among residents in Reggio Emilia province between 1996 and 2005 using several sources of data, such as death certificates, clinical records, hospital discharge registers and drug prescriptions. A total of 94 newly-diagnosed patients were identified. The average standardized incidence in the period was 2.0 and 1.0 cases/100,000/year, using the Italian and the world population, respectively, as reference. There was no variation in rates over time. Incidence was 1.3 in males and 0.8 in females. No cases were observed in patients under 35 years of age. Incidence increased after the age of 55 years, reaching a peak in the group aged 70-74 years and declining thereafter. We concluded that ALS incidence in this population was similar to that observed in other Italian regions and European countries, and no variation was identified during the study period.

  19. Frontotemporal Dysfunction in Amyotrophic Lateral Sclerosis: A Discriminant Function Analysis.

    Science.gov (United States)

    Nidos, Andreas; Kasselimis, Dimitrios S; Simos, Panagiotis G; Rentzos, Michael; Alexakis, Theodoros; Zalonis, Ioannis; Zouvelou, Vassiliki; Potagas, Constantin; Evdokimidis, Ioannis; Woolley, Susan C

    2016-01-01

    There is growing evidence for extramotor dysfunction (EMd) in amyotrophic lateral sclerosis (ALS), with a reported prevalence of up to 52%. In the present study, we explore the clinical utility of a brief neuropsychological battery for the investigation of cognitive, behavioral, and language deficits in patients with ALS. Thirty-four consecutive ALS patients aged 44-89 years were tested with a brief neuropsychological battery, including executive, behavioral, and language measures. Patients were initially classified as EMd or non-EMd based on their scores on the frontal assessment battery (FAB). Between-group comparisons revealed significant differences in all measures (p < 0.01). Discriminant analysis resulted in a single canonical function, with all tests serving as significant predictors. This function agreed with the FAB in 13 of 17 patients screened as EMd and identified extramotor deficits in 2 additional patients. Overall sensitivity and specificity estimates against FAB were 88.2%. We stress the importance of discriminant function analysis in clinical neuropsychological assessment and argue that the proposed neuropsychological battery may be of clinical value, especially when the option of extensive and comprehensive neuropsychological testing is limited. The psychometric validity of an ALS-frontotemporal dementia diagnosis using neuropsychological tests is also discussed. © 2015 S. Karger AG, Basel.

  20. Current view and perspectives in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Stéphane Mathis

    2017-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS, identified as a distinct clinical entity by Charcot since the end of the nineteenth century, is a devastating and fatal neurodegenerative disorder that affects motor neurons in the brain, brainstem and spinal cord. Survival of patients with ALS is associated with several factors such as clinical phenotype, age at onset, gender, early presence of respiratory failure, weight loss and treatment with Riluzole (the only disease-modifying drug approved for this disease. Nowadays, there is still no curative treatment for ALS: palliative care and symptomatic treatment are therefore essential components in the management of these patients. Nevertheless, the scientific knowledge in the field of ALS motor neuron degeneration is growing, with the prospect of new treatments. Based on this physiopathological knowledge, several new therapeutic targets are being studied, involving various mechanisms such as excitotoxicity, neuroinflammation, mitochondrial dysfunction, oxidative stress, RNA metabolism and other attractive concepts. Moreover, it is also important to identify reliable biomarkers that will be essential components for future therapeutic development and study design in ALS. In this review, we present the main recent advances and promising therapeutics and biomarkers in the field of ALS.

  1. [Amyotrophic lateral sclerosis--when planning is almost too late].

    Science.gov (United States)

    Praxmarer, Veronika; Lahrmann, Heinz

    2006-05-01

    Amyotrophic lateral sclerosis (ALS) is a disease with progressive muscle weakness, also affecting respiratory muscles. In the terminal phase most patients experience a progression. Nutrition, speech and breathing capacity decrease. It is important to inform the patient and relatives in time and to give them a chance to decide. "Care Planning" and "Advance Directives" especially concerning ventilation reduces fear and helps the doctors and carers to decide, following the will of the patient. Nobody knows the speed of the progression. The patient in this case had few subjective symptoms at the time of the family conference. Progression till death lasted one month only. Treatment of his dyspnoe was not optimised, but during care all decisions were based on the actual will of the patient. Generally nocturnal hypoventilation, for instance non-invasive ventilation by BiPAP-mode, can relieve symptoms of dyspnoe in ALS patients. Low-dose morphine and/or benzodiazepine relieve respiratory discomfort and remove the negative spiral of dysnoe-fear-dyspnoe. Oxygen therapy is usually not needed (only in the very last stages of the disease) and is not recommended especially during the night. Hypercapnia can occur because of hypoventilation. This can cause growing unconsciousness and maybe death during sleep. Prolonging life is only possible by invasive long-term ventilation with all the problems of intensive care measures. The patient could have been given low dose morphine from the time of the family conference. Ventilation by CPAP-mode was insufficient for him.

  2. Workplace exposures and the risk of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Fang, Fang; Quinlan, Patricia; Ye, Weimin; Barber, Marie K; Umbach, David M; Sandler, Dale P; Kamel, Freya

    2009-09-01

    Occupation has been suggested to play a role in amyotrophic lateral sclerosis (ALS) etiology, but detailed information on the importance of specific workplace exposures is lacking. Our aim was to assess the relationship between workplace exposures and the risk of ALS and to evaluate potential interactions between these exposures and smoking. We conducted a case-control study in New England between 1993 and 1996, comprising 109 cases and 253 controls who completed a structured interview covering occupations and workplace exposures. Unconditional logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for ALS. Analyses were conducted among the entire study population and after stratification by smoking. We observed a higher risk of ALS for construction workers excluding supervisors (OR = 2.9; 95% CI, 1.2-7.2) and precision metal workers (OR = 3.5; 95% CI, 1.2-10.5). Self-reported exposures to paint strippers; cutting, cooling, or lubricating oils; antifreeze or coolants; mineral or white spirits; and dry cleaning agents each appeared to be associated with a 60-90% higher risk. Specific chemicals related to a > 50% increase in risk of ALS included aliphatic chlorinated hydrocarbons, glycols, glycol ethers, and hexane. Relative risks associated with these workplace exposures and chemicals were greater among nonsmokers and persisted in mutually adjusted models. Our data suggest that certain occupations and workplace exposures may be associated with increased risk of ALS. These results need to be confirmed in independent populations.

  3. Financial cost of amyotrophic lateral sclerosis: a case study.

    Science.gov (United States)

    Obermann, M; Lyon, M

    2015-03-01

    There are only a few recently published reports of the cost of amyotrophic lateral sclerosis (ALS) care in the United States. Our objectives were to: 1) report annual and disease-duration costs; 2) provide costs related to specific care and services; 3) present costs by payor; and 4) identify strategies and resources that can be offered to patients to assist with the financial burden of ALS. Over a 10-year period (2001-2010), all expenses related to the cost of care for an individual patient were collected concurrently and then analyzed in 2012. Results showed that total disease-duration costs were $1,433,992 (85% paid by insurance, 9% paid by family, 6% paid by charities). The highest costs were for in-home caregivers ($669,150), ventilation ($212,430) and hospital care ($114,558). In conclusion, this case study illustrates costs of care for ALS as a burden for patients that may impact treatment decisions. Charity organizations and insurance case-managers provide services to patients that can help reduce this burden. Costs for specific services as well as resources identified by this study offer physicians and other healthcare providers data-based cost of care information and strategies to share with their patients.

  4. Brain perfusion imaging in amyotrophic lateral sclerosis with dementia

    International Nuclear Information System (INIS)

    Ishikawa, Takehisa; Morita, Mitsuya; Nakano, Imaharu

    2007-01-01

    Single photon emission computed tomography (SPECT) studies have been applied for evaluation of regional cerebral blood flow (rCBF) in various neurodegenerative disorders including amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALS-D). Brain perfusion SPECT using statistical image analysis is useful for accurate and objective diagnosis to evaluate slight decreases in rCBF, even in cases difficult to assess by visual inspection. We have used statistical parametric mapping (SPM), three-dimensional stereotactic surface projection (3D-SSP), easy Z-score imaging system (eZIS) as statistical image analyses. ALS-D cases, even if a case manifests minimal mentality change, showed obvious rCBF reduction in the bilateral prefrontal area with some irregularity and laterality of its decrease. This abnormality was clear in ALS-D compared with classic ALS. Our study has demonstrated that brain perfusion SPECT imaging using statistical image analyses is quite useful as an adjunct to presume the existence of dementia in ALS, even if ALS patients have trouble in verbal or manual communication of the language because of progressive bulbar symptoms and muscle weakness. Thus, for ALS patients with any subtle signs and symptoms suggesting dementia, we recommend a SPECT study with use of statistical image analyses. (author)

  5. 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 < 0.05) and more men with a normal body mass index than in the general population (47.2%, P < 0.001). The percentage of individuals who had never smoked was greater for the ALS cohort (55.8%, P ≤ 0.001), and the prevalence of dyslipidemia was lower (38.7%) compared with the general population (74.4%, P < 0.001). ALS patients had good cardiometabolic health, with evidence of a reduced vascular risk profile. Muscle Nerve 56: 721-725, 2017. © 2016 Wiley Periodicals, Inc.

  6. 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.

  7. Evaluation of muscle MRI in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Baba, Yuri; Kuroiwa, Yoshiyuki

    2005-01-01

    Various objective measurements can be used to diagnose amyotrophic lateral sclerosis (ALS). T2-weighted brain MRI images revealed high signal areas at the posterior limb of the internal capsules in ALS patients. Recently, muscle MRI proved useful to evaluate abnormalities of the muscle in myositis patients. Therefore, in the present study, we examined muscle MRI of leg muscles in ALS patients, and correlated MRI with functional measurements, such as muscle strength, and compound muscle action potential amplitude of the tibialis anterior (TA) after stimulation of the peroneal nerve. The subjects consisted of 10 ALS patients (7 males and 3 females), ranging in age from 49 to 87. Neurologic symptoms at the onset of ALS consisted of bulbar dysfunction in one patient, upper extremity involvement in three patients, and lower extremity involvement in six patients. Muscle MRI of the legs was performed in 9 (ALS patients. A peripheral nerve conduction study was performed on the peroneal nerve, with the recording electrode over the TA. The T2-weighted muscle MRI images revealed high signal aeras in the muscle in six ALS patients, whose muscle weakness existed predominantly in the lower extremities. Extracellular fluid accumulation has been proposed to be responsible for the signal increase of denervated muscles on T2-weighted muscle MRI images. We assume that muscle MRI is useful to demonstrate the distribution of muscle involvement in ALS patients and to assess the disease's stage. (author)

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Gonzalez-Bermejo, Jesus; Morélot-Panzini, Capucine; Salachas, François; Redolfi, Stefania; Straus, Christian; Becquemin, Marie-Hélène; Arnulf, Isabelle; Pradat, Pierre-François; Bruneteau, Gaëlle; Ignagni, Anthony R; Diop, Moustapha; Onders, Raymond; Nelson, Teresa; Menegaux, Fabrice; Meininger, Vincent; Similowski, Thomas

    2012-01-01

    In amyotrophic lateral sclerosis (ALS) patients, respiratory insufficiency is a major burden. Diaphragm conditioning by electrical stimulation could interfere with lung function decline by promoting the development of type 1 muscle fibres. We describe an ancillary study to a prospective, non-randomized trial (NCT00420719) assessing the effects of diaphragm pacing on forced vital capacity (FVC). Sleep-related disturbances being early clues to diaphragmatic dysfunction, we postulated that they would provide a sensitive marker. Stimulators were implanted laparoscopically in the diaphragm close to the phrenic motor point in 18 ALS patients for daily conditioning. ALS functioning score (ALSFRS), FVC, sniff nasal inspiratory pressure (SNIP), and polysomnographic recordings (PSG, performed with the stimulator turned off) were assessed before implantation and after four months of conditioning (n = 14). Sleep efficiency improved (69 ± 15% to 75 ± 11%, p = 0.0394) with fewer arousals and micro-arousals. This occurred against a background of deterioration as ALSFRS-R, FVC, and SNIP declined. There was, however, no change in NIV status or the ALSFRS respiratory subscore, and the FVC decline was mostly due to impaired expiration. Supporting a better diaphragm function, apnoeas and hypopnoeas during REM sleep decreased. In conclusion, in these severe patients not expected to experience spontaneous improvements, diaphragm conditioning improved sleep and there were hints at diaphragm function changes.

  13. Association between macronutrient intake and amyotrophic lateral sclerosis prognosis.

    Science.gov (United States)

    Kim, Boeun; Jin, Youri; Kim, Seung Hyun; Park, Yongsoon

    2018-04-24

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, and the nutritional state of ALS patients is associated with survival. The purpose of the present study was to investigate whether macronutrient intake at early stage of the disease was positively associated with survival and duration from symptom onset to death, tracheostomy, or non-invasive ventilation (NIV) in ALS. ALS patients diagnosed according to EI Escorial criteria were recruited from 2011 to 2016 and followed up until 2017, when they reached the endpoint of death, tracheostomy, or NIV use. Dietary intake was estimated based on a 24-hour recall conducted less than 2 years from symptom onset, and the survival time was defined as the duration from symptom onset to the endpoint. ALS patients were categorized as short-term group (n=79) and long-term group (n=69) according to the mean survival time (33.03±14.01 months). Short-term survival was negatively associated with fat, protein, and meat intake, and positively associated with carbohydrate intake after adjustment for confounders. In addition, the survival time was positively associated with fat, protein, and meat intake but was not associated with carbohydrate intake. The present study suggested that higher intake of fat and protein, particularly from meat at early stage of the disease, could prolong the survival of ALS patients. However, further clinical trials are necessary to confirm the beneficial effects of higher fat and protein intake on mortality in ALS patients.

  14. Factors predicting survival following noninvasive ventilation in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Peysson, S; Vandenberghe, N; Philit, F; Vial, C; Petitjean, T; Bouhour, F; Bayle, J Y; Broussolle, E

    2008-01-01

    The involvement of respiratory muscles is a major predicting factor for survival in amyotrophic lateral sclerosis (ALS). Recent studies show that noninvasive ventilation (NIV) can relieve symptoms of alveolar hypoventilation. However, factors predicting survival in ALS patients when treated with NIV need to be clarified. We conducted a retrospective study of 33 consecutive ALS patients receiving NIV. Ten patients had bulbar onset. We determined the median survivals from onset, diagnosis and initiation of NIV and factors predicting survival. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. The median initial and maximal total uses of NIV were 10 and 14 h/24h. The overall median survival from ALS onset was 34.2 months and worsened with increasing age and bulbar onset of the disease. The median survival from initiation of NIV was 8.4 months and was significantly poorer in patients with advanced age or with airway mucus accumulation. Survival from initiation of NIV was not influenced by respiratory parameters or bulbar symptoms. Advanced age at diagnosis and airway mucus accumulation represent poorer prognostic factors of ALS patients treated with NIV. NIV is a helpful treatment of sleep-disordered breathing, including patients with bulbar involvement. Copyright 2008 S. Karger AG, Basel.

  15. Non-invasive ventilation after surgery in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Olivieri, C; Castioni, C A; Livigni, S; Bersano, E; Cantello, R; Della Corte, F; Mazzini, L

    2014-04-01

    Surgery in patients affected by amyotrophic lateral sclerosis (ALS) presents a particular anesthetic challenge because of the risk of post-operative pulmonary complications. We report on the use of non-invasive ventilation (NIV) to prevent post-operative pulmonary complications (PPCs) in nine patients affected by ALS enrolled in a phase-1 clinical trial with stem cell transplantation. All patients were treated with autologous mesenchymal stem cells implanted into the spinal cord with a surgical procedure. Anesthesia was induced with propofol and maintained with remifentanil and sevoflurane. No muscle relaxant was used. After awakening and regain of spontaneous breathing, patients were tracheally extubated. Non-invasive ventilation through nasal mask was delivered and non-invasive positive pressure ventilation and continuous positive pressure ventilation were started. The average time on NIV after surgery was 3 h and 12 min. All patients regained stable spontaneous breathing after NIV discontinuation and had no episodes of respiratory failure until the following day. Our case series suggest that the use of NIV after surgery can be a safe strategy to prevent PPCs in patients affected by ALS. The perioperative procedure we chose for these patients appeared safe even in patients with advanced functional stage of the disease. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. 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.

  17. [Suspension of Respiratory Support in Patients with Amyotrophic Lateral Sclerosis].

    Science.gov (United States)

    Silberberg, Agustín A; Robetto, Josefina; Achával, Mora

    2018-01-01

    Decision making in advanced Amyotrophic Lateral Sclerosis (ALS) patients keeps on being a controversial issue. The aim of this work is to discuss ethical implications of withdrawing respiratory support treatment in patients with ALS. Through a bibliographic search on Pubmed database (2010-2016) we investigated whether or not the use of Non-Invasive Ventilation (NIV) and Mechanical Ventilation (MV) would increase survival and quality of life. We included 38 review articles. From these papers, results and ethical implications of initiating and mainly withdrawing respiratory support were analyzed. Survival time increased with NIV and with MV. Quality of life, above all according to physiological criteria, improved with NIV but regarding MV it remained controversial. Implementation and future withdrawal of MV seemed open to medical and ethical discussion. From a perspective of the intrinsic dignity of every human being, whatever its quality of life was, and knowing that no effective therapies for the underlying disease are available, the decision to remove MV in a patient with advanced ALS requires: knowledge of the will of the patient and, above all, evaluating whether this respiratory support measure is becoming objectively disproportionate.

  18. Noninvasive ventilation reduces energy expenditure in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Georges, Marjolaine; Morélot-Panzini, Capucine; Similowski, Thomas; Gonzalez-Bermejo, Jesus

    2014-02-07

    Amyotrophic lateral sclerosis (ALS) leads to chronic respiratory failure. Diaphragmatic dysfunction, a major driver of dyspnea and mortality, is associated with a shift of the burden of ventilation to extradiaphragmatic inspiratory muscles, including neck muscles. Besides, energy expenditure is often abnormally high in ALS, and this is associated with a negative prognostic value. We hypothesized that noninvasive ventilation (NIV) would relieve inspiratory neck muscles and reduce resting energy expenditure (REE). Using indirect calorimetry, we measured REE during spontaneous breathing (REESB) and NIV (REENIV) in 16 ALS patients with diaphragmatic dysfunction, during the first 3 months of NIV. Measured values were compared with predicted REE (REEpred)(Harris-Benedict equation). NIV abolished inspiratory neck muscle activity. Even though our patients were not hypermetabolic, on the contrary, with a REESB that was lower than REEpred (average 11%), NIV did reduce energy expenditure. Indeed, median REENIV, in this population with a mean body mass index of 21.4 kg.m-2, was 1149 kcal/24 h [interquartile 970-1309], lower than REESB (1197 kcal/24 h, 1054-1402; mean difference 7%; p = 0.03, Wilcoxon). REESB and REENIV were correlated with forced vital capacity and maximal inspiratory pressure. NIV can reduce energy expenditure in ALS patients probably by alleviating the ventilatory burden imposed on inspiratory neck muscles to compensate diaphragm weakness. It remains to be elucidated whether or not, in which population, and to what extent, NIV can be beneficial in ALS through the corresponding reduction in energy expenditure.

  19. Oximetry and indications for tracheotomy for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bach, John Robert; Bianchi, Carlo; Aufiero, Elaine

    2004-11-01

    To explore the use of oximetry as a guide for using respiratory aids and tracheotomy in the treatment of patients with amyotrophic lateral sclerosis (ALS). A retrospective review of all ALS patients presenting to a neuromuscular disease clinic since 1996. Patients who were symptomatic for nocturnal hypoventilation were prescribed noninvasive ventilation (NIV). Patients with assisted cough peak flows of NIV and MAC and the duration of normalization were recorded. When the baseline was not or could not be normalized, the time to acute respiratory failure and tracheotomy or death were recorded. Twenty-five patients became dependent on NIV, including 13 patients who received NIV continuously for a mean (+/- SD) period of 19.7 +/- 16.9 months, without desaturation (group 1). For another 76 patients, the daytime baseline Spo(2) level decreased to NIV/MAC (group 2) for a mean duration of 11.1 +/- 8.7 months before desaturation reoccurred for 27 patients. Of the latter patients, 11 underwent tracheotomy, 14 died in NIV or MAC. The long-term use of NIV and MAC, and the avoidance of tracheotomy is dependent on glottic function rather than on inspiratory or expiratory muscle failure.

  20. Impaired structural motor connectome in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Esther Verstraete

    Full Text Available Amyotrophic lateral sclerosis (ALS is a severe neurodegenerative disease selectively affecting upper and lower motor neurons. Patients with ALS suffer from progressive paralysis and eventually die on average after three years. The underlying neurobiology of upper motor neuron degeneration and its effects on the complex network of the brain are, however, largely unknown. Here, we examined the effects of ALS on the structural brain network topology in 35 patients with ALS and 19 healthy controls. Using diffusion tensor imaging (DTI, the brain network was reconstructed for each individual participant. The connectivity of this reconstructed brain network was compared between patients and controls using complexity theory without--a priori selected--regions of interest. Patients with ALS showed an impaired sub-network of regions with reduced white matter connectivity (p = 0.0108, permutation testing. This impaired sub-network was strongly centered around primary motor regions (bilateral precentral gyrus and right paracentral lobule, including secondary motor regions (bilateral caudal middle frontal gyrus and pallidum as well as high-order hub regions (right posterior cingulate and precuneus. In addition, we found a significant reduction in overall efficiency (p = 0.0095 and clustering (p = 0.0415. From our findings, we conclude that upper motor neuron degeneration in ALS affects both primary motor connections as well as secondary motor connections, together composing an impaired sub-network. The degenerative process in ALS was found to be widespread, but interlinked and targeted to the motor connectome.

  1. Longitudinal course of cortical thickness decline in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Schuster, Christina; Kasper, Elisabeth; Machts, Judith; Bittner, Daniel; Kaufmann, Jörn; Benecke, Reiner; Teipel, Stefan; Vielhaber, Stefan; Prudlo, Johannes

    2014-10-01

    To determine longitudinal rates of cortical atrophy in classical Amyotrophic lateral sclerosis (ALS) and ALS variants. Rates of cortical thinning were determined between 2 scans, 3-15 months apart, in 77 ALS patients: 51 classical, 12 upper motor neuron (UMN), and 14 lower motor neuron (LMN) ALS variants. Cortical thickness at the first assessment was compared with 60 healthy controls matched by age and gender. Atrophy rates were compared between patient sub-groups and correlated with disease duration, progression, and severity. Using a cross-sectional analysis, we found a significant difference in cortical thickness between ALS patients and controls in the motor and extra-motor areas (left medial orbito frontal gyrus, left inferior parietal gyrus, bilateral insular cortex, right fusiform gyrus, bilateral precuneus). Using a longitudinal analysis, we found a significant decline of cortical thickness in frontal, temporal, and parietal regions over the course of the study in ALS patients. Effects were independent of the clinical subtype, with exception of the precentral gyrus (p gyrus, the UMN-dominant subjects exhibited intermediate rates of atrophy, and the classical ALS patients exhibited no such change. Atrophy of the precentral gyrus in classical ALS indicates a floor effect at the first assessment, resulting in a lack of further atrophy over time. Structural loss of the precentral gyrus appears to be an early sign of classical ALS. Over time, patterns of cortical thinning in extra-motor areas can be identified in ALS, regardless of the phenotype.

  2. Impaired structural motor connectome in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Verstraete, Esther; Veldink, Jan H; Mandl, Rene C W; van den Berg, Leonard H; van den Heuvel, Martijn P

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease selectively affecting upper and lower motor neurons. Patients with ALS suffer from progressive paralysis and eventually die on average after three years. The underlying neurobiology of upper motor neuron degeneration and its effects on the complex network of the brain are, however, largely unknown. Here, we examined the effects of ALS on the structural brain network topology in 35 patients with ALS and 19 healthy controls. Using diffusion tensor imaging (DTI), the brain network was reconstructed for each individual participant. The connectivity of this reconstructed brain network was compared between patients and controls using complexity theory without--a priori selected--regions of interest. Patients with ALS showed an impaired sub-network of regions with reduced white matter connectivity (p = 0.0108, permutation testing). This impaired sub-network was strongly centered around primary motor regions (bilateral precentral gyrus and right paracentral lobule), including secondary motor regions (bilateral caudal middle frontal gyrus and pallidum) as well as high-order hub regions (right posterior cingulate and precuneus). In addition, we found a significant reduction in overall efficiency (p = 0.0095) and clustering (p = 0.0415). From our findings, we conclude that upper motor neuron degeneration in ALS affects both primary motor connections as well as secondary motor connections, together composing an impaired sub-network. The degenerative process in ALS was found to be widespread, but interlinked and targeted to the motor connectome.

  3. 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.

  4. Clinical care of patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Radunović, Aleksandar; Mitsumoto, Hiroshi; Leigh, P Nigel

    2007-10-01

    Although amyotrophic lateral sclerosis and its variants are readily recognised 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. We highlight the need for research on the effectiveness of gastrostomy, access to non-invasive ventilation and palliative care, communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. We recommend that the plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice.

  5. Impact of expiratory strength training in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Plowman, Emily K; Watts, Stephanie A; Tabor, Lauren; Robison, Raele; Gaziano, Joy; Domer, Amanda S; Richter, Joel; Vu, Tuan; Gooch, Clifton

    2016-06-01

    We evaluated the feasibility and impact of expiratory muscle strength training (EMST) on respiratory and bulbar function in persons with amyotrophic lateral sclerosis (ALS). Twenty-five ALS patients participated in this delayed intervention open-label clinical trial. Following a lead-in period, patients completed a 5-week EMST protocol. Outcome measures included: maximum expiratory pressure (MEP); physiologic measures of swallow and cough; and penetration-aspiration scale (PAS) scores. Of participants who entered the active phase of the study (n = 15), EMST was well tolerated and led to significant increases in MEPs and maximum hyoid displacement during swallowing post-EMST (P < 0.05). No significant differences were observed for PAS scores or cough spirometry measures. EMST was feasible and well tolerated in this small cohort of ALS patients and led to improvements in expiratory force-generating pressures and swallow kinematics. Further investigation is warranted to confirm these preliminary findings. Muscle Nerve 54: 48-53, 2016. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  6. Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Mazzini, Letizia; Mareschi, Katia; Ferrero, Ivana; Vassallo, Elena; Oliveri, Giuseppe; Boccaletti, Riccardo; Testa, Lucia; Livigni, Sergio; Fagioli, Franca

    2006-07-01

    Our study was aimed to evaluate the feasibility and safety of intraspinal cord implantation of autologous mesenchymal stem cells (MSCs) in a few well-monitored amyotrophic lateral sclerosis (ALS) patients. Seven patients affected by definite ALS were enrolled in the study and two patients were treated for compassionate use and monitored for at least 3 years. Bone marrow was collected from the posterior iliac crest according to the standard procedure and MSCs were expanded ex vivo according to Pittenger's protocol. The cells were suspended in 2 ml autologous cerebrospinal fluid and transplanted into the spinal cord by a micrometric pump injector. The in vitro expanded MSCs did not show any bacterial o fungal contamination, hemopoietic cell contamination, chromosomic alterations and early cellular senescence. No patient manifested major adverse events such as respiratory failure or death. Minor adverse events were intercostal pain irradiation and leg sensory dysesthesia, both reversible after a mean period of 6 weeks. No modification of the spinal cord volume or other signs of abnormal cell proliferation were observed. A significant slowing down of the linear decline of the forced vital capacity was evident in four patients 36 months after MSCs transplantation. Our results demonstrate that direct injection of autologous expanded MSCs into the spinal cord of ALS patients is safe, with no significant acute or late toxicity, and well tolerated. The clinical results seem to be encouraging.

  7. 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 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.

  8. Considerations for Clinical Neuropsychological Evaluation in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Woolley, Susan C; Rush, Beth K

    2017-11-01

    The clinical neuropsychologist has the opportunity to be uniquely involved in the evaluation and treatment of individuals with amyotrophic lateral sclerosis (ALS). We review the current literature that defines cognitive and behavioral symptoms in ALS, including current knowledge of the neuropathological and genetic underpinning for these symptoms. There are unique considerations for clinical neuropsychological evaluation and clinical research in ALS and we highlight these in this review. Specifically, we shed light on special factors that contribute to our understanding of cognitive and behavioral impairment in ALS, including co-morbid symptoms, differential diagnosis, and considerations for longitudinal tracking of phenotypes. We discuss the rationale for proposing a specific approach to such as cognitive screening, test selection, response modality consideration, and test-retest intervals. With this didactic overview, the clinical neuropsychologist has the potential to learn more about the heterogeneous presentation of motor and neuropsychological symptoms in ALS. Furthermore, the reader has the opportunity to understand what it takes to develop a valid assessment approach particularly when the phenotype of ALS remains undefined in some regards. This clinical practice review sets the stage for the clinical neuropsychologist to further contribute to our clinical and scientific understanding of ALS and cognition. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Factors affecting the diagnostic delay in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Cellura, Eleonora; Spataro, Rossella; Taiello, Alfonsa Claudia; La Bella, Vincenzo

    2012-07-01

    Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable (e.g., multifocal motor neuropathy) or epidemiologically more frequent (e.g., cervical myelopathy). To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it. We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 2000 and 2007. The median time from onset to diagnosis was 11 months (range: 6-21) for the whole ALS cohort, 10 months (range: 6-15) in bulbar-onset (n = 65) and 12 months (range: 7-23) in spinal-onset (n = 195) patients (p = 0.3). 31.1% of patients received other diagnoses before ALS and this led to a significant delay of the correct diagnosis in this group (other diagnoses before ALS, n = 81: median delay, 15 months [9.75-24.25] vs ALS, n = 179, median delay, 9 months [6-15.25], p heuristics might represent an important contributing factor. Furthermore, the length of the differential diagnosis from other disorders and delays in referral to the neurologist seems to be positively associated with the delay in diagnosis. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. 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.

  11. 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.

