[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.

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

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.

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

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

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

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

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

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

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

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.

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.

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.

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...

Primary lateral sclerosis mimicking atypical parkinsonism

DEFF Research Database (Denmark)

Norlinah, Ibrahim M; Bhatia, Kailash P; Østergaard, Karen

2007-01-01

of the atypical parkinsonian syndromes. Here we describe five patients initially referred with a diagnosis of levodopa-unresponsive atypical parkinsonism (n = 4) or primary progressive multiple sclerosis (n = 1), but subsequently found to have features consistent with PLS instead. Onset age varied from 49 to 67......Primary lateral sclerosis (PLS), the upper motor neurone variant of motor neurone disease, is characterized by progressive spinal or bulbar spasticity with minimal motor weakness. Rarely, PLS may present with clinical features resembling parkinsonism resulting in occasional misdiagnosis as one...... in all patients. Anterior horn cell involvement developed in three cases. Early gait disturbances resulting in falls were seen in all patients and none of them responded to dopaminergic medications. Two patients underwent dopamine transporter (DaT) SPECT scanning with normal results. Other features...

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.

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

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.

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.

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

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.

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.

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.

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...

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

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.

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.

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.

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.

[Non-invasive mechanical ventilation with a facial interface during sedation for a percutaneous endoscopic gastrostomy in a patient with amyotrophic lateral sclerosis].

Science.gov (United States)

González-Frasquet, M C; García-Covisa, N; Vidagany-Espert, L; Herranz-Gordo, A; Llopis-Calatayud, J E

2015-11-01

Amyotrophic lateral sclerosis is a chronic neurodegenerative disease of the central nervous system which affects the motor neurons and produces a progressive muscle weakness, leading to atrophy and muscle paralysis, and ultimately death. Performing a percutaneous endoscopic gastrostomy with sedation in patients with amyotrophic lateral sclerosis can be a challenge for the anesthesiologist. The case is presented of a 76-year-old patient who suffered from advanced stage amyotrophic lateral sclerosis, ASA III, in which a percutaneous endoscopic gastrostomy was performed with deep sedation, for which non-invasive ventilation was used as a respiratory support to prevent hypoventilation and postoperative respiratory complications. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

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).

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.

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

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.

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.

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

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.)

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.

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

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

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.

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.

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

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...

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...

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.)

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.

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.

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.

Predictors of noninvasive ventilation tolerance in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Gruis, K L; Brown, D L; Schoennemann, A; Zebarah, V A; Feldman, E L

2005-12-01

Noninvasive ventilation (NIV) appears to improve survival and quality of life in patients with amyotrophic lateral sclerosis (ALS), but little is known about predictors of NIV tolerance. NIV use was assessed and clinical predictors of tolerance were investigated, using predictive modeling, in ALS patients diagnosed and followed in our clinic until death over a 4-year time period. Patients were prescribed NIV based on current practice parameters when respiratory symptoms were present or forced vital capacity was less than 50%. We prescribed NIV in 52% (72) of patients. For those prescribed NIV, information regarding tolerance was available for 50 patients, with 72% (36) tolerant to its use. Tolerance was six times more likely in limb-onset than bulbar-onset ALS patients, with a trend toward reduced tolerance in those with lower forced vital capacity at NIV initiation. Age, gender, and duration of disease were not predictors of NIV tolerance. We conclude that a majority of ALS patients who are prescribed NIV can successfully become tolerant to its use.

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.

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.

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

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

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

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

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...

Intrinsic Membrane Hyperexcitability of Amyotrophic Lateral Sclerosis Patient-Derived Motor Neurons

Directory of Open Access Journals (Sweden)

Brian J. Wainger

2014-04-01

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease of the motor nervous system. We show using multielectrode array and patch-clamp recordings that hyperexcitability detected by clinical neurophysiological studies of ALS patients is recapitulated in induced pluripotent stem cell-derived motor neurons from ALS patients harboring superoxide dismutase 1 (SOD1, C9orf72, and fused-in-sarcoma mutations. Motor neurons produced from a genetically corrected but otherwise isogenic SOD1+/+ stem cell line do not display the hyperexcitability phenotype. SOD1A4V/+ ALS patient-derived motor neurons have reduced delayed-rectifier potassium current amplitudes relative to control-derived motor neurons, a deficit that may underlie their hyperexcitability. The Kv7 channel activator retigabine both blocks the hyperexcitability and improves motor neuron survival in vitro when tested in SOD1 mutant ALS cases. Therefore, electrophysiological characterization of human stem cell-derived neurons can reveal disease-related mechanisms and identify therapeutic candidates.

[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.

Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population.

Science.gov (United States)

Fournier, Christina N; Murphy, Alyssa; Loci, Lorena; Mitsumoto, Hiroshi; Lomen-Hoerth, Catherine; Kisanuki, Yasushi; Simmons, Zachary; Maragakis, Nicholas J; McVey, April L; Al-Lahham, Tawfiq; Heiman-Patterson, Terry D; Andrews, Jinsy; McDonnell, Erin; Cudkowicz, Merit; Atassi, Nazem

2016-03-01

The goals of this study were to characterize clinical and electrophysiologic findings of subjects with upper motor neuron disease and to explore feasibility of clinical trials in this population. Twenty northeast amyotrophic lateral sclerosis consortium (northeast amyotrophic lateral sclerosis) sites performed chart reviews to identify active clinical pure upper motor neuron disease patients. Patients with hereditary spastic paraplegia or meeting revised El Escorial electrodiagnostic criteria for amyotrophic lateral sclerosis were excluded. Patients were classified into 2 groups according to the presence or absence of minor electromyography (EMG) abnormalities. Two hundred thirty-three subjects with upper motor neuron disease were identified; 217 had available EMG data. Normal EMGs were seen in 140 subjects, and 77 had minor denervation. Mean disease duration was 84 (±80) months for the entire cohort with no difference seen between the 2 groups. No difference was seen in clinical symptoms, disability, or outcome measures between the 2 groups after correcting for multiple comparisons. Minor EMG abnormalities were not associated with phenotypic differences in a clinical upper motor neuron disease population. These findings suggest that subtle EMG abnormalities can not necessarily be used as a prognostic tool in patients with clinical upper motor neuron disease. This study also demonstrates the availability of a large number of patients with upper motor neuron diseases within the northeast amyotrophic lateral sclerosis network and suggests feasibility for conducting clinical trials in this population.

Prospective study on 12 patients of salivary glands radiotherapy as treatment of salivary stasis in patients suffering from amyotrophic lateral sclerosis

International Nuclear Information System (INIS)

Assouline, A.; Delanian, S.; Lenglet, T.; Bruneteau, G.; Le Forestier, N.; Salachas, F.; Lebouteux, M.; Abdelnour, M.; Meininger, V.; Pradat, P.F.

2011-01-01

The authors report a study which aimed at assessing the efficiency and tolerance of salivary gland radiotherapy in patients suffering from amyotrophic lateral sclerosis. Twelve patients have been treated by conformational irradiation after a planning scanography with support mask. Results are discussed in terms of salivary discomfort (almost immediate disappearance in 11 cases), and other minor effects. Although a greater number of patients is still needed, the treatment gives promising results. Short communication

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

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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.

Do patients with amyotrophic lateral sclerosis (ALS) have increased energy needs?

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Vaisman, Nachum; Lusaus, Michal; Nefussy, Beatrice; Niv, Eva; Comaneshter, Doron; Hallack, Ron; Drory, Vivian E

2009-04-15

Nutritional status is a prognostic factor for survival in amyotrophic lateral sclerosis (ALS) patients. We investigated the contribution of some of the components contributing to resting energy expenditure (REE) in order to determine whether potentially higher energy needs should be considered for these patients. Thirty three ALS patients and 33 age- and gender-matched healthy controls participated. REE was measured by an open-circuit indirect calorimeter, body composition by dual energy X-ray absorptiometry, and estimated caloric intake by 7-day food records. Patients had lower body mass indices and lower lean body mass (LBM) than healthy controls. REE values (as a percentage of predicted) was similar but increased when normalized by LBM (Plater. A model for predicting measured REE was constructed based on the different components, with 86% prediction of its variability. ALS is associated with increased REE. Various factors, such as poor caloric intake and mechanical ventilation, may mask this tendency. All the above parameters need to be considered during nutritional intervention to prevent additional muscle loss.

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

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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.

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

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Mariela Bettini

2011-12-01

Full Text Available Sporadic amyotrophic lateral sclerosis (sALS is considered a multifactorial disease with genetic and environmental factors causing motor neuron degeneration. OBJECTIVE: To describe the epidemiological and occupational characteristics of patients with sALS who attended the Ramos Mejía Hospital at Buenos Aires, Argentina. METHOD: We analyzed the medical records of sALS patients diagnosed between 2001 and 2008. All occupations were coded according to the International Standard Classification of Occupation (ISCO. RESULTS: 187 patients were assessed, 38.5% were women and 61.5% men. Mean age at diagnosis was 55 years. 16% of them came from rural areas; 68% of the studied population had no health insurance. 40% were employed in elementary occupations, 19 were technicians and 8 handicraftsmen. CONCLUSION: The most represented profession was elementary occupation. A large proportion of patients came from rural areas, which might suggest an increased risk of environmental exposure to an unknown agent in those regions.

Participation restrictions in ambulatory amyotrophic lateral sclerosis patients: Physical and psychological factors.

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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.

What influences patient decision-making in amyotrophic lateral sclerosis multidisciplinary care? A study of patient perspectives

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Hogden A

2012-11-01

Full Text Available Anne Hogden,1 David Greenfield,1 Peter Nugus,1 Matthew C Kiernan21Centre for Clinical Governance Research, Australian Institute of Health Innovation, University of New South Wales, 2Prince of Wales Clinical School, University of New South Wales, and Neuroscience Research Australia, Sydney, New South Wales, AustraliaBackground: Patients with amyotrophic lateral sclerosis (ALS are required to make decisions concerning quality of life and symptom management over the course of their disease. Clinicians perceive that patients’ ability to engage in timely decision-making is extremely challenging. However, we lack patient perspectives on this issue. This study aimed to explore patient experiences of ALS, and to identify factors influencing their decision-making in the specialized multidisciplinary care of ALS.Methods: An exploratory study was conducted. Fourteen patients from two specialized ALS multidisciplinary clinics participated in semistructured interviews that were audio recorded and transcribed. Data were analyzed for emergent themes.Results: Decision-making was influenced by three levels of factors, ie, structural, interactional, and personal. The structural factor was the decision-making environment of specialized multidisciplinary ALS clinics, which supported decision-making by providing patients with disease-specific information and specialized care planning. Interactional factors were the patient experiences of ALS, including patients’ reaction to the diagnosis, response to deterioration, and engagement with the multidisciplinary ALS team. Personal factors were patients’ personal philosophies, including their outlook on life, perceptions of control, and planning for the future. Patient approaches to decision-making reflected a focus on the present, rather than anticipating future progression of the disease and potential care needs.Conclusion: Decision-making for symptom management and quality of life in ALS care is enhanced when the

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

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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.

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

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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.

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)

Value of 18fluorodeoxyglucose-positron-emission tomography in amyotrophic lateral sclerosis: a prospective study.

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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

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...

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

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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.

[Regularities of fixation of brain serum antibodies from patients with lateral amyotrophic sclerosis in rabbit CNS].

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Musaeva, L S; Gannyshkina, I V; Zavalishin, I A; Markova, E D; Ivanova-Smolenskaia, I A

2002-01-01

Kuhns' indirect immunofluorescent test was used to study fixation of serum brain antibodies (Ab) of patients with bulbar, cervicothoracic, lumbosacral lateral amyotropic sclerosis (LAS) on brain sections of rabbits. The disease is characterized by formation of brain Ab complementary to various structures of nervous and glial cells, myelin of fibers from different conducting systems, vessels which exhibit both common and individual antigenic properties. It was found that fixation of antineuronal, antimyelin brain Ab of patients with bulbar, cervicothoracic and lumbosacral LAS in different CNS structures varies.

The Åstrand-Ryhming Test is not a Feasible Measure in Ambulatory Patients with Amyotrophic Lateral Sclerosis.

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van Groenestijn, Annerieke C; Verschuren, Olaf; Schröder, Carin D; van den Berg, Leonard H; Visser-Meily, Johanna M A

2016-11-29

Ambulatory patients with Amyotrophic Lateral Sclerosis (ALS) show a decreased aerobic capacity which may hamper the ability to perform activities of daily living. A standardized measure, however, for assessing aerobic capacity in patients with ALS during the disease course, is lacking. To examine the feasibility of the Åstrand-Ryhming (ÅR) test protocol longitudinally in ambulatory patients with amyotrophic lateral sclerosis (ALS). Seven ambulatory male patients with spinal ALS onset were assessed at baseline and at 4, 7 and 10 months' follow-up. Feasibility of the ÅR test protocol was analysed using percentage of: a) completed ÅR tests; b) achieved steady states; and c) predefined heart rates. Test completion decreased from 7/7 at baseline to 10/21 at follow-up due to ALS-related symptoms as fatigue, muscle weakness and cramps. Steady states and predefined heart rates were achieved in 12/17 and 17/17 of the completed tests, respectively. Overall, the feasibility of the ÅR test protocol declines from 5/7 at baseline to 7/21 at follow-up. The results suggest that changes in aerobic capacity in ambulatory patients with ALS could not be successfully monitored due to a diminished feasibility of the ÅR test protocol.

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.

A cognitive brain-computer interface for patients with amyotrophic lateral sclerosis.

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Hohmann, M R; Fomina, T; Jayaram, V; Widmann, N; Förster, C; Just, J; Synofzik, M; Schölkopf, B; Schöls, L; Grosse-Wentrup, M

2016-01-01

Brain-computer interfaces (BCIs) are often based on the control of sensorimotor processes, yet sensorimotor processes are impaired in patients suffering from amyotrophic lateral sclerosis (ALS). We devised a new paradigm that targets higher-level cognitive processes to transmit information from the user to the BCI. We instructed five ALS patients and twelve healthy subjects to either activate self-referential memories or to focus on a process without mnemonic content while recording a high-density electroencephalogram (EEG). Both tasks are designed to modulate activity in the default mode network (DMN) without involving sensorimotor pathways. We find that the two tasks can be distinguished after only one experimental session from the average of the combined bandpower modulations in the theta- (4-7Hz) and alpha-range (8-13Hz), with an average accuracy of 62.5% and 60.8% for healthy subjects and ALS patients, respectively. The spatial weights of the decoding algorithm show a preference for the parietal area, consistent with modulation of neural activity in primary nodes of the DMN. © 2016 Elsevier B.V. All rights reserved.

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

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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.)

Respiratory therapies for amyotrophic lateral sclerosis: a primer.

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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.

Coping strategies and psychological distress in caregivers of patients with Amyotrophic Lateral Sclerosis (ALS).

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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.

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...

Serum Nogo-A levels are not elevated in amyotrophic lateral sclerosis patients.

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Harel, Noam Y; Cudkowicz, Merit E; Brown, Robert H; Strittmatter, Stephen M

2009-09-01

Improved biomarkers would facilitate the diagnosis and treatment of amyotrophic lateral sclerosis (ALS). Muscle content of the neuritic outgrowth inhibitor Nogo-A is increased in patients with ALS and other denervating conditions. Seeking a less invasive diagnostic method, we sought to determine whether or not Nogo increases in the serum of ALS patients. We developed a dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) protocol to screen serum samples from 172 ALS patients and 172 healthy controls for Nogo-A immunoreactivity. Unexpectedly, there was a trend toward decreased levels of serum Nogo-A in ALS. Mean serum Nogo-A level in ALS patients was 0.71 nM (95% confidence interval (CI) 0.42-1.00), as opposed to 1.15 nM (95% CI 0.72-1.59) in healthy controls. A significantly larger percentage of healthy control sera (11.0% vs 4.7%) displayed markedly elevated levels of Nogo-A. Additional study is required to determine the factors that lead to elevated Nogo-A levels in a subset of both ALS patients and healthy controls.