  12. Marital status is a prognostic factor in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Spataro, R; Volanti, P; Lo Coco, D; La Bella, V

    2017-12-01

    Several variables have been linked to a shorter survival in patients with amyotrophic lateral sclerosis (ALS), for example, female sex, older age, site of disease onset, rapid disease progression, and a relatively short diagnostic delay. With regard to marital status, previous studies suggested that living with a partner might be associated to a longer survival and a higher likelihood to proceed to tracheostomy. Therefore, to further strengthen this hypothesis, we investigated the role of marital status as a prognostic variable in a cohort of ALS patients. We performed a retrospective analysis on 501 consecutive ALS patients for which a complete disease's natural history and clinical/demographic data were available. At diagnosis, 409 patients (81.6%) were married or lived with a stable partner, whereas 92 patients (18.4%) were single/widowed/divorced. In our ALS cohort, being married was associated with a median longer survival (married, 35 months [24-50] vs unmarried, 27 months [18-42]; Pmarried and unmarried patients were significantly different in many clinical and demographic variables, including age at disease onset, gender, body mass index, and number of children. Cox regression analysis showed that age at onset, diagnostic delay, and marital status were independent predictors of survival. In unmarried patients, female sex was also significantly associated with shorter survival. Marital status is a prognostic factor in ALS, and it significantly affects survival. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Infrastructure resources for clinical research in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Sherman, Alexander V; Gubitz, Amelie K; Al-Chalabi, Ammar; Bedlack, Richard; Berry, James; Conwit, Robin; Harris, Brent T; Horton, D Kevin; Kaufmann, Petra; Leitner, Melanie L; Miller, Robert; Shefner, Jeremy; Vonsattel, Jean Paul; Mitsumoto, Hiroshi

    2013-05-01

    Clinical trial networks, shared clinical databases, and human biospecimen repositories are examples of infrastructure resources aimed at enhancing and expediting clinical and/or patient oriented research to uncover the etiology and pathogenesis of amyotrophic lateral sclerosis (ALS), a rapidly progressive neurodegenerative disease that leads to the paralysis of voluntary muscles. The current status of such infrastructure resources, as well as opportunities and impediments, were discussed at the second Tarrytown ALS meeting held in September 2011. The discussion focused on resources developed and maintained by ALS clinics and centers in North America and Europe, various clinical trial networks, U.S. government federal agencies including the National Institutes of Health (NIH), the Agency for Toxic Substances and Disease Registry (ATSDR) and the Centers for Disease Control and Prevention (CDC), and several voluntary disease organizations that support ALS research activities. Key recommendations included 1) the establishment of shared databases among individual ALS clinics to enhance the coordination of resources and data analyses; 2) the expansion of quality-controlled human biospecimen banks; and 3) the adoption of uniform data standards, such as the recently developed Common Data Elements (CDEs) for ALS clinical research. The value of clinical trial networks such as the Northeast ALS (NEALS) Consortium and the Western ALS (WALS) Consortium was recognized, and strategies to further enhance and complement these networks and their research resources were discussed.

  14. The increasing importance of environmental conditions in amyotrophic lateral sclerosis

    Science.gov (United States)

    Riancho, Javier; Bosque-Varela, Pilar; Perez-Pereda, Sara; Povedano, Mónica; de Munaín, Adolfo López; Santurtun, Ana

    2018-04-01

    Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MNs). Although a small percentage of ALS has a familial origin, the vast majority of cases are sporadic in which genetic factors and environment interact with each other leading to disease onset in genetically predisposed individuals. In the current model of the disease, each individual has a determined genetic load, some degree of cell degeneration related to age and several risky environmental exposures. In this scenario, MN degeneration would occur when the sum of these factors reach a certain threshold. To date, an extensive list of environmental factors has been associated to ALS, including different categories, such as exposure to heavy metals and other toxicants, cyanotoxins or infectious agents. In addition, in recent years, lifestyle and other demographic parameters are gaining relevance in the genesis of the disease. Among them, physical activity, nutrition, body mass index, cardiovascular risk factors, autoimmune diseases and cancer are some of the conditions which have been related to the disease. In this review, we will discuss the potential mechanisms of environmental conditions in motor neuron degeneration. Understanding the role of each one of these factors as well as their interactions appears as a crucial step in order to develop new preventive, diagnostic and therapeutic approaches for ALS patients.

  15. Falls in multiple sclerosis.

    Science.gov (United States)

    Matsuda, Patricia N; Shumway-Cook, Anne; Bamer, Alyssa M; Johnson, Shana L; Amtmann, Dagmar; Kraft, George H

    2011-07-01

    To examine incidence, associated factors, and health care provider (HCP) response to falls in persons with multiple sclerosis (MS). Cross-sectional retrospective design. Community setting. Four hundred seventy-four persons with MS. Mailed survey questionnaire examined incidence, risk factors, and HCP response to falls in persons with MS who were dwelling in the community. Univariate and multiple ordinal regression analysis identified variables associated with single and multiple falls. Falls, causes and perceived reasons for falls, and HCP response. A total of 265 participants (58.2%) reported one or more falls in the previous 6 months, and 58.5% of falls were medically injurious. Trips/slips while walking accounted for 48% of falls. Factors associated with falls included use of a cane or walker (odds ratio [OR] 2.62; 95% confidence interval [CI] 1.66-4.14), income falls; recommended strategies included safety strategies (53.2%), use of gait assistive devices (42.1%), exercise/balance training (22.2%), and home modifications (16.6%). Factors associated with falls in persons with MS are similar to those in other populations with neurologic diseases. Despite the high incidence of falls, fewer than 50% of people with MS receive information about prevention of falls from an HCP. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. [Future challenges in multiple sclerosis].

    Science.gov (United States)

    Fernández, Óscar

    2014-12-01

    Multiple sclerosis occurs in genetically susceptible individuals, in whom an unknown environmental factor triggers an immune response, giving rise to a chronic and disabling autoimmune disease. Currently, significant progress is being made in our knowledge of the frequency and distribution of multiple sclerosis and its risk factors, genetics, pathology, pathogenesis, diagnostic and prognostic markers, and treatment. This has radically changed patients' and clinicians' expectations of multiple sclerosis and has raised hope that there will soon be a way to control the disease. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Albumin and multiple sclerosis.

    Science.gov (United States)

    LeVine, Steven M

    2016-04-12

    Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g., demyelination. Once in the CNS, albumin can participate in protective mechanisms. For example, due to its high concentration and molecular properties, albumin becomes a target for oxidation and nitration reactions. Furthermore, albumin binds metals and heme thereby limiting their ability to produce reactive oxygen and reactive nitrogen species. Albumin also has the potential to worsen disease. Similar to pathogenic processes that occur during epilepsy, extravasated albumin could induce the expression of proinflammatory cytokines and affect the ability of astrocytes to maintain potassium homeostasis thereby possibly making neurons more vulnerable to glutamate exicitotoxicity, which is thought to be a pathogenic mechanism in MS. The albumin quotient, albumin in cerebrospinal fluid (CSF)/albumin in serum, is used as a measure of blood-CSF barrier dysfunction in MS, but it may be inaccurate since albumin levels in the CSF can be influenced by multiple factors including: 1) albumin becomes proteolytically cleaved during disease, 2) extravasated albumin is taken up by macrophages, microglia, and astrocytes, and 3) the location of BBB damage affects the entry of extravasated albumin into ventricular CSF. A discussion of the roles that albumin performs during MS is put forth.

  19. Palliative care for patients in the USA with amyotrophic lateral sclerosis: current challenges

    Directory of Open Access Journals (Sweden)

    Houseman G

    2015-11-01

    Full Text Available Gail Houseman,1 Mary Kelley2 1The ALS Association Greater Philadelphia Chapter, Ambler, PA, USA; 2Department of Neurology, ALS Center at Penn Medicine, Philadelphia, PA, USA Abstract: Amyotrophic lateral sclerosis (ALS is a motor neuron disease that results in eventual paralysis of all voluntary muscles. Cognitive impairment may be a co-occurring condition with the ALS patient. Palliative care, which involves symptom management, is the most utilized treatment of choice. Managing the symptoms of ALS can be challenging. This paper provides experience-based facts on daily care provision in the USA and some practical guidelines. Keywords: amyotrophic lateral sclerosis, ALS, palliative care, challenges, symptom management

  20. 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

  1. 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

    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......Previous evidence for spatial clustering of amyotrophic lateral sclerosis is inconclusive. Studies that have identified apparent clusters have often been based on a small number of cases, which means the results may have occurred by chance processes. Also, most studies have used the geographic...... stages of the cases' life cycle, different conclusions about where potential risk factors may exist might result....

  2. Current concepts in multiple sclerosis

    International Nuclear Information System (INIS)

    Wiethoelter, Horst; Dichgans, Johannes

    1991-01-01

    This volume contains 9 articles dealing with the use of nuclear magnetic resonance imaging and positron emitted tomography in the diagnosis and staging of multiple sclerosis. (H.W.). refs.; figs.; tabs

  3. Multiple sclerosis and organic solvents

    DEFF Research Database (Denmark)

    Mortensen, J T; Brønnum-Hansen, Henrik; Rasmussen, K

    1998-01-01

    We investigated a possible causal relation between exposure to organic solvents in Danish workers (housepainters, typographers/printers, carpenters/cabinetmakers) and onset of multiple sclerosis. Data on men included in the Danish Multiple Sclerosis Register (3,241 men) were linked with data from......, and butchers. Over a follow-up period of 20 years, we observed no increase in the incidence of multiple sclerosis among men presumed to be exposed to organic solvents. It was not possible to obtain data on potential confounders, and the study design has some potential for selection bias. Nevertheless......, the study does not support existing hypotheses regarding an association between occupational exposure to organic solvents and multiple sclerosis....

  4. Multiple Sclerosis After Infectious Mononucleosis

    DEFF Research Database (Denmark)

    Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk

    2007-01-01

    BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis......, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish...... Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul...

  5. Defining active progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Börnsen, Lars; Ammitzbøll, Cecilie

    2017-01-01

    BACKGROUND: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). OBJECTIVE: To compare CSF biomarkers in active and inactive...

  6. Occupational therapy for multiple sclerosis.

    NARCIS (Netherlands)

    Steultjens, E.M.J.; Dekker, J.; Bouter, L.M.; Cardol, M.; Nes, J.C.M. van de; Ende, C.H.M. van den

    2003-01-01

    Background: Multiple sclerosis (MS) patients are referred to occupational therapy with complaints about fatigue, limb weakness, alteration of upper extremity fine motor coordination, loss of sensation and spasticity that causes limitations in performance of activities of daily living and social

  7. [Current therapy of multiple sclerosis].

    Science.gov (United States)

    Antonio García Merino, J

    2014-12-01

    Since the introduction of interferon beta 1 b for the treatment of multiple sclerosis, there has been a progressive increase in the number of drugs available for this disease. Currently, 11 drugs have been approved in Spain, and their indications depend on specific clinical characteristics. The present article reviews these indications and also discusses other medications without official approval that have also been used in multiple sclerosis. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  8. Viruses and Multiple Sclerosis

    Science.gov (United States)

    Virtanen, Jussi Oskari; Jacobson, Steve

    2016-01-01

    Multiple sclerosis (MS) is a heterogeneous disease that develops as an interplay between the immune system and environmental stimuli in genetically susceptible individuals. There is increasing evidence that viruses may play a role in MS pathogenesis acting as these environmental triggers. However, it is not known if any single virus is causal, or rather several viruses can act as triggers in disease development. Here, we review the association of different viruses to MS with an emphasis on two herpesviruses, Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6). These two agents have generated the most impact during recent years as possible co-factors in MS disease development. The strongest argument for association of EBV with MS comes from the link between symptomatic infectious mononucleosis and MS and from seroepidemiological studies. In contrast to EBV, HHV-6 has been found significantly more often in MS plaques than in MS normal appearing white matter or non-MS brains and HHV-6 re-activation has been reported during MS clinical relapses. In this review we also suggest new strategies, including the development of new infectious animal models of MS and antiviral MS clinical trials, to elucidate roles of different viruses in the pathogenesis of this disease. Furthermore, we introduce the idea of using unbiased sequence-independent pathogen discovery methodologies, such as next generation sequencing, to study MS brain tissue or body fluids for detection of known viral sequences or potential novel viral agents. PMID:22583435

  9. Management of dysphagia in Parkinson's disease and amyotrophic lateral sclerosis.

    Science.gov (United States)

    Luchesi, Karen Fontes; Kitamura, Satoshi; Mourão, Lucia Figueiredo

    2013-01-01

    To describe swallowing management in patients with amyotrophic lateral sclerosis (ALS) and Parkinson' disease (PD), to investigate whether physiopathology determines the choice of therapeutic approaches, and to investigate whether the disease duration modifies the therapeutic approaches. This is a long-term study comprising 24 patients with idiopathic PD and 27 patients with ALS. The patients were followed-up in a dysphagia outpatient clinic between 2006 and 2011. The patients underwent clinic evaluation and Fiberoptic Endoscopic Evaluation of Swallowing, Functional Oral Intake Scale, and therapeutic intervention every 3 months. The swallowing management was based on orientation about the adequate food consistency and volume, besides the necessary maneuvers or exercises to improve swallowing functionality. An exploratory analysis of data was used to investigate associations between the groups of disease (PD or ALS) and clinic aspects and to know about the association between the groups of diseases and the application of maneuver or exercises over the follow-up. The most frequent recommended maneuvers in PD were bolus effect (83.3%), bolus consistency (79.2%), and swallowing frequency (79%). To patients with ALS, the bolus consistency (92%) and the bolus effect (74.1%) were more recommended. Strengthening-tongue (p=0.01), tongue control (p=0.05), and vocal exercises (p<0.001) were significantly more recommended in PD than in ALS. Compensatory and sensorial maneuvers are more recommended to rehabilitee program in both diseases. The physiopathology of the diseases determined the choice of therapeutic approaches. The disease duration of the patients did not interfere directly in the therapeutic approaches.

  10. Edaravone and its clinical development for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Takei, Koji; Watanabe, Kazutoshi; Yuki, Satoshi; Akimoto, Makoto; Sakata, Takeshi; Palumbo, Joseph

    2017-10-01

    The etiology of amyotrophic lateral sclerosis (ALS) is unknown. Oxidative stress may be one of the major mechanisms involved. In vitro and in vivo data of edaravone suggest that it may possess broad free radical scavenging activity and protect neurons, glia, and vascular endothelial cells against oxidative stress. During the 1980s and 1990s, edaravone was developed for the treatment of acute ischemic stroke. In 2001, a clinical program in ALS was initiated and five clinical studies were conducted in Japan. Phase III studies were designed to rapidly evaluate (within a 24-week double-blind study window) functional changes using the Revised ALS Functional Rating Scale (ALSFRS-R) as a primary endpoint. The study populations were selected according to these considerations and were further refined as the studies proceeded. Although the first phase III study did not meet its primary endpoint, post-hoc analyses showed an apparent effect of edaravone, when additional patient inclusion criteria defined by ALSFRS-R score, pulmonary function, certainty of ALS diagnosis, and duration of disease were applied. This population was hypothesized not only to have retained broad functionality and normal respiratory function at study baseline but also to be likely to show measurable disease progression over 24 weeks. A second confirmatory phase III study applying these refinements in patient selection was prospectively designed and successfully documented a statistically significant difference between the edaravone and placebo groups in the ALSFRS-R primary endpoint. This paper describes and reviews data pertinent to the potential mechanism of action of edaravone, and reviews the development history of edaravone for the treatment of ALS.

  11. Misregulation of iron homeostasis in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    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. Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

    2016-12-13

    In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

  13. 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.

  14. 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.

  15. Longitudinal modeling to predict vital capacity in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jahandideh, Samad; Taylor, Albert A; Beaulieu, Danielle; Keymer, Mike; Meng, Lisa; Bian, Amy; Atassi, Nazem; Andrews, Jinsy; Ennist, David L

    2018-05-01

    Death in amyotrophic lateral sclerosis (ALS) patients is related to respiratory failure, which is assessed in clinical settings by measuring vital capacity. We developed ALS-VC, a modeling tool for longitudinal prediction of vital capacity in ALS patients. A gradient boosting machine (GBM) model was trained using the PRO-ACT (Pooled Resource Open-access ALS Clinical Trials) database of over 10,000 ALS patient records. We hypothesized that a reliable vital capacity predictive model could be developed using PRO-ACT. The model was used to compare FVC predictions with a 30-day run-in period to predictions made from just baseline. The internal root mean square deviations (RMSD) of the run-in and baseline models were 0.534 and 0.539, respectively, across the 7L FVC range captured in PRO-ACT. The RMSDs of the run-in and baseline models using an unrelated, contemporary external validation dataset (0.553 and 0.538, respectively) were comparable to the internal validation. The model was shown to have similar accuracy for predicting SVC (RMSD = 0.562). The most important features for both run-in and baseline models were "Baseline forced vital capacity" and "Days since baseline." We developed ALS-VC, a GBM model trained with the PRO-ACT ALS dataset that provides vital capacity predictions generalizable to external datasets. The ALS-VC model could be helpful in advising and counseling patients, and, in clinical trials, it could be used to generate virtual control arms against which observed outcomes could be compared, or used to stratify patients into slowly, average, and rapidly progressing subgroups.

  16. MRI and clinical features in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Waragai, M.

    1997-01-01

    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.)

  17. MRI and clinical features in amyotrophic lateral sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Matias-Guiu, Jordi A.; Pytel, Vanesa; Galan, Lucia; Valles-Salgado, Maria; Guerrero, Antonio; Moreno-Ramos, Teresa; Matias-Guiu, Jorge; Cabrera-Martin, Maria Nieves; Carreras, Jose Luis

    2016-01-01

    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 18 F-fluorodeoxyglucose (FDG), and amyloid-PET with 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 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.)

  19. Amyotrophic lateral sclerosis and assisted ventilation: how patients decide.

    Science.gov (United States)

    Lemoignan, Josée; Ells, Carolyn

    2010-06-01

    Throughout the course of their illness, people with amyotrophic lateral sclerosis (ALS) must make many treatment decisions; however, none has such a significant impact on quality of life and survival as decisions about assisted ventilation. The purpose of this study was to better understand the experience of decision-making about assisted ventilation for ALS patients. Using qualitative phenomenology methodology, 10 semi-structured interviews were conducted with persons with ALS and their caregivers to elicit factors that are pertinent to their decision-making process about assisted ventilation. Six main themes emerged from the interviews. (1) the meaning of the intervention - participants made a sharp distinction between non-invasive ventilation, which they viewed as a means to relieve symptoms of respiratory failure, and invasive ventilation, which they viewed as taking over their breathing and thereby saving their life when they otherwise would die, (2) the importance of context - including functional status, available supports, and financial implications, (3) the importance of values - with respect to communication, relationships, autonomy, life, and quality of life, (4) the effect of fears - particularly respiratory distress, chocking, running out of air, and the process of death itself, (5) the need for information - how use of assisted ventilation would impact daily life, how death from respiratory failure would occur, how caregivers and persons with ALS differ in their information needs and common misconceptions, and (6) adaptation to or acceptance of the intervention - a lengthy process that involved gradual familiarization with the equipment and its benefits. People with ALS and caregivers value autonomy in decision-making about assisted ventilation. Their decision-making process is neither wholly rational nor self-interested, and includes factors that health professionals should anticipate and address. Discussions about assisted ventilation and timing

  20. Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Mezzapesa, Domenico Maria; D'Errico, Eustachio; Tortelli, Rosanna; Distaso, Eugenio; Cortese, Rosa; Tursi, Marianna; Federico, Francesco; Zoccolella, Stefano; Logroscino, Giancarlo; Dicuonzo, Franca; Simone, Isabella Laura

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease.

  1. Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Domenico Maria Mezzapesa

    Full Text Available Amyotrophic lateral sclerosis (ALS has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  3. 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

  4. Midkine and multiple sclerosis.

    Science.gov (United States)

    Takeuchi, Hideyuki

    2014-02-01

    Multiple sclerosis (MS) is an autoimmune neurological disease characterized by inflammatory demyelination with subsequent neuronal damage in the CNS. MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have been thought as autoreactive Th1 and Th17 cell-mediated diseases. CD4(+) CD25(+) FoxP3(+) regulatory T-cell (Treg) plays a pivotal role in autoimmune tolerance, and tolerogenic dendritic cells (DCreg) drive the development of inducible Treg cells. Thus, a dysfunction in the development of Treg and DCreg leads to the development of autoimmune diseases. However, the factors that regulate Treg and DCreg are largely unknown. We recently showed that removal of midkine (MK) suppressed EAE due to an expansion of the Treg cell population as well as a decrease in the numbers of autoreactive Th1 and Th17 cells. MK decreased the Treg cell population by suppressing the phosphorylation of STAT5, which is essential for the expression of Foxp3, the master transcriptional factor of Treg cell differentiation. Furthermore, MK reduces the DCreg cell population by inhibiting the phosphorylation of STAT3, which is critical for DCreg development. Blockade of MK signalling by a specific RNA aptamer significantly elevated the population of DCreg and Treg cells and ameliorated EAE without detectable adverse effects. Therefore, the inhibition of MK may provide an effective therapeutic strategy against autoimmune diseases including MS. This article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4. © 2013 The British Pharmacological Society.

  5. 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

  6. 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

  7. 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 s...

  8. 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

  9. 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.

    Background and purposeThirty 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

  10. 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

    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 function was investigated

  11. Amyotrophic Lateral Sclerosis, a Multisystem Pathology: Insights into the Role of TNFα

    NARCIS (Netherlands)

    Tortarolo, Massimo; Lo Coco, Daniele; Veglianese, Pietro; Vallarola, Antonio; Giordana, Maria Teresa; Marcon, Gabriella; Beghi, Ettore; Poloni, Marco; Strong, Michael J.; Iyer, Anand M.; Aronica, Eleonora; Bendotti, Caterina

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is considered a multifactorial, multisystem disease in which inflammation and the immune system play important roles in development and progression. The pleiotropic cytokine TNFα is one of the major players governing the inflammation in the central nervous system

  12. 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.

  13. Survival in patients with amyotrophic lateral sclerosis, treated with an array of antioxidants

    NARCIS (Netherlands)

    Vyth, A.; Timmer, J. G.; Bossuyt, P. M.; Louwerse, E. S.; de Jong, J. M.

    1996-01-01

    Between 1983 and 1988 we treated 36 patients with sporadic amyotrophic lateral sclerosis (ALS) by an array of antioxidants and added other drugs to the regimen whenever a patient reported deterioration. Our customary prescription sequence was N-acetylcysteine (NAC); vitamins C and E;

  14. 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…

  15. Elastin cross-linking in the skin from patients with amyotrophic lateral sclerosis

    Science.gov (United States)

    Ono, S.; Yamauchi, M.

    1994-01-01

    Two cross-links unique to elastin, desmosine and isodesmosine were measured and compared in skin tissue (left upper arm) from 10 patients with amyotrophic lateral sclerosis (ALS) and from seven age-matched controls. The contents of desmosine and isodesmosine were significantly decreased (p elastin is affected in ALS.

  16. Euthanasia and physician-assisted suicide in amyotrophic lateral sclerosis: a prospective study

    NARCIS (Netherlands)

    Maessen, M.; Veldink, J.H.; Onwuteaka-Philipsen, B.D.; Hendricks, H.T.; Schelhaas, H.J.; Grupstra, H.F.; van der Wal, G.; Van den Berg, L.H.

    2014-01-01

    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

  17. 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

  18. Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways

    NARCIS (Netherlands)

    Cirulli, Elizabeth T.; Lasseigne, Brittany N.; Petrovski, Slavé; Sapp, Peter C.; Dion, Patrick A.; Leblond, Claire S.; Couthouis, Julien; Lu, Yi-Fan; Wang, Quanli; Krueger, Brian J.; Ren, Zhong; Keebler, Jonathan; Han, Yujun; Levy, Shawn E.; Boone, Braden E.; Wimbish, Jack R.; Waite, Lindsay L.; Jones, Angela L.; Carulli, John P.; Day-Williams, Aaron G.; Staropoli, John F.; Xin, Winnie W.; Chesi, Alessandra; Raphael, Alya R.; McKenna-Yasek, Diane; Cady, Janet; de Jong, J. M. B. Vianney; Kenna, Kevin P.; Smith, Bradley N.; Topp, Simon; Miller, Jack; Gkazi, Athina; Al-Chalabi, Ammar; van den Berg, Leonard H.; Veldink, Jan; Silani, Vincenzo; Ticozzi, Nicola; Shaw, Christopher E.; Baloh, Robert H.; Appel, Stanley; Simpson, Ericka; Lagier-Tourenne, Clotilde; Pulst, Stefan M.; Gibson, Summer; Trojanowski, John Q.; Elman, Lauren; McCluskey, Leo; Grossman, Murray; Baas, Frank; ten Asbroek, Anneloor L. M. A.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating neurological disease with no effective treatment. We report the results of a moderate-scale sequencing study aimed at increasing the number of genes known to contribute to predisposition for ALS. We performed whole-exome sequencing of 2869 ALS

  19. 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...

  20. 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.

  1. Involvement of corpus callosum in amyotrophic lateral sclerosis shown by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Zandijcke, M. van [Dept. of Neurology, Bruges (Belgium); Casselman, J. [Dept. of Medical Imaging, Bruges (Belgium)

    1995-05-01

    Abnormal high signal in the corticospinal tracts on MRI has been described in amyotrophic lateral sclerosis. We report a case with further high signal in fibres of the corpus callosum on proton density and T2-weighted spin-echo images, closely matching findings of earlier pathological reports. (orig.)

  2. 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…

  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. 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

    2018-02-01

    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.

  5. Involvement of corpus callosum in amyotrophic lateral sclerosis shown by MRI

    International Nuclear Information System (INIS)

    Zandijcke, M. van; Casselman, J.

    1995-01-01

    Abnormal high signal in the corticospinal tracts on MRI has been described in amyotrophic lateral sclerosis. We report a case with further high signal in fibres of the corpus callosum on proton density and T2-weighted spin-echo images, closely matching findings of earlier pathological reports. (orig.)

  6. The predictive value of respiratory function tests for non-invasive ventilation in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Tilanus, T.B.M.; Groothuis, J.T.; Broek-Pastoor, J.M.C. ten; Feuth, T.; Heijdra, Y.F.; Slenders, J.P.L.; Doorduin, J.; Engelen, B.G.M. van; Kampelmacher, M.J.; Raaphorst, J.

    2017-01-01

    BACKGROUND: Non-invasive ventilation (NIV) improves survival and quality of life in amyotrophic lateral sclerosis (ALS) patients. The timing of referral to a home ventilation service (HVS), which is in part based on respiratory function tests, has shown room for improvement. It is currently unknown

  7. 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

  8. The predictive value of respiratory function tests for non-invasive ventilation in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Tilanus, T. B. M.; Groothuis, J. T.; TenBroek-Pastoor, J. M. C.; Feuth, T. B.; Heijdra, Y. F.; Slenders, J. P. L.; Doorduin, J.; van Engelen, B. G.; Kampelmacher, M. J.; Raaphorst, J.

    2017-01-01

    Background: Non-invasive ventilation (NIV) improves survival and quality of life in amyotrophic lateral sclerosis (ALS) patients. The timing of referral to a home ventilation service (HVS), which is in part based on respiratory function tests, has shown room for improvement. It is currently unknown

  9. Genotype-Property Patient-Phenotype Relations Suggest that Proteome Exhaustion Can Cause Amyotrophic Lateral Sclerosis

    DEFF Research Database (Denmark)

    Kepp, Kasper Planeta

    2015-01-01

    Late-onset neurodegenerative diseases remain poorly understood as search continues for the perceived pathogenic protein species. Previously, variants in Superoxide Dismutase 1 (SOD1) causing Amyotrophic Lateral Sclerosis (ALS) were found to destabilize and reduce net charge, suggesting a pathogen...

  10. 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.

  11. Guidelines in motor neurone disease (MND)/amyotrophic lateral sclerosis (ALS) - from diagnosis to patient care.

    Science.gov (United States)

    Mitchell, J D

    2000-12-01

    This paper reviews the scope of current guidelines in motor neurone disease (MND)/amyotrophic lateral sclerosis (ALS) and examines issues which have arisen in the preparation of these documents. The review concludes with an evaluation of the impact of the guidelines which have been produced to date and looks towards potential future developments in this area.

  12. 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)…

  13. Mechanical cough augmentation techniques in amyotrophic lateral sclerosis/motor neuron disease

    OpenAIRE

    Rafiq, M.K.; Bradburn, M.; Mustfa, N.; Mcdermott, C.J.; Annane, D.

    2016-01-01

    © 2016 The Cochrane Collaboration.This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of mechanical insufflator/exsufflator (MI-E) and the breath-stacking technique for reducing morbidity and mortality and enhancing quality of life in people with amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND).

  14. [The differential diagnosis of amyotrophic lateral sclerosis and subacute herpes virus myelitis].

    Science.gov (United States)

    Levitsky, G N; Zavalishin, E E; Chub, R V; Morozova, E A; Serkov, S V

    2016-01-01

    Differential diagnosis of incurable and potentially curable neurological diseases is an urgent problem of modern neurology. The authors present a case report of subacute herpes virus myelitis, a rare complication of herpes infection by Varicella-Zoster virus. The differential diagnosis with amyotrophic lateral sclerosis is described.

  15. Weighted gene co-expression network analysis of the peripheral blood from Amyotrophic Lateral Sclerosis patients

    OpenAIRE

    DeYoung Joseph; Langfelder Peter; Fuller Tova F; Blauw Hylke M; van Es Michael A; van Vught Paul WJ; Horvath Steve; Saris Christiaan GJ; Wokke John HJ; Veldink Jan H; van den Berg Leonard H; Ophoff Roel A

    2009-01-01

    Abstract Background Amyotrophic Lateral Sclerosis (ALS) is a lethal disorder characterized by progressive degeneration of motor neurons in the brain and spinal cord. Diagnosis is mainly based on clinical symptoms, and there is currently no therapy to stop the disease or slow its progression. Since access to spinal cord tissue is not possible at disease onset, we investigated changes in...

  16. 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

  17. Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

    NARCIS (Netherlands)

    Gallo, Valentina; Vanacore, Nicola; Bueno-de-Mesquita, H. Bas; Vermeulen, Roel; Brayne, Carol; Pearce, Neil; Wark, Petra A.; Ward, Heather A.; Ferrari, Pietro; Jenab, Mazda; Andersen, Peter M.; Wennberg, Patrik; Wareham, Nicholas; Katzke, Verena; Kaaks, Rudolf; Weiderpass, Elisabete; Peeters, Petra H.; Mattiello, Amalia; Pala, Valeria; Barricante, Aurelio; Chirlaque, Maria Dolores; Travier, Noémie; Travis, Ruth C.; Sanchez, Maria Jose; Pessah-Rasmussen, Hélène; Petersson, Jesper; Tjønneland, Anne; Tumino, Rosario; Quiros, Jose Ramon; Trichopoulou, Antonia; Kyrozis, Andreas; Oikonomidou, Despoina; Masala, Giovanna; Sacerdote, Carlotta; Arriola, Larraitz; Boeing, Heiner; Vigl, Matthaeus; Claver-Chapelon, Francoise; Middleton, Lefkos; Riboli, Elio; Vineis, Paolo

    2016-01-01

    Previous case–control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the

  18. Physical activity and risk of Amyotrophic Lateral Sclerosis in a prospective cohort study

    NARCIS (Netherlands)

    Gallo, Valentina; Vanacore, Nicola; Bueno-de-Mesquita, H Bas; Vermeulen, Roel; Brayne, Carol; Pearce, Neil; Wark, Petra A; Ward, Heather A; Ferrari, Pietro; Jenab, Mazda; Andersen, Peter M; Wennberg, Patrik; Wareham, Nicholas; Katzke, Verena; Kaaks, Rudolf; Weiderpass, Elisabete; Peeters, Petra H; Mattiello, Amalia; Pala, Valeria; Barricante, Aurelio; Chirlaque, Maria-Dolores; Travier, Noémie; Travis, Ruth C; Sanchez, Maria-Jose; Pessah-Rasmussen, Hélène; Petersson, Jesper; Tjønneland, Anne; Tumino, Rosario; Quiros, Jose Ramon; Trichopoulou, Antonia; Kyrozis, Andreas; Oikonomidou, Despoina; Masala, Giovanna; Sacerdote, Carlotta; Arriola, Larraitz; Boeing, Heiner; Vigl, Matthaeus; Claver-Chapelon, Francoise; Middleton, Lefkos; Riboli, Elio; Vineis, Paolo

    Previous case-control studies have suggested a possible increased risk of Amyotrophic Lateral Sclerosis (ALS) with physical activity (PA), but this association has never been studied in prospective cohort studies. We therefore assessed the association between PA and risk of death from ALS in the

  19. Speech Deterioration in Amyotrophic Lateral Sclerosis (ALS) after Manifestation of Bulbar Symptoms

    Science.gov (United States)

    Makkonen, Tanja; Ruottinen, Hanna; Puhto, Riitta; Helminen, Mika; Palmio, Johanna

    2018-01-01

    Background: The symptoms and their progression in amyotrophic lateral sclerosis (ALS) are typically studied after the diagnosis has been confirmed. However, many people with ALS already have severe dysarthria and loss of adequate speech at the time of diagnosis. Speech-and-language therapy interventions should be targeted timely based on…

  20. Integration of structural and functional magnetic resonance imaging in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Douaud, Gwenaëlle; Filippini, Nicola; Knight, Steven; Talbot, Kevin; Turner, Martin R

    2011-12-01

    Amyotrophic lateral sclerosis as a system failure is a concept supported by the finding of consistent extramotor as well as motor cerebral pathology. The functional correlates of the structural changes detected using advanced magnetic resonance imaging techniques such as diffusion tensor imaging and voxel-based morphometry have not been extensively studied. A group of 25 patients with amyotrophic lateral sclerosis was compared to healthy control subjects using a multi-modal neuroimaging approach comprising T(1)-weighted, diffusion-weighted and resting-state functional magnetic resonance imaging. Using probabilistic tractography, a grey matter connection network was defined based upon the prominent corticospinal tract and corpus callosum involvement demonstrated by white matter tract-based spatial statistics. This 'amyotrophic lateral sclerosis-specific' network included motor, premotor and supplementary motor cortices, pars opercularis and motor-related thalamic nuclei. A novel analysis protocol, using this disease-specific grey matter network as an input for a dual-regression analysis, was then used to assess changes in functional connectivity directly associated with this network. A spatial pattern of increased functional connectivity spanning sensorimotor, premotor, prefrontal and thalamic regions was found. A composite of structural and functional magnetic resonance imaging measures also allowed the qualitative discrimination of patients from controls. An integrated structural and functional connectivity approach therefore identified apparently dichotomous processes characterizing the amyotrophic lateral sclerosis cerebral network failure, in which there was increased functional connectivity within regions of decreased structural connectivity. Patients with slower rates of disease progression showed connectivity measures with values closer to healthy controls, raising the possibility that functional connectivity increases might not simply represent a

  1. 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.

  2. Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols

    Science.gov (United States)

    Vejux, Anne; Namsi, Amira; Nury, Thomas; Moreau, Thibault; Lizard, Gérard

    2018-01-01

    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. PMID:29445325

  3. Advance care planning for patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Levi, Benjamin H; Simmons, Zachary; Hanna, Courtney; Brothers, Allyson; Lehman, Erik; Farace, Elana; Bain, Megan; Stewart, Renee; Green, Michael J

    2017-08-01

    To determine whether an advance care planning (ACP) decision-aid could improve communication about end-of-life treatment wishes between patients with amyotrophic lateral sclerosis (ALS) and their clinicians. Forty-four patients with ALS (>21, English-speaking, without dementia) engaged in ACP using an interactive computer based decision-aid. Before participants completed the intervention, and again three months later, their clinicians reviewed three clinical vignettes, and made treatment decisions (n = 18) for patients. After patients indicated their agreement with the team's decisions, concordance was calculated. The mean concordance between patient wishes and the clinical team decisions was significantly higher post-intervention (post = 91.9%, 95% CI = 87.8, 96.1, vs. pre = 52.4%, 95% CI = 41.9, 62.9; p <0.001). Clinical team members reported greater confidence that their decisions accurately represented each patient's wishes post-intervention (mean = 6.5) compared to pre-intervention (mean = 3.3, 1 = low, 10 = high, p <0.001). Patients reported high satisfaction (mean = 26.4, SD = 3.2; 6 = low, 30 = high) and low decisional conflict (mean = 28.8, SD = 8.2; 20 = low, 80 = high) with decisions about end-of-life care, and high satisfaction with the decision-aid (mean = 52.7, SD = 5.7, 20 = low, 60 = high). Patient knowledge regarding ACP increased post-intervention (pre = 47.8% correct responses vs. post = 66.3%; p <0.001) without adversely affecting patient anxiety or self-determination. A computer based ACP decision-aid can significantly improve clinicians' understanding of ALS patients' wishes with regard to end-of-life medical care.

  4. 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

  5. 1H-MR spectroscopy study in amyotrophic lateral sclerosis

    International Nuclear Information System (INIS)

    Han Jing; Ma Lin; Yu Shengyuan

    2009-01-01

    Objective: To characterize the features of proton magnetic resonance spectroscopy ( 1 H-MRS) on amyotrophic lateral sclerosis (ALS) and its correlations with clinical scale. Methods: Fifteen patients with definite or probable ALS and 15 age and gender matched normal controls were enrolled. 1 H-MRS was performed on a 3.0 T GE imaging system (GE Medical System, Milwaukee, Wisconsin, USA). TE-averaged point resolved selective spectroscopy was used. N-acetylaspartate (NAA), creatine (Cr), Glu and Glx (glutamate + glutamine) values of subcortical motor area and posterior limb of the internal capsule were acquired, t test was used to compare differences between groups, the correlations between the above values and clinical scale were analyzed. Results: The motor area and posterior limb of the internal capsule in ALS patients had significantly lower NAA/Cr (1.91±0.34, 1.53±0.17) compared with normal subjects (2.23±0.33, 1.66±0.07) (t=4.25,2.90,P=0.00,0.01). ALS patients had significantly higher Glu/Cr (0.34±0.05, 0.29±0.06) and Glx/Cr (0.40±0.04, 0.33±0.06), compared with normal subjects (0.30±0.03,0.25±0.04) and (0.32±0.05,0.26±0.03) (t=2.56, 2.40,7.34,5.30, P=0.02,0.03,0.00,0.00). The Norris scale of ALS patients were 57±8, ALSFRS were 29±4. The Norris scale was negatively correlated with Glx/Cr of primary motor cortex by lineal correlation analysis (r=-0.75, P=0.00), while ALSFRS had no correlation with Glx/Cr. Conclusions: Neuronal loss and Glu + Gln increase can be detected by using proton MRS in ALS patients. 1 H-MRS is an useful tool in reflecting the characteristic changes of metabolite in ALS. (authors)

  6. 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.)

  7. 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.

  8. Implementation of a population-based epidemiological rare disease registry: study protocol of the amyotrophic lateral sclerosis (ALS) - registry Swabia

    OpenAIRE

    Nagel, Gabriele; ?nal, Hatice; Rosenbohm, Angela; Ludolph, Albert C; Rothenbacher, Dietrich

    2013-01-01

    Abstract Background The social and medical impact of rare diseases is increasingly recognized. Amyotrophic lateral sclerosis (ALS) is the most prevalent of the motor neuron diseases. It is characterized by rapidly progressive damage to the motor neurons with a survival of 2–5 years for the majority of patients. The objective of this work is to describe the study protocol and the implementation steps of the amyotrophic lateral sclerosis (ALS) registry Swabia, located in the South of Germany. M...

  9. "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

  10. Multiple Sclerosis: Can It Cause Seizures?

    Science.gov (United States)

    ... multiple sclerosis and epilepsy? Answers from B Mark Keegan, M.D. Epileptic seizures are more common in ... controlled with anti-seizure medication. With B Mark Keegan, M.D. Lund C, et al. Multiple sclerosis ...

  11. Emotional Disorders in People with Multiple Sclerosis

    Science.gov (United States)

    ... Evidence-based Guideline for PATIENTS and their FAMILIES EMOTIONAL DISORDERS IN PEOPLE WITH MULTIPLE SCLEROSIS This fact sheet presents the current research on emotional disorders in multiple sclerosis (MS) and summarizes the ...

  12. Place of death in patients with amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    J. Escarrabill

    2014-07-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a degenerative neurological disorder that affects motor neurons. Involvement of respiratory muscles causes the failure of the ventilator pump with more or less significant bulbar troubles. ALS course is highly variable but, in most cases, this disease entails a very significant burden for patients and caregivers, especially in the end-of-life period.In order to analyze the characteristics of ALS patients who die at home (DH and in hospital (DHosp and to study the variability of clinical practice, a retrospective medical records analysis was performed (n = 77 from five hospitals. Variables: time elapsed since the onset of symptoms and the beginning of ventilation, characteristics of ventilation (device, mask and hours/day, and support devices and procedures. Results: In all, 14% of patients were ventilated by tracheotomy. From the analysis, 57% of patients were of DH. Mean time since the onset of symptoms was 35.93 ± 25.89 months, significantly shorter in patients who DHosp (29.28 ± 19.69 months than DH (41.12 ± 29.04 (p = 0.044. The percentage of patients with facial ventilation is higher in DHosp (11.4% vs 39.4%, p < 0.005.DH or not is related to a set of elements in which health resources, physician attitudes and support resources in the community play a role in the decision-making process. There is great variability between countries and between hospitals in the same country. Given the variability of circumstances in each territory, the place of death in ALS might not be the most important element; more important are the conditions under which the process unfolds. Resumo: A esclerose lateral amiotrófica (ELA é uma perturbação neurológica degenerativa que afeta os neurónios motores. O envolvimento dos músculos respiratórios causa a falha da bomba ventilatória, com problemas bulbares mais ou menos significativos. A evolução da ELA

  13. Treatment of Cognitive Impairment in Multiple Sclerosis

    OpenAIRE

    Pierson, Susan H.; Griffith, Nathan

    2006-01-01

    Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the co...

  14. 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.

  15. The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Harada, Masafumi; Kaji, Ryuji

    2016-05-01

    Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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

  17. 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

  18. 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

  19. Neuromyelitis optica and multiple sclerosis

    DEFF Research Database (Denmark)

    Bennett, J. L.; de Seze, J.; Lana-Peixoto, M.

    2015-01-01

    Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel...

  20. [Biological treatment of multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, P.S.; Sellebjerg, F.

    2008-01-01

    In 1996 interferon (IFN)beta was the first biopharmaceutical product to be approved for the treatment of relapsing-remitting multiple sclerosis (MS). In 2006 the more potent monoclonal antibody natalizumab was approved. Presently, a number of monoclonal antibodies are being studied, including ale...

  1. Uric acid in multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic

  2. The danish multiple sclerosis registry

    DEFF Research Database (Denmark)

    Brønnum-Hansen, Henrik; Koch-Henriksen, Nils; Stenager, Egon

    2011-01-01

    Introduction: The Danish Multiple Sclerosis (MS) Registry was established in 1956. Content: The register comprises data on all Danes who had MS in 1949 or who have been diagnosed since. Data on new cases and updated information on persons with an MS diagnosis already notified are continuously...

  3. The immunogenetics of multiple sclerosis

    DEFF Research Database (Denmark)

    Svejgaard, A.

    2008-01-01

    with complex genetic backgrounds. HLA controls immune response genes and HLA associations indicate the involvement of autoimmunity. Multiple sclerosis (MS) was one of the first conditions proven to be HLA associated involving primarily HLA class II factors. We review how HLA studies give fundamental...

  4. Laboratory diagnosis of multiple sclerosis

    International Nuclear Information System (INIS)

    Sand, T.; Stovner, L.J.; Rinck, P.A.; Nilsen, G.; Romslo, I.

    1991-01-01

    In 26 patients with multiple sclerosis 100% responded abnormally to magnetic resonance imaging of the brain. Lesions in the posterior fossa were observed in 18 patients. The auditory brain stem response was abnormal in 15 patients, and 22 had abnormal immunoglobulins in the cerebrospinal fluid. The correlation between abnormalities of the auditory brain stem response and the magnetic resonance images was greatest in a subgroup where the two investigations were performed within a ten day interval. Results from magnetic resonance imaging, evoked potentials and cerebrospinal fluid investigations were used to reclassify 13 of 15 patients with clinically ''possible'' or ''probable''multiple sclerosis to a higher level using Poser's criteria. Evoked potentials (the auditory brain stem response in particular) correlated best with clinical multiple sclerosis category. The authors recommend that the magnetic resonance imaging is established as a first-hand investigation in evaluation of multiple sclerosis. Evoked potentials and cerebrospinal fluid investigations may prove to be more specific, however, and these investigations should also be performed as a routine. 23 refs., 2 figs., 2 tabs

  5. Vascular aspects of multiple sclerosis

    NARCIS (Netherlands)

    D'haeseleer, Miguel; Cambron, Melissa; Vanopdenbosch, Ludo; De Keyser, Jacques

    Three types of vascular dysfunction have been described in multiple sclerosis (MS). First, findings from epidemiological studies suggest that patients with MS have a higher risk for ischaemic stroke than people who do not have MS. The underlying mechanism is unknown, but might involve endothelial

  6. 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.

  7. Treatment of Cognitive Impairment in Multiple Sclerosis

    Science.gov (United States)

    Pierson, Susan H.; Griffith, Nathan

    2006-01-01

    Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

  8. Clinical Research on Traditional Chinese Medicine compounds and their preparations for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Zhu, Jiayi; Shen, Lan; Lin, Xiao; Hong, Yanlong; Feng, Yi

    2017-12-01

    Amyotrophic lateral sclerosis (ALS) is a chronic, fatal neurodegenerative disease which leads to progressive muscle atrophy and paralysis. In order to summarize the characteristics of Traditional Chinese Medicine compounds and their preparations in the prevention and treatment of ALS through analyzing the mechanism, action site, and symptoms according to effective clinical research. We searched ALS, motor neuron disease, chemical drugs, herbal medicine, Chinese medicine, Traditional Chinese Medicine (TCM), and various combinations of these terms in databases including the PudMed, Springer, Ovid, Google, China National Knowledge Infrastructure, and Wanfang databases. It was found that the chemical drugs almost had not sufficient evidence to show their effectiveness in the treatment of ALS, except RILUZOLE. According to the characteristics of clinical symptoms of ALS, Chinese medicine practitioners believe that this disease belongs to the category of "atrophic disease". In clinical research, many Chinese herbal formulas had good clinical efficacies in the treatment of ALS with multiple targets, multiple links, and few side effects. And four kinds of dialectical treatment had been developed based on Clinical data analysis and the use of dialectical therapy: Benefiting the kidney; Declaring the lungs; Enhancing the Qi; and Dredging the meridian. In this review, we provide an overview of chemical drugs and Traditional Chinese Medicine compound and its preparations in therapy of ALS as well as how they may contribute to the ALS pathogenesis, thereby offering some clues for further studies. Copyright © 2017. Published by Elsevier Masson SAS.

  9. [Our first experiences with intermittent assisted ventilation in patients with amyotrophic lateral sclerosis].

    Science.gov (United States)

    Treuheit, T; Bartels, C; Hoffmann, B; Welte, T

    1999-10-01

    Amyotrophic lateral sclerosis is one of the most frequent neuromuscular diseases in adults. Chronic respiratory failures is an almost compulsory symptom in the progression of this disease, and in association with pulmonary infections, responsible for the majority of deaths. We report on a series of 43 patients. An advanced stage of clinical disease was seen in half of them. After detection of respiratory failure corresponding to the guidelines of muscle centres of the DGM (Deutsche Gesellschaft für Muskelerkrankungen), seven patients (16.3%) were willing to be provided with a system for intermittent non-invasive ventilation. All patients achieved stabilisation of respiratory function, both with respect to the normalisation of arterial gases and subjective improvement of well-being. During the course of treatment four patients deliberately underwent permanent invasive ventilation. In our opinion home ventilation is a valid additional tool in the palliative treatment of amyotrophic lateral sclerosis. The treatment, however, must be supported by an interdisciplinary team.

  10. Multiple sclerosis and herpesvirus interaction

    Directory of Open Access Journals (Sweden)

    Guilherme Sciascia do Olival

    2013-09-01

    Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

  11. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Spiegelman, Dan; McConkey, Brendan J; Vande Velde, Christine; Bouchard, Jean-Pierre; Lacomblez, Lucette; Pochigaeva, Ksenia; Salachas, Francois; Pradat, Pierre-Francois; Camu, William; Meininger, Vincent; Dupre, Nicolas; Rouleau, Guy A

    2008-05-01

    Recently, TDP-43 was identified as a key component of ubiquitinated aggregates in amyotrophic lateral sclerosis (ALS), an adult-onset neurological disorder that leads to the degeneration of motor neurons. Here we report eight missense mutations in nine individuals--six from individuals with sporadic ALS (SALS) and three from those with familial ALS (FALS)--and a concurring increase of a smaller TDP-43 product. These findings further corroborate that TDP-43 is involved in ALS pathogenesis.

  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. Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.

    Science.gov (United States)

    Johnson, Janel O; Pioro, Erik P; Boehringer, Ashley; Chia, Ruth; Feit, Howard; Renton, Alan E; Pliner, Hannah A; Abramzon, Yevgeniya; Marangi, Giuseppe; Winborn, Brett J; Gibbs, J Raphael; Nalls, Michael A; Morgan, Sarah; Shoai, Maryam; Hardy, John; Pittman, Alan; Orrell, Richard W; Malaspina, Andrea; Sidle, Katie C; Fratta, Pietro; Harms, Matthew B; Baloh, Robert H; Pestronk, Alan; Weihl, Conrad C; Rogaeva, Ekaterina; Zinman, Lorne; Drory, Vivian E; Borghero, Giuseppe; Mora, Gabriele; Calvo, Andrea; Rothstein, Jeffrey D; Drepper, Carsten; Sendtner, Michael; Singleton, Andrew B; Taylor, J Paul; Cookson, Mark R; Restagno, Gabriella; Sabatelli, Mario; Bowser, Robert; Chiò, Adriano; Traynor, Bryan J

    2014-05-01

    MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration.

  14. Diffusion tensor imaging and voxel based morphometry study in amyotrophic lateral sclerosis: relationships with motor disability

    OpenAIRE

    Thivard, Lionel; Pradat, Pierre‐François; Lehéricy, Stéphane; Lacomblez, Lucette; Dormont, Didier; Chiras, Jacques; Benali, Habib; Meininger, Vincent

    2007-01-01

    International audience; The aim of this study was to investigate the extent of cortical and subcortical lesions in amyotrophic lateral sclerosis (ALS) using, in combination, voxel based diffusion tensor imaging (DTI) and voxel based morphometry (VBM). We included 15 patients with definite or probable ALS and 25 healthy volunteers. Patients were assessed using the revised ALS Functional Rating Scale (ALSFRS-R). In patients, reduced fractional anisotropy was found in bilateral corticospinal tra...

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

    International Nuclear Information System (INIS)

    Abe, K.; Yorifuji, S.; Nishikawa, Y.

    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.)

  16. 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.

  17. 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

  18. The predictive value of respiratory function tests for non-invasive ventilation in amyotrophic lateral sclerosis

    OpenAIRE

    Tilanus, T. B. M.; Groothuis, J. T.; TenBroek-Pastoor, J. M. C.; Feuth, T. B.; Heijdra, Y. F.; Slenders, J. P. L.; Doorduin, J.; Van Engelen, B. G.; Kampelmacher, M. J.; Raaphorst, J.

    2017-01-01

    BACKGROUND: Non-invasive ventilation (NIV) improves survival and quality of life in amyotrophic lateral sclerosis (ALS) patients. The timing of referral to a home ventilation service (HVS), which is in part based on respiratory function tests, has shown room for improvement. It is currently unknown which respiratory function test predicts an appropriate timing of the initiation of NIV. METHODS: We analysed, retrospectively, serial data of five respiratory function tests: forced vital capacity...

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

    OpenAIRE

    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 and quality of life (QOL) is different in patients with ALS versus without ALS. A post hoc analysis was done with data from a previously published trial, in which all patients were instituted on NIV...

  20. Amyotrophic lateral sclerosis (ALS): three letters that change the people's life. For ever

    OpenAIRE

    Oliveira,Acary Souza Bulle; Pereira,Roberto Dias Batista

    2009-01-01

    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 mu...

  1. Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis.

    OpenAIRE

    Andersen, Tiina Maarit; Sandnes, Astrid; Brekka, Anne Kristine; Hilland, Magnus; Clemm, Hege; Fondenes, Ove; Tysnes, Ole Bjørn; Heimdal, John-Helge; Halvorsen, Thomas; Vollsæter, Maria; Røksund, Ola Drange

    2016-01-01

    Background: Most patients with amyotrophic lateral sclerosis (ALS) are treated with mechanical insufflation–exsufflation (MI-E) in order to improve cough. This method often fails in ALS with bulbar involvement, allegedly due to upper-airway malfunction. We have studied this phenomenon in detail with laryngoscopy to unravel information that could lead to better treatment. Methods: We conducted a cross-sectional study of 20 patients with ALS and 20 healthy age-matched and sex-matched v...

  2. Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis

    OpenAIRE

    Chen, YongPing; Wei, QianQian; Chen, XuePing; Li, ChunYu; Cao, Bei; Ou, RuWei; Hadano, Shinji; Shang, Hui-Fang

    2016-01-01

    Background: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. Methods: We ana...

  3. Masticatory muscle pain and progressive mouth opening limitation caused by amyotrophic lateral sclerosis: a case report.

    Science.gov (United States)

    Pang, Kang Mi; Park, Ji Woon

    2015-01-01

    This article reports a case of masticatory muscle pain and progressive limited mouth opening secondary to amyotrophic lateral sclerosis (ALS), popularly known as Lou Gehrig's disease. The symptoms were first mistaken as those of temporomandibular disorders, before fatty degeneration of all masticatory muscles were discovered on magnetic resonance imaging (MRI). ALS should be considered in the differential diagnosis process when the patient presents with longstanding progressive mouth opening limitation associated with pain. MRI could facilitate the diagnostic process.

  4. Cognitive and behavioural deficits associated with the orbitomedial prefrontal cortex in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Meier, Sandra L; Charleston, Alison J; Tippett, Lynette J

    2010-11-01

    Amyotrophic lateral sclerosis, a progressive disease affecting motor neurons, may variably affect cognition and behaviour. We tested the hypothesis that functions associated with orbitomedial prefrontal cortex are affected by evaluating the behavioural and cognitive performance of 18 participants with amyotrophic lateral sclerosis without dementia and 18 healthy, matched controls. We measured Theory of Mind (Faux Pas Task), emotional prosody recognition (Aprosodia Battery), reversal of behaviour in response to changes in reward (Probabilistic Reversal Learning Task), decision making without risk (Holiday Apartment Task) and aberrant behaviour (Neuropsychiatric Inventory). We also assessed dorsolateral prefrontal function, using verbal and written fluency and planning (One-touch Stockings of Cambridge), to determine whether impairments in tasks sensitive to these two prefrontal regions co-occur. The patient group was significantly impaired at identifying social faux pas, recognizing emotions and decision-making, indicating mild, but consistent impairment on most measures sensitive to orbitomedial prefrontal cortex. Significant levels of aberrant behaviour were present in 50% of patients. Patients were also impaired on verbal fluency and planning. Individual subject analyses involved computing classical dissociations between tasks sensitive to different prefrontal regions. These revealed heterogeneous patterns of impaired and spared cognitive abilities: 33% of participants had classical dissociations involving orbitomedial prefrontal tasks, 17% had classical dissociations involving dorsolateral prefrontal tasks, 22% had classical dissociations between tasks of both regions, and 28% had no classical dissociations. These data indicate subtle changes in behaviour, emotional processing, decision-making and altered social awareness, associated with orbitomedial prefrontal cortex, may be present in a significant proportion of individuals with amyotrophic lateral sclerosis

  5. Vitamin D Levels Predict Multiple Sclerosis Progression

    Science.gov (United States)

    ... Research Matters NIH Research Matters February 3, 2014 Vitamin D Levels Predict Multiple Sclerosis Progression Among people ... sclerosis (MS), those with higher blood levels of vitamin D had better outcomes during 5 years of ...

  6. 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

  7. Safety, tolerability, and cerebrospinal fluid penetration of ursodeoxycholic Acid in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Parry, Gareth J; Rodrigues, Cecilia M P; Aranha, Marcia M; Hilbert, Sarah J; Davey, Cynthia; Kelkar, Praful; Low, Walter C; Steer, Clifford J

    2010-01-01

    Amyotrophic lateral sclerosis is a progressive degenerative disease, which typically leads to death in 3 to 5 years. Neuronal cell death offers a potential target for therapeutic intervention. Ursodeoxycholic acid is a cytoprotective, endogenous bile acid that has been shown to be neuroprotective in experimental Huntington and Alzheimer diseases, retinal degeneration, and ischemic and hemorrhagic stroke. The objective of this research was to study the safety and the tolerability of ursodeoxycholic acid in amyotrophic lateral sclerosis and document effective and dose-dependent cerebrospinal fluid penetration. Eighteen patients were randomly assigned to receive ursodeoxycholic acid at doses of 15, 30, and 50 mg/kg of body weight per day. Serum and cerebrospinal fluid were obtained for analysis after 4 weeks of treatment. Treatment-emergent clinical and laboratory events were monitored weekly. Our data indicated that ursodeoxycholic acid is well tolerated by all subjects at all doses. We also showed that ursodeoxycholic acid is well absorbed after oral administration and crosses the blood-brain barrier in a dose-dependent manner. These results show excellent safety and tolerability of ursodeoxycholic acid. The drug penetrates the cerebrospinal fluid in a dose-dependent manner. A large, placebo-controlled clinical trial is needed to assess the efficacy of ursodeoxycholic acid in treating amyotrophic lateral sclerosis.

  8. 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.

  9. 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

  10. Multiple sclerosis in magnetic resonance

    International Nuclear Information System (INIS)

    Bekiesinska-Figatowska, M.; Walecki, J.; Stelmasiak, Z.

    1994-01-01

    The authors analyzed MR examination of 277 patients with multiple sclerosis. White matter hyperintesities in brain were found in 270 of them, in spinal cord in 32. The most frequently they were found in periventricular white matter, in subcortical localization and in the corpus callosum. MR examination allows the estimate the activity of the disease on the basis of the presence of edema around the plaques and their contrast enhancement with Gd-DTPA. About one third of all cases were accompanied by cortical brain atrophy (the most often seen in the frontal lobes), subcortical brain atrophy was less frequent. In about two third of all cases the corpus callosum atrophy was found. MR examination is a highly sensitive method of multiple sclerosis diagnosis, of the assessment of its activity and progression. (author)

  11. [Current description of multiple sclerosis].

    Science.gov (United States)

    Río, Jordi; Montalbán, Xavier

    2014-12-01

    Multiple sclerosis is a multifocal demyelinating disease leading to progressive neurodegeneration caused by an autoimmune response in genetically predisposed individuals. In the last few years, the knowledge and management of this disease has been revolutionized by a series of findings. The present article reviews pathological features of the disease, in which cortical involvement is increasingly implicated, and aspects related to novel pathogenic mechanisms, such as the role of the microbiota in the genesis of multiple sclerosis, as well as recent contributions from the fields of epidemiology and genetics. Also reviewed are the latest diagnostic criteria, which currently allow a much earlier diagnosis, with clear therapeutic implications. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  12. Cognitive deficits in multiple sclerosis

    DEFF Research Database (Denmark)

    Lund, H; Jønsson, A; Andresen, Jesper Graubæk

    2012-01-01

    of the cognitive impairment seen in MS and constitute a supplement to traditional measurement of T2 lesion volume. Materials and Methods - Fifty patients with clinically definite MS were included (38 women, 12 men). Patients were MR scanned, neuropsychologically tested, and evaluated clinically with the Kurtzke......Objectives - Although disease load in multiple sclerosis (MS) often is based on T2 lesion volumes, the changes in T2 of normal appearing brain tissue (NABT) are rarely considered. By means of magnetic resonance, (MR) we retrospectively investigated whether T2 changes in NABT explain part...... Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Impairment Scale (MSIS). Voxel-wise T2 estimates and total T2 lesion volume were tested for correlations with eight cognitive domains, a general cognitive dysfunction factor (CDF), and the two clinical scales. Results - We found distinct...

  13. Multiple sclerosis and birth order.

    Science.gov (United States)

    James, W H

    1984-01-01

    Studies on the birth order of patients with multiple sclerosis have yielded contradictory conclusions. Most of the sets of data, however, have been tested by biased tests. Data that have been submitted to unbiased tests seem to suggest that cases are more likely to occur in early birth ranks. This should be tested on further samples and some comments are offered on how this should be done. PMID:6707558

  14. Multiple sclerosis and birth order.

    OpenAIRE

    James, W H

    1984-01-01

    Studies on the birth order of patients with multiple sclerosis have yielded contradictory conclusions. Most of the sets of data, however, have been tested by biased tests. Data that have been submitted to unbiased tests seem to suggest that cases are more likely to occur in early birth ranks. This should be tested on further samples and some comments are offered on how this should be done.

  15. Multiple Sclerosis: Pathogenesis and Treatment

    OpenAIRE

    Loma, Ingrid; Heyman, Rock

    2011-01-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. It affects approximately 400,000 people in the United States and onset is usually during young adulthood. There are four clinical forms of MS, of which relapsing remitting type is the most common. As the etiology of MS is unknown, finding a cure will remain challenging. The main mechanism of injury appears to be inflammation and 8 agents are now FDA approved to help control MS. Th...

  16. Treatment Satisfaction in Multiple Sclerosis

    OpenAIRE

    Glanz, Bonnie I.; Musallam, Alexander; Rintell, David J.; Chitnis, Tanuja; Weiner, Howard L.; Healy, Brian C.

    2014-01-01

    Background: Disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) are associated with inconvenient methods of administration, significant side effects, and low adherence rates. This study was undertaken to compare treatment satisfaction in MS patients treated with interferon beta-1a intramuscular (IFNβ-1a IM), interferon beta-1a subcutaneous (IFNβ-1a SC), glatiramer acetate (GA), and natalizumab (NTZ), and to examine the associations between treatment satisfaction ra...

  17. Estrogen Treatment in Multiple Sclerosis

    OpenAIRE

    Gold, Stefan M; Voskuhl, Rhonda R

    2009-01-01

    Currently available treatments for multiple sclerosis reduce inflammatory lesions on MRI and decrease clinical relapses but have limited effects on disability. Novel treatment options that target both the inflammatory as well as the neurodegenerative component of the disease are therefore needed. A growing body of evidence from basic science and clinical studies supports the therapeutic potential of estrogens in MS. Mechanisms of action include both immunomodulatory and directly neuroprotecti...