[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.

Use of sugammadex in a patient with progressive muscular atrophy and in a patient with amyotrophic lateral sclerosis

Science.gov (United States)

Yoo, Jae Hwa; Kim, Soon Im; Park, Sun Young; Jun, Mi Roung; Kim, Yong Eun; Kim, Hyoung June

2017-01-01

Abstract Introduction: We herein present 2 cases involving the combination of rocuronium and sugammadex in patients with motor neuron disease. The patients were a 54-year-old man with progressive muscular atrophy who underwent removal of internal fixators in the arm and leg, and a 66-year-old woman with amyotrophic lateral sclerosis who underwent skin grafting in the left lower leg. General anesthesia was induced with propofol, rocuronium, and remifentanil and maintained with desflurane and remifentanil. At the end of the surgical procedure, we administered sugammadex. Three or 4 minutes after administration of sugammadex, the patients began to breathe spontaneously and were extubated without complications. Conclusion: Sugammadex can be used successfully to reverse neuromuscular blockade in patients with motor neuron disease. PMID:28591053

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 ...

Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.

Science.gov (United States)

Bourke, Stephen C; Tomlinson, Mark; Williams, Tim L; Bullock, Robert E; Shaw, Pamela J; Gibson, G John

2006-02-01

Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured. NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit. In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.

Chromogranin A levels in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Verde, Federico; Steinacker, Petra; Oeckl, Patrick; Weishaupt, Jochen H; Rosenbohm, Angela; Silani, Vincenzo; Ludolph, Albert C; Otto, Markus

2018-07-01

Chromogranin A (CgA) is a protein found in large dense-core vesicles of neuroendocrine cells and neurons and regulating secretion. A relevance to amyotrophic lateral sclerosis (ALS) was suggested as its overexpression accelerates disease onset in model systems and it interacts with mutant forms of SOD1. Recently, increased cerebrospinal fluid (CSF) CgA levels have been reported in ALS patients relative to controls. With the aim of confirming this finding, we measured CgA and phosphorylated neurofilament heavy chain (pNFH), an established ALS biomarker, in the CSF of 32 ALS patients and 32 disease controls. ALS patients had clearly increased pNFH levels (p < 0.0001), while CgA levels were only modestly lower relative to controls (p = 0.0265), with wide value overlap and consequently poor discriminative performance. CgA did not correlate with any disease parameters among ALS patients. Our findings suggest that CgA is not a promising clinical biomarker for ALS. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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

Patient-ventilator asynchrony, leaks and sleep in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Vrijsen, Bart; Testelmans, Dries; Belge, Catharina; Vanpee, Goele; Van Damme, Philip; Buyse, Bertien

2016-01-01

Sleeping with non-invasive ventilation (NIV) in amyotrophic lateral sclerosis appears to be accompanied by a high patient-ventilator asynchrony (PVA) index. This prospective observational cohort study quantifies PVA and leaks, and searches for effects of these events on sleep after polysomnographic NIV titration. Full-video polysomnography, with incorporation of transcutaneous carbon dioxide and ventilator software, was used to analyse sleep epoch-by-epoch and respiratory events and PVA breath-by-breath in 35 patients (17 non-bulbar). After diagnostic polysomnography, NIV was titrated during three consecutive nights. Sleep, PVA and leaks were evaluated at discharge and after one month. Results showed that non-bulbar patients improved in sleep architecture and oxygen and carbon dioxide levels while bulbar patients only improved oxygen saturation. PVA remained present at discharge (non-bulbar 54 (21-101) and bulbar 31 (9-39)/h sleep) and one month (non-bulbar 31 (9-39) and bulbar 32 (17-55)/h sleep), with ineffective effort as most prominent asynchrony. Leaks also persisted after titration (non-bulbar 16.6 (3.1-44.6) and bulbar 5.1 (0.0-19.5)% of total sleep time (TST)) and one month (non-bulbar 7.7 (1.4-29.3) and bulbar 12.7 (0.0-35.2)% TST). PVA and leaks have none to minor effect on sleep architecture. In conclusion, although PVA and leaks remain present after meticulous NIV titration, these events seem not to interfere with sleep.

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.

Performance predictors of brain-computer interfaces in patients with amyotrophic lateral sclerosis

Science.gov (United States)

Geronimo, A.; Simmons, Z.; Schiff, S. J.

2016-04-01

Objective. Patients with amyotrophic lateral sclerosis (ALS) may benefit from brain-computer interfaces (BCI), but the utility of such devices likely will have to account for the functional, cognitive, and behavioral heterogeneity of this neurodegenerative disorder. Approach. In this study, a heterogeneous group of patients with ALS participated in a study on BCI based on the P300 event related potential and motor-imagery. Results. The presence of cognitive impairment in these patients significantly reduced the quality of the control signals required to use these communication systems, subsequently impairing performance, regardless of progression of physical symptoms. Loss in performance among the cognitively impaired was accompanied by a decrease in the signal-to-noise ratio of task-relevant EEG band power. There was also evidence that behavioral dysfunction negatively affects P300 speller performance. Finally, older participants achieved better performance on the P300 system than the motor-imagery system, indicating a preference of BCI paradigm with age. Significance. These findings highlight the importance of considering the heterogeneity of disease when designing BCI augmentative and alternative communication devices for clinical applications.

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

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

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

Science.gov (United States)

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

2016-12-01

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. Arterial blood gasses were assessed next to QOL by generic as well as disease-specific questionnaires. 77 patients started NIV: 30 with ALS and 47 without. Both groups showed significant improvements in blood gasses after 2 and 6 months. Compared to the non-ALS group, the ALS group had significantly worse scores after 6 months in MRF-28, SRI, HADS and SF-36 than the non-ALS group. This study shows that NIV improves gas exchange, both in patients with and without ALS. QOL improves markedly more in patients without ALS than in those with ALS, in whom only some domains improve. Our observation of little or no effect in ALS patients warrants a large study limited to ALS patients only.

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.

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

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.

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

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 ...

Factors predicting survival in amyotrophic lateral sclerosis patients on non-invasive ventilation.

Science.gov (United States)

Gonzalez Calzada, Nuria; Prats Soro, Enric; Mateu Gomez, Lluis; Giro Bulta, Esther; Cordoba Izquierdo, Ana; Povedano Panades, Monica; Dorca Sargatal, Jordi; Farrero Muñoz, Eva

2016-01-01

Non invasive ventilation (NIV) improves quality of life and extends survival in amyotrophic lateral sclerosis (ALS) patients. However, few data exist about the factors related to survival. We intended to assess the predictive factors that influence survival in patients after NIV initiation. Patients who started NIV from 2000 to 2014 and were tolerant (compliance ≥ 4 hours) were included; demographic, disease related and respiratory variables at NIV initiation were analysed. Statistical analysis was performed using the Kaplan-Meier test and Cox proportional hazard models. 213 patients were included with median survival from NIV initiation of 13.5 months. In univariate analysis, the identified risk factors for mortality were severity of bulbar involvement (HR 2), Forced Vital Capacity (FVC) % (HR 0.99) and ALSFRS-R (HR 0.97). Multivariate analysis showed that bulbar involvement (HR 1.92) and ALSFRS-R (HR 0.97) were independent predictive factors of survival in patients on NIV. In our study, the two prognostic factors in ALS patients following NIV were the severity of bulbar involvement and ALSFRS-R at the time on NIV initiation. A better assessment of bulbar involvement, including evaluation of the upper airway, and a careful titration on NIV are necessary to optimize treatment efficacy.

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...

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

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.)

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...

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.

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic lateral sclerosis (LiCALS) [Eudract number: 2008-006891-31].

Science.gov (United States)

Al-Chalabi, Ammar; Shaw, Pamela J; Young, Carolyn A; Morrison, Karen E; Murphy, Caroline; Thornhill, Marie; Kelly, Joanna; Steen, I Nicholas; Leigh, P Nigel

2011-09-21

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival) at the end of the study (15 months from entry), compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3) at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L), plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network). 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D), and the Hospital Anxiety and Depression Scale.Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive), vital capacity ≥ 60% of predicted within 1 month prior to

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS [Eudract number: 2008-006891-31

Directory of Open Access Journals (Sweden)

Kelly Joanna

2011-09-01

Full Text Available Abstract Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, no patients had died (i.e., 100% survival at the end of the study (15 months from entry, compared to 71% surviving in the riluzole-only group. Although the trial can be criticised on several grounds, there is a substantial rationale from other laboratory studies that lithium is worth investigating therapeutically in amyotrophic lateral sclerosis. Methods/Design LiCALS is a multi-centre double-blind randomised parallel group controlled trial of the efficacy, safety, and tolerability of lithium carbonate (LiCO3 at doses to achieve stable 'therapeutic' plasma levels (0.4-0.8 mmol/L, plus standard treatment, versus matched placebo plus standard treatment, in patients with amyotrophic lateral sclerosis. The study will be based in the UK, in partnership with the MND Association and DeNDRoN (the Dementias and Neurodegnerative Diseases Clinical Research Network. 220 patients will be recruited. All patients will be on the standard treatment for ALS of riluzole 100 mg daily. The primary outcome measure will be death from any cause at 18 months defined from the date of randomisation. Secondary outcome measures will be changes in three functional rating scales, the ALS Functional Rating Scale-Revised, The EuroQOL (EQ-5D, and the Hospital Anxiety and Depression Scale. Eligible patients will have El Escorial Possible, Laboratory-supported Probable, Probable or Definite amyotrophic lateral sclerosis with disease duration between 6 months and 36 months (inclusive, vital

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,

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

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...

[Health-related quality of life in patients with amyotrophic lateral sclerosis].

Science.gov (United States)

Sánchez-López, C R; Perestelo-Pérez, L; Ramos-Pérez, C; López-Bastida, J; Serrano-Aguilar, P

2014-01-01

Progressive deterioration in patients with amyotrophic lateral sclerosis (ALS) has a major impact on their health-related quality of life (HRQOL). The objectives of this study are to evaluate HRQOL in a sample of patients diagnosed with ALS and estimate the predictive capability of a set of sociodemographic variables for the different scales covered by a general health survey. A total of 63 patients diagnosed with ALS were assessed using a sociodemographic questionnaire and the SF-36 general health survey. The sociodemographic variables studied were sex, age, presence of a caregiver, employment status, and time from diagnosis of disease. The SF-36 survey shows positive correlations between the different scales composing it, which proves its reliability. The mean scores obtained for each of the SF-36 scales were higher in men than in women, although the only statistically significant difference was for the Physical Role scale. The lowest age range (less than 56 years) presented the highest mean scores for most of these dimensions. Most of the variance in the test is explained by the variable 'presence of caregiver'. The SF-36 health survey has been confirmed as a valid and useful tool for evaluating HRQOL in ALS patients, and it discriminates between patients in different states of health according to their level of dependency. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

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

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.

Dysgraphia in Patients with Primary Lateral Sclerosis: A Speech-Based Rehearsal Deficit?

Science.gov (United States)

Zago, S.; Poletti, B.; Corbo, M.; Adobbati, L.; Silani, V.

2008-01-01

The present study aims to demonstrate that errors when writing are more common than expected in patients affected by primary lateral sclerosis (PLS) with severe dysarthria or complete mutism, independent of spasticity. Sixteen patients meeting Pringle’s et al. [34] criteria for PLS underwent standard neuropsychological tasks and evaluation of writing. We assessed writing abilities in spelling through dictation in which a set of words, non-words and short phrases were presented orally and by composing words using a set of preformed letters. Finally, a written copying task was performed with the same words. Relative to controls, PLS patients made a greater number of spelling errors in all writing conditions, but not in copy task. The error types included: omissions, transpositions, insertions and letter substitutions. These were equally distributed on the writing task and the composition of words with a set of preformed letters. This pattern of performance is consistent with a spelling impairment. The results are consistent with the concept that written production is critically dependent on the subvocal articulatory mechanism of rehearsal, perhaps at the level of retaining the sequence of graphemes in a graphemic buffer. In PLS patients a disturbance in rehearsal opportunity may affect the correct sequencing/assembly of an orthographic representation in the written process. PMID:19096141

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.)

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 ...

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

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 ...

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: A cross-sectional study

NARCIS (Netherlands)

E. Majounie (Elisa); A. Renton (Alan); K. Mok (Kin); E.G.P. Dopper (Elise); A. Waite (Adrian); S. Rollinson (Sara); A. Chiò (Adriano); G. Restagno (Gabriella); N. Nicolaou (Nayia); J. Simón-Sánchez (Javier); J.C. van Swieten (John); Y. Abramzon (Yevgeniya); J. Johnson (Janel); M. Sendtner (Michael); R. Pamphlett (Roger); R. Orrell (Richard); S. Mead (Simon); K.C. Sidle (Katie); H. Houlden (Henry); J.D. Rohrer (Jonathan Daniel); K.E. Morrison (Karen); H. Pall (Hardev); D. Talbot; O. Ansorge (Olaf); D.G. Hernandez (Dena); S. Arepalli (Sampath); M. Sabatelli (Mario); G. Mora (Gabriele); J.C. Corbo (Joseph); F. Giannini (Fabio); A. Calvo (Andrea); E. Englund (Elisabet); G. Borghero (Giuseppe); O.A.M. Floris; A. Remes (Anne); H. Laaksovirta (Hannu); L. McCluskey (Leo); J.Q. Trojanowski (John); V.M. Deerlin (Vivianna); G.D. Schellenberg (Gerard); M.A. Nalls (Michael); V.E. Drory (Vivian E); C.S. Lu (Chin-Song); T.-H. Yeh (Tu-Hsueh); H. Ishiura (Hiroyuki); Y. Takahashi (Yukari); S. Tsuji (Shoji); I. Le Ber (Isabelle); A. Brice; C. Drepper (Carsten); N. Williams (Nigel); J. Kirby (Janine); P.J. Shaw (Pamela); J. Hardy (John); P.J. Tienari (Pentti); P. Heutink (Peter); H. Morris (Huw); S. Pickering-Brown (Stuart); B.J. Traynor (Bryan)

2012-01-01

textabstractBackground: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods: We screened 4448 patients diagnosed with

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

[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.

“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

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

Sleep and Fasciculations in Amyothropic Lateral Sclerosis

Czech Academy of Sciences Publication Activity Database

Šonka, K.; Fiksa, J.; Horváth, E.; Kemlink, D.; Süssová, J.; Böhm, J.; Šebesta, Václav; Volná, J.; Nevšímalová, S.

2004-01-01

Roč. 8, č. 1 (2004), s. 25-30 ISSN 1432-9123 R&D Projects: GA MZd NF5999 Keywords : amyothropic lateral sclerosis ALS * fasciculation * fragmentary myoclonus * periodic leg movements in sleep PLMS * polysomnography PSG * electromyography EMG * REM sleep Subject RIV: BD - Theory of Information

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.

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.

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.

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

Science.gov (United States)

Okada, Masamitsu; Yamashita, Satoshi; Ueyama, Hidetsugu; Ishizaki, Masatoshi; Maeda, Yasushi; Ando, Yukio

2018-06-01

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. 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. 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. 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.

Altered cortical activation during action observation in amyotrophic lateral sclerosis patients: a parametric functional MRI study

Energy Technology Data Exchange (ETDEWEB)

Li, Haiqing; Li, Yuxin; Yin, Bo; Tang, Weijun; Yu, Xiangrong; Geng, Daoying [Huashan Hospital, Department of Radiology, Fudan University, Shanghai (China); Chen, Yan [Fudan University, Department of Neurology, Huashan Hospital, Shanghai (China); Huang, Weiyuan [People' s Hospital of Hainan Province, Department of Radiology, Haikou, Hainan Province (China); Zhang, Biyun [Nanjing University of Traditional Chinese Medicine, Department of radiotherapy, Affiliated Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

2015-09-15

To investigate functional cerebral abnormalities in patients with amyotrophic lateral sclerosis (ALS) using functional magnetic resonance imaging (fMRI) during action observation. Thirty patients with ALS and 30 matched healthy controls underwent fMRI with an experimental paradigm while observing a video of repetitive flexion-extension of the fingers at three frequency levels or three complexity levels, alternated with periods of a static hand. A parametric analysis was applied to determine the effects of each of the two factors. Action observation activated similar neural networks as the research on execution of action in the ALS patients and healthy subjects in several brain regions related to the mirror-neuron system (MNS). In the ALS patients, in particular, the dorsal lateral premotor cortex (dPMC), inferior parietal gyrus (IPG), and SMA, were more activated compared with the activation in the controls. Increased activation within the primary motor cortex (M1), dPMC, inferior frontal gyrus (IFG), and superior parietal gyrus (SPG) mainly correlated with hand movement frequency/complexity in the videos in the patients compared with controls. The findings indicated an ongoing compensatory process occurring within the higher order motor-processing system of ALS patients, likely to overcome the loss of function. (orig.)

Altered cortical activation during action observation in amyotrophic lateral sclerosis patients: a parametric functional MRI study

International Nuclear Information System (INIS)

Li, Haiqing; Li, Yuxin; Yin, Bo; Tang, Weijun; Yu, Xiangrong; Geng, Daoying; Chen, Yan; Huang, Weiyuan; Zhang, Biyun

2015-01-01

To investigate functional cerebral abnormalities in patients with amyotrophic lateral sclerosis (ALS) using functional magnetic resonance imaging (fMRI) during action observation. Thirty patients with ALS and 30 matched healthy controls underwent fMRI with an experimental paradigm while observing a video of repetitive flexion-extension of the fingers at three frequency levels or three complexity levels, alternated with periods of a static hand. A parametric analysis was applied to determine the effects of each of the two factors. Action observation activated similar neural networks as the research on execution of action in the ALS patients and healthy subjects in several brain regions related to the mirror-neuron system (MNS). In the ALS patients, in particular, the dorsal lateral premotor cortex (dPMC), inferior parietal gyrus (IPG), and SMA, were more activated compared with the activation in the controls. Increased activation within the primary motor cortex (M1), dPMC, inferior frontal gyrus (IFG), and superior parietal gyrus (SPG) mainly correlated with hand movement frequency/complexity in the videos in the patients compared with controls. The findings indicated an ongoing compensatory process occurring within the higher order motor-processing system of ALS patients, likely to overcome the loss of function. (orig.)

Effects of non-invasive ventilation and posture on chest wall volumes and motion in patients with amyotrophic lateral sclerosis: a case series

OpenAIRE

Magalh?es, Cristiana M.; Fregonezi, Guilherme A.; Vidigal-Lopes, Mauro; Vieira, Bruna S. P. P.; Vieira, Danielle S. R.; Parreira, Ver?nica F.

2016-01-01

ABSTRACT Background The effects of non-invasive ventilation (NIV) on the breathing pattern and thoracoabdominal motion of patients with amyotrophic lateral sclerosis (ALS) are unknown. Objectives 1) To analyze the influence of NIV on chest wall volumes and motion assessed by optoelectronic plethysmography in ALS patients and 2) to compare these parameters in the supine and sitting positions to those of healthy individuals (without NIV). Method Nine ALS patients were evaluated in the supine...

Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

NARCIS (Netherlands)

Majounie, E.; Renton, A.E.; Mok, K.; Dopper, E.G.P.; Waite, A.; Rollinson, S.; Chio, A.; Restagno, G.; Nicolaou, N.; Simon-Sanchez, J.; van Swieten, J.C.; Abramzon, Y.; Johnson, J.O.; Sendtner, M.; Pamphlett, R.; Orrell, R.W.; Mead, S.; Sidle, K.C.; Houlden, H.; Rohrer, J.D.; Morrison, K.E.; Pall, H.; Talbot, K.; Ansorge, O.; Hernandez, D.G.; Arepalli, S.; Sabatelli, M.; Mora, G.; Corbo, M.; Giannini, F.; Calvo, A.; Englund, E.; Borghero, G.; Foris, G.L.; Remes, A.M.; Laaksovirta, H.; McCluskey, L.; Trojanowski, J.Q.; Van Deerlin, V.M.; Schellenberg, G.D.; Nalls, M.A.; Drory, V.E.; Lu, C.S.; Yeh, T.H.; Ishiura, H.; Takahashi, Y.; Tsuji, S.; Le Ber, I.; Brice, A.; Drepper, C.; Williams, N.; Kirby, J.; Shaw, P.; Hardy, J.; Tienari, P.J.; Heutink, P.; Morris, H.R.; Pickering-Brown, S.; Traynor, B.J.

2012-01-01

Background: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods: We screened 4448 patients diagnosed with ALS (El

Physician perceptions about living organ donation in patients with Amyotrophic Lateral Sclerosis.

Science.gov (United States)

Ansari, S; Bromberg, M B; Gibson, S B

2017-09-01

Patients with Amyotrophic Lateral Sclerosis (ALS) have expressed desire to become living organ donors but are unable to do so with current organ donation policies. Our objective is to assess ALS patient's interest in organ donation, and perceived concerns of this practice by ALS neurologists. An electronic survey was administered to ALS neurologists across the United States regarding living organ donation in ALS patients prior to respiratory failure. 52 complete responses were received from 121 invites. 67% (35/52) of neurologists expressed no concerns about living organ donation in ALS patients, and 33% had concerns. The concerns related to respiratory failure, anesthesia exposure and renal dysfunction. With their concerns addressed, 71% of neurologists reported that they would endorse living organ donation. 49% of neurologists reported being asked by a patient for information regarding living organ donation. ALS neurologists felt that 22.8% of ALS patients (median 19%) would be interested in learning more about organ donation, while only 6% of neurologists broach this subject with their patients. Our results indicate that 1 in every 4 ALS patients may be interested in exploring options for living organ donation, and this topic is not routinely addressed by ALS clinics. These results indicate an unexplored area of patient interest. To honor a patient's wishes to donate, the transplant community will have to accommodate living organ donation from terminally ill patients, and address neurologist concerns. Such a practice could benefit two groups of patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

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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.

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

Quality of life in amyotrophic lateral sclerosis patients and caregivers: Impact of assistive communication from early stages.

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Londral, Ana; Pinto, Anabela; Pinto, Susana; Azevedo, Luis; De Carvalho, Mamede

2015-12-01

In this study we performed a longitudinal investigation to assess the impact of early introduction of assistive communication devices (ACDs) on quality of life (QoL) in amyotrophic lateral sclerosis (ALS) patients and their caregivers. Patients were followed for 7-10 months (3 evaluation periods). Bulbar-onset ALS patients (N = 27) and paired caregivers (N = 17) were included. Fifteen randomly selected patients received early support in ACD use. Patients were assessed using the ALS Functional Rating Scale-revised (ALSFRS-R), the McGill QoL (MQoL), the Communication Effectiveness Index (CETI), and performance in writing; and caregivers were assessed with the MQoL and World Health Organization Quality of Life questionnaire (WHOQOL-BREF). Patients with early support had higher MQoL Psychological and MQoL Existential well-being domains; caregivers had higher MQoL Support domain and their MQoL Psychological domain positively associated with patient CETI. Most patients could communicate using a touchscreen keyboard to write, even when handwriting and speech were not possible. Early intervention with an ACD seems to have a positive impact on QoL and gives patients the opportunity to improve skills for communication in later disease stages. © 2015 Wiley Periodicals, Inc.

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

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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)

Respiratory exercise in amyotrophic lateral sclerosis.

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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.

Percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis: Mortality and complications.

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Carbó Perseguer, J; Madejón Seiz, A; Romero Portales, M; Martínez Hernández, J; Mora Pardina, J S; García-Samaniego, J

2018-03-26

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that causes severe dysphagia and weight loss. Percutaneous endoscopic gastrostomy (PEG) is currently the technique of choice for the enteral nutrition of these patients. To analyse mortality and complications in a series of patients diagnosed with ALS who underwent PEG, and to evaluate factors related to patient survival after the procedure. We performed a prospective, observational study including all patients diagnosed with ALS and treated by our hospital's Gastroenterology Department in the period 1997-2013. We studied mortality, complications, and clinical and biochemical parameters, and correlated these with the survival rate. The study included a total of 57 patients, of whom 49 were ultimately treated with PEG. ALS onset was bulbar in 30 patients and spinal in 19. Mortality during the procedure and at 30 days was 2% (n = 1). Six patients (12.2%) experienced major complications; 17 (34.7%) experienced less serious complications which were easily resolved with conservative treatment. No significant differences were observed in forced vital capacity, albumin level, or age between patients with (n = 6) and without (n = 43) major complications. PEG is an effective, relatively safe procedure for the enteral nutrition of patients with ALS, although not without morbidity and mortality. Neither forced vital capacity nor the form of presentation of ALS were associated with morbidity in PEG. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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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.

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...

Safety and efficacy of rasagiline as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomised, double-blind, parallel-group, placebo-controlled, phase 2 trial.

Science.gov (United States)

Ludolph, Albert C; Schuster, Joachim; Dorst, Johannes; Dupuis, Luc; Dreyhaupt, Jens; Weishaupt, Jochen H; Kassubek, Jan; Weiland, Ulrike; Petri, Susanne; Meyer, Thomas; Grosskreutz, Julian; Schrank, Berthold; Boentert, Matthias; Emmer, Alexander; Hermann, Andreas; Zeller, Daniel; Prudlo, Johannes; Winkler, Andrea S; Grehl, Torsten; Heneka, Michael T; Wollebæk Johannesen, Siw; Göricke, Bettina

2018-06-18

Rasagiline, a monoamine oxidase B inhibitor with neuroprotective potential in Parkinson's disease, has shown a disease-modifying effect in the SOD1-Gly93Ala low-expressing mouse model of amyotrophic lateral sclerosis, both alone and in combination with riluzole. We sought to test whether or not rasagiline 1 mg/day can prolong survival in patients with amyotrophic lateral sclerosis also receiving riluzole. Patients with possible, probable, or definite amyotrophic lateral sclerosis were enrolled to our randomised, placebo-controlled, parallel-group, double-blind, phase 2 trial from 15 German network for motor neuron diseases (MND-NET) centres (university hospitals or clinics). Eligible patients were aged at least 18 years, had onset of progressive weakness within the 36 months before the study, had disease duration of more than 6 months and less than 3 years, and had a best-sitting slow vital capacity of at least 50%. After a 4-week screening period, eligible patients were randomly assigned (1:1) to receive either rasagiline (1 mg/day) or placebo in addition to riluzole (100 mg/day), after stratification for site of onset (bulbar or spinal) and study centre. Patients and all personnel assessing outcome parameters were masked to treatment allocation. Patients were followed up 2, 6, 12, and 18 months after randomisation. The primary endpoint was survival time, defined as the time to death or time to study cutoff date (ie, the last patient's last visit plus 14 days). Analyses of primary outcome and safety measures were done in all patients who received at least one dose of trial treatment (intention-to-treat population). The trial is registered with ClinicalTrials.gov, number NCT01879241. Between July 2, 2013, and Nov 11, 2014, 273 patients were screened for eligibility, and 252 patients were randomly assigned to receive rasagiline (n=127) or placebo (n=125). 126 patients taking rasagiline and 125 taking placebo were included in the intention-to-treat analysis. For the

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

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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.

Amyotrophic lateral sclerosis: update and new developments

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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

Evidence of social understanding impairment in patients with amyotrophic lateral sclerosis.

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Marco Cavallo

Full Text Available The present study aims at clarifying the nature of the Theory of Mind (ToM deficits associated with Amyotrophic Lateral Sclerosis (ALS. ToM is the ability to attribute mental states such as intentions and beliefs to others in order to understand and predict their behaviour and to behave accordingly. Several neuroimaging studies reported the prefrontal cortices as the brain region underlying a key ToM ability, i.e. the comprehension of social intentions. Dysfunction of the prefrontal cortices in patients with ALS has been indicated by a range of neuroimaging studies. The frontal syndrome that appears to characterize up to 50% of ALS has been noted to be similar to the profile that characterizes patients with frontotemporal dementia (FTD, a neurodegenerative condition characterised by ToM deficits. In the present paper, we hypothesize that the performance of patients with ALS is significantly worse than healthy controls' performance on tasks requiring the comprehension of social contexts, whereas patients' performance is comparable to healthy controls' performance on tasks not requiring the comprehension of social contexts. To this end, we tested 15 patients with ALS with an experimental protocol that distinguishes between private (non-social intentions and social intentions. The pattern of results followed the experimental hypothesis: the performance of patients with ALS and healthy controls significantly differed on the comprehension of social context only, with an impairment in patients with ALS. Single case analysis confirmed the findings at an individual level. The present study is the first which has examined and compared the understanding of social and non-social contexts in patients with ALS and shown a specific and selective deficit in the former only. The current findings further support the notion of a continuum of cognitive dysfunction ranging from ALS to FTD, with parallel cognitive profiles in both disorders.

Evidence of social understanding impairment in patients with amyotrophic lateral sclerosis.

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Cavallo, Marco; Adenzato, Mauro; Macpherson, Sarah E; Karwig, Gillian; Enrici, Ivan; Abrahams, Sharon

2011-01-01

The present study aims at clarifying the nature of the Theory of Mind (ToM) deficits associated with Amyotrophic Lateral Sclerosis (ALS). ToM is the ability to attribute mental states such as intentions and beliefs to others in order to understand and predict their behaviour and to behave accordingly. Several neuroimaging studies reported the prefrontal cortices as the brain region underlying a key ToM ability, i.e. the comprehension of social intentions. Dysfunction of the prefrontal cortices in patients with ALS has been indicated by a range of neuroimaging studies. The frontal syndrome that appears to characterize up to 50% of ALS has been noted to be similar to the profile that characterizes patients with frontotemporal dementia (FTD), a neurodegenerative condition characterised by ToM deficits. In the present paper, we hypothesize that the performance of patients with ALS is significantly worse than healthy controls' performance on tasks requiring the comprehension of social contexts, whereas patients' performance is comparable to healthy controls' performance on tasks not requiring the comprehension of social contexts. To this end, we tested 15 patients with ALS with an experimental protocol that distinguishes between private (non-social) intentions and social intentions. The pattern of results followed the experimental hypothesis: the performance of patients with ALS and healthy controls significantly differed on the comprehension of social context only, with an impairment in patients with ALS. Single case analysis confirmed the findings at an individual level. The present study is the first which has examined and compared the understanding of social and non-social contexts in patients with ALS and shown a specific and selective deficit in the former only. The current findings further support the notion of a continuum of cognitive dysfunction ranging from ALS to FTD, with parallel cognitive profiles in both disorders.

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...

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...

The Balloon-Based Manometry Evaluation of Swallowing in Patients with Amyotrophic Lateral Sclerosis

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Jerzy Tomik

2017-03-01

Full Text Available The aim of the study was to analyse the disturbances of the oro-pharyngeal swallowing phase of dysphagia in amyotrophic lateral sclerosis (ALS patients with the use of specific manometric measurements and to evaluate their plausible association with the duration of the disease. Seventeen patients with ALS were evaluated with manometric examinations of the oral and pharyngeal part of the gastrointestinal tract. Tests were carried out by using the oesophageal balloon-based method with four balloon transducers located 5 cm away from each other. The following manometric parameters were analysed: the base of tongue contraction (BTC and the upper oesophageal sphincter pressure (UESP, and the hypopharyngeal suction pump (HSP as well as the oro-pharyngeal, pharyngeal and hypopharyngeal transit time and average pharyngeal bolus velocity (oropharyngeal transit time (OTT, pharyngeal transit time (PTT, hypopharyngeal transit time (HTT and average pharyngeal bolus velocity (APBV, respectively. Manomatric examinations during swallowing in patients with ALS showed significant weakness of BTC, a decrease of HSP and a decrease of the velocity of bolus transit inside the pharynx which were particularly marked between the first and the third examination. Manometric examinations of the oro-pharyngeal part of the gastrointestinal tract are useful and supportive methods in the analysis of swallowing disturbances in ALS patients.