  18. Cell Death-Autophagy Loop and Glutamate-Glutamine Cycle in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Shu Yuan

    2017-07-01

    Full Text Available Although we know that amyotrophic lateral sclerosis (ALS is correlated with the glutamate-mediated corticomotor neuronal hyperexcitability, detailed ALS pathology remains largely unexplained. While a number of drugs have been developed, no cure exists so far. Here, we propose a hypothesis of neuronal cell death—incomplete autophagy positive-feedback loop—and summarize the role of the neuron-astrocyte glutamate-glutamine cycle in ALS. The disruption of these two cycles might ideally retard ALS progression. Cerebrovascular injuries (such as multiple embolization sessions and strokes induce neuronal cell death and the subsequent autophagy. ALS impairs autophagosome-lysosome fusion and leads to magnified cell death. Trehalose rescues this impaired fusion step, significantly delaying the onset of the disease, although it does not affect the duration of the disease. Therefore, trehalose might be a prophylactic drug for ALS. Given that a major part of neuronal glutamate is converted from glutamine through neuronal glutaminase (GA, GA inhibitors may decrease the neuronal glutamate accumulation, and, therefore, might be therapeutic ALS drugs. Of these, Ebselen is the most promising one with strong antioxidant properties.

  19. [Evaluation and treatment of dysphagia in amyotrophic lateral sclerosis and Parkinson's disease].

    Science.gov (United States)

    Yamamoto, Toshiyuki

    2011-11-01

    As both amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) exhibit a variety of patterns of dysphagia, appropriate symptomatic treatment is provided after evaluation of swallowing function through videofluoroscopic examination of swallowing. In ALS, disease progression is rapid, therefore, respiratory function, swallowing function and nutritional status should be evaluated regularly. When the oral or pharyngeal stage of swallowing are affected early in dysphagia, adjusting swallowing volume and varying consistency can be beneficial in ALS. When all stages of swallowing are impaired in ALS, such complications as pneumonia, dehydration and malnutrition, are observed. In such patients, it is necessary to consider an alternative to oral dietary intake. In PD, dysphagia is not necessarily associated with severity of parkinsonism and can appear at any time during the course of the disease. Dysphagia in PD can occur at any stage of swallowing and frequently accompanies multiple abnormalities. In particular, aspiration is an important risk factor for pneumonia in PD. The effect of L-dopa treatment for dysphagia is often insufficient; however, this treatment remains the first choice because dysphagia is exacerbated during off state. Rehabilitation for dysphagia in PD has also some effect.

  20. Predicting Speech Intelligibility Decline in Amyotrophic Lateral Sclerosis Based on the Deterioration of Individual Speech Subsystems

    Science.gov (United States)

    Yunusova, Yana; Wang, Jun; Zinman, Lorne; Pattee, Gary L.; Berry, James D.; Perry, Bridget; Green, Jordan R.

    2016-01-01

    Purpose To determine the mechanisms of speech intelligibility impairment due to neurologic impairments, intelligibility decline was modeled as a function of co-occurring changes in the articulatory, resonatory, phonatory, and respiratory subsystems. Method Sixty-six individuals diagnosed with amyotrophic lateral sclerosis (ALS) were studied longitudinally. The disease-related changes in articulatory, resonatory, phonatory, and respiratory subsystems were quantified using multiple instrumental measures, which were subjected to a principal component analysis and mixed effects models to derive a set of speech subsystem predictors. A stepwise approach was used to select the best set of subsystem predictors to model the overall decline in intelligibility. Results Intelligibility was modeled as a function of five predictors that corresponded to velocities of lip and jaw movements (articulatory), number of syllable repetitions in the alternating motion rate task (articulatory), nasal airflow (resonatory), maximum fundamental frequency (phonatory), and speech pauses (respiratory). The model accounted for 95.6% of the variance in intelligibility, among which the articulatory predictors showed the most substantial independent contribution (57.7%). Conclusion Articulatory impairments characterized by reduced velocities of lip and jaw movements and resonatory impairments characterized by increased nasal airflow served as the subsystem predictors of the longitudinal decline of speech intelligibility in ALS. Declines in maximum performance tasks such as the alternating motion rate preceded declines in intelligibility, thus serving as early predictors of bulbar dysfunction. Following the rapid decline in speech intelligibility, a precipitous decline in maximum performance tasks subsequently occurred. PMID:27148967

  1. 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.

  2. 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.

  3. Level of neurotoxic metals in amyotrophic lateral sclerosis: A population-based case-control study.

    Science.gov (United States)

    Bocca, Beatrice; Forte, Giovanni; Oggiano, Riccardo; Clemente, Simonetta; Asara, Yolande; Peruzzu, Angela; Farace, Cristiano; Pala, Salvatore; Fois, Alessandro Giuseppe; Pirina, Pietro; Madeddu, Roberto

    2015-12-15

    The association between exposure to toxic metals and amyotrophic lateral sclerosis (ALS) was explored in a population-based case-control study in the Sardinia island (Italy), a region characterized by elevated rates of ALS cases. In 34 patients with ALS (mean age, 62 ± 10 years) and 30 controls (mean age, 65 ± 11 years), Al, Cd, Hg, Mn and Pb were determined in blood, hair and urine by sector field inductively coupled mass spectrometry. Results indicated that, in blood, concentrations of Al (p=0.045) and Pb were higher (p=0.026) in ALS patients than in control subjects. In hair, a depletion of Al (p=0.006) and Mn (p=0.032) concentrations in ALS subjects respect to controls was found. In urine, no significant differences between cases and controls were observed. Thus, some metals seemed to be associated with ALS degeneration, but a definitive conclusion is still far considering the multiple risk factors (genetic mutations, environmental toxicants and stressors) involved in the disease. Finally, the interpretation that deregulated metal concentrations can be a consequence of the degenerative process, rather than a cause, is also valid. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. 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.

  5. Uncoupling of Protein Aggregation and Neurodegeneration in a Mouse Amyotrophic Lateral Sclerosis Model.

    Science.gov (United States)

    Lee, Joo-Yong; Kawaguchi, Yoshiharu; Li, Ming; Kapur, Meghan; Choi, Su Jin; Kim, Hak-June; Park, Song-Yi; Zhu, Haining; Yao, Tso-Pang

    2015-01-01

    Aberrant accumulation of protein aggregates is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although a buildup of protein aggregates frequently leads to cell death, whether it is the key pathogenic factor in driving neurodegenerative disease remains controversial. HDAC6, a cytosolic ubiquitin-binding deacetylase, has emerged as an important regulator of ubiquitin-dependent quality control autophagy, a lysosome-dependent degradative system responsible for the disposal of misfolded protein aggregates and damaged organelles. Here, we show that in cell models HDAC6 plays a protective role against multiple disease-associated and aggregation-prone cytosolic proteins by facilitating their degradation. We further show that HDAC6 is required for efficient localization of lysosomes to protein aggregates, indicating that lysosome targeting to autophagic substrates is regulated. Supporting a critical role of HDAC6 in protein aggregate disposal in vivo, genetic ablation of HDAC6 in a transgenic SOD1G93A mouse, a model of ALS, leads to dramatic accumulation of ubiquitinated SOD1G93A protein aggregates. Surprisingly, despite a robust buildup of SOD1G93A aggregates, deletion of HDAC6 only moderately modified the motor phenotypes. These findings indicate that SOD1G93A aggregation is not the only determining factor to drive neurodegeneration in ALS, and that HDAC6 likely modulates neurodegeneration through additional mechanisms beyond protein aggregate clearance. © 2015 S. Karger AG, Basel.

  6. Magnetic resonance in multiple sclerosis

    International Nuclear Information System (INIS)

    Scotti, G.; Caputo, D.; Cazzullo, C.L.

    1986-01-01

    Magnetic Resonance Imaging was performed in more than 200 patients with clinical suspicion or knowledge of Multiple Sclerosis. One hundred and forty-seven (60 males and 87 females) had MR evidence of multiple sclerosis lesions. The MR signal of demyelinating plaques characteristically has prolonged T1 and T2 relaxation times and the T2-weighted spin-echo sequences are generally superior to the T1-weighted images because the lesions are better visualized as areas of increased signal intensity. MR is also able to detect plaques in the brainstem, cerebellum and within the cervical spinal cord. MR appears to be an important, non-invasive method for the diagnosis of Multiple Sclerosis and has proven to be diagnostically superior to CT, evoked potentials (EP) and CSF examination. In a selected group of 30 patients, with the whole battery of the relevant MS studies, MR was positive in 100%, CT in 33,3%, EP in 56% and CSF examination in 60%. In patients clinically presenting only with signs of spinal cord involvement or optic neuritis or when the clinical presentation is uncertain MR has proven to be a very useful diagnostic tool for diagnosis of MS by demonstrating unsuspected lesions in the cerebral hemispheres. (orig.)

  7. Multiple sclerosis: current immunological aspects

    Directory of Open Access Journals (Sweden)

    Carlos Cuevas-García

    2017-02-01

    Full Text Available Multiple sclerosis is the most common inflammatory, chronic and degenerative condition of the central nervous system, and represents the first cause of disability in young adults. In Mexico, 11 to 20 out of every 100 000 people suffer from this disease. The causes of multiple sclerosis remain unknown, but several theories have been proposed on its origin: the interaction of environmental factors, viral infectious factors and genetic and immune susceptibility of each individual patient, which induce an autoimmune response and promote neuronal/axonal degeneration. In this review, the immune reaction main components and neurodegeneration present in multiple sclerosis are analyzed, as well as the inflammatory cascade associated with demyelination. Available treatments’ main purpose is to modulate aspects related to the adaptive immune response (B and T cells. The therapeutic challenge will be antigen-specific immune-tolerance induction, for example, with the use of tolerance protocols with peptides or DNA or nanoparticles vaccines. Future therapies should aim to control innate components (microglia, macrophages, astrocytes and to promote remyelination. To optimize the treatment, a combined therapeutic approach targeting the control of inflammatory and neurodegenerative components of the disease and monitoring of biomarkers will be necessary.

  8. Mechanical ventilation for amyotrophic lateral sclerosis/motor neuron disease.

    Science.gov (United States)

    Radunovic, Aleksandar; Annane, Djillali; Rafiq, Muhammad K; Brassington, Ruth; Mustfa, Naveed

    2017-10-06

    Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease, is a fatal neurodegenerative disease. Neuromuscular respiratory failure is the most common cause of death, which usually occurs within two to five years of the disease onset. Supporting respiratory function with mechanical ventilation may improve survival and quality of life. This is the second update of a review first published in 2009. To assess the effects of mechanical ventilation (tracheostomy-assisted ventilation and non-invasive ventilation (NIV)) on survival, functional measures of disease progression, and quality of life in ALS, and to evaluate adverse events related to the intervention. We searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL Plus, and AMED on 30 January 2017. We also searched two clinical trials registries for ongoing studies. Randomised controlled trials (RCTs) and quasi-RCTs involving non-invasive or tracheostomy-assisted ventilation in participants with a clinical diagnosis of ALS, independent of the reported outcomes. We included comparisons with no intervention or the best standard care. For the original review, four review authors independently selected studies for assessment. Two review authors reviewed searches for this update. All review authors independently extracted data from the full text of selected studies and assessed the risk of bias in studies that met the inclusion criteria. We attempted to obtain missing data where possible. We planned to collect adverse event data from the included studies. For the original Cochrane Review, the review authors identified two RCTs involving 54 participants with ALS receiving NIV. There were no new RCTs or quasi-RCTs at the first update. One new RCT was identified in the second update but was excluded for the reasons outlined below.Incomplete data were available for one published study comparing early and late initiation of

  9. 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

  10. 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.

  11. 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.

  12. Essential trace elements in amyotrophic lateral sclerosis (ALS): Results in a population of a risk area of Italy.

    Science.gov (United States)

    Forte, Giovanni; Bocca, Beatrice; Oggiano, Riccardo; Clemente, Simonetta; Asara, Yolande; Sotgiu, Maria Alessandra; Farace, Cristiano; Montella, Andrea; Fois, Alessandro Giuseppe; Malaguarnera, Michele; Pirina, Pietro; Madeddu, Roberto

    2017-09-01

    Sardinian (Italy) island population has a uniquely high incidence of amyotrophic lateral sclerosis (ALS). Essential trace element levels in blood, hair, and urine of ALS Sardinian patients were investigated in search of valid biomarkers to recognize and predict ALS. Six elements (Ca, Cu, Fe, Mg, Se, and Zn) were measured in 34 patients compared to 30 age- and sex-matched healthy controls by a validated method. Levels of Ca and Cu in blood and of Se and Zn in hair were significantly higher in ALS than in controls, while urinary excretion of Mg and Se was significantly decreased. The selected cut-off concentrations for these biomarkers may distinguish patients with or without ALS with sufficient sensitivity and specificity. Many positive (as Se-Cu and Se-Zn) and negative associations (as Ca-Mg and Ca-Zn) between elements suggested that multiple metals involved in multiple mechanisms have a role in the ALS degeneration.

  13. Does vagotomy protect against multiple sclerosis?

    Science.gov (United States)

    Sundbøll, Jens; Horváth-Puhó, Erzsébet; Adelborg, Kasper; Svensson, Elisabeth

    2017-07-01

    To examine the association between vagotomy and multiple sclerosis. We conducted a matched cohort study of all patients who underwent truncal or super-selective vagotomy and a comparison cohort, by linking Danish population-based medical registries (1977-1995). Hazard ratios (HRs) for multiple sclerosis, adjusting for potential confounders were computed by means of Cox regression analysis. Median age of multiple sclerosis onset corresponded to late onset multiple sclerosis. No association with multiple sclerosis was observed for truncal vagotomy (0-37 year adjusted HR=0.91, 95% confidence interval [CI]: 0.48-1.74) or super-selective vagotomy (0-37 year adjusted HR=1.28, 95% CI: 0.79-2.09) compared with the general population. We found no association between vagotomy and later risk of late onset multiple sclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Multiple sclerosis: a geographical hypothesis.

    Science.gov (United States)

    Carlyle, I P

    1997-12-01

    Multiple sclerosis remains a rare neurological disease of unknown aetiology, with a unique distribution, both geographically and historically. Rare in equatorial regions, it becomes increasingly common in higher latitudes; historically, it was first clinically recognized in the early nineteenth century. A hypothesis, based on geographical reasoning, is here proposed: that the disease is the result of a specific vitamin deficiency. Different individuals suffer the deficiency in separate and often unique ways. Evidence to support the hypothesis exists in cultural considerations, in the global distribution of the disease, and in its historical prevalence.

  15. Suicide attempts in multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Elsebeth Nylev; Jensen, Børge; Stenager, Maria

    2011-01-01

    The purposes of the study were (1) to estimate the risk of suicide attempts in multiple sclerosis (MS) patients in Denmark and compare the risk to the background population in the County of Funen, Denmark; (2) to estimate the risk of suicide attempts in MS patients receiving immunomodulating...... therapy compared with untreated patients. The Danish MS Registry, the Danish MS Treatment Registry and the Suicide Attempt Registry are linked and merged together using a person identification number given to all persons residing in Denmark. Among 404 MS patients, 15 patients had attempted suicide...

  16. [Special cases of multiple sclerosis].

    Science.gov (United States)

    Mendibe Bilbao, Mar

    2014-12-01

    Multiple sclerosis is a chronic disease that usually occurs in young people and affects them for the rest of their lives. Patients and their families usually have a series of doubts and questions on everyday matters and all types of situations that occur during the distinct stages of life and which can influence the course of the disease. The aim of this review is to provide specific answers to these questions. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  17. Symptomatic management in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Pushkar Shah

    2015-01-01

    Full Text Available Multiple sclerosis (MS is the commonest cause of disability in young adults. While there is increasing choice and better treatments available for delaying disease progression, there are still, very few, effective symptomatic treatments. For many patients such as those with primary progressive MS (PPMS and those that inevitably become secondary progressive, symptom management is the only treatment available. MS related symptoms are complex, interrelated, and can be interdependent. It requires good understanding of the condition, a holistic multidisciplinary approach, and above all, patient education and empowerment.

  18. Correlation of isotopic cisternographic patterns in multiple sclerosis with CSF IgG values

    International Nuclear Information System (INIS)

    Bartolini, S.; Inzitari, D.; Castagnoli, A.; Amaducci, L.

    1982-01-01

    Thirty-eight patients with multiple sclerosis (MS) were examined with isotopic cisternography (IC) in order to study cerebrospinal fluid (CSF) dynamics. Cisternography was also performed in 15 patients with amyotrophic lateral sclerosis and in 14 with senile dementia of the Alzheimer type as controls. IC pattern of ''mixed'' type was found in 18 MS patients and all those with Alzheimer senile dementia examined, while the IC examination did not show abnormality in any of 15 patients with amyotrophic lateral sclerosis. In MS patients, the abnormal IC picture proved to be significantly correlated with the CSF IgG values as calculated by Link's and Tourtelotte's formulas. The abnormal IC in MS may be due to altered CSF reabsorption or increased transependymal flow, or it may be related to the abnormal concentration of IgG

  19. The Edinburgh Cognitive and Behavioural ALS Screen in a Chinese Amyotrophic Lateral Sclerosis Population.

    Directory of Open Access Journals (Sweden)

    Shan Ye

    Full Text Available The existing screening batteries assessing multiple neuropsychological functions are not specific to amyotrophic lateral sclerosis (ALS patients and are limited to their physical dysfunctions, whereas category cognitive tests are too time-consuming to assess all the domains. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS was recently developed as a fast and easy cognitive screening tool specifically designed for patients. The purpose of the study was to validate the effectiveness of the Chinese version in Chinese ALS populations.Eighty-four ALS patients and 84 age-, gender- and education-matched healthy controls were included in this cross-sectional study. All the participants took the ECAS, Mini-Mental State Examination (MMSE and Frontal Assessment Battery (FAB. Primary caregivers of patients were interviewed for behavioural and psychiatric changes.Significant differences were noted in language (p = 0.01, fluency, executive function, ALS-specific functions, and ECAS total score (p<0.01 between ALS patients and controls. The cut-off value of the total ECAS score was 81.92. Cognitive impairment was observed in 35.71% of patients, and 27.38% exhibited behavioural abnormalities. The ECAS total score had a medium correlation with education year. Memory was more easily impaired in the lower education group, whereas verbal fluency and language function tended to be preserved in the higher education group. The average time of ECAS was only 18 minutes.The Chinese version of the ECAS is the first screening battery assessing multiple neuropsychological functions specially designed for the ALS population in China, which provides an effective and rapid tool to screen cognitive and behavioural impairments.

  20. 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

  1. 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...

  2. 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

  3. Cognitive Impairment in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Farnaz Etesam

    2014-01-01

    Full Text Available Cognitive impairment can emerge in the earliest phases of multiple sclerosis. It strongly impacts different aspects of Multiple Sclerosis (MS patients' lives, like employment, social relationships and the overall quality of life; thus, its on-time recognition and treatment is mandatory. This paper discusses issues, diagnostic methods and treatment options for cognitive dysfunctions in MS. This paper is a descriptive review of the related studies in the recent 10 years, performing a keyword search in the main databases4T. Cognitive impairment mostly involves aspects of information processing, memory and executive functioning in MS. Neuropsychological tests like MACFIMS and BRB-N are recommended for its assessment. Still, there is no fully efficient treatment for cognitive impairment. Researchers have shown some positive effects, using disease-modifying therapies and cognitive rehabilitation. Depression, pain, fatigue and other factors influencing cognitive functions must be paid attention to4T. Recognizing cognitive impairment as a major symptom for MS, makes studying this subject one of the priorities in dealing with the disease. Therefore, a consecutive research for identification and management of this part of quality of life in MS patients is obligatory4T.4T

  4. The diagnosis of multiple sclerosis

    International Nuclear Information System (INIS)

    Sanders, E.A.C.M.

    1982-01-01

    This thesis describes recently developed research methods for the diagnosis of multiple sclerosis. In Chapter X the use of the CT-scan in the detection of hemispheral or cerebellar lesions is discussed. In chapter XIII the results of the application of all methods to a group of 89 patients with definite, probable or possible multiple sclerosis and to a group of 25 purely optic neuritis patients are presented. With the aid of the CT-scan, hypo- or hyperdense areas in the white matter of the cerebral hemispheres were found in 52% of the 114 patients. Most reports ascribe these lesions to demyelinating cerebral plaques. The CT-scan showed no cerebellar or brainstem lesions. The CT-scan is independent of the duration of, and degree of incapacitation due to, the disease and can be helpful in giving a definite diagnosis in an early stage of the disease. The CT-scan will always play an important role for the differential diagnosis. (Auth.)

  5. 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.)

  6. 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.

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

    International Nuclear Information System (INIS)

    Marini, Cecilia; Cistaro, Angelina; Fania, Piercarlo; Campi, Cristina; Perasso, Annalisa; Massone, Anna Maria; Calvo, Andrea; Moglia, Cristina; Canosa, Antonio; Cammarosano, Stefania; Chio, Adriano; Caponnetto, Claudia; Nobili, Flavio Mariano; Novi, Giovanni; Scialo, Carlo; Mancardi, Gianluigi; Beltrametti, Mauro C.; Buschiazzo, Ambra; Pomposelli, Elena; Morbelli, Silvia; Sambuceti, Gianmario; Bagnara, Maria Claudia; Bruzzi, Paolo; Piana, Michele

    2016-01-01

    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 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, 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 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. 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.)

  8. Reproduction and the risk of multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, Melinda; Koch-Henriksen, Nils Iørgen; Pfleger, Claudia Christina

    2013-01-01

    The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men.......The incidence of multiple sclerosis (MS) in Denmark has doubled in women since 1970, whereas it has been almost unchanged in men....

  9. Demyelination of subcortical nuclei in multiple sclerosis

    International Nuclear Information System (INIS)

    Krutenkova, E; Aitmagambetova, G; Khodanovich, M; Yarnykh, V; Bowen, J; Gangadharan, B; Henson, L; Mayadev, A; Repovic, P; Qian, P

    2016-01-01

    Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. (paper)

  10. Demyelination of subcortical nuclei in multiple sclerosis

    Science.gov (United States)

    Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

    2016-02-01

    Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

  11. Current issues in the respiratory care of patients with amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Marco Orsini

    2015-10-01

    Full Text Available Amyotrophic lateral sclerosis is a progressive neuromuscular disease, resulting in respiratory muscle weakness, reduced pulmonary volumes, ineffective cough, secretion retention, and respiratory failure. Measures as vital capacity, maximal inspiratory and expiratory pressures, sniff nasal inspiratory pressure, cough peak flow and pulse oximetry are recommended to monitor the respiratory function. The patients should be followed up by a multidisciplinary team, focused in improving the quality of life and deal with the respiratory symptoms. The respiratory care approach includes airway clearance techniques, mechanically assisted cough and noninvasive mechanical ventilation. Vaccination and respiratory pharmacological support are also recommended. To date, there is no enough evidence supporting the inspiratory muscle training and diaphragmatic pacing.

  12. 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.

  13. 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.

  14. Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam

    International Nuclear Information System (INIS)

    Perl, D.P.; Gajdusek, D.C.; Garruto, R.M.; Yanagihara, R.T.; Gibbs, C.J.

    1982-01-01

    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

  15. Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Browne, Elisse C; Parakh, Sonam; Duncan, Luke F; Langford, Steven J; Atkin, Julie D; Abbott, Belinda M

    2016-04-01

    Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

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

    International Nuclear Information System (INIS)

    Takahashi, Hirohide; Snow, B.J.; Bhatt, M.H.; Peppard, R.; Eisen, A.; Calne, D.B.

    1993-01-01

    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

  17. Genetic causes of amyotrophic lateral sclerosis: new genetic analysis methodologies entailing new opportunities and challenges

    Science.gov (United States)

    Marangi, Giuseppe; Traynor, Bryan J.

    2018-01-01

    The genetic architecture of amyotrophic lateral sclerosis (ALS) is being increasingly understood. In this far-reaching review, we examine what is currently known about ALS genetics and how these genes were initially identified. We also discuss the various types of mutations that might underlie this fatal neurodegenerative condition and outline some of the strategies that might be useful in untangling them. These include expansions of short repeat sequences, common and low-frequency genetic variations, de novo mutations, epigenetic changes, somatic mutations, epistasis, oligogenic and polygenic hypotheses. PMID:25316630

  18. 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

  19. [Types of ventilatory support and their indications in amyotrophic lateral sclerosis].

    Science.gov (United States)

    Perrin, C

    2006-06-01

    Respiratory muscle weakness represents the major cause of mortality in patients with amyotrophic lateral sclerosis (ALS). As a result, ventilatory assistance is an important part of disease management. Nowadays, noninvasive ventilation (NIV) has become the first choice modality for most patients and represents an alternative to tracheostomy intermittent positive-pressure ventilation. Although, some consensus guidelines have been proposed to initiate NIV in patients with restrictive chronic respiratory failure, these criteria are discussed regarding ALS. While the current consensus recommends that NIV may be used in symptomatic patients with hypercapnia or forced vital capacityNIV is proposed in the literature and reported in this paper.

  20. 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.

  1. [An early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development].

    Science.gov (United States)

    Abe, Koji

    2018-03-28

    The present review focuses an early history of Japanese amyotrophic lateral sclerosis (ALS)-related diseases and the current development. In relation to foreign previous reports, five topics are introduced and discussed on ALS with dementia, ALS/Parkinsonism dementia complex (ALS/PDC), familial ALS (FALS), spinal bulbar muscular atrophy (SBMA), and multisystem involvement especially in cerebellar system of ALS including ALS/SCA (spinocerebellar ataxia) crossroad mutation Asidan. This review found the great contribution of Japanese reports on the above five topics, and confirmed the great development of ALS-related diseases over the past 120 years.

  2. Computerized tomography in multiple sclerosis

    International Nuclear Information System (INIS)

    Delouvrier, J.J.; Tritschler, J.L.; Desbleds, M.T.; Cambier, J.; Nahum, H.

    1980-01-01

    The double scan CT method was applied to a homogeneous population of 50 multiple sclerosis patients and the following features were studied: well defined low-density areas, localized contrast enhancements, cerebral atrophy and white matter homogeneity. The analyses of the variance of the white matter (centrum ovale) can disclose those lesions which individually do not surpass the visibility threshold. The lesions that are localized in the white matter are mainly periventricular, most often multiple, and they do not displace the neighbouring structures. By revealing a large number of clinically silent cerebral lesions, the cerebral CT becomes a highly important diagnostic tool. The value of the CT examinations seems to be of major importance each time that the clinical diagnosis is hesitant, particularly when faced with medullary signs or an initial neurological episode. (C.F.)

  3. Investigating the contribution of VAPB/ALS8 loss of function in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; El Oussini, Hajer; Bercier, Valérie; Gros-Louis, François; Valdmanis, Paul N; McDearmid, Jonathan; Mejier, Inge A; Dion, Patrick A; Dupre, Nicolas; Hollinger, David; Sinniger, Jérome; Dirrig-Grosch, Sylvie; Camu, William; Meininger, Vincent; Loeffler, Jean-Philippe; René, Frédérique; Drapeau, Pierre; Rouleau, Guy A; Dupuis, Luc

    2013-06-15

    The mutations P56S and T46I in the gene encoding vesicle-associated membrane protein-associated protein B/C (VAPB) cause ALS8, a familial form of amyotrophic lateral sclerosis (ALS). Overexpression of mutant forms of VAPB leads to cytosolic aggregates, suggesting a gain of function of the mutant protein. However, recent work suggested that the loss of VAPB function could be the major mechanism leading to ALS8. Here, we used multiple genetic and experimental approaches to study whether VAPB loss of function might be sufficient to trigger motor neuron degeneration. In order to identify additional ALS-associated VAPB mutations, we screened the entire VAPB gene in a cohort of ALS patients and detected two mutations (A145V and S160Δ). To directly address the contribution of VAPB loss of function in ALS, we generated zebrafish and mouse models with either a decreased or a complete loss of Vapb expression. Vapb knockdown in zebrafish led to swimming deficits. Mice knocked-out for Vapb showed mild motor deficits after 18 months of age yet had innervated neuromuscular junctions (NMJs). Importantly, overexpression of VAPB mutations were unable to rescue the motor deficit caused by Vapb knockdown in zebrafish and failed to cause a toxic gain-of-function defect on their own. Thus, Vapb loss of function weakens the motor system of vertebrate animal models but is on its own unable to lead to a complete ALS phenotype. Our findings are consistent with the notion that VAPB mutations constitute a risk factor for motor neuron disease through a loss of VAPB function.

  4. Variation in worldwide incidence of amyotrophic lateral sclerosis: a meta-analysis.

    Science.gov (United States)

    Marin, Benoît; Boumédiene, Farid; Logroscino, Giancarlo; Couratier, Philippe; Babron, Marie-Claude; Leutenegger, Anne Louise; Copetti, Massimilano; Preux, Pierre-Marie; Beghi, Ettore

    2017-02-01

    To assess the worldwide variation of amyotrophic lateral sclerosis (ALS) incidence, we performed a systematic review and meta-analysis of population-based data published to date. We reviewed Medline and Embase up to June 2015 and included all population-based studies of newly diagnosed ALS cases, using multiple sources for case ascertainment. ALS crude and standardized incidence (on age and sex using the US 2010 population) were calculated. Random effect meta-analysis and meta-regression were performed using the subcontinent as the main study level covariate. Sources of heterogeneity related to the characteristics of the study population and the study methodology were investigated. Among 3216 records, 44 studies were selected, covering 45 geographical areas in 11 sub-continents. A total of 13 146 ALS cases and 825 million person-years of follow-up (PYFU) were co-nsidered. The overall pooled worldwide crude ALS incidence was at 1.75 (1.55-1.96)/100 000 PYFU; 1.68 (1.50-1.85)/100 000 PYFU after standardization. Heterogeneity was identified in ALS standardized incidence between North Europe [1.89 (1.46-2.32)/100 000 PYFU] and East Asia [0.83 (0.42-1.24)/100 000 PYFU, China and Japan P = 0.001] or South Asia [0.73 (0.58-0.89)/100 000/PYFU Iran, P = 0.02]. Conversely, homogeneous rates have been reported in populations from Europe, North America and New Zealand [pooled ALS standardized incidence of 1.81 (1.66-1.97)/100 000 PYFU for those areas]. This review confirms a heterogeneous distribution worldwide of ALS, and sets the scene to sustain a collaborative study involving a wide international consortium to investigate the link between ancestry, environment and ALS incidence. © The Author 2016. Published by Oxford University Press on behalf of the International Epidemiological Association

  5. Aberrant regulation of DNA methylation in amyotrophic lateral sclerosis: a new target of disease mechanisms.

    Science.gov (United States)

    Martin, Lee J; Wong, Margaret

    2013-10-01

    Amyotrophic lateral sclerosis (ALS) is the third most common adult-onset neurodegenerative disease. A diagnosis is fatal owing to degeneration of motor neurons in brain and spinal cord that control swallowing, breathing, and movement. ALS can be inherited, but most cases are not associated with a family history of the disease. The mechanisms causing motor neuron death in ALS are still unknown. Given the suspected complex interplay between multiple genes, the environment, metabolism, and lifestyle in the pathogenesis of ALS, we have hypothesized that the mechanisms of disease in ALS involve epigenetic contributions that can drive motor neuron degeneration. DNA methylation is an epigenetic mechanism for gene regulation engaged by DNA methyltransferase (Dnmt)-catalyzed methyl group transfer to carbon-5 in cytosine residues in gene regulatory promoter and nonpromoter regions. Recent genome-wide analyses have found differential gene methylation in human ALS. Neuropathologic assessments have revealed that motor neurons in human ALS show significant abnormalities in Dnmt1, Dnmt3a, and 5-methylcytosine. Similar changes are seen in mice with motor neuron degeneration, and Dnmt3a was found abundantly at synapses and in mitochondria. During apoptosis of cultured motor neuron-like cells, Dnmt1 and Dnmt3a protein levels increase, and 5-methylcytosine accumulates. Enforced expression of Dnmt3a, but not Dnmt1, induces degeneration of cultured neurons. Truncation mutation of the Dnmt3a catalytic domain and Dnmt3a RNAi blocks apoptosis of cultured neurons. Inhibition of Dnmt catalytic activity with small molecules RG108 and procainamide protects motor neurons from excessive DNA methylation and apoptosis in cell culture and in a mouse model of ALS. Thus, motor neurons can engage epigenetic mechanisms to cause their degeneration, involving Dnmts and increased DNA methylation. Aberrant DNA methylation in vulnerable cells is a new direction for discovering mechanisms of ALS

  6. Demyelination versus remyelination in progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Bramow, Stephan; Frischer, Josa M; Lassmann, Hans

    2010-01-01

    The causes of incomplete remyelination in progressive multiple sclerosis are unknown, as are the pathological correlates of the different clinical characteristics of patients with primary and secondary progressive disease. We analysed brains and spinal cords from 51 patients with progressive...... multiple sclerosis by planimetry. Thirteen patients with primary progressive disease were compared with 34 with secondary progressive disease. In patients with secondary progressive multiple sclerosis, we found larger brain plaques, more demyelination in total and higher brain loads of active demyelination...... compared with patients with primary progressive disease. In addition, the brain density of plaques with high-grade inflammation and active demyelination was highest in secondary progressive multiple sclerosis and remained ~18% higher than in primary progressive multiple sclerosis after adjustments...