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

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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.

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

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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.

Ultrasound assessment of diaphragmatic function in patients with amyotrophic lateral sclerosis.

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Fantini, Riccardo; Mandrioli, Jessica; Zona, Stefano; Antenora, Federico; Iattoni, Andrea; Monelli, Marco; Fini, Nicola; Tonelli, Roberto; Clini, Enrico; Marchioni, Alessandro

2016-07-01

Evaluation of diaphragm function in Amyotrophic Lateral Sclerosis (ALS) is critical in determining when to commence non-invasive mechanical ventilation (NIV). Currently, forced vital capacity (FVC) and sniff nasal inspiratory pressure (SNIP) are volitional measures for this evaluation, but require collaboration and are poorly specific. The primary aim of this study was to assess whether diaphragmatic thickness measured by ultrasound (US) correlates with lung function impairment in ALS patients. The secondary aim was then to compare US diaphragm thickness index (ΔTdi) with a new parameter (ΔTmax index). 41 patients with ALS and 30 healthy subjects were enrolled in the study. All subjects underwent spirometry, SNIP and diaphragm US evaluation, while arterial blood gases were measured in some patients only. US assessed diaphragm thickness (Tdi) at tidal volume (Vt) or total lung capacity (TLC), and their ratio (ΔTmax) were recorded. Changes (Δ) in Tdi indices during tidal volume (ΔTdiVt) and maximal inspiration (ΔTdiTLC) were also assessed. ΔTdiTLC (p <0.001) and ΔTmax (p = 0.007), but not ΔTdiVt, differed between patients and controls. Significant correlation (p < 0.05) was found between ΔTdiTLC, ΔTmax and FVC. The ROC curve analysis for comparison of individual testing showed better accuracy with Δtmax than with ΔtdiTLC for FVC (AUC 0.76 and 0.27) and SNIP (AUC 0.71 and 0.25). Diaphragm thickness assessed by ultrasound significantly correlates with global respiratory alterations in patients with ALS. ΔTmax represents a new US index of early diaphragmatic dysfunction, better related with the routinely performed lung function tests. © 2016 Asian Pacific Society of Respirology.

Application of botulinum toxin to reduce the saliva in patients with amyotrophic lateral sclerosis.

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Manrique, Dayse

2005-01-01

To demonstrate the effect of local application of Botox(R) in patients with amyotrophic lateral sclerosis (ALS), following our 2002 institutional protocol of sialorrhea treatment. Clinical prospective. Five patients with ALS assisted at Clinic of Otolaryngology of AACD (Associação de Assistência à Criança Deficiente). They were all submitted to local application of Botox in salivary glands and followed up for a year. The protocol consisted of clinical questionnaire about the inability of swallowing saliva and its repercussions in quality of life. Patients were submitted to previous odontological treatment, had intolerance to the adverse effects of anti-cholinergic agents and had not used Botox for at least six months. The application was guided by ultrasound and the doses were 30U in one point for submandibular gland, and 20U in two points for each parotid gland, after topic anesthetic with prilocaine. Five patients with ALS with sialorrhea, aged 45 to 59 years, were submitted to Botox salivary glands application. We observed that the symptoms of sialorrhea changed dramatically in four patients. Three patients stayed almost four months without complaints with repercussion in quality of life. No patient presented local or systemic effects with local injection of Botox.

Dysarthria and quality of life in patients with amyotrophic lateral sclerosis

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Lavoisier Leite Neto

Full Text Available ABSTRACT Purpose: to analyze the impact of dysarthria on the quality of life in patients with amyotrophic lateral sclerosis. Methods: the study consisted of 32 subjects, divided into two groups (control group and study group who underwent an initial interview for background information, followed by an evaluation based on the Dysarthria Assessment Protocol and completion of quality of life questionnaire "Living with Dysarthria - (LwD". Exploratory data analysis was collected through mean, median, SD, minimum and maximum measures. A comparison was performed between the studied groups and a correlation was carried out between scores. The significance level adopted was 5%. Results: according to the findings, all sub-items analyzed by the dysarthria assessment protocol were statically significant (p <0.001 when comparing the groups. Regarding quality of life, a moderate positive correlation (p = 0.0008; Spearman's coefficient = 0.75202 was observed between the total score of the two protocols used, indicating that the higher the degree of dysarthria, the worse the Quality of Life (QOL of the subject, according to the parameters evaluated. Conclusion: dysarthria affects all speech parameters herein assessed, in varying degrees, negatively impacting communication and quality of life.

CSF glial markers correlate with survival in amyotrophic lateral sclerosis.

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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.

ILAE type 3 hippocampal sclerosis in patients with anti-GAD-related epilepsy.

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Glover, Robert L; DeNiro, Lauren V; Lasala, Patrick A; Weidenheim, Karen M; Graber, Jerome J; Boro, Alexis

2015-08-01

To describe the neuropathologic findings and clinical course of 2 patients who underwent temporal lobectomy for medically refractive epilepsy and were later found to have high anti-glutamic acid decarboxylase (GAD) concentrations. Small case series. Neuropathologic examination of both patients revealed International League Against Epilepsy (ILAE) type 3 hippocampal sclerosis. Following surgery, both developed signs and symptoms of stiff person syndrome and later cerebellar ataxia. Laboratory studies demonstrated high concentrations of anti-GAD antibodies in both patients. These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD-related neurologic syndrome in some instances.

Accepting or declining non-invasive ventilation or gastrostomy in amyotrophic lateral sclerosis: patients' perspectives.

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Greenaway, L P; Martin, N H; Lawrence, V; Janssen, A; Al-Chalabi, A; Leigh, P N; Goldstein, L H

2015-01-01

The objective was to identify factors associated with decisions made by patients with amyotrophic lateral sclerosis (ALS) to accept or decline non-invasive ventilation (NIV) and/or gastrostomy in a prospective population-based study. Twenty-one people with ALS, recruited from the South-East ALS Register who made an intervention decision during the study timeframe underwent a face-to-face in-depth interview, with or without their informal caregiver present. Sixteen had accepted an intervention (11 accepted gastrostomy, four accepted NIV and one accepted both interventions). Five patients had declined gastrostomy. Thematic analysis revealed three main themes: (1) patient-centric factors (including perceptions of control, acceptance and need, and aspects of fear); (2) external factors (including roles played by healthcare professionals, family, and information provision); and (3) the concept of time (including living in the moment and the notion of 'right thing, right time'). Many aspects of these factors were inter-related. Decision-making processes for the patients were found to be complex and multifaceted and reinforce arguments for individualised (rather than 'algorithm-based') approaches to facilitating decision-making by people with ALS who require palliative interventions.

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

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

Screening UBQLN-2 in French frontotemporal lobar degeneration and frontotemporal lobar degeneration-amyotrophic lateral sclerosis patients.

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Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Pariente, Jérémie; Brice, Alexis; Kabashi, Edor

2013-08-01

The ubiquilin-2 gene (UBQLN-2) is the only amyotrophic lateral sclerosis (ALS)-related gene mapping on the X chromosome. Mutations in the PXX domain of UBQLN-2 have been first described in ALS patients with a mutational frequency of 2.6% in familial ALS cases with no evidence of male-to-male transmission. Different populations have been further tested with mutations largely distributed in the gene and lower frequency of positive cases. To determine the genetic contribution of UBQLN-2 in frontotemporal lobar degeneration (FTLD) and FTLD-ALS, we screened a cohort of 136 French patients, identifying a missense variant (c.1006A>G; p.T336A) in 1 FTLD patient whose biological relevance to disease is questionable. We conclude that UBQLN-2 mutations related to ALS/FTLD are extremely rare in French FTLD and FTLD-ALS patients and should not be analyzed systematically. Copyright © 2013. Published by Elsevier Inc.

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.

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.

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

Characteristics of sleep dysfunction and sleep - disordered breathing in amyotrophic lateral sclerosis patients

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Fang WANG

2017-10-01

Full Text Available Objective To study the characteristics of sleep architecture and sleep - disordered breathing (SDB in patients with amyotrophic lateral sclerosis (ALS using polysomnography (PSG. Methods A total of 36 patients with ALS were recruited in this study. According to symptoms of medulla oblongata, the patients were divided into limb involvement group (N = 14 and bulbar palsy group (N = 22. Detailed record of the patients was made including general information and chief complaints of sleep dysfunction and SDB, which covered sleep initiation and maintenance disorders, arousals, difficulty in breathing and snoring, nocturnal polyuria, restless legs syndrome (RLS and muscle soreness. Appel Amyotrophic Lateral Sclerosis (AALS Scores were used to assess bulbar function, breathing function,myodynamia and limbs function. PSG was performed to monitor EEG, EOG, EMG, ECG, position, snore, gas flow of mouth and nose, chest breathing, pulse oxygen saturation (SpO2 and sleep-related parameters including total sleep time (TST, sleep efficiency (SE, sleep latency (SL, awakening times, percentage of different non-rapid eye movement (NREM and rapial eye movement (REM, and apnea hypopnea index (AHI. Pearson correlation analysis evaluated the relationship between AHI of REM, periodic limb movements (PLM and clinical information, AALS Scores. Results Bulbar palsy group had higher scores in AALS Scores (P = 0.007, bulbar function (P = 0.000 and breathing function (P = 0.000, and lower score in upper limb myodynamia (P = 0.016 than limb involvement group. Both 2 groups showed disturbed sleep architecture in the performance of sleep fragmentation. Bulbar palsy group had more awakening times (P = 0.027, lower percentage of REM sleep (P = 0.009 and less PLM (P = 0.020 than limb involvement group. The main respiratory event of 2 groups was hypopnea. Bulbar palsy group had higher AHI (P = 0.038 and AHI of REM and NREM (P = 0.031, 0.049 than limb involvement group. Pearson

Radiation therapy for hypersalivation: a prospective study in 50 amyotrophic lateral sclerosis patients.

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Assouline, Avi; Levy, Antonin; Abdelnour-Mallet, Maya; Gonzalez-Bermejo, Jesus; Lenglet, Timothée; Le Forestier, Nadine; Salachas, François; Bruneteau, Gaelle; Meininger, Vincent; Delanian, Sylvie; Pradat, Pierre-François

2014-03-01

This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (Pprotocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition. Copyright © 2014 Elsevier Inc. All rights reserved.

Quality of life and psychosocial issues in ventilated patients with amyotrophic lateral sclerosis and their caregivers.

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Kaub-Wittemer, Dagmar; Steinbüchel, Nicole von; Wasner, Maria; Laier-Groeneveld, Gerhard; Borasio, Gian Domenico

2003-10-01

Non-invasive ventilation (NIV) is an efficient palliative measure for symptoms of chronic hypoventilation in patients with amyotrophic lateral sclerosis (ALS), and can also lengthen survival. A subset of ALS patients undergoes tracheostomy ventilation (TV) for life prolongation. We investigated the quality of life (QOL) and psychosocial situation of 52 home ventilated ALS patients and their caregivers. The battery included sociodemographic, generic, and disease-specific variables, as well as the Profile of Mood States and the Munich Quality of Life Dimensions List. Data were compared between the NIV (n=32) and the TV (n=21) groups. Mean ventilation time was 14 months for NIV and 35 months for TV. Eighty-one percent of TV patients had been tracheotomized without informed consent. The data show a good overall QOL for both NIV and TV patients, but a very high burden of care for TV caregivers, 30% of whom rated their own QOL lower than their patient's QOL. Sexuality was an important issue. Thus, any assessment of QOL in a home palliative care situation should include the primary caregivers.

Unexpected death of a ventilator-dependent amyotrophic lateral sclerosis patient

Directory of Open Access Journals (Sweden)

M. di Paolo

2013-07-01

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

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

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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.

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

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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.

ILAE type 3 hippocampal sclerosis in patients with anti-GAD–related epilepsy

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DeNiro, Lauren V.; Lasala, Patrick A.; Weidenheim, Karen M.; Graber, Jerome J.; Boro, Alexis

2015-01-01

Objective: To describe the neuropathologic findings and clinical course of 2 patients who underwent temporal lobectomy for medically refractive epilepsy and were later found to have high anti–glutamic acid decarboxylase (GAD) concentrations. Methods: Small case series. Results: Neuropathologic examination of both patients revealed International League Against Epilepsy (ILAE) type 3 hippocampal sclerosis. Following surgery, both developed signs and symptoms of stiff person syndrome and later cerebellar ataxia. Laboratory studies demonstrated high concentrations of anti-GAD antibodies in both patients. Conclusions: These cases suggest that ILAE type 3 hippocampal sclerosis may be immunologically related to and may exist as part of a broader anti-GAD–related neurologic syndrome in some instances. PMID:26161431

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

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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.

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.

Elevated levels of ferritin in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

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Zheng, Y; Gao, L; Wang, D; Zang, D

2017-08-01

The aim of the study was to detect changes in the levels of ferritin heavy chain (FHC), ferritin light chain (FLC), and transferrin in the cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients and to analyze the correlations between the levels of these proteins and various clinical parameters. Cerebrospinal fluid and serum samples were obtained from 54 ALS patients and 46 non-inflammatory neurological disease control (non-INDC) patients. CSF and serum FHC, FLC, and transferring levels were measured via the enzyme-linked immunosorbent method using a commercial ELISA kit, and the times from onset (durations), ALS functional rating scale-revised (ALSFRS-r) scores, and disease progression rates (DPRs) were analyzed by registered neurologists. Statistical analysis was performed via Prism software. Compared with controls, ALS patients exhibited significantly increased FHC and FLC levels in CSF, which were positively correlated with DPR and negatively correlated with duration. Serum transferrin levels were significantly increased in ALS patients but were not correlated with disease progression. FHC and FLC in CSF rapidly increased as the disease worsened. This study demonstrated that the clinical measurement of FHC and FLC in CSF may be beneficial for disease differentiation and evaluating progression in patients with ALS. Compared with levels in serum, the levels of FHC and FLC in CSF might be more reliable for diagnosing and assessing the progression of ALS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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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.

Alterations in the Masticatory System in Patients with Amyotrophic Lateral Sclerosis.

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Riera-Punet, Nina; Martinez-Gomis, Jordi; Paipa, Andrés; Povedano, Monica; Peraire, Maria

To determine the effect of amyotrophic lateral sclerosis (ALS) on aspects of masticatory function and to assess the relationship between ALS and the prevalence of traumatic mucosal lesions caused by oral self-injury. A total of 153 ALS patients and 23 control subjects participated in this cross-sectional study. Clinical characteristics including site of onset, medication, type of feeding, and use of noninvasive mechanical ventilation were recorded. The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) protocol and a specific questionnaire to assess aspects of masticatory dysfunction and frequency of self-injury of the oral mucosa were applied to all participants. Maximum mandibular range of motion, maximum bite force, and maximum finger-thumb grip force were determined and tested with Mann Whitney, Kruskal-Wallis, or chi-square tests. P < .05 was considered significant. Maximum unassisted and assisted mouth opening, protrusion, left laterotrusion, and finger-thumb grip force were significantly reduced in both spinal- (n = 102) and bulbar-onset (n = 40) patients compared to the control group; however, bite force was reduced only in bulbar-onset patients. ALS patients with tube feeding (n = 16) had the greatest reduction in maximum bite force and mandibular opening. There was no relationship between TMD and ALS. Oral self-injury due to biting was more frequent in the ALS group (29.9%) than in the control group (8.7%) and in the bulbar-onset group (55.0%) compared to the spinal- (20.8%) and respiratory-onset (18.2%) groups. Of the ALS patients in the study, 10% sought dental treatment related to the condition. The ALS patients in this study had a reduction in finger-thumb grip force that was twice as great as the reduction in bite force. The maximum range of mandibular movement was also reduced, especially in bulbar-onset patients. ALS patients did not have a higher prevalence of TMD but did have more traumatic mucosal injury than controls. The dentist

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

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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.

Reduced brain N-acetyl-aspartate in frontal lobes suggests neuronal loss in patients with amyotrophic lateral sclerosis.

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Giroud, M; Walker, P; Bernard, D; Lemesle, M; Martin, D; Baudouin, N; Brunotte, F; Dumas, R

1996-06-01

We performed proton magnetic resonance spectroscopy (1H-MRS) in three patients with amyotrophic lateral sclerosis (ALS) to evaluate the distribution and extent of cortical neuronal damage as demonstrated by decreased N-acetyl-aspartate (NAA) levels. We examined primary motor (precentral gyrus) and parietal neocortical (superior parietal gyrus) regions. ALS was defined with lower and upper motor neuron signs. Compared with matched healthy controls, ALS patients had a significant decrease in NAA levels in the primary motor cortex (p upper motor neuron signs present in the ALS, come from a neuronal loss within the primary motor cortex and may explain the frontal syndrome associated with ALS. Second clinical applications of 1H-MRS could include identification of extent of upper motor neuron involvement, aiding diagnosis of syndromes presenting with an ALS-like syndrome.

Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study.

LENUS (Irish Health Repository)

Byrne, Susan

2012-03-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons, associated with frontotemporal dementia (FTD) in about 14% of incident cases. We assessed the frequency of the recently identified C9orf72 repeat expansion in familial and apparently sporadic cases of ALS and characterised the cognitive and clinical phenotype of patients with this expansion.

Frequency-Specific Abnormalities of Intrinsic Functional Connectivity Strength among Patients with Amyotrophic Lateral Sclerosis: A Resting-State fMRI Study

OpenAIRE

Li, Fangjun; Zhou, Fuqing; Huang, Muhua; Gong, Honghan; Xu, Renshi

2017-01-01

The classical concept that amyotrophic lateral sclerosis (ALS) is a degenerative disorder characterized by the loss of upper and lower motor neurons is agreed. However, more and more studies have suggested the involvement of some extra-motor regions. The aim of this study is to investigate the frequency-related alteration pattern of intrinsic functional connectivity strength (FCS) at the voxel-wise level in the relatively early-stage of ALS on a whole brain scale. In this study, 21 patients w...

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

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

Effectiveness of assisted and unassisted cough capacity in amyotrophic lateral sclerosis patients.

Science.gov (United States)

Sancho, Jesús; Servera, Emilio; Bañuls, Pilar; Marín, Julio

2017-11-01

Decreased cough capacity during a respiratory infection is one of the main causes of acute respiratory failure and hospitalisation in amyotrophic lateral sclerosis (ALS). To determine whether a respiratory measurement could identify the effectiveness of cough capacity in ALS during a respiratory infection. This was a prospective study of all ALS patients who were treated at a respiratory care unit due to a respiratory infection from 2012 to 2016. The effectiveness of unassisted and assisted coughing was evaluated and respiratory function tests were performed during the acute episode. Forty-eight ALS patients were enrolled, with only four having an effective unassisted cough. The variable which predicted unassisted cough effectiveness was peak cough flow (PCF) (OR 4499.27; 95%CI 3.60-3219086.19; p = 0.022) with a cut-off point of 2.77 L/s (166 L/min). For manually assisted coughing, the predictor of cough effectiveness was manually assisted PCF (cut-off point of 2.82-169 L/min) (OR 2198.602; 95% CI 3.750-1351691.42; p = 0.019). Mechanically assisted PCF (cut-off point of 2.95-177 L/min) was found to be the predictor of mechanically assisted coughing effectiveness (OR 23.40; 95% CI 2.11-258.96; p = 0.010). During a respiratory infection in ALS patients, the effectiveness of assisted and unassisted cough capacity depends on the PCF generated.

Is survival improved by the use of NIV and PEG in amyotrophic lateral sclerosis (ALS)? A post-mortem study of 80 ALS patients

OpenAIRE

Burkhardt, Christian; Neuwirth, Christoph; Sommacal, Andreas; Andersen, Peter M.; Weber, Markus

2017-01-01

Background: Non-invasive ventilation (NIV) and percutaneous gastrostomy (PEG) are guideline-recommended interventions for symptom management in amyotrophic lateral sclerosis (ALS). Their effect on survival is controversial and the impact on causes of death is unknown. Objective: To investigate the effect of NIV and PEG on survival and causes of death in ALS patients. Methods: Eighty deceased ALS patients underwent a complete post mortem analysis for causes of death between 2003 and 2015. Fort...

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...

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

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...

Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis.

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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.

Surgical improvement of speech disorder caused by amyotrophic lateral sclerosis.

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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.

Cardiometabolic health and risk of amyotrophic lateral sclerosis.

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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.

Stem-cell transplantation into the frontal motor cortex in amyotrophic lateral sclerosis patients.

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Martinez, Hector R; Gonzalez-Garza, Maria T; Moreno-Cuevas, Jorge E; Caro, Enrique; Gutierrez-Jimenez, Eugenio; Segura, Jose J

2009-01-01

Amyotrophic lateral sclerosis (ALS) is characterized by the selective death of motor neurons. CD133(+) stem cells are known to have the capacity to differentiate into neural lineages. Stem cells may provide an alternative treatment for ALS and other neurodegenerative diseases. Five men and five women (aged 38-62 years) with confirmed ALS were included in this study. Our institutional ethics and research committees approved the protocol. After informed consent was obtained, patients underwent Hidrogen-Magnetic Resonance Imaging (H-MRI) spectroscopy and were given scores according to an ALS functional rating scale, Medical Research Council power muscle scale and daily living activities. Bone marrow was stimulated with 300 microg filgrastim subcutaneously daily for 3 days. Peripheral blood mononuclear cells were obtained after admission by leukapheresis. The cell suspension was conjugated with anti-human CD133 superparamagnetic microbeads, and linked cells were isolated in a magnetic field. The isolated cells (2.5-7.5x10(5)) were resuspended in 300 microL of the patient's cerebrospinal fluid, and implanted in motor cortexes using a Hamilton syringe. Ten patients with confirmed ALS without transplantation were used as a control group. Patients were followed up for a period of 1 year. The autologous transplantation of CD133(+) stem cells into the frontal motor cortex is a safe and well-tolerated procedure in ALS patients. The survival of treated patients was statistically higher (P=0.01) than untreated control patients. Stem-cell transplantation in the motor cortex delays ALS progression and improves quality of life.

Inspiratory muscle training in patients with Amyotrophic Lateral Sclerosis: A systematic review.

Science.gov (United States)

Eidenberger, Margit; Nowotny, Silvia

2014-01-01

Amyotrophic Lateral Sclerosis is a neurodegenerative disease with rapid involvement of the inspiratory muscles, leading to respiratory insufficiency. Death often occurs by aspiration and pneumonia. Endurance- and strength therapy within ALS are discussed controversially. To review the current literature to assess the efficacy of inspiratory muscle training for ALS. Systematic review, using databases as PubMed, PEDro, Cochrane and Google Scholar. Inspiratory muscle training vs. sham training or inspiratory muscle training alone. Inspiratory muscle strength, dyspnoea, quality of life and survival time. Four studies could be included in this review, two RCT's, one pre-experimental study and one with a historical control group. In total 73 patients underwent inspiratory muscle training. Studies varied in onset of the training, the training protocol and the outcomes measured. At time, there is limited evidence that inspiratory muscle training leads to strengthening of inspiratory muscles in ALS. Improvements made were minor, in only a few parameters and also in control groups. Survival time was significantly longer in the experimental group in one study. Interesting suppositions (diaphragm training vs. other IM training, improvement of chest wall and lung compliance) need to be examined in robustly designed future trials, defining exact therapeutic windows and interventions.

Amyotrophic lateral sclerosis-like presentation in a HIV-positive patient.

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Anand, Kuljeet Singh; Wadhwa, Ankur; Garg, Jyoti; Mahajan, Rakesh Kumar

2014-01-01

There has been several reports of an MND like syndrome in HIV-1 infection, however the data is still sparse. Furthermore, HIV-associated amyotrophic lateral sclerosis (ALS) syndrome differs from the classical ALS in some key aspects.. A 44-year-old male presented with a history of insidious onset and gradually progressive asymmetric weakness of lower limbs. He also complained of thinning in both legs, the left leg more than the right since 1 year along with spontaneous twitching of muscles in both the thighs. On neurological examination, the assessment of higher mental functions was normal. There were no cranial nerve deficits. Motor power was grade 5/5 (Medical Research Council scale) in both the upper limbs and 4+ at hips and knees bilaterally, 5 at right ankle, and 4+ at left ankle. All the deep tendon reflexes were brisk with extensor planter responses. There were no cerebellar signs or sensory deficits. HIV-1 was reactive in enzyme-linked immunosorbent assay. Electrophysiological studies were conducted per the MND protocol.None of the nerves studied showed an abnormal drop in compound muscle action potential amplitude with proximal stimulation. There was evidence of diffuse spontaneous activity, which manifests as fibrillation and fasciculation potentials in most muscles tested . Overall there seems to be sufficient evidence to implicate HIV as a potential cause of an ALS-like disorder, but one must also consider the possibility of coincidental HIV infection in patients who have sporadic ALS. © The Author(s) 2014.

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

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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.

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

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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.

What influences patient decision-making in amyotrophic lateral sclerosis multidisciplinary care? A study of patient perspectives.

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Hogden, Anne; Greenfield, David; Nugus, Peter; Kiernan, Matthew C

2012-01-01

Patients with amyotrophic lateral sclerosis (ALS) are required to make decisions concerning quality of life and symptom management over the course of their disease. Clinicians perceive that patients' ability to engage in timely decision-making is extremely challenging. However, we lack patient perspectives on this issue. This study aimed to explore patient experiences of ALS, and to identify factors influencing their decision-making in the specialized multidisciplinary care of ALS. An exploratory study was conducted. Fourteen patients from two specialized ALS multidisciplinary clinics participated in semistructured interviews that were audio recorded and transcribed. Data were analyzed for emergent themes. Decision-making was influenced by three levels of factors, ie, structural, interactional, and personal. The structural factor was the decision-making environment of specialized multidisciplinary ALS clinics, which supported decision-making by providing patients with disease-specific information and specialized care planning. Interactional factors were the patient experiences of ALS, including patients' reaction to the diagnosis, response to deterioration, and engagement with the multidisciplinary ALS team. Personal factors were patients' personal philosophies, including their outlook on life, perceptions of control, and planning for the future. Patient approaches to decision-making reflected a focus on the present, rather than anticipating future progression of the disease and potential care needs. Decision-making for symptom management and quality of life in ALS care is enhanced when the patient's personal philosophy is supported by collaborative relationships between the patient and the multidisciplinary ALS team. Patients valued the support provided by the multidisciplinary team; however, their focus on living in the present diverged from the efforts of health professionals to prepare patients and their carers for the future. The challenge facing health

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

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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.

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

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…

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...

Relevance of the pyramidal syndrome in amyotrophic lateral sclerosis.

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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.

Amyotrophic lateral sclerosis and assisted ventilation: how patients decide.

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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

Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report.

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Isse, Naohi; Miura, Yoh; Obata, Toshiyuki; Takahara, Noriko

2013-12-30

L-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia. A 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient's ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily). This case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient's serum ammonium levels.

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.

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.)

Endogenous progesterone is associated to amyotrophic lateral sclerosis prognostic factors.

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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.

Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.

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Nagase, Midori; Yamamoto, Yorihiro; Miyazaki, Yusuke; Yoshino, Hiide

2016-05-01

Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined. Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.

CT fluoroscopy-guided percutaneous gastrostomy with loop gastropexy and peel-away sheath trocar technique in 31 amyotrophic lateral sclerosis patients

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De Bucourt, Maximilian; Collettini, Federico; Althoff, Christian; Streitparth, Florian; Greupner, Johannes; Hamm, Bernd (Dept. of Radiology, Charite - Univ. Medicine, Berlin (Germany)), Email: mdb@charite.de; Teichgraeber, U.K. (Dept. of Radiology, Jena Univ. (Germany))

2012-04-15

Background: In amyotrophic lateral sclerosis (ALS) patients with respiratory impairment and/or advanced disease, performing even mild sedation - as is usually necessary for percutaneous endoscopic gastrostomy (PEG) placements - is fraught with risk. These patients are often referred to Interventional Radiology for alternative percutaneous gastrostomy tube placement options. Purpose: To report our experience with CT fluoroscopy-guided percutaneous gastrostomy with a novel loop gastropexy and peel-away sheath trocar technique in ALS patients as an alternative to endoscopic techniques. Material and Methods: A consecutive series of 31 amyotrophic lateral sclerosis patients in whom endoscopic gastrostomy was considered too dangerous or impossible to perform underwent CT-guided percutaneous gastropexy and gastrostomy and prospective follow-up. All procedures were performed with a 15 FR Freka Pexact gastrostomy kit, a 16-row CT scanner (Aquilion 16) and single shot CT fluoroscopy mode. Results: The procedure was performed successfully in 30 of 31 patients (20 men, 11 women; median age 60 years, range 38-80 years). In the remaining case the stomach was punctured under CT fluoroscopy and CO2 insufflation was initiated thereafter, leading to successful gastrostomy without prior gastropexy and without further adverse events during follow-up. Two patients reported unproblematic exchange of a balloon tube due to skin irritations with no further adverse events. One patient reported accidental displacement of an exchanged new balloon tube in domestic environment due to balloon leakage: A new balloon tube was easily re-inserted in a hospital the same day. No serious adverse events such as peritonitis, persistent local bleeding, systemic blood loss, or any local infection requiring surgical intervention were observed. Until August 11, 2011 follow-up resulted in 7473 cumulative gastrostomy-days from the date of first placement. Conclusion: Initial results suggest that the described

CT fluoroscopy-guided percutaneous gastrostomy with loop gastropexy and peel-away sheath trocar technique in 31 amyotrophic lateral sclerosis patients

International Nuclear Information System (INIS)

De Bucourt, Maximilian; Collettini, Federico; Althoff, Christian; Streitparth, Florian; Greupner, Johannes; Hamm, Bernd; Teichgraeber, U.K.

2012-01-01

Background: In amyotrophic lateral sclerosis (ALS) patients with respiratory impairment and/or advanced disease, performing even mild sedation - as is usually necessary for percutaneous endoscopic gastrostomy (PEG) placements - is fraught with risk. These patients are often referred to Interventional Radiology for alternative percutaneous gastrostomy tube placement options. Purpose: To report our experience with CT fluoroscopy-guided percutaneous gastrostomy with a novel loop gastropexy and peel-away sheath trocar technique in ALS patients as an alternative to endoscopic techniques. Material and Methods: A consecutive series of 31 amyotrophic lateral sclerosis patients in whom endoscopic gastrostomy was considered too dangerous or impossible to perform underwent CT-guided percutaneous gastropexy and gastrostomy and prospective follow-up. All procedures were performed with a 15 FR Freka Pexact gastrostomy kit, a 16-row CT scanner (Aquilion 16) and single shot CT fluoroscopy mode. Results: The procedure was performed successfully in 30 of 31 patients (20 men, 11 women; median age 60 years, range 38-80 years). In the remaining case the stomach was punctured under CT fluoroscopy and CO2 insufflation was initiated thereafter, leading to successful gastrostomy without prior gastropexy and without further adverse events during follow-up. Two patients reported unproblematic exchange of a balloon tube due to skin irritations with no further adverse events. One patient reported accidental displacement of an exchanged new balloon tube in domestic environment due to balloon leakage: A new balloon tube was easily re-inserted in a hospital the same day. No serious adverse events such as peritonitis, persistent local bleeding, systemic blood loss, or any local infection requiring surgical intervention were observed. Until August 11, 2011 follow-up resulted in 7473 cumulative gastrostomy-days from the date of first placement. Conclusion: Initial results suggest that the described

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...