  7. Chromosomal radiosensitivity in patients with multiple sclerosis

    International Nuclear Information System (INIS)

    Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia; Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria; Groudeva, Violeta; Hadjidekova, Savina; Domínguez, Inmaculada

    2013-01-01

    Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

  8. Chromosomal radiosensitivity in patients with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Milenkova, Maria; Milanov, Ivan; Kmetska, Ksenia [III Neurological Clinic, University Hospital Saint Naum, Sofia (Bulgaria); Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria [Laboratory of Radiation Genetics, NCRRP, Sofia (Bulgaria); Groudeva, Violeta [Department of Diagnostic Imaging, University Hospital St. Ekaterina, Sofia (Bulgaria); Hadjidekova, Savina [Department of Medical Genetics, Medical University, Sofia (Bulgaria); Domínguez, Inmaculada, E-mail: idomin@us.es [Department of Cell Biology, Faculty of Biology, University of Seville, Avda. Reina Mercedes 6, 41012 (Spain)

    2013-09-15

    Highlights: • We studied radiosensitivity to in vitro γ-irradiated lymphocytes from MS patients. • Immunotherapy in RRMS patients reduced the yield of radiation induced MN. • The group of treated RRMS accounts for the low radiosensitivity in MS patients. • Spontaneous yield of MN was similar in treated and untreated RRMS patients. - Abstract: Multiple sclerosis is a clinically heterogeneous autoimmune disease leading to severe neurological disability. Although during the last years many disease-modifying agents as treatment options for multiple sclerosis have been made available, their mechanisms of action are still not fully determined. In the present study radiosensitivity in lymphocytes of patients with relapsing–remitting multiple sclerosis, secondary progressive multiple sclerosis and healthy controls was investigated. Whole blood cultures from multiple sclerosis patients and healthy controls were used to analyze the spontaneous and radiation-induced micronuclei in binucleated lymphocytes. A subgroup of patients with relapsing–remitting multiple sclerosis was treated with immunomodulatory agents, interferon β or glatiramer acetate. The secondary progressive multiple sclerosis patients group was not receiving any treatment. Our results reveal that the basal DNA damage was not different between relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls. No differences between gamma-irradiation induced micronuclei frequencies in binucleated cells from relapsing–remitting and secondary progressive multiple sclerosis patients, and healthy controls were found either. Nevertheless, when we compared the radiation induced DNA damage in binucleated cells from healthy individuals with the whole group of patients, a reduction in the frequency of micronuclei was obtained in the patients group. Induced micronuclei yield was significantly lower in the irradiated samples from treated relapsing–remitting multiple

  9. 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

  10. Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis

    International Nuclear Information System (INIS)

    Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

    2010-01-01

    Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

  11. Statin treatment in multiple sclerosis

    DEFF Research Database (Denmark)

    Pihl-Jensen, Gorm; Tsakiri, Anna; Frederiksen, Jette Lautrup

    2015-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease that leads to progressive disability. Statins [hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors] are widely prescribed drugs in hypercholesterolemia. They exert immunomodulatory and neurotrophic effects and are attractive...... candidates for MS treatment due to reliable safety profiles and favorable costs. Studies of statins in a murine MS model and in open-label trials in MS have shown decreased disease severity. OBJECTIVE: Our objective was to assess current evidence to support statin treatment in MS and clinically isolated......)-β treatment in RRMS, one of statin monotherapy in CIS, one of statin monotherapy in optic neuritis (ON)/CIS, and one of statin monotherapy in secondary progressive MS (SPMS)]. Three trials with eligible characteristics had not been published in peer-reviewed journals and were therefore not included. Due...

  12. Implicit Memory in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    G. Latchford

    1993-01-01

    Full Text Available A number of neuropsychological studies have revealed that memory problems are relatively common in patients with multiple sclerosis (MS. It may be useful to compare MS with conditions such as Huntington's disease (HD, which have been referred to as subcortical dementia. A characteristic of these conditions may be an impairment in implicit (unconscious memory, but not in explicit (conscious memory. The present study examined the functioning of explicit and implicit memory in MS. Results showed that implicit memory was not significantly impaired in the MS subjects, and that they were impaired on recall but not recognition. A correlation was found between implicit memory performance and disability status in MS patients. Findings also suggest the possibility of long-term priming of implicit memory in the control subjects. The implications of these results are discussed.

  13. Cognitive dysfunction in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Joana eGuimarães

    2012-05-01

    Full Text Available In Multiple Sclerosis (MS prevalence studies of community and clinical samples, indicate that 45–60% of patients are cognitively impaired. These cognitive dysfunctions have been traditionally described as heterogeneous, but more recent studies suggest that there is a specific pattern of MS-related cognitive dysfunctions. With the advent of disease-modifying medications for MS and emphasis on early intervention and treatment, detection of cognitive impairment at its earliest stage becomes particularly important. In this review the authors address: the cognitive domains most commonly impaired in MS (memory, attention, executive functions, speed of information processing and visual spatial abilities; the physiopathological mechanism implied in MS cognitive dysfunction and correlated brain MRI features; the importance of neuropsychological assessment of MS patients in different stages of the disease and the influence of its course on cognitive performance; the most used tests and batteries for neuropsychological assessment; therapeutic strategies to improve cognitive abilities.

  14. Connected health and multiple sclerosis.

    Science.gov (United States)

    Cohen, M

    2018-04-18

    There is as yet no consensual definition of "connected health". In general, the term refers to the growing use of technology and, in particular, mobile technology in medicine. Over the past 10 years, there have been an increasing number of published reports on the wide-ranging and heterogeneous fields involving the application of technology in medicine, ranging from telemedicine to tools to improve patients' evaluation and monitoring by physicians, as well as a multitude of patient-centered applications. They also represent promising tools in the field of clinical research. This report is a review of the importance of using this technology in the management of multiple sclerosis patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  15. A Bibliometric Assessment of Global Ice Bucket Challenge (Amyotrophic Lateral Sclerosis) Research.

    Science.gov (United States)

    Ram, Shri

    2016-10-01

    This study is a quantitative and qualitative assessment of the global research trends on amyotrophic lateral sclerosis (ALS) (popularly known as Ice Bucket Challenge), through related literatures retrieved from SCOPUS multidisciplinary database for the period 1974-2013. This study is aimed at analyzing the literature on ALS in terms of document type, language, annual growth, productive country, journal, authors, subject, and most cited articles. The bibliographic data for this study was retrieved from the SCOPUS database using keywords 'amyotrophic lateral sclerosis', 'motor neurone disease', 'Charcot disease', 'Lou Gehrig's disease', 'Ice Bucket Challenge' available in title, abstract, and keyword fields of Scopus database from 1974 to 2013. The literature analysis included 21,750 articles during the period from 1974 to 2013 in different areas of ALS. USA was the most productive country in terms of literature produced, while Neurology was the most productive journal. An intensive awareness created by 'Ice Bucket Challenge' has attracted masses, and an intensive growth of literature is pertinent on ALS. The results of this study are expressed in terms of growth of literature, output of individual countries, and authors, and will be helpful in collaborative research in future.

  16. Tracheostomy and invasive mechanical ventilation in amyotrophic lateral sclerosis: decision-making factors and survival analysis.

    Science.gov (United States)

    Kimura, Fumiharu

    2016-04-28

    Invasive and/or non-invasive mechanical ventilation are most important options of respiratory management in amyotrophic lateral sclerosis. We evaluated the frequency, clinical characteristics, decision-making factors about ventilation and survival analysis of 190 people with amyotrophic lateral sclerosis patients from 1990 until 2013. Thirty-one percentage of patients underwent tracheostomy invasive ventilation with the rate increasing more than the past 20 years. The ratio of tracheostomy invasive ventilation in patients >65 years old was significantly increased after 2000 (25%) as compared to before (10%). After 2010, the standard use of non-invasive ventilation showed a tendency to reduce the frequency of tracheostomy invasive ventilation. Mechanical ventilation prolonged median survival (75 months in tracheostomy invasive ventilation, 43 months in non-invasive ventilation vs natural course, 32 months). The life-extending effects by tracheostomy invasive ventilation were longer in younger patients ≤65 years old at the time of ventilation support than in older patients. Presence of partners and care at home were associated with better survival. Following factors related to the decision to perform tracheostomy invasive ventilation: patients ≤65 years old: greater use of non-invasive ventilation: presence of a spouse: faster tracheostomy: higher progression rate; and preserved motor functions. No patients who underwent tracheostomy invasive ventilation died from a decision to withdraw mechanical ventilation. The present study provides factors related to decision-making process and survival after tracheostomy and help clinicians and family members to expand the knowledge about ventilation.

  17. 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.

  18. Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis etiology and survival.

    Science.gov (United States)

    Beard, John D; Kamel, Freya

    2015-01-01

    Rates of amyotrophic lateral sclerosis (ALS) have been reported to be higher among US military veterans, who currently number more than 21 million, but the causal factor(s) has not been identified. We conducted a review to examine the weight of evidence for associations between military service, deployments, and exposures and ALS etiology and survival. Thirty articles or abstracts published through 2013 were reviewed. Although the current evidence suggests a positive association with ALS etiology, it is too limited to draw firm conclusions regarding associations between military service and ALS etiology or survival. Some evidence suggests that deployment to the 1990-1991 Persian Gulf War may be associated with ALS etiology, but there is currently no strong evidence that any particular military exposure is associated with ALS etiology. Future studies should address the limitations of previous ones, such as reliance on mortality as a surrogate for incidence, a dearth of survival analyses, lack of clinical data, low statistical power, and limited exposure assessment. The Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis (GENEVA) Study is one such study, but additional research is needed to determine whether military-related factors are associated with ALS and to assess potential prevention strategies. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  19. Metabolomics in amyotrophic lateral sclerosis: how far can it take us?

    Science.gov (United States)

    Blasco, H; Patin, F; Madji Hounoum, B; Gordon, P H; Vourc'h, P; Andres, C R; Corcia, P

    2016-03-01

    Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. Alongside identification of aetiologies, development of biomarkers is a foremost research priority. Metabolomics is one promising approach that is being utilized in the search for diagnosis and prognosis markers. Our aim is to provide an overview of the principal research in metabolomics applied to ALS. References were identified using PubMed with the terms 'metabolomics' or 'metabolomic' and 'ALS' or 'amyotrophic lateral sclerosis' or 'MND' or 'motor neuron disorders'. To date, nine articles have reported metabolomics research in patients and a few additional studies examined disease physiology and drug effects in patients or models. Metabolomics contribute to a better understanding of ALS pathophysiology but, to date, no biomarker has been validated for diagnosis, principally due to the heterogeneity of the disease and the absence of applied standardized methodology for biomarker discovery. A consensus on best metabolomics methodology as well as systematic independent validation will be an important accomplishment on the path to identifying the long-awaited biomarkers for ALS and to improve clinical trial designs. © 2016 EAN.

  20. Long-term effects of edaravone on survival of patients with amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Masamitsu Okada

    2018-06-01

    Full Text Available Background and purpose: Oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS. Edaravone, a free radical scavenger, was approved as a therapeutic drug for ALS in 2015 in Japan. A phase 3 clinical trial demonstrated a smaller decline in ALS functional scale scores compared with placebo. However, the long-term effects of edaravone on ALS patients remain unclear. This study aimed to retrospectively investigate the long-term effects of edaravone on the survival of ALS patients. Methods: We retrospectively analyzed 27 consecutive patients with ALS who were treated with edaravone and 30 consecutive ALS patients who were not treated with edaravone between 2010 and 2016. Results: The differences of ALSFRS-R scores from baseline to 6 months was significantly reduced in the edaravone group, compared to the control group. The changes in serum creatinine, as a possible marker of ALS severity, from baseline to 6 and 12 months were significantly improved in the edaravone group, compared to the control group. The survival rate was significantly improved in the edaravone group compared with control patients. Conclusion: Our retrospective single-center analysis suggests slower progression and better prognosis of ALS patients with edaravone treatment. Further investigation, including prospective multicenter analysis, is warranted to confirm the usefulness of edaravone for a better prognosis of ALS. Keywords: Amyotrophic lateral sclerosis, Oxidative stress, Edaravone, Long-term effect, Survival

  1. 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.

  2. Daytime Mouthpiece for Continuous Noninvasive Ventilation in Individuals With Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Bédard, Marie-Eve; McKim, Douglas A

    2016-10-01

    Noninvasive ventilation (NIV) is commonly used to provide ventilatory support for individuals with amyotrophic lateral sclerosis (ALS). Once 24-h ventilation is required, the decision between invasive tracheostomy ventilation and palliation is often faced. This study describes the use and outcomes of daytime mouthpiece ventilation added to nighttime mask ventilation for continuous NIV in subjects with ALS as an effective alternative. This was a retrospective study of 39 subjects with ALS using daytime mouthpiece ventilation over a 17-y period. Thirty-one subjects were successful with mouthpiece ventilation, 2 were excluded, 2 stopped because of lack of motivation, and 4 with bulbar subscores of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (b-ALSFRS-R) between 0 and 3 physically failed to use it consistently. No subject in the successful group had a b-ALSFRS-R score of NIV and mouthpiece ventilation were 648 (176-2,188) and 286 (41-1,769) d, respectively. Peak cough flow with lung-volume recruitment >180 L/min at initiation of mouthpiece ventilation was associated with a longer survival (637 ± 468 vs 240 ± 158 d (P = .01). Mouthpiece ventilation provides effective ventilation and prolonged survival for individuals with ALS requiring full-time ventilatory support and maintaining adequate bulbar function. Copyright © 2016 by Daedalus Enterprises.

  3. Absence of airway secretion accumulation predicts tolerance of noninvasive ventilation in subjects with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vandenberghe, Nadia; Vallet, Anne-Evelyne; Petitjean, Thierry; Le Cam, Pierre; Peysson, Stéphane; Guérin, Claude; Dailler, Frédéric; Jay, Sylvie; Cadiergue, Vincent; Bouhour, Françoise; Court-Fortune, Isabelle; Camdessanche, Jean-Philippe; Antoine, Jean-Christophe; Philit, François; Beuret, Pascal; Bin-Dorel, Sylvie; Vial, Christophe; Broussolle, Emmanuel

    2013-09-01

    To assess factors that predict good tolerance of noninvasive ventilation (NIV), in order to improve survival and quality of life in subjects with amyotrophic lateral sclerosis. We conducted a prospective study in subjects with amyotrophic lateral sclerosis and requiring NIV. The primary end point was NIV tolerance at 1 month. Subjects, several of whom failed to complete the study, were classified as "tolerant" or "poorly tolerant," according to the number of hours of NIV use (more or less than 4 h per night, respectively). Eighty-one subjects, 73 of whom also attended the 1-month follow-up visit, participated over 34 months. NIV tolerance after the first day of utilization predicted tolerance at 1 month (77.6% and 75.3% of subjects, respectively). Multivariate analysis disclosed 3 factors predicting good NIV tolerance: absence of airway secretions accumulation prior to NIV onset (odds ratio 11.5); normal bulbar function at initiation of NIV (odds ratio 8.5); and older age (weakly significant, odds ratio 1.1). Our study reveals 3 factors that are predictive of good NIV tolerance, in particular the absence of airway secretion accumulation, which should prompt NIV initiation before its appearance.

  4. 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.

  5. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. A validated HPLC assay to monitor riluzole plasma or serum concentrations in patients with amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    van Kan, H. J. M.; Spieksma, M.; Groeneveld, G. J.; Toraño, J. Sastre; van den Berg, L. H.; Guchelaar, H. J.

    2004-01-01

    A specific, accurate and precise high-performance liquid chromatographic assay was developed for the determination of riluzole, a drug used to treat patients with amyotrophic lateral sclerosis. Samples were treated by extraction with dichloromethane followed by reversed-phase chromatography with

  8. 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

  9. 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

  10. 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

  11. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial

    NARCIS (Netherlands)

    Cudkowicz, Merit E.; van den Berg, Leonard H.; Shefner, Jeremy M.; Mitsumoto, Hiroshi; Mora, Jesus S.; Ludolph, Albert; Hardiman, Orla; Bozik, Michael E.; Ingersoll, Evan W.; Archibald, Donald; Meyers, Adam L.; Dong, Yingwen; Farwell, Wildon R.; Kerr, Douglas A.; Henderson, R.; Kiernan, M.; Mathers, S.; Vucic, S.; de Bleecker, J.; Robberecht, W.; Briemberg, H.; Genge, A.; Korngut, L.; Matte, G.; Shoesmith, C.; Zinman, L.; Camu, W.; Desnuelle, C.; Destee, A.; Meininger, V.; Pouget, J.; Grehl, T.; Grosskreutz, J.; Ludolph, A.; Meyer, T.; Petri, S.; Hardiman, O.; de Visser, M.; Voermans, N.; van den Berg, L.; de Rivera, F. J. R.; Gamez, J.; Carbonell, J. G.; Pardina, J. S. Mora; Povedano, M.; Persson, L.; Ronnevi, L.-O.; Al-Chalabi, A.; Morrison, K.; Shaw, P.

    2013-01-01

    In a phase 2 study, dexpramipexole (25-150 mg twice daily) was well tolerated for up to 9 months and showed a significant benefit at the high dose in a combined assessment of function and mortality in patients with amyotrophic lateral sclerosis. We aimed to assess efficacy and safety of

  12. Dexpramipexole versus placebo for patients with amyotrophic lateral sclerosis (EMPOWER): a randomised, double-blind, phase 3 trial

    NARCIS (Netherlands)

    Cudkowicz, M.E.; Berg, L.H. van den; Shefner, J.M.; Mitsumoto, H.; Mora, J.S.; Ludolph, A.; Hardiman, O.; Bozik, M.E.; Ingersoll, E.W.; Archibald, D.; Meyers, A.L.; Dong, Y.; Farwell, W.R.; Kerr, D.A.; Voermans, N.C.; et al.,

    2013-01-01

    BACKGROUND: In a phase 2 study, dexpramipexole (25-150 mg twice daily) was well tolerated for up to 9 months and showed a significant benefit at the high dose in a combined assessment of function and mortality in patients with amyotrophic lateral sclerosis. We aimed to assess efficacy and safety of

  13. Association of a Locus in the CAMTA1 Gene With Survival in Patients With Sporadic Amyotrophic Lateral Sclerosis

    NARCIS (Netherlands)

    Fogh, Isabella; Lin, Kuang; Tiloca, Cinzia; Rooney, James; Gellera, Cinzia; Diekstra, Frank P; Ratti, Antonia; Shatunov, Aleksey; van Es, Michael A; Proitsi, Petroula; Jones, Ashley; Sproviero, William; Chiò, Adriano; McLaughlin, Russell Lewis; Sorarù, Gianni; Corrado, Lucia; Stahl, Daniel; Del Bo, Roberto; Cereda, Cristina; Castellotti, Barbara; Glass, Jonathan D; Newhouse, Steven; Dobson, Richard; Smith, Bradley N; Topp, Simon; van Rheenen, Wouter; Meininger, Vincent; Melki, Judith; Morrison, Karen E; Shaw, Pamela J; Leigh, P Nigel; Andersen, Peter M; Comi, Giacomo P; Ticozzi, Nicola; Mazzini, Letizia; D'Alfonso, Sandra; Traynor, Bryan J; Van Damme, Philip; Robberecht, Wim; Brown, Robert H; Landers, John E; Hardiman, Orla; Lewis, Cathryn M; van den Berg, Leonard H; Shaw, Christopher E; Veldink, Jan H; Silani, Vincenzo; Al-Chalabi, Ammar; Powell, John

    Importance: Amyotrophic lateral sclerosis (ALS) is a devastating adult-onset neurodegenerative disorder with a poor prognosis and a median survival of 3 years. However, a significant proportion of patients survive more than 10 years from symptom onset. Objective: To identify gene variants

  14. Guidelines in motor neurone disease (MND)/amyotrophic lateral sclerosis (ALS)--from diagnosis to patient care.

    Science.gov (United States)

    Mitchell, J D

    2000-12-01

    This paper reviews the scope of current guidelines in motor neurone disease (MND)/amyotrophic lateral sclerosis (ALS) and examines issues which have arisen in the preparation of these documents. The review concludes with an evaluation of the impact of the guidelines which have been produced to date and looks towards potential future developments in this area.

  15. Multiple sclerosis and other white matter diseases

    International Nuclear Information System (INIS)

    Zimmerman, R.A.

    1991-01-01

    The diagnosis of multiple sclerosis (MS) by computerized tomography and nuclear magnetic resonance are shown, including the examination of cerebral spinal fluid. Lymphocytic, foamy histiocytic perivascular cuffing, degenerated oligodendrocytes, and microglia proliferation with relative axonal sparing are presented. In the latter stage of the chronic MS plaque there is sclerosis with microcystic formation with complete demyelination and organization. (author)

  16. Nuclear magnetic resonance relaxation in multiple sclerosis

    DEFF Research Database (Denmark)

    Larsson, H B; Barker, G J; MacKay, A

    1998-01-01

    OBJECTIVES: The theory of relaxation processes and their measurements are described. An overview is presented of the literature on relaxation time measurements in the normal and the developing brain, in experimental diseases in animals, and in patients with multiple sclerosis. RESULTS...... AND CONCLUSION: Relaxation time measurements provide insight into development of multiple sclerosis plaques, especially the occurrence of oedema, demyelination, and gliosis. There is also evidence that normal appearing white matter in patients with multiple sclerosis is affected. What is now needed are fast...

  17. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [11C]-PBR28

    Directory of Open Access Journals (Sweden)

    Nicole R. Zürcher

    2015-01-01

    Full Text Available Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [11C]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38–68 years and ten age- and [11C]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33–65 years completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (pFWE < 0.05. Region of interest analysis revealed increased [11C]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15 compared to controls (1.03, p < 0.05. In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05, and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = –0.66, p < 0.05. Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [11C]-PBR28 as a marker of treatments that target neuroinflammation.

  18. Suicide among Danes with multiple sclerosis

    DEFF Research Database (Denmark)

    Brønnum-Hansen, H; Stenager, E; Nylev Stenager, E

    2005-01-01

    OBJECTIVE: To compare the suicide risk among Danish citizens with multiple sclerosis with that of the general population, and to evaluate changes over 45 years. METHODS: The study was based on linkage of the Danish Multiple Sclerosis Registry to the Cause of Death Registry. It comprised all 10...... taken their own lives, whereas the expected number of suicides was 54.2 (29.1 men, 25.1 women). Thus the suicide risk among persons with multiple sclerosis was more than twice that of the general population (SMR = 2.12). The increased risk was particularly high during the first year after diagnosis (SMR...... = 3.15). CONCLUSIONS: The risk of suicide in multiple sclerosis was almost twice as high as expected more than 20 years after diagnosis. The excess suicide risk has not declined since 1953....

  19. Respiratory muscle training for multiple sclerosis

    NARCIS (Netherlands)

    Rietberg, Marc B.; Veerbeek, Janne M.; Gosselink, Rik; Kwakkel, Gert; van Wegen, Erwin E.H.

    2017-01-01

    Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and

  20. Defining the clinical course of multiple sclerosis

    DEFF Research Database (Denmark)

    Lublin, Fred D; Reingold, Stephen C; Cohen, Jeffrey A

    2014-01-01

    Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts...

  1. Recent advances in multiple sclerosis therapy

    International Nuclear Information System (INIS)

    Gonsette, R.E.; Delmotte, P.

    1989-01-01

    Seven papers in this volume are in INIS scope, one dealing with autoradiographic detection of multiple sclerosis plaques with radiologands, and the others with magnetic resonance imaging of MS lesions. (H.W.). refs.; figs.; tabs

  2. Plasma homocysteine levels in multiple sclerosis

    NARCIS (Netherlands)

    Ramsaransing, G S M; Fokkema, M R; Teelken, A; Arutjunyan, A V; Koch, M; De Keyser, J

    Background: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). Objective: To investigate if and why plasma homocysteine levels are increased in MS, and whether

  3. Nerve excitability changes related to axonal degeneration in amyotrophic lateral sclerosis: Insights from the transgenic SOD1(G127X) mouse model

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Alvarez Herrero, Susana; Pinchenko, Volodymyr

    2012-01-01

    Motor nerve excitability studies by "threshold tracking" in amyotrophic lateral sclerosis (ALS) revealed heterogeneous abnormalities in motor axon membrane function possibly depending on disease stage. It remains unclear to which extent the excitability deviations reflect a pathogenic mechanism...

  4. Potassium channel abnormalities are consistent with early axon degeneration of motor axons in the G127X SOD1 mouse model of amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Maglemose, Rikke; Hedegaard, Anne; Lehnhoff, Janna

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease, which selectively affects upper and lower motoneurones. The underlying pathophysiology of the disease is complex but electrophysiological studies of peripheral nerves in ALS patients as well as human autopsy studies indicate...

  5. 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.

  6. Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial

    NARCIS (Netherlands)

    van Groenestijn, Annerieke C.; van de Port, Ingrid G. L.; Schröder, Carin D.; Post, Marcel W. M.; Grupstra, Hepke F.; Kruitwagen, Esther T.; van der Linde, Harmen; van Vliet, Reinout O.; van de Weerd, Margreet G. H.; van den Berg, Leonard H.; Lindeman, Eline

    2011-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disorder affecting motor neurons in the spinal cord, brainstem and motor cortex, leading to muscle weakness. Muscle weakness may result in the avoidance of physical activity, which exacerbates disuse weakness and

  7. 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

  8. Gait Characteristics in Adolescents With Multiple Sclerosis.

    Science.gov (United States)

    Kalron, Alon; Frid, Lior; Menascu, Shay

    2017-03-01

    Multiple sclerosis is a progressive autoimmune disease of the central nervous system. A presentation of multiple sclerosis before age18 years has traditionally been thought to be rare. However, during the past decade, more cases have been reported. We examined gait characteristics in 24 adolescents with multiple sclerosis (12 girls, 12 boys). Mean disease duration was 20.4 (S.D. = 24.9) months and mean age was 15.5 (S.D. = 1.1) years. The mean expanded disability status scale score was 1.7 (S.D. = 0.7) indicating minimal disability. Outcomes were compared with gait and the gait variability index value of healthy age-matched adolescents. Adolescents with multiple sclerosis walked slower with a wider base of support compared with age-matched healthy control subjects. Moreover, the gait variability index was lower in the multiple sclerosis group compared with the values in the healthy adolescents: 85.4 (S.D. = 8.1) versus 96.5 (S.D. = 7.4). We present gait parameters of adolescents with multiple sclerosis. From a clinical standpoint, our data could improve management of walking dysfunction in this relatively young population. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Comparing methods to combine functional loss and mortality in clinical trials for amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    van Eijk RPA

    2018-03-01

    Full Text Available Ruben PA van Eijk,1 Marinus JC Eijkemans,2 Dimitris Rizopoulos,3 Leonard H van den Berg,4,* Stavros Nikolakopoulos5,* 1Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands; 2Department of Biostatistics, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands; 4Department of Neurology, University Medical Center Utrecht, Utrecht, the Netherlands; 5Department of Biostatistics, University Medical Center Utrecht, Utrecht, the Netherlands *These authors contributed equally to this work Objective: Amyotrophic lateral sclerosis (ALS clinical trials based on single end points only partially capture the full treatment effect when both function and mortality are affected, and may falsely dismiss efficacious drugs as futile. We aimed to investigate the statistical properties of several strategies for the simultaneous analysis of function and mortality in ALS clinical trials. Methods: Based on the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT database, we simulated longitudinal patterns of functional decline, defined by the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R and conditional survival time. Different treatment scenarios with varying effect sizes were simulated with follow-up ranging from 12 to 18 months. We considered the following analytical strategies: 1 Cox model; 2 linear mixed effects (LME model; 3 omnibus test based on Cox and LME models; 4 composite time-to-6-point decrease or death; 5 combined assessment of function and survival (CAFS; and 6 test based on joint modeling framework. For each analytical strategy, we calculated the empirical power and sample size. Results: Both Cox and LME models have increased false-negative rates when treatment exclusively affects either function or survival. The joint model has superior power compared to other strategies. The composite end point

  10. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  11. Islamic fasting and multiple sclerosis

    Science.gov (United States)

    2014-01-01

    Background Month-long daytime Ramadan fasting pose s major challenges to multiple sclerosis (MS) patients in Muslim countries. Physicians should have practical knowledge on the implications of fasting on MS. We present a summary of database searches (Cochrane Database of Systematic Reviews, PubMed) and a mini-symposium on Ramadan fasting and MS. In this symposium, we aimed to review the effect of fasting on MS and suggest practical guidelines on management. Discussion In general, fasting is possible for most stable patients. Appropriate amendment of drug regimens, careful monitoring of symptoms, as well as providing patients with available evidence on fasting and MS are important parts of management. Evidence from experimental studies suggests that calorie restriction before disease induction reduces inflammation and subsequent demyelination and attenuates disease severity. Fasting does not appear to have unfavorable effects on disease course in patients with mild disability (Expanded Disability Status Scale (EDSS) score ≤3). Most experts believed that during fasting (especially in summer), some MS symptoms (fatigue, fatigue perception, dizziness, spasticity, cognitive problems, weakness, vision, balance, gait) might worsen but return to normal levels during feasting. There was a general consensus that fasting is not safe for patients: on high doses of anti-convulsants, anti-spastics, and corticosteroids; with coagulopathy or active disease; during attacks; with EDSS score ≥7. Summary These data suggest that MS patients should have tailored care. Fasting in MS patients is a challenge that is directly associated with the spiritual belief of the patient. PMID:24655543

  12. [Oral treatments in multiple sclerosis].

    Science.gov (United States)

    Meca-Lallana, José Eustasio; Hernández-Clares, Rocío; Carreón-Guarnizo, Ester

    2014-12-01

    The development of new disease-modifying drugs (DMD) in relapsing-remitting multiple sclerosis (RRMS), which share the common denominator of oral administration, considerably improves patient expectations in terms of effectiveness, tolerability and treatment adherence compared with currently available drugs. However, the common route of administration of these drugs does not mean that they are equivalent, since the heading of "oral route" encompasses drugs with distinct indications and mechanisms of action, as well as heterogeneous results in terms of efficacy and safety, allowing treatment to be personalized according to the each patient' s characteristics. Currently, four oral DMD are available or in an advanced stage of clinical development: fingolimod, teriflunomide, dimethyl fumarate and laquinimod. In pivotal trials versus placebo, these molecules reduced the annualized rate of exacerbations versus placebo by 54%, 31%, 53% and 23%, respectively, the risk of progression of disability by 31%, 30%, 38% and 36%, and the number of active lesions showing contrast uptake on magnetic resonance imaging by 82%, 80%, 90% and 37%, respectively. Based on the risk/benefit ratio, fingolimod is indicated in patients with suboptimal response to initial DMD or in severe rapidly progressing RRMS, while the remaining drugs can be used as first-line options. Clinical experience with these treatments will provide new data on safety and effectiveness, which will be determinant when establishing therapeutic algorithms. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Remyelination Therapy in Multiple Sclerosis.

    Science.gov (United States)

    Harlow, Danielle E; Honce, Justin M; Miravalle, Augusto A

    2015-01-01

    Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high-throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in preclinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.

  14. Remyelination Therapy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Danielle E. Harlow

    2015-12-01

    Full Text Available Multiple Sclerosis (MS is an immune-mediated disorder of the central nervous system that results in destruction of the myelin sheath that surrounds axons and eventual neurodegeneration. Current treatments approved for the treatment of relapsing forms of MS target the aberrant immune response and successfully reduce the severity of attacks and frequency of relapses. Therapies are still needed that can repair damage particularly for the treatment of progressive forms of MS for which current therapies are relatively ineffective. Remyelination can restore neuronal function and prevent further neuronal loss and clinical disability. Recent advancements in our understanding of the molecular and cellular mechanisms regulating myelination, as well as the development of high throughput screens to identify agents that enhance myelination, have lead to the identification of many potential remyelination therapies currently in pre-clinical and early clinical development. One problem that has plagued the development of treatments to promote remyelination is the difficulty in assessing remyelination in patients with current imaging techniques. Powerful new imaging technologies are making it easier to discern remyelination in patients, which is critical for the assessment of these new therapeutic strategies during clinical trials. This review will summarize what is currently known about remyelination failure in MS, strategies to overcome this failure, new therapeutic treatments in the pipeline for promoting remyelination in MS patients, and new imaging technologies for measuring remyelination in patients.

  15. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  16. Natalizumab therapy of multiple sclerosis.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    Multiple sclerosis (MS) is the commonest disabling neurological disease of young and middle-aged adults affecting 1 million persons world wide. The illness begins with a relapsing-remitting MS course in 85%-90% of patients; the other 10%-15% have a primary progressive onset MS. Our current understanding is that MS is an autoimmune disorder with an inflammatory T-cell attack on myelin or some component of the oligodendrocyte--myelin structure. Relapses of disease activity result in plaques of demyelination with destruction of myelin and, to a lesser, extent axons. Lymphocytes within the central nervous system tissue recruit more cells leading to an inflammatory cascade that causes myelin damage, axonal disruption, and neuronal death. If the plaque occurs in a vocal area of the central nervous system then symptoms relating to that area result. However, magnetic resonance imaging shows that approximately 10 times more lesions occur in asymptomatic areas of the brain. Recovery from an initial relapse may appear relatively complete but persistent inflammation results in axonal injury and residual disability results. With time and accumulated lesion load, secondary degeneration of denuded axons results in the phase of secondary progressive MS usually 15-20 years after onset.

  17. Pediatric multiple sclerosis in Venezuela

    Directory of Open Access Journals (Sweden)

    Joaquín A. Peña

    2012-04-01

    Full Text Available OBJECTIVE: To describe the epidemiological and clinical characteristics of Venezuelan pediatric patients with multiple sclerosis (MS. METHODS: Database records from the National Program for MS were searched for patients with an established diagnosis of MS whose first symptoms appeared before age 18. RESULTS: The national database held records of 1.710 patients; 3.8% had onset of the first symptoms before age 18. 46.7% were boys, yielding an F:M ratio of 1.13:1. Many children had a disease onset characterized by motor impairment (30.7%, brainstem/cerebellum and spinal cord affectation (27.6%, headache (26%. Less frequent symptoms were sensory symptoms (8% and optic neuritis (7%. DISCUSSION: Pediatric MS patients in Venezuela represent a significant proportion of all MS cases. The clinical pattern is characterized by motor symptoms at onset, and predominantly monosymptomatic presentation with a relapsing-remitting pattern. This is the first systematic attempt to estimate the prevalence of pediatric MS in Venezuela.

  18. MRI findings of multiple sclerosis

    International Nuclear Information System (INIS)

    Choi, Min Yun; Sol, Chang Hyo; Chung, Choon Phill; Kim, Byung Soo; Park, Byung Ho

    1993-01-01

    Nine patients of clinically definite multiple sclerosis (MS) were examined by magnetic resonance imaging (MRI) at 1.0 T. The MS plaques were seen in the brain and spinal cord in eight and three patients, respectively. The frequent sites of MS plaques were periventricular white matter, brain stem, and cervical cord. The shape of most brain MS plaques was round or finger-like configuration. The MS plaques showed high signal intensity on T2 weighted images and low or iso signal intensity on T1 weighted images in all nine cases. Contrast enhancement was seen in 4 cases. Mild brain atrophy was noted in 2 cases and mass effect in 1 case. The sites of cord MS plaques in three patients were C2-C4, C2-C5, and C4-C6 levels respectively. The core MS plaques showed high signal intensity on T2 weighted image and contrast enhancement on Gd-DTPA enhanced T1 weighted images in all 3 case with mild cord expansion in 2 cases. In conclusion, MRI is a useful diagnosis tool in evaluating the MS plaques involved central nervous system

  19. Correlation of Creatine Kinase Levels with Clinical Features and Survival in Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Hongfei Tai

    2017-07-01

    Full Text Available ObjectiveTo evaluate serum creatine kinase (CK levels of amyotrophic lateral sclerosis (ALS patients and to explore the relationship between CK levels and the clinical characteristics and survival prognosis of ALS patients.MethodsWe analyzed the CK levels of 185 ALS patients who underwent long-term follow-up. The relationship between CK levels and clinical features including sex, age, disease duration, site of onset, body mass index (BMI, serum creatinine (Cr, and spontaneous electromyographic activity was analyzed by univariate analysis and multiple linear regression. Kaplan–Meier and Cox proportional hazards models were used to explore whether CK levels were independently correlated with survival prognosis of ALS.ResultsBaseline serum CK was raised in 43% of participants. The median CK level was 160 U/L (range: 20–2,574 U/L, and 99% of patients had a baseline serum CK level less than 1,000 U/L. CK levels were significantly higher in male patients than in female patients [204 (169 versus 117 (111 U/L, p < 0.001] and in patients with limb onset ALS than with bulbar onset ALS (p < 0.001. CK levels were also correlated with serum Cr (p = 0.011 and the spontaneous potential score of electromyography (EMG (p = 0.037 but not correlated with age (p = 0.883, disease duration (p = 0.116, or BMI (p = 0.481. Log CK was independently correlated with survival of ALS patients (HR = 0.457, 95% confidence interval 0.221–0.947, p = 0.035 after adjusting for age, sex, site of onset, serum Cr, and BMI.ConclusionSerum CK levels of ALS patients were correlated with sex, site of onsite, serum Cr, and spontaneous activity in EMG. Serum CK could be an independent prognostic factor for survival of ALS patients.

  20. Altered nucleocytoplasmic proteome and transcriptome distributions in an in vitro model of amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Jee-Eun Kim

    Full Text Available Aberrant nucleocytoplasmic localization of proteins has been implicated in many neurodegenerative diseases. Evidence suggests that cytoplasmic mislocalization of nuclear proteins such as transactive response DNA-binding protein 43 (TDP-43 and fused in sarcoma (FUS may be associated with neurotoxicity in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration. This study investigated the changes in nucleocytoplasmic distributions of the proteome and transcriptome in an in vitro model of ALS. After subcellular fractionation of motor neuron-like cell lines expressing wild-type or G93A mutant hSOD1, quantitative mass spectrometry and next-generation RNA sequencing (RNA-seq were performed for the nuclear and cytoplasmic compartments. A subset of the results was validated via immunoblotting. A total of 1,925 proteins were identified in either the nuclear or cytoplasmic fractions, and 32% of these proteins were quantified in both fractions. The nucleocytoplasmic distribution of 37 proteins was significantly changed in mutant cells with nuclear and cytoplasmic shifts in 13 and 24 proteins, respectively (p<0.05. The proteins shifted towards the nucleus were enriched regarding pathways of RNA transport and processing (Dhx9, Fmr1, Srsf3, Srsf6, Tra2b, whereas protein folding (Cct5, Cct7, Cct8, aminoacyl-tRNA biosynthesis (Farsb, Nars, Txnrd1, synaptic vesicle cycle (Cltc, Nsf, Wnt signalling (Cltc, Plcb3, Plec, Psmd3, Ruvbl1 and Hippo signalling (Camk2d, Plcb3, Ruvbl1 pathways were over-represented in the proteins shifted to the cytoplasm. A weak correlation between the changes in protein and mRNA levels was found only in the nucleus, where mRNA was relatively abundant in mutant cells. This study provides a comprehensive dataset of the nucleocytoplasmic distribution of the proteome and transcriptome in an in vitro model of ALS. An integrated analysis of the nucleocytoplasmic distribution of the proteome and transcriptome demonstrated

  1. Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Park, Susanna B; Vucic, Steve; Cheah, Benjamin C; Lin, Cindy S-Y; Kirby, Adrienne; Mann, Kristy P; Zoing, Margie C; Winhammar, Jennica; Kiernan, Matthew C

    2015-12-01

    Abnormalities in membrane excitability and Na(+) channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na(+) channel blocker and membrane stabiliser flecainide in ALS. A double-blind, placebo-controlled, randomised clinical trial of flecainide (200 mg/day) for 32-weeks with a 12-week lead-in phase was conducted in participants with probable or definite ALS recruited from multiple Australian centres (ANZCT Registry number ACTRN12608000338369). Patients were reviewed by a cardiologist to rule out cardiac contraindications. Participants were randomly assigned (1:1) to flecainide or placebo using stratified permuted blocks by a central pharmacy. The primary outcome measure was the slope of decline of the ALS Functional Rating Scale-revised (ALS FRS-r) during the treatment period. Between March 11, 2008 and July 1, 2010, 67 patients were screened, 54 of whom were randomly assigned to receive flecainide (26 patients) or placebo (28 patients). Four patients in the flecainide group and three patients in the placebo group withdrew from the study. One patient in the flecainide group died during the study, attributed to disease progression. Flecainide was generally well tolerated, with no serious adverse events reported in either group. There was no significant difference in the rate of decline in the primary outcome measure ALS-FRS-r between placebo and flecainide treated patients (Flecainide 0.65 [95% CI 0.49 to 0.98]; Placebo 0.81 [0.49 to 2.12] P = 0.50). However, the rate of decline of the neurophysiological index was significantly reduced in the flecainide group (Flecainide 0.06 [0.01 to 0.11]; Placebo 0.14 [0.09 to 0.19], P = 0.02). Placebo-treated patients demonstrated greater CMAP amplitude reduction during the course of the study in the subset of patients with a reduced baseline CMAP amplitude (Flecainide: - 15 ± 12%; Placebo - 59 ± 12%; P = 0.03). Flecainide

  2. Neuroleptics as therapeutic compounds stabilizing neuromuscular transmission in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Patten, Shunmoogum A; Aggad, Dina; Martinez, Jose; Tremblay, Elsa; Petrillo, Janet; Armstrong, Gary Ab; La Fontaine, Alexandre; Maios, Claudia; Liao, Meijiang; Ciura, Sorana; Wen, Xiao-Yan; Rafuse, Victor; Ichida, Justin; Zinman, Lorne; Julien, Jean-Pierre; Kabashi, Edor; Robitaille, Richard; Korngut, Lawrence; Parker, J Alexander; Drapeau, Pierre

    2017-11-16

    Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. We screened libraries of compounds in C. elegans, validated hits in zebrafish, and tested the most potent molecule in mice and in a small clinical trial. We identified a class of neuroleptics that restored motility in C. elegans and in zebrafish, and the most potent was pimozide, which blocked T-type Ca2+ channels in these simple models and stabilized neuromuscular transmission in zebrafish and enhanced it in mice. Finally, a short randomized controlled trial of sporadic ALS subjects demonstrated stabilization of motility and evidence of target engagement at the neuromuscular junction. Simple genetic models are, thus, useful in identifying promising compounds for the treatment of ALS, such as neuroleptics, which may stabilize neuromuscular transmission and prolong survival in this disease.

  3. Inefficient skeletal muscle oxidative function flanks impaired motor neuron recruitment in Amyotrophic Lateral Sclerosis during exercise.

    Science.gov (United States)

    Lanfranconi, F; Ferri, A; Corna, G; Bonazzi, R; Lunetta, C; Silani, V; Riva, N; Rigamonti, A; Maggiani, A; Ferrarese, C; Tremolizzo, L

    2017-06-07

    This study aimed to evaluate muscle oxidative function during exercise in amyotrophic lateral sclerosis patients (pALS) with non-invasive methods in order to assess if determinants of reduced exercise tolerance might match ALS clinical heterogeneity. 17 pALS, who were followed for 4 months, were compared with 13 healthy controls (CTRL). Exercise tolerance was assessed by an incremental exercise test on cycle ergometer measuring peak O 2 uptake ([Formula: see text]O 2peak ), vastus lateralis oxidative function by near infrared spectroscopy (NIRS) and breathing pattern ([Formula: see text]E peak ). pALS displayed: (1) 44% lower [Formula: see text]O 2peak vs. CTRL (p motor units recruitment, is a major determinant of pALS clinical heterogeneity and working capacity exercise tolerance. CPET and NIRS are useful tools for detecting early stages of oxidative deficiency in skeletal muscles, disclosing individual impairments in the O 2 transport and utilization chain.

  4. Cutaneous somatic and autonomic nerve TDP-43 deposition in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ren, Yuting; Liu, Wenxiu; Li, Yifan; Sun, Bo; Li, Yanran; Yang, Fei; Wang, Hongfen; Li, Mao; Cui, Fang; Huang, Xusheng

    2018-05-26

    To evaluate the involvement of the sensory and autonomic nervous system in amyotrophic lateral sclerosis (ALS) and to determine whether TDP-43/pTDP-43 deposits in skin nerve fibers signify a valuable biomarker for ALS. Eighteen patients with ALS and 18 age- and sex-matched control subjects underwent physical examinations, in addition to donating skin biopsies from the distal leg. The density of epidermal, Meissner's corpuscle (MC), sudomotor, and pilomotor nerve fibers were measured. Confocal microscopy was used to determine the cutaneous somatic and autonomic nerve fiber density and TDP-43/pTDP-43 deposition. Intraepidermal nerve fiber density (IENFD) was reduced in individuals with ALS (P nerve fiber density (SGNFD) (P nerve fiber density (PNFD) (P nerve fibers may indicate an important role in the underlying pathogenesis of ALS. This observation might be used as a potential biomarker for diagnosing ALS.

  5. CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs.

    Science.gov (United States)

    Wang, Lixia; Yi, Fei; Fu, Lina; Yang, Jiping; Wang, Si; Wang, Zhaoxia; Suzuki, Keiichiro; Sun, Liang; Xu, Xiuling; Yu, Yang; Qiao, Jie; Belmonte, Juan Carlos Izpisua; Yang, Ze; Yuan, Yun; Qu, Jing; Liu, Guang-Hui

    2017-05-01

    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.

  6. Semantic memory assessment in 15 patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Hervieu-Bègue, M; Rouaud, O; Graule Petot, A; Catteau, A; Giroud, M

    2016-01-01

    A total of 30 to 50% of amyotrophic lateral sclerosis patients suffer from cognitive disorders. The aim of the study is to characterize these disorders and to assess semantic memory in non-demented ALS patients. The secondary aim is to look for a link between disease type and neuropsychological characteristics. Patients were followed in an ALS center in Dijon. The following neuropsychological tests were used in this study: Folstein test, BREF test, verbal fluency, Isaac test, GRESEM test and TOP 30 test. Fifteen ALS patients were included. Nine of them (60%) were suffering from a semantic memory disorder. There was no correlation between ALS characteristics and the semantic memory disorder. This is the first study to reveal a semantic memory disorder in ALS. This result accentuates the hypothesis that ALS and semantic dementia are two phenotypes of the same degenerative process linked to TDP 43 proteinopathy. Copyright © 2016. Published by Elsevier Masson SAS.

  7. 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.

  8. 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.

  9. Epidemiology of amyotrophic lateral sclerosis patients in a centre in Buenos Aires

    Directory of Open Access Journals (Sweden)

    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.

  10. [Virus-like inclusions in the myocytes of the skeletal muscle in lateral amyotrophic sclerosis].

    Science.gov (United States)

    Musaeva, L S; Sakharova, A V; Zavalishin, I A

    2004-01-01

    Microscopic examination of musculus gastrocnemius biopsies was made in four cases of sporadic lateral amyotrophic sclerosis (LAS). The validity of the clinical diagnosis was confirmed by detected neurotrophic atrophy of the muscular fibers typical for LAS. Electron microscopic study revealed virus-like inclusions 200-450 nm in size in sarcoplasm of myocytes of all the patients. The inclusions consist of lined cells of hexagonal shape at the distance of 37-41 nm from each other. The inclusions resemble enteroviruses but are not identical to them both by size and structure of their elements. There were also specific ultrastructural changes of myocytes corresponding to viral infection. The above virus-like inclusions should be considered as specific structures formed as a result of metabolic shifts caused by productive action on the cell of infective or unknown factor.

  11. 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.

  12. 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.

  13. Association study between XRCC1 gene polymorphisms and sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    Coppedè, Fabio; Migheli, Francesca; Lo Gerfo, Annalisa; Fabbrizi, Maria Rita; Carlesi, Cecilia; Mancuso, Michelangelo; Corti, Stefania; Mezzina, Nicoletta; del Bo, Roberto; Comi, Giacomo P; Siciliano, Gabriele; Migliore, Lucia

    2010-01-01

    The aim of the present study was to investigate the possible contribution of three common functional polymorphisms in the DNA repair protein X-ray repair cross-complementing group 1 (XRCC1), namely Arg194Trp (rs1799782), Arg280His (rs25489) and Arg399Gln (rs25487), to sporadic amyotrophic lateral sclerosis (SALS). We genotyped 206 Italian SALS patients and 203 matched controls for XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphisms by means of PCR/RFLP technique, searching for association between any of the studied polymorphisms and disease risk, age and site of onset. We observed a statistically significant difference in XRCC1 Gln399 allele frequencies between SALS cases and controls (0.39/0.28; p=0.001). The present study suggests that the XRCC1 Arg399Gln polymorphism might contribute to SALS risk.

  14. Maple Syrup Decreases TDP-43 Proteotoxicity in a Caenorhabditis elegans Model of Amyotrophic Lateral Sclerosis (ALS).

    Science.gov (United States)

    Aaron, Catherine; Beaudry, Gabrielle; Parker, J Alex; Therrien, Martine

    2016-05-04

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing death of the motor neurons. Proteotoxicity caused by TDP-43 protein is an important aspect of ALS pathogenesis, with TDP-43 being the main constituent of the aggregates found in patients. We have previously tested the effect of different sugars on the proteotoxicity caused by the expression of mutant TDP-43 in Caenorhabditis elegans. Here we tested maple syrup, a natural compound containing many active molecules including sugars and phenols, for neuroprotective activity. Maple syrup decreased several age-dependent phenotypes caused by the expression of TDP-43(A315T) in C. elegans motor neurons and requires the FOXO transcription factor DAF-16 to be effective.

  15. Monitoring Progression of Amyotrophic Lateral Sclerosis Using Ultrasound Morpho-Textural Muscle Biomarkers: A Pilot Study.

    Science.gov (United States)

    Martínez-Payá, Jacinto J; Ríos-Díaz, José; Medina-Mirapeix, Francesc; Vázquez-Costa, Juan F; Del Baño-Aledo, María Elena

    2018-01-01

    The need is increasing for progression biomarkers that allow the loss of motor neurons in amyotrophic lateral sclerosis (ALS) to be monitored in clinical trials. In this prospective longitudinal study, muscle thickness, echointensity, echovariation and gray level co-occurrence matrix textural features are examined as possible progression ultrasound biomarkers in ALS patients during a 5-mo follow-up period. We subjected 13 patients to 3 measurements for 20 wk. They showed a significant loss of muscle, an evident tendency to loss of thickness and increased echointensity and echovariation. In regard to textural parameters, muscle heterogeneity tended to increase as a result of the neoformation of non-contractile tissue through denervation. Considering some limitations of the study, the quantitative muscle ultrasound biomarkers evaluated showed a promising ability to monitor patients affected by ALS. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

  16. Manganese concentration in the spinal cords and blood corpuscles of amyotrophic lateral sclerosis patients

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Satoru; Toyoshima, Masanori; Otsuki, Yuzo; Nagata, Hiroshi; Nakamura, Shigenobu (Kyoto Univ. (Japan). Faculty of Medicine)

    1981-11-01

    Manganese concentration in the spinal cord tissues and the blood corpuscles from patients with amyotrophic lateral sclerosis (ALS) and other diseases were measured by neutron activation analysis. The mean manganese concentration in the spinal cord from ALS patients was significantly higher than that from control subjects, especially in the anterior horn of the cervical cord. In order to determine the manganese concentration in blood corpuscles by neutron activation analysis, it was necessary to subtract /sup 56/Mn derived from the /sup 56/Fe(n, p)/sup 56/Mn reaction. The mean Mn concentration in the blood corpuscles from ALS patients seems to be lower than that from patients with other diseases. Fe, Se, Rb and Zn concentrations in the blood corpuscles from ALS patients were not different from those of patients with other diseases.

  17. 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.)

  18. Elemental imbalance studies by INAA on extra neural tissues from amyotrophic lateral sclerosis patients

    International Nuclear Information System (INIS)

    Tandon, L.; Ehmann, W.D.

    1995-01-01

    Human kidney and liver tissues were studied for generalized elemental imbalances in amyotrophic lateral sclerosis (ALS) by instrumental neutron activation analysis (INAA). Iron was significantly increased (p<0.05) in ALS kidneys and Co and Fe (marginal, p<0.10) were increased in ALS liver compared with their respective controls. Mercury values were almost two-fold higher for ALS kidney and 17% higher for ALS liver as compared with their respective controls, However, the Hg data exhibited large variations and ALS-control differences were not significant. Data from the present study are discussed with reference to the role of metallothioneins (MT) in ALS, and a possible linkage between a free radical mediated mechanism and degeneration of cells in ALS is also explored. (author). 43 refs., 2 tabs

  19. 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.

  20. 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.

  1. 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.)

  2. Manganese concentration in the spinal cords and blood corpuscles of amyotrophic lateral sclerosis patients

    International Nuclear Information System (INIS)

    Miyata, Satoru; Toyoshima, Masanori; Otsuki, Yuzo; Nagata, Hiroshi; Nakamura, Shigenobu

    1981-01-01

    Manganese concentration in the spinal cord tissues and the blood corpuscles from patients with amyotrophic lateral sclerosis (ALS) and other diseases were measured by neutron activation analysis. The mean manganese concentration in the spinal cord from ALS patients was significantly higher than that from control subjects, especially in the anterior horn of the cervical cord. In order to determine the manganese concentration in blood corpuscles by neutron activation analysis, it was necessary to subtract 56 Mn derived from the 56 Fe(n, p) 56 Mn reaction. The mean Mn concentration in the blood corpuscles from ALS patients seems to be lower than that from patients with other diseases. Fe, Se, Rb and Zn concentrations in the blood corpuscles from ALS patients were not different from those of patients with other diseases. (author)

  3. Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits

    International Nuclear Information System (INIS)

    Hecht, M.J.; Neundoerfer, B.; Fellner, C.; Fellner, F.A.; Schmid, A.

    2005-01-01

    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.)

  4. Emerging understanding of the genotype-phenotype relationship in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Goutman, Stephen A; Chen, Kevin S; Paez-Colasante, Ximena; Feldman, Eva L

    2018-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive, noncurable neurodegenerative disorder of the upper and lower motor neurons causing weakness and death within a few years of symptom onset. About 10% of patients with ALS have a family history of the disease; however, ALS-associated genetic mutations are also found in sporadic cases. There are over 100 ALS-associated mutations, and importantly, several genetic mutations, including C9ORF72, SOD1, and TARDBP, have led to mechanistic insight into this complex disease. In the clinical realm, knowledge of ALS genetics can also help explain phenotypic heterogeneity, aid in genetic counseling, and in the future may help direct treatment efforts. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. 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.

  6. Functional Connectivity Changes in Resting-State EEG as Potential Biomarker for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Iyer, Parameswaran Mahadeva; Egan, Catriona; Pinto-Grau, Marta; Burke, Tom; Elamin, Marwa; Nasseroleslami, Bahman; Pender, Niall; Lalor, Edmund C; Hardiman, Orla

    2015-01-01

    Amyotrophic Lateral Sclerosis (ALS) is heterogeneous and overlaps with frontotemporal dementia. Spectral EEG can predict damage in structural and functional networks in frontotemporal dementia but has never been applied to ALS. 18 incident ALS patients with normal cognition and 17 age matched controls underwent 128 channel EEG and neuropsychology assessment. The EEG data was analyzed using FieldTrip software in MATLAB to calculate simple connectivity measures and scalp network measures. sLORETA was used in nodal analysis for source localization and same methods were applied as above to calculate nodal network measures. Graph theory measures were used to assess network integrity. Cross spectral density in alpha band was higher in patients. In ALS patients, increased degree values of the network nodes was noted in the central and frontal regions in the theta band across seven of the different connectivity maps (pEEG has potential utility as a biomarker in ALS.

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

    Science.gov (United States)

    Bede, Peter; Oliver, David; Stodart, James; van den Berg, Leonard; Simmons, Zachary; O Brannagáin, Doiminic; Borasio, Gian Domenico; Hardiman, Orla

    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. To conduct a systematic analysis of the type, level and timing of specialist palliative care intervention in ALS. Despite an international consensus that ALS management should adopt a multidisciplinary approach, integration of palliative care into ALS management varies considerably across health care systems. Late referral to palliative services in ALS is not uncommon and may impact negatively on the quality of life of ALS patients and their caregivers. However, common themes and principles of engagement can be identified across different jurisdictions, and measurement systems have been established that can assess the impact of palliative care intervention. There is considerable evidence that palliative care intervention improves quality of life in patients and carers. International consensus guidelines would assist in the development of a framework for active palliative care engagement in ALS and other neurodegenerative diseases.

  8. Transcranial brainstem sonography as a diagnostic tool for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Prell, Tino; Schenk, Annekathrin; Witte, Otto W; Grosskreutz, Julian; Günther, Albrecht

    2014-06-01

    Diagnosing amyotrophic lateral sclerosis (ALS) can be difficult, particularly in the early stage of disease; therefore, we evaluated the use of transcranial stem sonography (TCS) to improve early detection of the disease. In this cross-sectional study, 94 patients with sporadic ALS and 46 age- and gender-matched healthy controls were evaluated by TCS according to a standardized protocol used to diagnose Parkinson's disease. Approximately half (48%) of the patients with ALS showed a clear (> 0.25 cm(2)) mesencephalic hyperechogenic structure, 20% showed a possible (laterally. In conclusion, although the neuropathological correlation to hyperechogenicity remains unclear, TCS is an easy, feasible and reproducible technique that could serve as an additional diagnostic tool and as a surrogate biomarker in ALS.

  9. A protocol for identification of early bulbar signs in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Ball, L J; Willis, A; Beukelman, D R; Pattee, G L

    2001-10-15

    The purpose of this project is to identify characteristics that may be of assistance in establishing the diagnosis and monitoring early progression of bulbar dysfunction in patients with Amyotrophic Lateral Sclerosis (ALS). Early identification of bulbar dysfunction would assist in clinical trials and management decisions. A database of 218 clinic visits of patients with ALS was developed and formed the basis for these analyses. As a framework for the description of our methodology, the Disablement Model [World Health Organization. WHO International classification of impairment, activity, and participation: beginner's guide. In: WHO, editor. Beta-1 draft for field trials; 1999] was utilized. Our data identified that the strongest early predictors of bulbar speech dysfunction include altered voice quality (laryngeal control), speaking rate, and communication effectiveness. A protocol for measuring these speech parameters was therefore undertaken. This paper presents the protocol used to measure these bulbar parameters.

  10. 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.

  11. [Value of split hand in the differential diagnosis of amyotrophic lateral sclerosis and cervical spondylotic amyotrophy].

    Science.gov (United States)

    Jiang, M; Yan, X; Yan, L R; Zhan, Y B; Hu, H T

    2017-12-19

    Objective: To investigate the value of split hand in the differential diagnosis of amyotrophic lateral sclerosis(ALS) and cervical spondylotic amyotrophy (CSA). Methods: A total of 62 ALS patients, 57 CSA patients and 65 normal controls who visited the Neurology and Spine Department of Beijing Jishuitan Hospital from May 2013 to June 2017 were enrolled into this study.The amplitudes of compound muscle action potentials (CMAP) were recorded from abductor digiti minimi (ADM) and abductor pollicis brevis (APB). Moreover, the ratio of CMAP amplitude between ADM and APB (ADM/APB) was calculated. Results: The ADM/APB of the ALS group (1.93±1.97)was significantly higher than that of the normal control group (0.92±0.22)( P differentiation of ALS and CSA.