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

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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.

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

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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.

The genotype-phenotype landscape of familial amyotrophic lateral sclerosis in Australia.

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McCann, E P; Williams, K L; Fifita, J A; Tarr, I S; O'Connor, J; Rowe, D B; Nicholson, G A; Blair, I P

2017-09-01

Amyotrophic lateral sclerosis (ALS) is a clinically and genetically heterogeneous fatal neurodegenerative disease. Around 10% of ALS cases are hereditary. ALS gene discoveries have provided most of our understanding of disease pathogenesis. We aimed to describe the genetic landscape of ALS in Australia by assessing 1013 Australian ALS patients for known ALS mutations by direct sequencing, whole exome sequencing or repeat primed polymerase chain reaction. Age of disease onset and disease duration were used for genotype-phenotype correlations. We report 60.8% of Australian ALS families in this cohort harbour a known ALS mutation. Hexanucleotide repeat expansions in C9orf72 accounted for 40.6% of families and 2.9% of sporadic patients. We also report ALS families with mutations in SOD1 (13.7%), FUS (2.4%), TARDBP (1.9%), UBQLN2 (.9%), OPTN (.5%), TBK1 (.5%) and CCNF (.5%). We present genotype-phenotype correlations between these genes as well as between gene mutations. Notably, C9orf72 hexanucleotide repeat expansion positive patients experienced significantly later disease onset than ALS mutation patients. Among SOD1 families, p.I114T positive patients had significantly later onset and longer survival. Our report highlights a unique spectrum of ALS gene frequencies among patients from the Australian population, and further, provides correlations between specific ALS mutations with disease onset and/or duration. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis.

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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.

Dysphagia in amyotrophic lateral sclerosis: prevalence and clinical findings.

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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.

Iyengar Yoga Therapy Intervention for Ischial Pressure Ulcers in a Patient with Amyotrophic Lateral Sclerosis: A Case Study.

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Ribeiro, Subbappa

2015-09-01

Although some research suggests that the formation of pressure ulcers is rare in patients with amyotrophic lateral sclerosis (ALS), several patients have nonetheless developed this problem. To date, however, no case reports in the literature have described patients with ALS who develop ischial pressure ulcers. Outside of the ALS literature, evidence suggests that ischial pressure ulcers frequently develop in wheelchair users and also in patients treated in various health care settings. A patient diagnosed with ALS reported the development of ischial pressure ulcers after consistent immobility for 1 year (32 months after her ALS diagnosis). This patient, who was sitting on the wounds, was treated with ointment and morphine; the latter was ineffective in controlling the pain. Moving the patient from sitting to supine, lateral, or semilateral positions, either on the bed or wheelchair, to separate the ulcers from the surface of the chair or bed was deemed impossible because of exaggeration of other symptoms, including shortness of breath and pain in other parts of the body. A new method of postural alignment was developed to alleviate the pain associated with the pressure ulcer. This method, Iyengar yoga therapy, which uses props to reposition a patient, alleviated pain and healing of two pressure ulcers of the patient after 3 weeks of starting this intervention. Although the ischial pressure ulcers were successfully treated in a patient with ALS, further study is necessary to investigate the effectiveness of this postural alignment intervention in ALS and other patient populations for the management of ischial pressure ulcers.

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

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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

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

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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.

Effects of non-invasive ventilation on objective sleep and nocturnal respiration in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Boentert, Matthias; Brenscheidt, Inga; Glatz, Christian; Young, Peter

2015-09-01

In amyotrophic lateral sclerosis (ALS), non-invasive ventilation (NIV) is indicated if sleep-disordered breathing (SDB), daytime hypercapnia, or significant diaphragmatic weakness is present. We investigated both short-term and long-term effects of NIV on objective measures of sleep and nocturnal respiration in patients with ALS. Polysomnography (PSG) and transcutaneous capnography were conducted for diagnosis of SDB (T0), for treatment initiation (T1), and follow-up 3, 9, and 15 months later (T2, T3, and T4, respectively). Records from 65 patients were retrospectively analyzed at T0 and T1. At subsequent timepoints, the number of full data sets decreased since follow-up sleep studies frequently included polygraphy rather than PSG (T2, 38 patients, T3, 17 patients, T4, 11 patients). At T0, mean age was 63.2 years, 29 patients were female, and 22 patients had bulbar ALS. Immediate sequelae of NIV initiation included significant increases of slow wave sleep, rapid eye movement sleep, and oxygen saturation. Mean apnea-hypopnea index, respiratory rate, and the maximum transcutaneous carbon dioxide tension were reduced. At T2-T4, normoxia and normocapnia were preserved. Sleep quality measures showed no alteration as diurnal use of NIV gradually increased reflecting disease progression. In contrast to previous reports, improvement of sleep and respiratory outcomes was found in both non-bulbar and bulbar patients. NIV significantly improves objective sleep quality and SDB in the first night of treatment in patients with bulbar and non-bulbar ALS. NIV warrants nocturnal normoventilation without deterioration of sleep quality in the long run with only minor changes to ventilator settings.

Novel mutations in TARDBP (TDP-43 in patients with familial amyotrophic lateral sclerosis.

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Nicola J Rutherford

2008-09-01

Full Text Available The TAR DNA-binding protein 43 (TDP-43 has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U, defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V were identified in the analysis of 92 familial ALS patients (3.3%, while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis.

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.

[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.

Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: clinical features and survival analysis.

Science.gov (United States)

Spataro, Rossella; Bono, Valeria; Marchese, Santino; La Bella, Vincenzo

2012-12-15

Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic lateral sclerosis (ALS) patients with a respiratory failure or when the non-invasive ventilation (NIV) is no longer effective. We evaluated the clinical characteristics and survival of a cohort of tracheostomized ALS patients, followed in a single ALS Clinical Center. Between 2001 and 2010, 87 out of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in 25. After tracheostomy, most patients were followed up through telephone interviews to caregivers. A complete survival analysis could be performed in fifty-two TMV patients. 31.3% ALS patients underwent tracheostomy, with a male prevalence (M/F=1.69) and a median age of 61 years (interquartile range=47-66). After tracheostomy, nearly all patients were under home care. TMV ALS patients were more likely than non-tracheostomized (NT) patients to be implanted with a PEG device, although the bulbar-/spinal-onset ratio did not differ between the two groups. Kaplan-Meyer analysis showed that tracheostomy increases median survival (TMV, 47 months vs NT, 31 months, p=0.008), with the greatest effect in patients younger than 60 at onset (TMV ≤ 60 years, 57.5 months vs NT ≤ 60 years, 38.5 months, p=0.002). TMV is increasingly performed in ALS patients. Nearly all TMV patients live at home and most of them are fed through a PEG device. Survival after tracheostomy is generally increased, with the stronger effect in patients younger than 60. This survival advantage is apparently lost when TMV is performed in patients older than 60. The results of this study might be useful for the decision-making process of patients and their families about this advanced palliative care. Copyright © 2012. Published by Elsevier B.V.

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.

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)

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.

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

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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

Study of the HFE gene common polymorphisms in French patients with sporadic amyotrophic lateral sclerosis.

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Praline, Julien; Blasco, Hélène; Vourc'h, Patrick; Rat, Valérian; Gendrot, Chantal; Camu, William; Andres, Christian R

2012-06-15

Our objective was to investigate whether the C282Y (p.Cys 282 Tyr) and H63D (p. His 63 Asp) HFE polymorphisms were associated with sporadic amyotrophic lateral sclerosis (SALS) in the French population. We searched for a relation of HFE polymorphisms with the clinical characteristics of the disease. The HFE polymorphisms were studied in 824 patients with SALS and 583 controls. We compared the frequency of the polymorphisms between SALS and controls groups by univariate and multivariate statistics, taking into account gender, site, age-at-onset and survival. We did not observe significant difference in the frequency of H63D polymorphism between SALS and control group. We observed a significant difference for C282Y between patients and controls with a low frequency of the Y allele in patients (3.2%) compared to our control group (5.9%). Disease duration, distribution of gender, site-of-onset, age-at-onset did not differ between groups taking into account genotypes of each polymorphism. Our results in this large cohort of ALS patients indicate that H63D polymorphism is not associated with SALS in the French population. This conclusion does not exclude a weak effect of the HFE gene polymorphisms in certain ALS populations, or an effect of other rare HFE gene variants. Copyright © 2012 Elsevier B.V. All rights reserved.

The investigation of genetic and clinical features in Chinese patients with juvenile amyotrophic lateral sclerosis.

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Liu, Z-J; Lin, H-X; Liu, G-L; Tao, Q-Q; Ni, W; Xiao, B-G; Wu, Z-Y

2017-09-01

Juvenile amyotrophic lateral sclerosis (JALS) occurs at an age of onset below 25 years with a heterogeneous disease onset location, variable progression and survival time. To investigate whether an ALS gene profile could resolve any aspects of clinical symptom heterogeneity, we have used targeted sequencing technology in a cohort of 12 JALS patients of Chinese descent. We detected 5 likely pathogenic mutations, 2 in familial probands and 3 in sporadic patients. One was a known TARDBP mutation (p.G348V) and 4 were FUS frameshift mutations including a known p.Gln519Ilefs*9 mutation and 3 novel mutations, p.Gly515Valfs*14, p.Gly486Profs*30, and p.Arg498Alafs*32. Of the 4 FUS mutations, 2 were able to be confirmed as de novo mutations. The TARDBP mutation carrier showed a classic ALS phenotype. All patients with FUS mutations experienced limb weakness at an early age and developed bulbar symptoms during the disease course. FUS mutations have previously been associated with increased JALS disease progression, however, we found a large range 12 to 84 months in disease survival (mean 58.2 months). Our results justify future screening for variants in FUS as it remains the most frequent genetic determinant of early onset, JALS (found in 30% of our patients). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bulbar impairment score and survival of stable amyotrophic lateral sclerosis patients after noninvasive ventilation initiation.

Science.gov (United States)

Sancho, Jesús; Martínez, Daniel; Bures, Enric; Díaz, José Luis; Ponz, Alejandro; Servera, Emilio

2018-04-01

There is general agreement that noninvasive ventilation (NIV) prolongs survival in amyotrophic lateral sclerosis (ALS) and that the main cause of NIV failure is the severity of bulbar dysfunction. However, there is no evidence that bulbar impairment is a contraindication for NIV. The aim of this study was to determine the effect of bulbar impairment on survival in ALS patients with NIV. ALS patients for whom NIV was indicated were included. Those patients who refused NIV were taken as the control group. 120 patients who underwent NIV and 20 who refused NIV were included. The NIV group presented longer survival (median 18.50 months, 95% CI 12.62-24.38 months) than the no-NIV group (3.00 months, 95% CI 0.82-5.18 months) (pNIV, adjusted for NIV failure, were severity of bulbar dysfunction (hazard ratio (HR) 0.5, 95% CI 0.92-0.97; p=0.001) and time spent with oxygen saturation measured by pulse oximetry NIV (HR 1.12, 95% CI 1.01-1.24; p=0.02). Severe bulbar impairment in ALS does not always prevent NIV from being used, but the severity of bulbar dysfunction at NIV initiation and %sleep S pO 2 NIV appear to be the main prognostic factors of NIV failure in ALS.

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.

Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.

Science.gov (United States)

Meoded, Avner; Morrissette, Arthur E; Katipally, Rohan; Schanz, Olivia; Gotts, Stephen J; Floeter, Mary Kay

2015-01-01

Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

Science.gov (United States)

McDermott, Christopher J; Bradburn, Mike J; Maguire, Chin; Cooper, Cindy L; Baird, Wendy O; Baxter, Susan K; Cohen, Judith; Cantrill, Hannah; Dixon, Simon; Ackroyd, Roger; Baudouin, Simon; Bentley, Andrew; Berrisford, Richard; Bianchi, Stephen; Bourke, Stephen C; Darlison, Roy; Ealing, John; Elliott, Mark; Fitzgerald, Patrick; Galloway, Simon; Hamdalla, Hisham; Hanemann, C Oliver; Hughes, Philip; Imam, Ibrahim; Karat, Dayalan; Leek, Roger; Maynard, Nick; Orrell, Richard W; Sarela, Abeezar; Stradling, John; Talbot, Kevin; Taylor, Lyn; Turner, Martin; Simonds, Anita K; Williams, Tim; Wedzicha, Wisia; Young, Carolyn; Shaw, Pamela J

2016-06-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to

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.

MRI and SPECT findings in amyotrophic lateral sclerosis. Demonstration of upper motor neurone involvement by clinical neuroimaging

Energy Technology Data Exchange (ETDEWEB)

Ukada, F.; Sawada, H.; Seriu, N.; Shindou, K.; Nishitani, N.; Kameyama, M. (Sumitomo Hospital, Osaka (Japan). Dept. of Neurology)

1992-10-01

MRI was performed in 21 patients and single photon emission computed tomography (SPECT) with N-isopropyl-p-[sup 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.).

[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.

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.

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

Genetic analysis of patients with familial and sporadic amyotrophic lateral sclerosis in a Brazilian Research Center.

Science.gov (United States)

Chadi, Gerson; Maximino, Jessica Ruivo; Jorge, Frederico Mennucci de Haidar; Borba, Fabrício Castro de; Gilio, Joyce Meire; Callegaro, Dagoberto; Lopes, Camila Galvão; Santos, Samantha Nakamura Dos; Rebelo, Gabriela Natania Sales

2017-05-01

To investigate gene mutations in familial form (FALS) and sporadic form (SALS) of amyotrophic lateral sclerosis (ALS) in a highly miscegenated population. Frequencies of mutations in the C9orfF72, TARDBP, SOD1, FUS and VAPB genes were investigated in a cohort of FALS (n = 39) and SALS (n = 189) subjects from the Research Centre of the University of São Paulo School of Medicine. All patients were subjected to C9orf72 and TARDBP analyses. SOD1, FUS and VAPB were also evaluated in FALS subjects. Mutations were identified in FALS (61.3%) and SALS (5.3%) patients. Mutations in C9orf72 (12.8%, >45 GGGGCC hexanucleotide repeats), VAPB (43.6%, P56S) and SOD1 (7.7%, L145S) were identified in FALS subjects. Pathogenic C9orf72 expansions (2.64%) were identified in some SALS patients. Similar changes of TARDBP were found in SALS (2.64%) but not in FALS subjects. No FUS mutations were seen in any FALS subjects. TARDBP and C9orf72 mutations in this cohort were similar to those found in other centres worldwide. VAPB mutation (P56S) was highly prevalent in Brazilian FALS patients.

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

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

Analysis of the diagnostic pathway and delay in patients with amyotrophic lateral sclerosis in the Valencian Community.

Science.gov (United States)

Vázquez-Costa, J F; Martínez-Molina, M; Fernández-Polo, M; Fornés-Ferrer, V; Frasquet-Carrera, M; Sevilla-Mantecón, T

2018-06-11

Amyotrophic lateral sclerosis (ALS) is an insidious, clinically heterogeneous neurodegenerative disease associated with a diagnostic delay of approximately 12 months. No study conducted to date has analysed the diagnostic pathway in Spain. We gathered data on variables related to the diagnostic pathway and delay for patients diagnosed with ALS between October 2013 and July 2017. The study included 143 patients with ALS (57% men; 68% spinal onset). Patients were diagnosed in public centres in 86% of cases and in private centres in 14%.The mean diagnostic delay was 13.1 months (median 11.7). Patients were examined by neurologists a mean time of 7.9 months after symptom onset, with diagnosis being made 5.2 months later. Half of all patients underwent unnecessary diagnostic tests and multiple electrophysiological studies before diagnosis was established. Diagnostic delay was longer in cases of spinal onset (P = .008) due to onset of the disease in the lower limbs. No differences were found between the public and private healthcare systems (P = .897). The diagnostic delay in ALS in Spain is similar to that of neighboring countries and seems to depend on disease-related factors, not on the healthcare system. Patients with lower-limb onset ALS constitute the greatest diagnostic challenge. Misdiagnosis is frequent, and partly attributable to an incorrect approach or erroneous interpretation of electrophysiological studies. Specific training programmes for neurologists and general neurophysiologists and early referral to reference centers may help to reduce diagnostic delay. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

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)

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),

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),

Decision Making About Gastrostomy and Noninvasive Ventilation in Amyotrophic Lateral Sclerosis.

Science.gov (United States)

Martin, Naomi H; Lawrence, Vanessa; Murray, Joanna; Janssen, Anna; Higginson, Irene; Lyall, Rebecca; Burman, Rachel; Leigh, P Nigel; Al-Chalabi, Ammar; Goldstein, Laura H

2016-08-01

We used thematic analysis to investigate factors affecting decision making about gastrostomy and noninvasive ventilation (NIV) by people with Amyotrophic Lateral Sclerosis (ALS) from the viewpoint of the health care professionals (HCPs) supporting them. We conducted 20 in-depth interviews with 19 HCPs nominated by people with ALS who had made a decision to accept or decline NIV or gastrostomy. We found the main themes influencing decision making were patient-centric, caregiver-related or related to HCPs' own beliefs, perspectives, and actions. HCPs felt patients should be, and were, in control of decision making, although caregivers and HCPs played a role. The patient's evaluation of quality of life, the desirability of prolonging life, and acceptance of the disease and its progression by both patient and caregiver were the most important factors identified by HCPs. HCPs should be aware of the importance of multiprofessional discussions, and the potential influences (identified above) that might require discussion with patients and caregivers. © The Author(s) 2015.

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

International Nuclear Information System (INIS)

Assouline, Avi; Levy, Antonin; Abdelnour-Mallet, Maya; Gonzalez-Bermejo, Jesus; Lenglet, Timothée; Le Forestier, Nadine

2014-01-01

Purpose: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Methods and Materials: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. Results: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10 −6 ). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (−77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Conclusion: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition

Radiation Therapy for Hypersalivation: A Prospective Study in 50 Amyotrophic Lateral Sclerosis Patients

Energy Technology Data Exchange (ETDEWEB)

Assouline, Avi, E-mail: avi.assouline@ccpsc.fr [Department of Radiation Oncology, Centre Clinique de la Porte de Saint Cloud, Boulogne-Billancourt (France); Department of Radiation Oncology, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris (APHP), Paris (France); Levy, Antonin [Department of Radiation Oncology, Gustave Roussy, Université Paris-Sud XI, Villejuif (France); Abdelnour-Mallet, Maya [Service Evaluation Pharmaceutique et Bon Usage (SEPBU), Unité Evaluation Scientifique, Bon Usage et Information (ESBUI), APHP AGEPS/pôle Pharmacie Hospitalière, Hôpitaux de Paris - PHHP, Paris (France); Gonzalez-Bermejo, Jesus [Departement of Pneumology and Intensive Care, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris (France); Lenglet, Timothée [Departement of Nervous System Diseases, Paris ALS center, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris (France); Le Forestier, Nadine [Departement of Nervous System Diseases, Paris ALS center, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris (France); Département de Recherche ES3, Emmanuel Hirsch, EA 1610 Études sur les Sciences et les Techniques, Université Paris-Sud XI, Paris (France); and others

2014-03-01

Purpose: This study aimed to evaluate the efficiency and the tolerance of radiation therapy (RT) on salivary glands in a large series of amyotrophic lateral sclerosis (ALS) patients with hypersalivation. Methods and Materials: Fifty ALS patients that had medically failure pretreatment were included in this prospective study. RT was delivered through a conventional linear accelerator with 6-MV photons and 2 opposed beams fields including both submandibular glands and two-thirds of both parotid glands. Total RT dose was 10 Gy in 2 fractions (n=30) or 20 Gy in 4 fractions (n=20). RT efficacy was assessed with the 9-grade Sialorrhea Scoring Scale (SSS), recently prospectively validated as the most effective and sensitive tool to measure sialorrhea in ALS patients. Results: At the end of RT, all patients had improved: 46 had a complete response (92% CR, SSS 1-3) and 4 had a partial response (8% PR, SSS 4-5). A significant lasting salivary reduction was observed 6 months after RT completion: there was 71% CR and 26% PR, and there was a significant SSS reduction versus baseline (P<10{sup −6}). There was no grade 3 to 4 toxicity, and most side effects (34%) occurred during RT. Nine patients (18%) underwent a second salivary gland RT course, with a 3-months mean delay from the first RT, resulting in a SSS decrease (−77%). Both RT dose regimens induced a significant SSS decrease with no significant toxicity. There were, however, more patients with CR/PR in the 20-Gy protocol (P=.02), and 8 of 9 patients (89%) receiving a second RT course had previously been treated within the 10-Gy protocol. Conclusion: Radiation therapy of 20 Gy in 4 fractions is an efficient and safe treatment for ALS patients with sialorrhea. A shorter RT course (10 Gy in 2 fractions) may be proposed in patients in poor medical condition.

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.

The eye-tracking computer device for communication in amyotrophic lateral sclerosis.

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Spataro, R; Ciriacono, M; Manno, C; La Bella, V

2014-07-01

To explore the effectiveness of communication and the variables affecting the eye-tracking computer system (ETCS) utilization in patients with late-stage amyotrophic lateral sclerosis (ALS). We performed a telephone survey on 30 patients with advanced non-demented ALS that were provisioned an ECTS device. Median age at interview was 55 years (IQR = 48-62), with a relatively high education (13 years, IQR = 8-13). A one-off interview was made and answers were later provided with the help of the caregiver. The interview included items about demographic and clinical variables affecting the daily ETCS utilization. The median time of ETCS device possession was 15 months (IQR = 9-20). The actual daily utilization was 300 min (IQR = 100-720), mainly for the communication with relatives/caregiver, internet surfing, e-mailing, and social networking. 23.3% of patients with ALS (n = 7) had a low daily ETCS utilization; most reported causes were eye-gaze tiredness and oculomotor dysfunction. Eye-tracking computer system is a valuable device for AAC in patients with ALS, and it can be operated with a good performance. The development of oculomotor impairment may limit its functional use. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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van Eijk RPA

2018-03-01

increases false-negative rates among all treatment scenarios. To detect a 15% reduction in ALSFRS-R decline and 34% decline in hazard with 80% power after 18 months, the Cox model requires 524 patients, the LME model 794 patients, the omnibus test 526 patients, the composite end point 1,274 patients, the CAFS 576 patients and the joint model 464 patients. Conclusion: Joint models have superior statistical power to analyze simultaneous effects on survival and function and may circumvent pitfalls encountered by other end points. Optimizing trial end points is essential, as selecting suboptimal outcomes may disguise important treatment clues. Keywords: joint models, CAFS, clinical trials, amyotrophic lateral sclerosis

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

Amyotrophic lateral sclerosis

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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

Mechanisms of Neuroprotection by Protein Disulphide Isomerase in Amyotrophic Lateral Sclerosis

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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.

Amyotrophic lateral sclerosis and the clinical potential of dexpramipexole

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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

Multiple sclerosis: Left advantage for auditory laterality in dichotic tests of central auditory processing and relationship of psychoacoustic tests with the Multiple Sclerosis Disability Scale-EDSS.

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Peñaloza López, Yolanda Rebeca; Orozco Peña, Xóchitl Daisy; Pérez Ruiz, Santiago Jesús

2018-04-03

To evaluate the central auditory processing disorders in patients with multiple sclerosis, emphasizing auditory laterality by applying psychoacoustic tests and to identify their relationship with the Multiple Sclerosis Disability Scale (EDSS) functions. Depression scales (HADS), EDSS, and 9 psychoacoustic tests to study CAPD were applied to 26 individuals with multiple sclerosis and 26 controls. Correlation tests were performed between the EDSS and psychoacoustic tests. Seven out of 9 psychoacoustic tests were significantly different (P<.05); right or left (14/19 explorations) with respect to control. In dichotic digits there was a left-ear advantage compared to the usual predominance of RDD. There was significant correlation in five psychoacoustic tests and the specific functions of EDSS. The left-ear advantage detected and interpreted as an expression of deficient influences of the corpus callosum and attention in multiple sclerosis should be investigated. There was a correlation between psychoacoustic tests and specific EDSS functions. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

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

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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...

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

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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.

Meditation training for people with amyotrophic lateral sclerosis and their caregivers.

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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.

Parkinson's disease-like midbrain hyperechogenicity is frequent in amyotrophic lateral sclerosis.

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Fathinia, Panteha; Hermann, Andreas; Reuner, Ulrike; Kassubek, Jan; Storch, Alexander; Ludolph, Albert C

2013-02-01

Clinical and neuroimaging data suggest impairment of the nigrostriatal system in amyotrophic lateral sclerosis (ALS). We thus hypothesized whether Parkinson's disease (PD)-like midbrain sonography findings are also present in ALS. Eighty-six patients with the diagnosis of possible or definite ALS according to revised El Escorial criteria were examined by transcranial B-mode sonography compared to 76 age- and gender-matched controls and 33 PD patients. Hyperechogenic areas of the midbrain representing the substantia nigra were measured planimetrically using standard protocols. In subjects with sufficient temporal acoustic bone windows, mean midbrain hyperechogenic areas were significantly higher in ALS (0.251 ± 0.104 cm(2)) and PD patients (0.286 ± 0.078 cm(2)) compared to controls (0.091 ± 0.054 cm(2)) with no significant difference between ALS and PD patients (one-way ANOVA: F value = 94.3; P diagnosis and differential diagnosis of PD and ALS alike.

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...

The cervical cord in amyotrophic lateral sclerosis. A comparison of the CT-myelography with pathological observation

International Nuclear Information System (INIS)

Sugamiya, Hitoshi; Tokumaru, Yukio; Arai, Kimihito; Hirayama, Keizo

1995-01-01

The spinal cord with amyotrophic lateral sclerosis was macroscopically examined in five patients using CT-myelography (CTM) and autopsied specimens. The autopsied ages were from 48 to 75 years old (average: 64), and their clinical follow-up periods were from 0.8 to 4.0 years (average: 1.9). Muscular atrophy developed from an upper limb in three patients, whereas from a lower limb in one case and from bulbar muscles in another case. Cervical CTM was performed at C3 to C7 cervical vertebrae less than one year (four cases) and 1.9 years (one case) prior to autopsy. The macroscopical examination of the CTM and autopsied specimens showed the following characteristics: Two patients, whose clinical courses were less than one year from the onset, showed no abnormalities. Three patients, whose clinical courses were more than one year from the onset, showed a marked cervical flattening and concave of the posterolateral fissure, especially at the lower cervical level. It was supposed that this lower cervical abnormalities caused pronounced amyotrophy in the upper limbs and pyramidal tract sign of the lower limbs. Although muscular atrophy was asymmetric in one case, the spinal cord was symmetric in macroscopic appearance in both CTM and autopsied specimens. It was concluded that marked flattening and concave at the posterolateral fissure of the lower cervical spinal cord were revealed by CTM in patients whose clinical courses of amyotrophic lateral sclerosis were more than one year from the onset. (author)

The cervical cord in amyotrophic lateral sclerosis. A comparison of the CT-myelography with pathological observation

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Sugamiya, Hitoshi; Tokumaru, Yukio; Arai, Kimihito; Hirayama, Keizo [Chiba Univ. (Japan). School of Medicine

1995-08-01

The spinal cord with amyotrophic lateral sclerosis was macroscopically examined in five patients using CT-myelography (CTM) and autopsied specimens. The autopsied ages were from 48 to 75 years old (average: 64), and their clinical follow-up periods were from 0.8 to 4.0 years (average: 1.9). Muscular atrophy developed from an upper limb in three patients, whereas from a lower limb in one case and from bulbar muscles in another case. Cervical CTM was performed at C3 to C7 cervical vertebrae less than one year (four cases) and 1.9 years (one case) prior to autopsy. The macroscopical examination of the CTM and autopsied specimens showed the following characteristics: Two patients, whose clinical courses were less than one year from the onset, showed no abnormalities. Three patients, whose clinical courses were more than one year from the onset, showed a marked cervical flattening and concave of the posterolateral fissure, especially at the lower cervical level. It was supposed that this lower cervical abnormalities caused pronounced amyotrophy in the upper limbs and pyramidal tract sign of the lower limbs. Although muscular atrophy was asymmetric in one case, the spinal cord was symmetric in macroscopic appearance in both CTM and autopsied specimens. It was concluded that marked flattening and concave at the posterolateral fissure of the lower cervical spinal cord were revealed by CTM in patients whose clinical courses of amyotrophic lateral sclerosis were more than one year from the onset. (author).

Axonal excitability properties in amyotrophic lateral sclerosis.

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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.

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

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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.

Impact of an early respiratory care programme with non-invasive ventilation adaptation in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Vitacca, M; Montini, A; Lunetta, C; Banfi, P; Bertella, E; De Mattia, E; Lizio, A; Volpato, E; Lax, A; Morini, R; Paneroni, M

2018-03-01

Forced vital capacity (FVC) NIV) in amyotrophic lateral sclerosis (ALS). It was hypothesized that a very early start of NIV could lengthen the free interval before death compared to later-start NIV; as a secondary outcome, the survival rate of patients on NIV without tracheotomy was also evaluated. This retrospective study was conducted on 194 ALS patients, divided into a later group (LG) with FVC NIV prescription (n = 129) and a very early group (VEG) with FVC ≥80% at NIV prescription (n = 65). Clinical and respiratory functional data and time free to death between groups over a 3-year follow-up were compared. At 36 months from diagnosis, mortality was 35% for the VEG versus 52.7% for the LG (P = 0.022). Kaplan-Meier survival curves adjusted for tracheotomy showed a lower probability of death (P = 0.001) for the VEG as a whole (P = 0.001) and for the non-bulbar (NB) subgroup (P = 0.007). Very early NIV was protective of survival for all patients [hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.28-0.74; P = 0.001] and for the NB subgroup (HR 0.43; 95% CI 0.23-0.79; P = 0.007), whilst a tracheotomy was protective for all patients (HR 0.27; 95% CI 0.15-0.50; P = 0.000) and both NB (HR 0.26; 95% CI 0.12-0.56; P = 0.001) and bulbar subgroups (HR 0.29; 95% CI 0.11-0.77; P = 0.013). Survival in VEG patients on NIV without tracheotomy was three times that for the LG (43.1% vs. 14.7%). Very early NIV prescription prolongs the free time from diagnosis to death in NB ALS patients whilst tracheotomy reduces the mortality risk in all patients. © 2017 EAN.

Current view and perspectives in amyotrophic lateral sclerosis

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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.

Outcomes of percutaneous endoscopic gastrostomy tube insertion in respiratory impaired amyotrophic lateral sclerosis patients under noninvasive ventilation.

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Czell, David; Bauer, Matthias; Binek, Janek; Schoch, Otto D; Weber, Markus

2013-05-01

Percutaneous endoscopic gastrostomy (PEG) tube placement in amyotrophic lateral sclerosis (ALS) patients with impaired respiratory function is associated with an increased risk of peri-procedural and post-interventional complications. It was the aim of the study to analyze peri- and post-interventional complications and survival after PEG tube placement under noninvasive ventilation (NIV) in ALS patients with various degrees of respiratory impairment. Twenty-six subjects were included in this retrospective case study. Prior to PEG tube placement, training with ventilatory support via an oronasal mask was performed with ALS subjects on the pneumology ward. PEG placement was then performed under continuous NIV. FVC, sniff nasal inspiratory pressure, and demographic data were assessed. Complication rates and 1-month and overall survival rates were analyzed. There were no deaths within 24 hours after PEG placement. One subject died within the first month. The mean survival rate after PEG was 12 ± 10 months (range 0.6-42 months). There was no difference in post-PEG survival between subjects with moderately (> 50%) and severely (NIV in ALS subjects.