  12. Anterior cysts of the spine: a difficult differential diagnosis to amyotrophic lateral sclerosis.

    Science.gov (United States)

    Schmalbach, S; Petri, S; Götz, F; Dengler, R; Krampfl, K

    2008-11-01

    We describe three patients referred to our ALS/MND clinic with suspected diagnosis of amyotrophic lateral sclerosis (ALS). The patients were all male, middle aged, and their initial symptoms were weakness and fasciculations in upper limb muscles. Results of clinical and electrophysiological examination in all cases were in accordance with possible ALS according to the revised El Escorial criteria. Other conditions mimicking ALS appeared to be excluded by extensive technical examinations and laboratory tests. Only repeated MRI examinations revealed anterior spinal cysts several years after symptom onset. This report intends to highlight this rare and difficult differential diagnosis of ALS and underlines the value of the revised El Escorial criteria in conjunction with electrophysiology to asses the certainty of the diagnosis ALS.

  13. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders.

    Science.gov (United States)

    Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

    2016-04-05

    Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  14. Mindfulness as a Protective Factor for the Burden of Caregivers of Amyotrophic Lateral Sclerosis Patients.

    Science.gov (United States)

    Pagnini, Francesco; Phillips, Deborah; Bosma, Colin M; Reece, Andrew; Langer, Ellen

    2016-01-01

    Caregivers of people with severe chronic conditions, such as amyotrophic lateral sclerosis (ALS), are at risk of developing depression and anxiety and reduced quality of life. Few studies have explored protective factors in this population and none investigated the role of mindfulness. The study aimed to examine the relationship between mindfulness and health-related outcomes in a population of ALS caregivers. We conducted an online survey with ALS caregivers, and again at 4-month follow-up, to assess mindfulness, burden, quality of life, anxiety, and depression. The associations between mindfulness and the other outcomes were evaluated both cross-sectionally and longitudinally. Mindfulness correlated negatively with burden, depression, and anxiety and positively with quality of life, maintaining stability through time. Our results showed that mindfulness is positively related to quality of life and negatively related to level of burden. We suggest that this construct can represent a preventative factor toward the negative effects of caregiving. © 2015 Wiley Periodicals, Inc.

  15. The experience of meditation for people with amyotrophic lateral sclerosis and their caregivers - a qualitative analysis.

    Science.gov (United States)

    Marconi, Anna; Gragnano, Gaia; Lunetta, Christian; Gatto, Ramona; Fabiani, Viviana; Tagliaferri, Aurora; Rossi, Gabriella; Sansone, Valeria; Pagnini, Francesco

    2016-09-01

    There is a lack of studies about psychological interventions for people with amyotrophic lateral sclerosis (ALS) and their caregivers. We investigated the experience of a meditation training program tailored for ALS needs. People with ALS (pALS) and their caregivers that joined a meditation program for ALS were interviewed at the end of the program. Verbatims were analyzed with a qualitative approach. Both pALS and their caregivers reported a positive impact on their psychological well-being, promoted by an increase in acceptance and non-judgmental attitude. Furthermore, coping strategies seem to improve, with a positive effect on resilience skills. The ALS meditation training program seems to be an effective psychological intervention for the promotion of well-being in pALS and their caregivers.

  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. Oxidized/misfolded superoxide dismutase-1: the cause of all amyotrophic lateral sclerosis?

    Science.gov (United States)

    Kabashi, Edor; Valdmanis, Paul N; Dion, Patrick; Rouleau, Guy A

    2007-12-01

    The identification in 1993 of superoxide dismutase-1 (SOD1) mutations as the cause of 10 to 20% of familial amyotrophic lateral sclerosis cases, which represents 1 to 2% of all amyotrophic lateral sclerosis (ALS) cases, prompted a substantial amount of research into the mechanisms of SOD1-mediated toxicity. Recent experiments have demonstrated that oxidation of wild-type SOD1 leads to its misfolding, causing it to gain many of the same toxic properties as mutant SOD1. In vitro studies of oxidized/misfolded SOD1 and in vivo studies of misfolded SOD1 have indicated that these protein species are selectively toxic to motor neurons, suggesting that oxidized/misfolded SOD1 could lead to ALS even in individuals who do not carry an SOD1 mutation. It has also been reported that glial cells secrete oxidized/misfolded mutant SOD1 to the extracellular environment, where it can trigger the selective death of motor neurons, offering a possible explanation for the noncell autonomous nature of mutant SOD1 toxicity and the rapid progression of disease once the first symptoms develop. Therefore, considering that sporadic (SALS) and familial ALS (FALS) cases are clinically indistinguishable, the toxic properties of mutated SOD1 are similar to that of oxidized/misfolded wild-type SOD1 (wtSOD1), and secreted/extracellular misfolded SOD1 is selectively toxic to motor neurons, we propose that oxidized/misfolded SOD1 is the cause of most forms of classic ALS and should be a prime target for the design of ALS treatments.

  18. 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.

  19. 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.

  20. 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.

  1. 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 P a CO 2 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.

  2. Progression and effect of cognitive-behavioral changes in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Bock, Meredith; Duong, Y-Nhy; Kim, Anthony; Allen, Isabel; Murphy, Jennifer; Lomen-Hoerth, Catherine

    2017-12-01

    To prospectively evaluate the progression of cognitive-behavioral function in amyotrophic lateral sclerosis (ALS) and examine the association of cognitive-behavioral deficits with disease progression, patient quality of life (QOL), and caregiver burden. We evaluated cognitive-behavioral function using the Amyotrophic Lateral Sclerosis Cognitive Behavioral Screen at enrollment and after 7 months in a cohort of patients with ALS. Paired t tests were used to evaluate the change in the 2 assessments. Linear regression and Kruskal-Wallis tests were applied to investigate how initial cognitive or behavioral status related to outcomes. The mean test-retest interval was 6.8 months (SD 1.6). Cognitive status of the study population (n = 49) overall did not change over the study period ( p = 0.06) despite progression of motor weakness ( p cognitive change. Patients initially classified as behaviorally normal showed increased behavioral problems over time ( t = -2.8, p = 0.009). Decline in cognitive (β = -1.3, p = 0.03) and behavioral (β = -0.76, p = 0.002) status predicted increasing caregiver burden. Behavioral abnormalities predicted decline in forced vital capacity and ALS Functional Rating Scale-Revised score ( p = 0.008, 0.012) in the study population and patient QOL in the most severely affected group ( t = 4.3, p = 0.003). Cognitive-behavioral change is a key aspect of disease heterogeneity in ALS. Executive function in ALS overall remains stable over 7 months as detected by an administered screening tool. However, patients may develop caregiver-reported behavioral symptoms in that time period. Screening for caregiver-reported symptoms has a particular utility in predicting future clinical decline, increased caregiver burden, and worsening patient QOL.

  3. Intraspinal neural stem cell transplantation in amyotrophic lateral sclerosis: phase 1 trial outcomes.

    Science.gov (United States)

    Feldman, Eva L; Boulis, Nicholas M; Hur, Junguk; Johe, Karl; Rutkove, Seward B; Federici, Thais; Polak, Meraida; Bordeau, Jane; Sakowski, Stacey A; Glass, Jonathan D

    2014-03-01

    The US Food and Drug Administration-approved trial, "A Phase 1, Open-Label, First-in-Human, Feasibility and Safety Study of Human Spinal Cord-Derived Neural Stem Cell Transplantation for the Treatment of Amyotrophic Lateral Sclerosis, Protocol Number: NS2008-1," is complete. Our overall objective was to assess the safety and feasibility of stem cell transplantation into lumbar and/or cervical spinal cord regions in amyotrophic lateral sclerosis (ALS) subjects. Preliminary results have been reported on the initial trial cohort of 12 ALS subjects. Here, we describe the safety and functional outcome monitoring results for the final trial cohort, consisting of 6 ALS subjects receiving 5 unilateral cervical intraspinal neural stem cell injections. Three of these subjects previously received 10 total bilateral lumbar injections as part of the earlier trial cohort. All injections utilized a novel spinal-mounted stabilization and injection device to deliver 100,000 neural stem cells per injection, for a dosing range up to 1.5 million cells. Subject assessments included detailed pre- and postsurgical neurological outcome measures. The cervical injection procedure was well tolerated and disease progression did not accelerate in any subject, verifying the safety and feasibility of cervical and dual-targeting approaches. Analyses on outcome data revealed preliminary insight into potential windows of stem cell biological activity and identified clinical assessment measures that closely correlate with ALS Functional Rating Scale-Revised scores, a standard assessment for ALS clinical trials. This is the first report of cervical and dual-targeted intraspinal transplantation of neural stem cells in ALS subjects. This approach is feasible and well-tolerated, supporting future trial phases examining therapeutic dosing and efficacy. © 2014 Child Neurology Society/American Neurological Association.

  4. Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Kim, Sungha; Kim, Jae Kyoun; Son, Mi Ju; Kim, Dongwoung; Song, Bongkeun; Son, Ilhong; Kang, Hyung Won; Lee, Jongdeok; Kim, Sungchul

    2018-04-13

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2-3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin. This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016-5-4 and 2016-34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration. This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS. Korean National Clinical Trial Registry CRIS; KCT

  5. Structural and diffusion imaging versus clinical assessment to monitor amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Arturo Cardenas-Blanco

    2016-01-01

    Full Text Available Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects upper and lower motor neurons. Observational and intervention studies can be tracked using clinical measures such as the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R but for a complete understanding of disease progression, objective in vivo biomarkers of both central and peripheral motor pathway pathology are highly desirable. The aim of this study was to determine the utility of structural and diffusion imaging as central nervous system biomarkers compared to the standard clinical measure, ALSFRS-R, to track longitudinal evolution using three time-point measurements. N = 34 patients with ALS were scanned and clinically assessed three times at a mean of three month time intervals. The MRI biomarkers were structural T1-weighted volumes for cortical thickness measurement as well as deep grey matter volumetry, voxel-based morphometry and diffusion tensor imaging (DTI. Cortical thickness focused specifically on the precentral gyrus while quantitative DTI biomarkers focused on the corticospinal tracts. The evolution of imaging biomarkers and ALSFRS-R scores over time were analysed using a mixed effects model that accounted for the scanning interval as a fixed effect variable, and, the initial measurements and time from onset as random variables. The mixed effects model showed a significant decrease in the ALSFRS-R score, (p  0.5. In addition, deep grey matter volumetry and voxel-based morphometry also identified no significant changes. Furthermore, the availability of three time points was able to indicate that there was a linear progression in both clinical and fractional anisotropy measures adding to the validity of these results. The results indicate that DTI is clearly a superior imaging marker compared to atrophy for tracking the evolution of the disease and can act as a central nervous biomarker in longitudinal studies. It

  6. Specific Physical Exercise Improves Energetic Metabolism in the Skeletal Muscle of Amyotrophic-Lateral- Sclerosis Mice

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    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.

  7. Nutrition Facts in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Paolo Riccio

    2015-02-01

    Full Text Available The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness.

  8. Hearing disorders in multiple sclerosis.

    Science.gov (United States)

    Furst, Miriam; Levine, Robert A

    2015-01-01

    Multiple sclerosis (MS) is a disease that is both a focal inflammatory and a chronic neurodegenerative disease. The focal inflammatory component is characterized by destruction of central nervous system myelin, including the spinal cord; as such it can impair any central neural system, including the auditory system. While on the one hand auditory complaints in MS patients are rare compared to other senses, such as vision and proprioception, on the other hand auditory tests of precise neural timing are never "silent." Whenever focal MS lesions are detected involving the pontine auditory pathway, auditory tests requiring precise neural timing are always abnormal, while auditory functions not requiring such precise timing are often normal. Azimuth sound localization is accomplished by comparing the timing and loudness of the sound at the two ears. Hence tests of azimuth sound localization must obligatorily involve the central nervous system and particularly the brainstem. Whenever a focal lesion was localized to the pontine auditory pathway, timing tests were always abnormal, but loudness tests were not. Moreover, a timing test that included only high-frequency sounds was very often abnormal, even when there was no detectable focal MS lesion involving the pontine auditory pathway. This test may be a marker for the chronic neurodegenerative aspect of MS, and, as such could be used to complement the magnetic resonance imaging scan in monitoring the neurodegenerative aspect of MS. Studies of MS brainstem lesion location and auditory function have led to advances in understanding how the human brain processes sound. The brain processes binaural sounds independently for time and level in a two-stage process. The first stage is at the level of the superior olivary complex (SOC) and the second at a level rostral to the SOC. © 2015 Elsevier B.V. All rights reserved.

  9. Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Necla Keskin

    2013-08-01

    Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

  10. Proteasomes remain intact, but show early focal alteration in their composition in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Agar, Jeffrey N; Hong, Yu; Taylor, David M; Minotti, Sandra; Figlewicz, Denise A; Durham, Heather D

    2008-06-01

    In amyotrophic lateral sclerosis caused by mutations in Cu/Zn-superoxide dismutase (SOD1), altered solubility and aggregation of the mutant protein implicates failure of pathways for detecting and catabolizing misfolded proteins. Our previous studies demonstrated early reduction of proteasome-mediated proteolytic activity in lumbar spinal cord of SOD1(G93A) transgenic mice, tissue particularly vulnerable to disease. The purpose of this study was to identify any underlying abnormalities in proteasomal structure. In lumbar spinal cord of pre-symptomatic mice [postnatal day 45 (P45) and P75], normal levels of structural 20S alpha subunits were incorporated into 20S/26S proteasomes; however, proteasomal complexes separated by native gel electrophoresis showed decreased immunoreactivity with antibodies to beta3, a structural subunit of the 20S proteasome core, and beta5, the subunit with chymotrypsin-like activity. This occurred prior to increase in beta5i immunoproteasomal subunit. mRNA levels were maintained and no association of mutant SOD1 with proteasomes was identified, implicating post-transcriptional mechanisms. mRNAs also were maintained in laser captured motor neurons at a later stage of disease (P100) in which multiple 20S proteins are reduced relative to the surrounding neuropil. Increase in detergent-insoluble, ubiquitinated proteins at P75 provided further evidence of stress on mechanisms of protein quality control in multiple cell types prior to significant motor neuron death.

  11. Brain white matter demyelinating lesions and amyotrophic lateral sclerosis in a patient with C9orf72 hexanucleotide repeat expansion.

    Science.gov (United States)

    Oliveira Santos, Miguel; Caldeira, Inês; Gromicho, Marta; Pronto-Laborinho, Ana; de Carvalho, Mamede

    2017-10-01

    A hexanucleotide repeat expansion in the C9orf72 gene is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. It has been described before four patients with multiple sclerosis (MS) and C9orf72-ALS. However, C9orf72 positivity is not associated with increased risk of MS. Inflammatory pathways related to NF-κB have been linked to ALS and MS, and appear to be important in C9orf72-ALS patients. A 42-year-old woman presented with progressive bulbar symptoms for 9 months. Neurological examination disclosed spastic dysarthria, atrophic tongue with fasciculations, brisk jaw and limb tendon reflexes, and bilateral Hoffman sign. Electrophysiological assessment confirmed ALS. Brain MRI revealed multiple and bilateral juxtacortical and periventricular inflammatory changes, some with gadolinium-enhancement, configuring a probable MS-like pattern. CSF evaluation was unremarkable, with no oligoclonal bands. Visual and somatosensory evoked potentials were normal. Follow-up brain MRI 6 months later showed two new lesions in two relatively characteristic locations of MS, with no gadolinium-enhancement. Genetic screening revealed a C9orf72 expansion. As patient had no clinical manifestation of MS, a diagnosis of radiologically isolated syndrome was considered. We speculate that these demyelinating lesions might facilitate expressivity of C9orf72 expansion, through NF-κB activation. This plausible association may lead to the identification of a therapeutic target in this subgroup of C9orf72-ALS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Multiple sclerosis - etiology and diagnostic potential.

    Science.gov (United States)

    Kamińska, Joanna; Koper, Olga M; Piechal, Kinga; Kemona, Halina

    2017-06-30

    Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS) damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPSM), primary progressive multiple sclerosis (PPMS), and progressive-relapsing multiple sclerosis (RPMS). Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald's diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of different diagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

  13. Multiple sclerosis - etiology and diagnostic potential

    Directory of Open Access Journals (Sweden)

    Joanna Kamińska

    2017-06-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory and demyelinating disease of autoimmune originate. The main agents responsible for the MS development include exogenous, environmental, and genetic factors. MS is characterized by multifocal and temporally scattered central nervous system (CNS damage which lead to the axonal damage. Among clinical courses of MS it can be distinguish relapsing-remitting multiple sclerosis (RRMS, secondary progressive multiple sclerosis (SPSM, primary progressive multiple sclerosis (PPMS, and progressive-relapsing multiple sclerosis (RPMS. Depending on the severity of signs and symptoms MS can be described as benign MS or malignant MS. MS diagnosis is based on McDonald’s diagnostic criteria, which link clinical manifestation with characteristic lesions demonstrated by magnetic resonance imaging (MRI, cerebrospinal fluid (CSF analysis, and visual evoked potentials. Among CSF laboratory tests used to the MS diagnosis are applied: Tibbling & Link IgG index, reinbegrams, and CSF isoelectrofocusing for oligoclonal bands detection. It should be emphasized, that despite huge progress regarding MS as well as the availability of differentdiagnostics methods this disease is still a diagnostic challenge. It may result from fact that MS has diverse clinical course and there is a lack of single test, which would be of appropriate diagnostic sensitivity and specificity for quick and accurate diagnosis.

  14. Depression and anxiety in a case series of amyotrophic lateral sclerosis: frequency and association with clinical features.

    Science.gov (United States)

    Prado, Laura de Godoy Rousseff; Bicalho, Isabella Carolina Santos; Vidigal-Lopes, Mauro; Prado, Vitor de Godoy Rousseff; Gomez, Rodrigo Santiago; de Souza, Leonardo Cruz; Teixeira, Antônio Lúcio

    2017-01-01

    To investigate the frequency of anxiety and depression and their association with clinical features of amyotrophic lateral sclerosis. This is a cross-sectional and descriptive study including a consecutive series of patients with sporadic amyotrophic lateral sclerosis according to Awaji's criteria. Patients underwent clinical and psychiatric assessment (anxiety and depression symptoms). We included 76 patients. The men/women ratio was 1.6:1. Participants' mean age at disease onset was 55 years (SD±12.1). Sixty-six patients (86.8%) were able to complete psychiatric evaluation. Clinically significant anxiety was found in 23 patients (34.8%) while clinically significant depression was found in 24 patients (36.4%). When we compared patients with and without depression a significant difference was seen only in the frequency of anxiety symptoms (pescala funcional. Foi encontrada correlação positiva entre os sintomas de ansiedade e depressão (pescala funcional.

  15. Positron emission tomography neuroimaging in amyotrophic lateral sclerosis: what is new?

    International Nuclear Information System (INIS)

    Quartuccio, N.; Van Weehaeghe, D.; Van Laere, K.; Cistaro, A.; Jonsson, C.; Pagani, M.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a neuro degenerative disease involving upper and lower motor neurons, extra-motor neurons, microglia and astrocytes. The neuro degenerative process results in progressive muscle paralysis and even in cognitive impairment. Within the complex diagnostic work-up, positron emission tomography (PET) represents a valuable imaging tool in the assessment of patients with ALS. PET, by means of different radiotracers (i.e. 18 F-fluorodeoxyglucose, 6-[ 18 F]fluoro-L-dopa, [ 11 C]flumazenil) can assess the status of the wide range of brain regions and neural circuits, which can be affected by ALS. Furthermore, experimental radio compounds have been developed for the evaluation of white matter, which plays a role in the progression of the disease. Here we present a comprehensive review including in different sections the most relevant PET studies: studies investigating ALS and ALS-mimicking conditions (especially primary lateral sclerosis and other neuro degenerative diseases), articles selecting specific subsets of patients (with bulbar or spinal onset), studies investigating patients with familial type of ALS, studies evaluating the role of the white matter in ALS and papers evaluating the diagnostic sensitivity of PET in ALS patients

  16. The Use of Stem Cells to Model Amyotrophic Lateral Sclerosis and Frontotemporal Dementia: From Basic Research to Regenerative Medicine

    OpenAIRE

    Hedges, Erin C.; Mehler, Vera J.; Nishimura, Agnes L.

    2016-01-01

    In recent years several genes have linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) as a spectrum disease; however little is known about what triggers their onset. With the ability to generate patient specific stem cell lines from somatic cells, it is possible to model disease without the need to transfect cells with exogenous DNA. These pluripotent stem cells have opened new avenues for identification of disease phenotypes and their relation to specific molecular ...

  17. An Autopsy Case of Amyotrophic Lateral Sclerosis with Waldenström Macroglobulinemia and Anti-MAG Gammopathy

    Directory of Open Access Journals (Sweden)

    Snejana Jurici

    2011-12-01

    Full Text Available We report the case of a 71-year-old woman with typical signs of bulbar amyotrophic lateral sclerosis (ALS associated with immunoglobulin M (IgM monoclonal gammopathy and anti-MAG (myelin-associated glycoprotein antibodies. This unusual association between ALS and anti-MAG antibodies has previously been reported in a single case. Our present case, at neuropathological examination, demonstrated no causative link between anti-MAG antibodies and ALS.

  18. Patient-derived olfactory mucosa for study of the non-neuronal contribution to amyotrophic lateral sclerosis pathology

    OpenAIRE

    García-Escudero, V.; Rosales, M.; Muñoz, J.L.; Scola, E.; Medina, J.; Khalique, H.; Garaulet, G.; Rodriguez, A.; Lim, F.

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease which currently has no cure. Research using rodent ALS models transgenic for mutant superoxide dismutase 1 (SOD1) has implicated that glial-neuronal interactions play a major role in the destruction of motor neurons, but the generality of this mechanism is not clear as SOD1 mutations only account for less than 2% of all ALS cases. Recently, this hypothesis was backed up by observation of similar effects using astrocyte...

  19. Is the effect of non-invasive ventilation on survival in amyotrophic lateral sclerosis age-dependent?

    OpenAIRE

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

    2013-01-01

    Background Hypoventilation due to respiratory muscle atrophy is the most common cause of death as a result of amyotrophic lateral sclerosis (ALS). Patients aged over 65?years and presenting bulbar symptoms are likely to have a poorer prognosis. The aim of the study was to assess the possible impact of age and treatment with non-invasive ventilation (NIV) on survival in ALS. Based on evidence from earlier studies, it was hypothesized that NIV increases rates of survival regardless of age. Meth...

  20. Cranial Neuropathy in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Mine Hayriye Sorgun

    2011-09-01

    Full Text Available OBJECTIVE: It has been reported that cranial neuropathy findings could be seen in the neurologic examination of multiple sclerosis (MS patients, although brain magnetic resonance imaging (MRI may not reveal any lesion responsible for the cranial nerve involvement. The aim of this study was to determine the frequency of brainstem and cranial nerve involvement, except for olfactory and optic nerves, during MS attacks, and to investigate the rate of an available explanation for the cranial neuropathy findings by lesion localization on brain MRI. METHODS: Ninety-five attacks of 86 MS patients were included in the study. The patients underwent a complete neurological examination, and cranial nerve palsies (CNP were determined during MS attacks. RESULTS: CNP were found as follows: 3rd CNP in 7 (7.4%, 4th CNP in 1 (1.1%, 5th CNP in 6 (6.3%, 6th CNP in 12 (12.6%, 7th CNP in 5 (5.3%, 8th CNP in 4 (4.2%, and 9th and 10th CNP in 2 (2.1% out of 95 attacks. Internuclear ophthalmoplegia (INO was detected in 5 (5.4%, nystagmus in 37 (38.9%, vertigo in 9 (6.3%, and diplopia in 14 (14.7% out of 95 attacks. Pons, mesencephalon and bulbus lesions were detected in 58.7%, 41.5% and 21.1% of the patients, respectively, on the brain MRI. Cranial nerve palsy findings could not be explained by the localization of the lesions on brainstem MRI in 5 attacks; 2 of them were 3rd CNP (1 with INO, 2 were 6th CNP and 1 was a combination of 6th, 7th and 8th CNP. CONCLUSION: The most frequently affected cranial nerve and brainstem region in MS patients is the 6th cranial nerve and pons, respectively. A few of the MS patients have normal brainstem MRI, although they have cranial neuropathy findings in the neurologic examination.

  1. Registers of multiple sclerosis in Denmark

    DEFF Research Database (Denmark)

    Koch-Henriksen, N; Magyari, M; Laursen, B

    2015-01-01

    between a number of different environmental exposures in the past and the subsequent risk of MS. Some of these studies have been able to exonerate suspected risk factors. The other register, the nationwide Danish Multiple Sclerosis Treatment Register, is a follow-up register for all patients who have......There are two nationwide population-based registers for multiple sclerosis (MS) in Denmark. The oldest register is The Danish Multiple Sclerosis Registry (DMSR), which is an epidemiological register for estimation of prevalence and incidence of MS and survival, and for identifying exposures earlier...... received disease-modifying treatments since 1996. It has, in particular, contributed to the knowledge of the role of antibodies against the biological drugs used for the treatment of MS....

  2. Retinal layer segmentation in multiple sclerosis

    DEFF Research Database (Denmark)

    Petzold, Axel; Balcer, Laura J; Calabresi, Peter A

    2017-01-01

    BACKGROUND: Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal...... layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT. METHODS: In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people...... with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified...

  3. Report by the Spanish Foundation for the Brain on the social impact of amyotrophic lateral sclerosis and other neuromuscular disorders.

    Science.gov (United States)

    Camacho, A; Esteban, J; Paradas, C

    A thorough knowledge of the socioeconomic scope of neuromuscular disease is essential for managing resources and raising social awareness. Our group reviewed current data on the epidemiology, mortality and dependence rates, and socioeconomic impact of amyotrophic lateral sclerosis and neuromuscular diseases in Spain. We also recorded how neurological care for these patients is organised. Neuromuscular disorders are a very heterogeneous group of diseases, and some are very rare. These disorders account for between 2.8% and 18% of the total motives for a neurological consultation. In Spain, prevalence and incidence figures for amyotrophic lateral sclerosis are similar to those in other countries; however, figures for patients with other neuromuscular diseases are not known. Since the diseases are chronic, progressive, and debilitating, they cause considerable disability and dependence, which in turn directly affects healthcare and social costs associated with the disease. The costs generated by one patient with amyotrophic lateral sclerosis or Duchenne disease have been calculated at about 50 000 euros per year. Neuromuscular disease shows aetiological, diagnostic, and prognostic complexity, and it requires multidisciplinary management. Follow-up for these patients should be entrusted to specialised units. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. New management algorithms in multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg

    2014-01-01

    complex. The purpose of the review has been to work out new management algorithms for treatment of relapsing-remitting multiple sclerosis including new oral therapies and therapeutic monoclonal antibodies. RECENT FINDINGS: Recent large placebo-controlled trials in relapsing-remitting multiple sclerosis......PURPOSE OF REVIEW: Our current treatment algorithms include only IFN-β and glatiramer as available first-line disease-modifying drugs and natalizumab and fingolimod as second-line therapies. Today, 10 drugs have been approved in Europe and nine in the United States making the choice of therapy more...

  5. Reproductive History and Risk of Multiple Sclerosis

    DEFF Research Database (Denmark)

    Nielsen, N. M.; Jorgensen, K. T.; Stenager, E.

    2011-01-01

    Background: It has been suggested that reproductive factors may be involved in the etiology of multiple sclerosis (MS). We studied associations of reproductive history with MS risk in a population-based setting. Methods: Using national databases, we established a cohort comprising 4.4 million...... Danish men and women born between 1935 and 1989 and alive in 1968 or later. We obtained information about their live-born children, pregnancy losses, pregnancy complications, and infertility diagnoses. MS cases in the cohort were identified through 2004 in the Danish Register of Multiple Sclerosis...

  6. Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases.

    Science.gov (United States)

    Arru, G; Mameli, G; Deiana, G A; Rassu, A L; Piredda, R; Sechi, E; Caggiu, E; Bo, M; Nako, E; Urso, D; Mariotto, S; Ferrari, S; Zanusso, G; Monaco, S; Sechi, G; Sechi, L A

    2018-03-31

    Human endogenous retroviruses (HERV) K/W seem to play a role in fostering and exacerbation of some neurological diseases, including amyotrophic lateral sclerosis (ALS). Given these findings, the immunity response against HERV-K and HERV-W envelope surface (env-su) glycoprotein antigens in serum and cerebrospinal fluid (CSF) was investigated for ALS, multiple sclerosis (MS) and Alzheimer's disease patients and in healthy controls. Four antigenic peptides derived respectively from HERV-K and HERV-W env-su proteins were studied in 21 definite or probable ALS patients, 26 possible or definite relapsing-remitting MS patients, 18 patients with Alzheimer's disease and 39 healthy controls. An indirect enzyme-linked immunosorbent assay was set up to detect specific antibodies (Abs) against env-su peptides. Amongst the measured levels of Abs against the four different HERV-K peptide fragments, only HERV-K env-su 19-37 was significantly elevated in ALS compared to other groups, both in serum and CSF. Instead, amongst the Abs levels directed against the four different HERV-W peptide fragments, only HERV-W env-su 93-108 and HERV-W env-su 248-262 were significantly elevated, in the serum and CSF of the MS group compared to other groups. In ALS patients, the HERV-K env-su 19-37 Abs levels were significantly correlated with clinical measures of disease severity, both in serum and CSF. Increased circulating levels of Abs directed against the HERV-W env-su 93-108 and HERV-W env-su 248-262 peptide fragments could serve as possible biomarkers in patients with MS. Similarly, increased circulating levels of Abs directed against the HERV-K env-su 19-37 peptide fragment could serve as a possible early novel biomarker in patients with ALS. © 2018 EAN.

  7. The risk of fracture in incident multiple sclerosis patients

    DEFF Research Database (Denmark)

    Bazelier, Marloes T; Bentzen, Joan; Vestergaard, Peter

    2012-01-01

    Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling.......Patients with multiple sclerosis (MS) may be at increased risk of fractures owing to osteoporosis and falling....

  8. Multiple Sclerosis, Personal Stories | NIH MedlinePlus the Magazine

    Science.gov (United States)

    ... of this page please turn Javascript on. Feature: Multiple Sclerosis Personal Stories: Nicole Lemelle, Iris Young, Michael Anthony, ... something quite different for a person living with multiple sclerosis, such as his girlfriend's brother, Chuy. The more ...

  9. What's new in multiple sclerosis spasticity research? Poster session highlights.

    Science.gov (United States)

    Linker, Ralf

    2017-11-01

    Each year at the Multiple Sclerosis Experts Summit, relevant research in the field of multiple sclerosis spasticity is featured in poster sessions. The main studies presented at this year's meeting are summarized herein.

  10. Cognitive impairment in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kutashov V.A.

    2016-06-01

    Full Text Available Aim: to identify the degree of cognitive impairment (CN and to optimize the treatment of patients with multiple sclerosis (MS. Material and methods. A total of 695 patients (278 men and 417 women were ranged from 18 to 63 years. The mean age was 30.2±0.7 years: women (417 28.5±0.5 years, while for men (278 31.8±0.7 years. Relaps-ing-remitting type (RT of MS was established in 520 patients (74.8%, secondary progressive type (VPT MS in 132 patients (18.9% and primary progressive type (PPT MS in 10 patients (1.5%. Clinically isolated syndrome (CIS was detected in 33 patients (4.8%. The diagnosis of MS 662 patients according to the criteria McDonald etal. (2005. Score of neurologic deficit was carried out on an extended scale of disability (Expanded Disability Status Scale — EDSS. CN were evaluated by conventional tests. To estimate the orientation in time, assessment of short-term and long-term memory, attention and concentration, as well as executive functions, memory, language, evaluation of optical-spatial activities, conceptual thinking, the account used by the Montreal Cognitive Assessment Scale (MoCA. For the screening of dementia with a primary lesion of the frontal lobes and subcortical cerebral structures used battery frontal test to assess frontal dysfunction. Results. The ratio of male (265 and female (397 was 1:1.5. The severity of the condition patients EDSS scale ranged from 1.5 to 8.0 points, and the average score was 3.5±1.2. In the group of patients with RT RS average score EDSS was more than a half (2.5±1.1, than in the group of patients with MS VAC (5.5±1.2 and POS PC (6.5±1.2. In the study of history, it was found that the development of the RS (662 patients was preceded by the following conditions: a viral infection in 277 patients (41.84%; fatigue in 147 patients (22.21%; transferred psycho-emotional load from 218 (32.93%; after pregnancy and childbirth in 20 patients (3.02%. Conclusion. Among the patients with MS

  11. The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Chen, Han-Jou; Mitchell, Jacqueline C; Novoselov, Sergey; Miller, Jack; Nishimura, Agnes L; Scotter, Emma L; Vance, Caroline A; Cheetham, Michael E; Shaw, Christopher E

    2016-05-01

    Detergent-resistant, ubiquitinated and hyperphosphorylated Tar DNA binding protein 43 (TDP-43, encoded by TARDBP) neuronal cytoplasmic inclusions are the pathological hallmark in ∼95% of amyotrophic lateral sclerosis and ∼60% of frontotemporal lobar degeneration cases. We sought to explore the role for the heat shock response in the clearance of insoluble TDP-43 in a cellular model of disease and to validate our findings in transgenic mice and human amyotrophic lateral sclerosis tissues. The heat shock response is a stress-responsive protective mechanism regulated by the transcription factor heat shock factor 1 (HSF1), which increases the expression of chaperones that refold damaged misfolded proteins or facilitate their degradation. Here we show that manipulation of the heat shock response by expression of dominant active HSF1 results in a dramatic reduction of insoluble and hyperphosphorylated TDP-43 that enhances cell survival, whereas expression of dominant negative HSF1 leads to enhanced TDP-43 aggregation and hyperphosphorylation. To determine which chaperones were mediating TDP-43 clearance we over-expressed a range of heat shock proteins (HSPs) and identified DNAJB2a (encoded by DNAJB2, and also known as HSJ1a) as a potent anti-aggregation chaperone for TDP-43. DNAJB2a has a J domain, allowing it to interact with HSP70, and ubiquitin interacting motifs, which enable it to engage the degradation of its client proteins. Using functionally deleted DNAJB2a constructs we demonstrated that TDP-43 clearance was J domain-dependent and was not affected by ubiquitin interacting motif deletion or proteasome inhibition. This indicates that TDP-43 is maintained in a soluble state by DNAJB2a, leaving the total levels of TDP-43 unchanged. Additionally, we have demonstrated that the levels of HSF1 and heat shock proteins are significantly reduced in affected neuronal tissues from a TDP-43 transgenic mouse model of amyotrophic lateral sclerosis and patients with

  12. Leukocyte-derived microparticles and scanning electron microscopic structures in two fractions of fresh cerebrospinal fluid in amyotrophic lateral sclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Zachau Anne C

    2012-09-01

    Full Text Available Abstract Introduction Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder characterized by degeneration of motoneuron cells in anterior spinal horns. There is a need for early and accurate diagnosis with this condition. In this case report we used two complementary methods: scanning electron microscopy and fluorescence-activated cell sorting. This is the first report to our knowledge of microparticles in the cerebrospinal fluid of a patient with amyotrophic lateral sclerosis. Case presentation An 80-year-old Swedish man of Caucasian ethnicity presented to our facility with symptoms of amyotrophic lateral sclerosis starting a year before his first hospital examination, such as muscle weakness and twitching in his right hand progressing to arms, body and leg muscles. Electromyography showed classical neurophysiological findings of amyotrophic lateral sclerosis. Routine blood sample results were normal. A lumbar puncture was performed as a routine investigation and his cerebrospinal fluid was normal with regard to cell count and protein levels, and there were no signs of inflammation. However, scanning electron microscopy and fluorescence-activated cell sorting showed pronounced abnormalities compared to healthy controls. Flow cytometry analysis of two fractions of cerebrospinal fluid from our patient with amyotrophic lateral sclerosis was used to measure the specific binding of antibodies to CD42a, CD144 and CD45, and of phosphatidylserine to lactadherin. Our patient displayed over 100 times more phosphatidylserine-positive microparticles and over 400 times more cell-derived microparticles of leukocyte origin in his cerebrospinal fluid compared to healthy control subjects. The first cerebrospinal fluid fraction contained about 50% more microparticles than the second fraction. The scanning electron microscopy filters used with cerebrospinal fluid from our patient were filled with compact aggregates of spherical particles of

  13. Secular Trends of Amyotrophic Lateral Sclerosis: The Piemonte and Valle d'Aosta Register.

    Science.gov (United States)

    Chiò, Adriano; Mora, Gabriele; Moglia, Cristina; Manera, Umberto; Canosa, Antonio; Cammarosano, Stefania; Ilardi, Antonio; Bertuzzo, Davide; Bersano, Enrica; Cugnasco, Paolo; Grassano, Maurizio; Pisano, Fabrizio; Mazzini, Letizia; Calvo, Andrea

    2017-09-01

    This study reports the long-term epidemiologic trends of amyotrophic lateral sclerosis (ALS) based on a prospective register. To examine the 20-year epidemiologic trends of ALS in the Piemonte and Valle d'Aosta regions of Italy. The Piemonte and Valle d'Aosta Register for ALS (PARALS) is an epidemiologic prospective register that covers 2 Italian regions (population of 4 476 931 inhabitants according to the 2011 census) from January 1, 1995, through December 31, 2014. Case ascertainment is based on multiple sources (neurologic departments, hospital discharge archives, and mortality records). Incidence rates are age and sex standardized for the Italian population of the 2011 census. Age-period-cohort (APC) analysis was performed using a Poisson regression model. The primary study outcomes were long-term incidence and prevalence rates of ALS using a prospective design and their determinants. During the study period, a total of 2702 patients (mean [SD] age at onset, 65.7 [11.1] years; 1246 [46.1%] female and 1456 [53.9%] male) received a diagnosis of ALS between 1995 and 2014, corresponding to a crude annual incidence rate of 3.03 per 100 000 population (95% CI, 2.85-3.23) and an adjusted incidence rate of 2.78 per 100 000 population (95% CI, 2.57-2.96). The age-adjusted incidence rate increased in the 2 decades of the study (1995-2004: 2.66; 95% CI, 2.50-2.83; 2005-2014: 2.89; 95% CI, 2.71-3.07; P = .04), mostly in women. The adjusted rate ratio of men to women decreased from 1.27:1 (1995-2004) to 1.17:1 (2005-2014). The analysis of deviance for the APC regression models indicated that the drift variable is relevant in explaining the variation of ALS incidence rates over time in the overall population (change in deviance, 4.6553; P = .03) and in women (change in deviance, 3.8821; P = .05) but not in men (change in deviance, 0.77215; P = .38). A total of 479 patients with ALS were alive and had not undergone tracheostomy at the prevalence day

  14. Military service, deployments, and exposures in relation to amyotrophic lateral sclerosis etiology.

    Science.gov (United States)

    Beard, John D; Engel, Lawrence S; Richardson, David B; Gammon, Marilie D; Baird, Coleen; Umbach, David M; Allen, Kelli D; Stanwyck, Catherine L; Keller, Jean; Sandler, Dale P; Schmidt, Silke; Kamel, Freya

    2016-05-01

    Factors underlying a possible excess of amyotrophic lateral sclerosis (ALS) among military veterans remain unidentified. Limitations of previous studies on this topic include reliance on ALS mortality as a surrogate for ALS incidence, low statistical power, and sparse information on military-related factors. We evaluated associations between military-related factors and ALS using data from a case-control study of U.S. military veterans. From 2005 to 2010, we identified medical record-confirmed ALS cases via the National Registry of Veterans with ALS and controls via the Veterans Benefits Administration's Beneficiary Identification and Records Locator System database. In total, we enrolled 621 cases and 958 frequency-matched controls in the Genes and Environmental Exposures in Veterans with Amyotrophic Lateral Sclerosis study. We collected information on military service and deployments and 39 related exposures. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We used inverse probability weighting to adjust for potential bias from confounding, missing covariate data, and selection arising from a case group that disproportionately included long-term survivors and a control group that may or may not differ from U.S. military veterans at large. The odds of ALS did not differ for veterans of the Air Force, Army, Marines, and Navy. We found higher odds of ALS for veterans whose longest deployment was World War II or the Korean War and a positive trend with total years of all deployments (OR=1.27; 95% CI: 1.06, 1.52). ALS was positively associated with exposure to herbicides for military purposes, nasopharyngeal radium, personal pesticides, exhaust from heaters or generators, high-intensity radar waves, contaminated food, explosions within one mile, herbicides in the field, mixing and application of burning agents, burning agents in the field, and Agent Orange in the field, with ORs between 1.50 and 7

  15. Onset symptoms in paediatric multiple sclerosis

    DEFF Research Database (Denmark)

    Boesen, Magnus Spangsberg; Sellebjerg, Finn; Blinkenberg, Morten

    2014-01-01

    INTRODUCTION: Paediatric multiple sclerosis (MS) carries a relatively higher mortality and morbidity than adult MS. Paediatric MS symptoms and paraclinical findings at the first demyelinating event have never before been characterised in a Danish setting. The aim of this study was to compare...

  16. Accelerated Cure Project for Multiple Sclerosis

    Science.gov (United States)

    ... questions and enable an era of optimized MS treatment. Read more... The Accelerated Cure Project for MS is a non-profit, 501(c)(3) tax-exempt organization whose mission is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

  17. Myeloproliferative neoplasms in five multiple sclerosis patients

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis

    2013-01-01

    The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007-2012. We describe the patients' history and treatment...

  18. Pharmacologic treatment of depression in multiple sclerosis

    NARCIS (Netherlands)

    Koch, Marcus W.; Glazenborg, Arjon; Uyttenboogaart, Maarten; Mostert, Jop; De Keyser, Jacques

    2011-01-01

    Background Depression is a common problem in patients with multiple sclerosis (MS). It is unclear which pharmacologic treatment is the most effective and the least harmful. Objectives To investigate the efficacy and tolerability of pharmacologic treatments for depression in patients with MS. Search

  19. Hematopoietic stem cell transplantation in multiple sclerosis

    DEFF Research Database (Denmark)

    Rogojan, C; Frederiksen, J L

    2009-01-01

    Intensive immunosuppresion followed by hematopoietic stem cell transplantation (HSCT) has been suggested as potential treatment in severe forms of multiple sclerosis (MS). Since 1995 ca. 400 patients have been treated with HSCT. Stabilization or improvement occurred in almost 70% of cases at least...

  20. Multiple sclerosis: general features and pharmacologic approach

    International Nuclear Information System (INIS)

    Nielsen Lagumersindez, Denis; Martinez Sanchez, Gregorio

    2009-01-01

    Multiple sclerosis is an autoimmune, inflammatory and desmyelinization disease central nervous system (CNS) of unknown etiology and critical evolution. There different etiological hypotheses talking of a close interrelation among predisposing genetic factors and dissimilar environmental factors, able to give raise to autoimmune response at central nervous system level. Hypothesis of autoimmune pathogeny is based on study of experimental models, and findings in biopsies of affected patients by disease. Accumulative data report that the oxidative stress plays a main role in pathogenesis of multiple sclerosis. Oxygen reactive species generated by macrophages has been involved as mediators of demyelinization and of axon damage, in experimental autoimmune encephalomyelitis and strictly in multiple sclerosis. Disease diagnosis is difficult because of there is not a confirmatory unique test. Management of it covers the treatment of acute relapses, disease modification, and symptoms management. These features require an individualized approach, base on evolution of this affection, and tolerability of treatments. In addition to diet, among non-pharmacologic treatments for multiple sclerosis it is recommended physical therapy. Besides, some clinical assays have been performed in which we used natural extracts, nutrition supplements, and other agents with promising results. Pharmacology allowed neurologists with a broad array of proved effectiveness drugs; however, results of research laboratories in past years make probable that therapeutical possibilities increase notably in future. (Author)

  1. The risk of multiple sclerosis in nurses

    DEFF Research Database (Denmark)

    Stenager, Egon; Brønnum-Hansen, Henrik; Koch-Henriksen, Nils

    2003-01-01

    The incidence of multiple sclerosis (MS) in nurses during the period 1980-1996 was calculated in a nationwide study. The cohort consisted of 69,428 nurses, 2185 men and 67,243 women. Sixty (two men and 58 women) with definite MS were observed, whereas 69.3 were expected. We found no significant...

  2. The socioeconomic consequences of multiple sclerosis

    DEFF Research Database (Denmark)

    Jennum, Poul; Wanscher, Benedikte; Frederiksen, Jette

    2012-01-01

    Multiple sclerosis (MS) has serious negative effects on health-, social-, and work-related issues for the patients and their families, thus causing significant socioeconomic burden. The objective of the study was to determine healthcare costs and indirect illness costs in MS patient in a national...

  3. The association between multiple sclerosis and uveitis

    DEFF Research Database (Denmark)

    Olsen, Tine Gadegaard; Frederiksen, Jette

    2016-01-01

    The association between multiple sclerosis (MS) and uveitis has been questioned. Nerve tissue and eye tissue develop from the same embryonic cells; thus, MS and uveitis could be etiologically associated. In published studies, the prevalence of MS in patients with uveitis differe from 0.7% to 30...

  4. Psychiatric co-morbidity in multiple sclerosis

    DEFF Research Database (Denmark)

    Hoang, Huong; Laursen, Bjarne; Stenager, Elsebeth N

    2015-01-01

    BACKGROUND: Studies of depression and anxiety in multiple sclerosis (MS) patients have reported higher rates in MS patients than the general population. OBJECTIVE: To estimate the risk of depression and anxiety and the use of tricyclic antidepressant and selective serotonin reuptake inhibitors...

  5. MYO9B polymorphisms in multiple sclerosis

    DEFF Research Database (Denmark)

    Kemppinen, A.; Suvela, M.; Tienari, P.J.

    2009-01-01

    Single-nucleotide polymorphisms (SNPs) in the 3' region of myosin IXB (MYO9B) gene have recently been reported to associate with different inflammatory or autoimmune diseases. We monitored for the association of MYO9B variants to multiple sclerosis (MS) in four Northern European populations. First...

  6. Antigen-specific therapies in multiple sclerosis

    NARCIS (Netherlands)

    Noort, J.M. van

    1998-01-01

    Multiple sclerosis is the major neurological disease of young adults in the western world, affecting about 1 per 1,000. It is characterised by chronic or recurrent lesions of inflammatory damage in the white matter of the central nervous system. Within such lesions, the protective myelin sheath is

  7. Monoclonal Antibodies for Relapsing Multiple Sclerosis

    DEFF Research Database (Denmark)

    Blinkenberg, Morten; Soelberg Sørensen, Per

    2017-01-01

    Treatment of multiple sclerosis (MS) has improved considerably over the last decade because of new insights into MS pathology and biotechnological advances. This has led to the development of new potent pharmaceutical compounds targeting different processes in the complex autoimmune pathology...... the context of different treatment strategies. Finally, we consider the most important future developments....

  8. Concordance for multiple sclerosis in Danish twins

    DEFF Research Database (Denmark)

    Hansen, T; Skytthe, Axel; Stenager, Egon

    2005-01-01

    The occurrence of multiple sclerosis (MS) in twins has not previously been studied in complete nationwide data sets. The existence of almost complete MS and twin registries in Denmark ensures that essentially unbiased samples of MS cases among twins can be obtained. In this population-based study...

  9. Treating fatigue in multiple sclerosis : Aerobic training

    NARCIS (Netherlands)

    Heine, M

    2016-01-01

    Multiple sclerosis (MS) is considered a chronic and debilitating autoimmune-mediated inflammatory and neurodegenerative disorder of the central nervous system. It is the number one neurological condition in young adults, affecting approximately 17.000 people in the Netherlands. Patients with MS

  10. Lung volume recruitment in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Nadim Srour

    Full Text Available INTRODUCTION: Pulmonary function abnormalities have been described in multiple sclerosis including reductions in forced vital capacity (FVC and cough but the time course of this impairment is unknown. Peak cough flow (PCF is an important parameter for patients with respiratory muscle weakness and a reduced PCF has a direct impact on airway clearance and may therefore increase the risk of respiratory tract infections. Lung volume recruitment is a technique that improves PCF by inflating the lungs to their maximal insufflation capacity. OBJECTIVES: Our goals were to describe the rate of decline of pulmonary function and PCF in patients with multiple sclerosis and describe the use of lung volume recruitment in this population. METHODS: We reviewed all patients with multiple sclerosis referred to a respiratory neuromuscular rehabilitation clinic from February 1999 until December 2010. Lung volume recruitment was attempted in patients with FVC <80% predicted. Regular twice daily lung volume recruitment was prescribed if it resulted in a significant improvement in the laboratory. RESULTS: There were 79 patients included, 35 of whom were seen more than once. A baseline FVC <80% predicted was present in 82% of patients and 80% of patients had a PCF insufficient for airway clearance. There was a significant decline in FVC (122.6 mL/y, 95% CI 54.9-190.3 and PCF (192 mL/s/y, 95% 72-311 over a median follow-up time of 13.4 months. Lung volume recruitment was associated with a slower decline in FVC (p<0.0001 and PCF (p = 0.042. CONCLUSION: Pulmonary function and cough decline significantly over time in selected patients with multiple sclerosis and lung volume recruitment is associated with a slower rate of decline in lung function and peak cough flow. Given design limitations, additional studies are needed to assess the role of lung volume recruitment in patients with multiple sclerosis.

  11. The Danish Multiple Sclerosis Treatment Register

    Directory of Open Access Journals (Sweden)

    Magyari M

    2016-10-01

    Full Text Available Melinda Magyari,1,3 Nils Koch-Henriksen,1,2 Per Soelberg Sørensen3 1Danish Multiple Sclerosis Registry, Department of Neurology, Rigshospitalet, Copenhagen, 2Department of Clinical Epidemiology, Clinical Institute, University of Aarhus, Aarhus, 3Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim of the database: The Danish Multiple Sclerosis Treatment Register (DMSTR serves as a clinical quality register, enabling the health authorities to monitor the quality of the disease-modifying treatment, and it is an important data source for epidemiological research. Study population: The DMSTR includes all patients with multiple sclerosis who had been treated with disease-modifying drugs since 1996. At present, more than 8,400 patients have been registered in this database. Data are continuously entered online into a central database from all sites in Denmark at start and at regular visits. Main variables: Include age, sex, onset year and year of the diagnosis, basic clinical information, and information about treatment, side effects, and relapses. Descriptive data: Notification is done at treatment start, and thereafter at every scheduled clinical visit 3 months after treatment start, and thereafter every 6 months. The longitudinally collected information about the disease activity and side effects made it possible to investigate the clinical efficacy and adverse events of different disease-modifying therapies. Conclusion: The database contributed to a certain harmonization of treatment procedures in Denmark and will continue to be a major factor in terms of quality in clinical praxis, research and monitoring of adverse events, and plays an important role in research. Keywords: multiple sclerosis, epidemiology, immunomodulatory treatment, neutralizing antibodies, observational studies, registry research, disease modifying therapy

  12. [Multiple sclerosis, loss of functionality and gender].

    Science.gov (United States)

    Bravo-González, Félix; Álvarez-Roldán, Arturo

    2017-12-01

    To identify the type of support and assistance that patients with multiple sclerosis need in order to cope with the loss of functionality, and to show how gender affects the perception of these needs. Interpretative-phenomenological qualitative study. Granada (Spain). Year: 2014. Intentional sample: 30 patients and 20 family caregivers. Data were gathered from 26 interviews and 4 focus groups. The data were coded and analysed with the NVivo programme. The multiple sclerosis patients and family caregivers had different perceptions of the loss of capacity to undertake activities of daily living. Being able to self care was considered the last vestige of autonomy. The women with multiple sclerosis tried to take on the responsibility of housework, but the male caregivers became gradually involved in these tasks. Gender roles were redefined with respect to housekeeping. The multiple sclerosis patients showed a need for emotional support. Some of the men had abandoned the stereotype of the strong male as a result of the decline in their health. Adaptations in the home took place without planning them in advance. The use of mobility devices started on an occasional basis. A fear of stigma was an obstacle for regular use of assistive technology. Health care for people with multiple sclerosis should include family caregivers. Gender influences the perception that caregivers and patients have of the assistance they require to maximise their quality of life. This flags up several intervention areas for the follow-up and long-term care of these patients by the healthcare system. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  13. Integrated MRI and [11 C]-PBR28 PET Imaging in Amyotrophic Lateral sclerosis.

    Science.gov (United States)

    Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Reynolds, Beverly; Pijanowski, Olivia; Chonde, Daniel B; Izquierdo Garcia, David; Mainero, Caterina; Catana, Ciprian; Chan, James; Babu, Suma; Paganoni, Sabrina; Hooker, Jacob M; Atassi, Nazem

    2018-05-08

    To characterize [ 11 C]-PBR28 brain uptake using positron emission tomography (PET) in people with amyotrophic lateral sclerosis (ALS), and primary lateral sclerosis (PLS). We have previously shown increased [ 11 C]-PBR28 uptake in the precentral gyrus in a small group of ALS patients. Herein, we confirm our initial finding, study the longitudinal changes, and characterize the gray vs. white matter distribution of [ 11 C]-PBR28 uptake in a larger cohort of patients with ALS and PLS. Eighty-five participants including 53 ALS, 11 PLS and 21 healthy controls underwent integrated [ 11 C]-PBR28 PET-MR brain imaging. Patients were clinically assessed using the upper motor neuron burden (UMNB), and the revised ALS functional rating scale (ALSFRS-R). [ 11 C]-PBR28 uptake was quantified as standardized uptake value ratio (SUVR), and compared between groups. Cortical thickness, and fractional anisotropy were compared between groups and correlated with SUVR and the clinical data. [ 11 C]-PBR28 uptake and ALSFRS-R were compared longitudinally over six-month in ten ALS individuals. Whole brain voxel-wise, surface-based and region of interest analyses revealed increased [ 11 C]-PBR28 uptake in the precentral and paracentral gyri in ALS, and in the sub-cortical white matter for the same regions in PLS, compared to controls. The increase in [ 11 C]-PBR28 uptake co-localized and correlated with cortical thinning, reduced fractional anisotropy, increased mean diffusivity, and correlated with higher UMNB score. No significant changes were detected in [ 11 C]-PBR28 uptake over six-month despite clinical progression. Glial activation measured by in vivo [ 11 C]-PBR28 PET is increased in pathologically relevant regions in people with ALS and correlates with clinical measures. This article is protected by copyright. All rights reserved. © 2018 American Neurological Association.

  14. Rate of familial amyotrophic lateral sclerosis: a systematic review and meta-analysis.

    LENUS (Irish Health Repository)

    Byrne, Susan

    2012-02-01

    BACKGROUND: The population rate of familial amyotrophic lateral sclerosis (FALS) is frequently reported as 10%. However, a systematic review and meta-analysis of the true population based frequency of FALS has never been performed. METHOD: A Medline literature review identified all original articles reporting a rate of FALS. Studies were grouped according to the type of data presented and examined for sources of case ascertainment. A systematic review and meta-analysis of reported rates of FALS was then conducted to facilitate comparison between studies and calculate a pooled rate of FALS. RESULTS: 38 papers reported a rate of FALS. Thirty-three papers were included in analysis and the rate of FALS for all studies was 4.6% (95% CI 3.9% to 5.5%). Restricting the analysis to prospective population based registry data revealed a rate of 5.1% (95% CI 4.1% to 6.1%). The incidence of FALS was lower in southern Europe. There was no correlation between rate of FALS and reported SOD1 mutation rates. CONCLUSION: The rate of FALS among prospective population based registries is 5.1% (CI 4.1 to 6.1%), and not 10% as is often stated. Further detailed prospective population based studies of familial ALS are required to confirm this rate.

  15. Climatic factors associated with amyotrophic lateral sclerosis: a spatial analysis from Taiwan.

    Science.gov (United States)

    Tsai, Ching-Piao; Tzu-Chi Lee, Charles

    2013-11-01

    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 age-standardised 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.

  16. 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.

  17. SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Le Ber, Isabelle; Camuzat, Agnès; Guerreiro, Rita; Bouya-Ahmed, Kawtar; Bras, Jose; Nicolas, Gael; Gabelle, Audrey; Didic, Mira; De Septenville, Anne; Millecamps, Stéphanie; Lenglet, Timothée; Latouche, Morwena; Kabashi, Edor; Campion, Dominique; Hannequin, Didier; Hardy, John; Brice, Alexis

    2013-11-01

    Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget disease of bone and amyotrophic lateral sclerosis (ALS). Recently, SQSTM1 mutations were confirmed in ALS, and mutations were also identified in 3 patients with frontotemporal dementia (FTD), suggesting a role for SQSTM1 in FTD. To evaluate the exact contribution of SQSTM1 to FTD and FTD with ALS (FTD-ALS) in an independent cohort of patients. A SQSTM1 mutation was first identified in a multiplex family with FTD by use of whole-exome sequencing. To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort of patients with FTD or FTD-ALS, with no mutations in known FTD and ALS genes. Primary care or referral center. An overall cohort of 188 French patients, including 132 probands with FTD and 56 probands with FTD-ALS. Frequency of SQSTM1 mutations in patients with FTD or FTD-ALS; description of associated phenotypes. We identified 4 heterozygous missense mutations in 4 unrelated families with FTD; only 1 family had clinical symptoms of Paget disease of bone, and only 1 family had clinical symptoms of FTD-ALS, possibly owing to the low penetrance of some of the clinical manifestations. Although the frequency of the mutations is low in our series (4 of 188 patients [2%]), our results, similar to those already reported, support a direct pathogenic role of p62 in different types of FTD.

  18. Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Kabashi, Edor; Agar, Jeffrey N; Taylor, David M; Minotti, Sandra; Durham, Heather D

    2004-06-01

    Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a familial form of amyotrophic lateral sclerosis (fALS). The present study demonstrated impaired proteasomal function in the lumbar spinal cord of transgenic mice expressing human SOD-1 with the ALS-causing mutation G93A (SOD-1(G93A)) compared to non-transgenic littermates (LM) and SOD-1(WT) transgenic mice. Chymotrypsin-like activity was decreased as early as 45 days of age. By 75 days, chymotrypsin-, trypsin-, and caspase-like activities of the proteasome were impaired, at about 50% of control activity in lumbar spinal cord, but unchanged in thoracic spinal cord and liver. Both total and specific activities of the proteasome were reduced to a similar extent, indicating that a change in proteasome function, rather than a decrease in proteasome levels, had occurred. Similar decreases of total and specific activities of the proteasome were observed in NIH 3T3 cell lines expressing fALS mutants SOD-1(G93A) and SOD-1(G41S), but not in SOD-1(WT) controls. Although overall levels of proteasome were maintained in spinal cord of SOD-1(G93A) transgenic mice, the level of 20S proteasome was substantially reduced in lumbar spinal motor neurons relative to the surrounding neuropil. It is concluded that impairment of the proteasome is an early event and contributes to ALS pathogenesis.

  19. Deciphering spreading mechanisms in amyotrophic lateral sclerosis: clinical evidence and potential molecular processes.

    Science.gov (United States)

    Pradat, Pierre-François; Kabashi, Edor; Desnuelle, Claude

    2015-10-01

    The aim of this review is to refer to recent arguments supporting the existence of specific propagation mechanisms associated with spreading of neuron injury in amyotrophic lateral sclerosis (ALS). Misfolded ALS-linked protein accumulation can induce aggregation of their native equivalent isoforms through a mechanism analogous to the infectious prion proteins initiation and its propagation. Although ALS is clinically heterogeneous, a shared characteristic is the focal onset and the progressive extension to all body regions. Being viewed until now as just summation of the increased number of affected neurons, dispersion is now rather considered as the result of a seeded self-propagating process. A sequential regional spreading pattern is supported by the distribution of TDP-43 aggregates in ALS autopsy cases. Electrophysiology and advanced neuroimaging methods also recently provided some evidence for propagation of lesions both in the brain and spinal cord, more longitudinal studies being still needed. Lesions are supposed to spread cell-to-cell regionally or through connected neuronal pathway. At the molecular level, the prion-like spreading is an emerging mechanism hypothesis, but other machineries such as those that are in charge of dealing with misfolded proteins and secretion of deleterious peptides may be involved in the propagation of neuron loss. Deciphering the mechanisms underlying spreading of ALS symptoms is of crucial importance to better understand this neurodegenerative disease, build new and appropriate animal models and to define novel therapeutic targets.

  20. TARDBP and FUS mutations associated with amyotrophic lateral sclerosis: summary and update.

    Science.gov (United States)

    Lattante, Serena; Rouleau, Guy A; Kabashi, Edor

    2013-06-01

    Mutations in the TAR DNA Binding Protein gene (TARDBP), encoding the protein TDP-43, were identified in amyotrophic lateral sclerosis (ALS) patients. Interestingly, TDP-43 positive inclusion bodies were first discovered in ubiquitin-positive, tau-negative ALS and frontotemporal dementia (FTD) inclusion bodies, and subsequently observed in the majority of neurodegenerative disorders. To date, 47 missense and one truncating mutations have been described in a large number of familial (FALS) and sporadic (SALS) patients. Fused in sarcoma (FUS) was found to be responsible for a previously identified ALS6 locus, being mutated in both FALS and SALS patients. TARDBP and FUS have a structural and functional similarity and most of mutations in both genes are also clustered in the C-terminus of the proteins. The molecular mechanisms through which mutant TDP-43 and FUS may cause motor neuron degeneration are not well understood. Both proteins play an important role in mRNA transport, axonal maintenance, and motor neuron development. Functional characterization of these mutations in in vitro and in vivo systems is helping to better understand how motor neuron degeneration occurs. This report summarizes the biological and clinical relevance of TARDBP and FUS mutations in ALS. All the data reviewed here have been submitted to a database based on the Leiden Open (source) Variation Database (LOVD) and is accessible online at www.lovd.nl/TARDBP, www.lovd.nl/FUS. © 2013 Wiley Periodicals, Inc.