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.

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

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.

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.

Prospective study on 12 patients of salivary glands radiotherapy as treatment of salivary stasis in patients suffering from amyotrophic lateral sclerosis; etude prospective sur 12 patients de radiotherapie des glandes salivaires comme traitement de la stase salivaire chez des patients atteints de sclerose laterale amyotrophique

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Assouline, A.; Delanian, S. [Oncologie radiotherapie, centre clinique de la Porte-de-Saint-Cloud, Boulogne (France); Lenglet, T.; Bruneteau, G.; Le Forestier, N.; Salachas, F.; Lebouteux, M.; Abdelnour, M.; Meininger, V.; Pradat, P.F. [Departement des maladies du systeme nerveux, groupe hospitalier Pitie-Salpetriere, AP-HP, Paris (France)

2011-10-15

The authors report a study which aimed at assessing the efficiency and tolerance of salivary gland radiotherapy in patients suffering from amyotrophic lateral sclerosis. Twelve patients have been treated by conformational irradiation after a planning scanography with support mask. Results are discussed in terms of salivary discomfort (almost immediate disappearance in 11 cases), and other minor effects. Although a greater number of patients is still needed, the treatment gives promising results. Short communication

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...

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

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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.

Widespread temporo-occipital lobe dysfunction in amyotrophic lateral sclerosis.

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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.

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

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DeYoung Joseph

2009-08-01

Full Text Available 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 gene expression profiles in whole blood of ALS patients. Results Our transcriptional study showed dramatic changes in blood of ALS patients; 2,300 probes (9.4% showed significant differential expression in a discovery dataset consisting of 30 ALS patients and 30 healthy controls. Weighted gene co-expression network analysis (WGCNA was used to find disease-related networks (modules and disease related hub genes. Two large co-expression modules were found to be associated with ALS. Our findings were replicated in a second (30 patients and 30 controls and third dataset (63 patients and 63 controls, thereby demonstrating a highly significant and consistent association of two large co-expression modules with ALS disease status. Ingenuity Pathway Analysis of the ALS related module genes implicates enrichment of functional categories related to genetic disorders, neurodegeneration of the nervous system and inflammatory disease. The ALS related modules contain a number of candidate genes possibly involved in pathogenesis of ALS. Conclusion This first large-scale blood gene expression study in ALS observed distinct patterns between cases and controls which may provide opportunities for biomarker development as well as new insights into the molecular mechanisms of the disease.

Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis

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Sivak, Stefan [Comenius University, Clinic of Neurology, Jessenius Faculty of Medicine, Martin (Slovakia); Jessenius Medical Faculty, Clinic of Neurology, Martin (Slovakia); Bittsansky, Michal; Dobrota, Dusan [Comenius University, Department of Medical Biochemistry, Jessenius Faculty of Medicine, Martin (Slovakia); Kurca, Egon; Turcanova-Koprusakova, Monika; Grofik, Milan; Nosal, Vladimir [Comenius University, Clinic of Neurology, Jessenius Faculty of Medicine, Martin (Slovakia); Polacek, Hubert [Comenius University, Clinic of Radiodiagnostics, Jessenius Faculty of Medicine, Martin (Slovakia)

2010-12-15

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting upper and lower motor neurons. Due to relative fast progression of the disease, early diagnosis is essential. Proton magnetic resonance spectroscopy ({sup 1}H-MRS) is used for objectivization of upper motor neuron (UMN) lesions. The aim of this study was to assess the use of {sup 1}H-MRS in the early stages of ALS. Eleven patients with clinically definite (n = 2), probable (n = 7), and probable laboratory-supported (n = 2) diagnosis of ALS with disease duration of less than 14 months were studied. Control group consists of 11 sex- and age-matched healthy subjects. All subjects underwent assessment of functional disability using revised ALS Functional Rating Scale (ALSFRS-R) and single-voxel {sup 1}H-MRS examination of both precentral gyri, pons, medulla oblongata, and occipital lobe. Spectra were evaluated with LCModel software. The mean disease duration was 6.5 {+-} 3.5 months. The median ALSFRS-R was 42. Significant decrease between patient and control groups was found in the NAA/Cre ratio in the left and right precentral gyri (p = 0.008, p = 0.040). Other metabolite ratios in other areas did not show significant differences. Total ALSFRS-R score weakly positively correlated with NAA/Cre ratio in the left precentral gyrus (p = 0.047). {sup 1}H-MRS is sensitive to detect metabolic changes caused by neurodegeneration processes during ALS and can be used for detection of UMN dysfunction. These MRS changes in the early stages of ALS are most prominent in motor cortex. (orig.)

Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis

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Sivak, Stefan; Bittsansky, Michal; Dobrota, Dusan; Kurca, Egon; Turcanova-Koprusakova, Monika; Grofik, Milan; Nosal, Vladimir; Polacek, Hubert

2010-01-01

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting upper and lower motor neurons. Due to relative fast progression of the disease, early diagnosis is essential. Proton magnetic resonance spectroscopy ( 1 H-MRS) is used for objectivization of upper motor neuron (UMN) lesions. The aim of this study was to assess the use of 1 H-MRS in the early stages of ALS. Eleven patients with clinically definite (n = 2), probable (n = 7), and probable laboratory-supported (n = 2) diagnosis of ALS with disease duration of less than 14 months were studied. Control group consists of 11 sex- and age-matched healthy subjects. All subjects underwent assessment of functional disability using revised ALS Functional Rating Scale (ALSFRS-R) and single-voxel 1 H-MRS examination of both precentral gyri, pons, medulla oblongata, and occipital lobe. Spectra were evaluated with LCModel software. The mean disease duration was 6.5 ± 3.5 months. The median ALSFRS-R was 42. Significant decrease between patient and control groups was found in the NAA/Cre ratio in the left and right precentral gyri (p = 0.008, p = 0.040). Other metabolite ratios in other areas did not show significant differences. Total ALSFRS-R score weakly positively correlated with NAA/Cre ratio in the left precentral gyrus (p = 0.047). 1 H-MRS is sensitive to detect metabolic changes caused by neurodegeneration processes during ALS and can be used for detection of UMN dysfunction. These MRS changes in the early stages of ALS are most prominent in motor cortex. (orig.)

Protocol for a double-blind randomised placebo-controlled trial of lithium carbonate in patients with amyotrophic Lateral Sclerosis (LiCALS) [Eudract number: 2008-006891-31

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Kelly Joanna; Thornhill Marie; Murphy Caroline; Morrison Karen E; Young Carolyn A; Shaw Pamela J; Al-Chalabi Ammar; Steen I Nicholas; Leigh P Nigel

2011-01-01

Abstract Background Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disorder characterised by loss of motor neurons leading to severe weakness and death from respiratory failure within 3-5 years. Riluzole prolongs survival in ALS. A published report has suggested a dramatic effect of lithium carbonate on survival. 44 patients were studied, with 16 randomly selected to take LiCO3 and riluzole and 28 allocated to take riluzole alone. In the group treated with lithium, n...

Positive effects of tertiary centres for amyotrophic lateral sclerosis on outcome and use of hospital facilities.

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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.

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

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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

2016-07-01

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. To identify gene variants influencing survival in ALS. This genome-wide association study (GWAS) analyzed survival in data sets from several European countries and the United States that were collected by the Italian Consortium for the Genetics of ALS and the International Consortium on Amyotrophic Lateral Sclerosis Genetics. The study population included 4256 patients with ALS (3125 [73.4%] deceased) with genotype data extended to 7 174 392 variants by imputation analysis. Samples of DNA were collected from January 1, 1993, to December 31, 2009, and analyzed from March 1, 2014, to February 28, 2015. Cox proportional hazards regression under an additive model with adjustment for age at onset, sex, and the first 4 principal components of ancestry, followed by meta-analysis, were used to analyze data. Survival distributions for the most associated genetic variants were assessed by Kaplan-Meier analysis. Among the 4256 patients included in the analysis (2589 male [60.8%] and 1667 female [39.2%]; mean [SD] age at onset, 59 [12] years), the following 2 novel loci were significantly associated with ALS survival: at 10q23 (rs139550538; P = 1.87 × 10-9) and in the CAMTA1 gene at 1p36 (rs2412208, P = 3.53 × 10-8). At locus 10q23, the adjusted hazard ratio for patients with the rs139550538 AA or AT genotype was 1.61 (95% CI, 1.38-1.89; P = 1.87 × 10-9), corresponding to an 8-month reduction in survival compared with TT carriers. For rs2412208 CAMTA1, the adjusted hazard ratio for patients with the GG or GT genotype was 1.17 (95% CI, 1.11-1.24; P = 3.53 × 10-8), corresponding to a 4-month reduction in survival compared with TT carriers. This GWAS robustly identified 2 loci at genome-wide levels of

Nutritional intervention for amyotrophic lateral sclerosis.

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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.

Amyotrophic lateral sclerosis in Slovenia – analysis of patient population at the Ljubljana Institute of Clinical Neurophysiology

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Mojca Kirbiš

2015-09-01

Full Text Available Backgorund: Data on epidemiology and disease characteristics of amyotrophic lateral sclerosis (ALS are geographically limited and no systematically collected data exist for slovenian patients. We performed a retrospective descriptive study on clinical attributes and disease course of patients with ALS treated at the Institute of clinical neurophysiology (ICN, University Medical Centre Ljubljana since the foundation of a specialised ALS group.Methods:  All 271 patients treated at ICN in the 10-year period between 2003 and 2012 were analysed. Data on basic demographic characteristics, phenotype of disease onset, diagnostic delay, survival, family history, use of percutaneous gastrostomy (PEG, of non-invasive ventilation and of riluzole were obtained.Results:  Mean age at symptoms onset was 62.7 ± 11.4 years, median diagnostic delay 11 (IQ range  7–19 months and mean survival from time of enrolment 16.4 ± 15.1 months.  179 (66.1%patients had spinal onset disease and 71 (26.2% bulbar onset disease. Factors associated with longer survival were lower age at enrolment, longer diagnostic delay and use of PEG. The proportion of patients using non-invasive ventilatory support was rising through the analysed years.Conclusions: Disease characteristics and survival in our series are similar to data from other tertiary care centres. The need for non-invasive ventilatory support in ALS patients is increasing.

Two consecutive pregnancies in early and late stage of amyotrophic lateral sclerosis.

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Sarafov, Stayko; Doitchinova, Maryana; Karagiozova, Zhvka; Slancheva, Boriana; Dengler, Reinhard; Petri, Susanne; Kollewe, Katja

2009-01-01

There are few reports on pregnancies in sporadic and familial amyotrophic lateral sclerosis (ALS). We report on a young woman with sporadic ALS who gave birth twice during the course of her disease. The first pregnancy occurred 13 months after the onset of symptoms, and one month after diagnosis. The pregnancy was uncomplicated and resulted in vaginal delivery of a healthy boy. Fifteen months later, when she was already bed-ridden, she became pregnant again. She received a percutaneous endoscopic gastrostomy in the 21st gestational week and underwent early Caesarean section in the 34th week of gestation. The child was ventilated for 72 h in a neonatological unit. The patient was tracheotomized and ventilated two months later, i.e. 47 months after symptom onset, and died nine months later from gastrointestinal haemorrhage. Her two children have developed without abnormalities to date. This case confirms that pregnancies in early-stage ALS can develop normally and may result in uncomplicated vaginal delivery. Pregnancies in late stages may be critical for mother and child, and early delivery by Caesarean section may become necessary although neonatal outcome can be good.

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

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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

Involvement of corpus callosum in amyotrophic lateral sclerosis shown by MRI

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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.)

Involvement of corpus callosum in amyotrophic lateral sclerosis shown by MRI

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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.)

Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case series

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Ueno Hiroki

2011-12-01

Full Text Available Abstract Introduction Previous studies have shown widespread multisystem degeneration in patients with sporadic amyotrophic lateral sclerosis who develop a total locked-in state and survive under mechanical ventilation for a prolonged period of time. However, the disease progressions reported in these studies were several years after disease onset. There have been no reports of long-term follow-up with brain imaging of patients with familial amyotrophic lateral sclerosis at an advanced stage of the disease. We report the cases of siblings with amyotrophic lateral sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding optineurin, in whom brain computed tomography scans were followed up for more than 20 years. Case presentation The patients were a Japanese brother and sister. The elder sister was 33 years of age at the onset of disease, which began with muscle weakness of her left lower limb. Two years later she required mechanical ventilation. She became bedridden at the age of 34, and died at the age of 57. A computed tomography scan of her brain at the age of 36 revealed no abnormality. Atrophy of her brain gradually progressed. Ten years after the onset of mechanical ventilation, atrophy of her whole brain, including the cerebral cortex, brain stem and cerebellum, markedly progressed. Her younger brother was 36 years of age at the onset of disease, which presented as muscle weakness of his left upper limb. One year later, he showed dysphagia and dysarthria, and tracheostomy ventilation was performed. He became bedridden at the age of 37 and died at the age of 55. There were no abnormal intracranial findings on brain computed tomography scans obtained at the age of 37 years. At the age of 48 years, computed tomography scans showed marked brain atrophy with ventricular dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his elder sister. Conclusion We conclude that a homozygous deletion

Severe brain atrophy after long-term survival seen in siblings with familial amyotrophic lateral sclerosis and a mutation in the optineurin gene: a case series.

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Ueno, Hiroki; Kobatake, Keitaro; Matsumoto, Masayasu; Morino, Hiroyuki; Maruyama, Hirofumi; Kawakami, Hideshi

2011-12-12

Previous studies have shown widespread multisystem degeneration in patients with sporadic amyotrophic lateral sclerosis who develop a total locked-in state and survive under mechanical ventilation for a prolonged period of time. However, the disease progressions reported in these studies were several years after disease onset. There have been no reports of long-term follow-up with brain imaging of patients with familial amyotrophic lateral sclerosis at an advanced stage of the disease. We report the cases of siblings with amyotrophic lateral sclerosis with homozygous deletions of the exon 5 mutation of the gene encoding optineurin, in whom brain computed tomography scans were followed up for more than 20 years. The patients were a Japanese brother and sister. The elder sister was 33 years of age at the onset of disease, which began with muscle weakness of her left lower limb. Two years later she required mechanical ventilation. She became bedridden at the age of 34, and died at the age of 57. A computed tomography scan of her brain at the age of 36 revealed no abnormality. Atrophy of her brain gradually progressed. Ten years after the onset of mechanical ventilation, atrophy of her whole brain, including the cerebral cortex, brain stem and cerebellum, markedly progressed. Her younger brother was 36 years of age at the onset of disease, which presented as muscle weakness of his left upper limb. One year later, he showed dysphagia and dysarthria, and tracheostomy ventilation was performed. He became bedridden at the age of 37 and died at the age of 55. There were no abnormal intracranial findings on brain computed tomography scans obtained at the age of 37 years. At the age of 48 years, computed tomography scans showed marked brain atrophy with ventricular dilatation. Subsequently, atrophy of the whole brain rapidly progressed as in his elder sister. We conclude that a homozygous deletion-type mutation in the optineurin gene may be associated with widespread

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

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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

Ethical considerations in the management of amyotrophic lateral sclerosis.

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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.

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

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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...

Mutations in the PFN1 gene are not a common cause in patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration in France.

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Lattante, Serena; Le Ber, Isabelle; Camuzat, Agnès; Brice, Alexis; Kabashi, Edor

2013-06-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are 2 adult onset neurological disorders with overlapping symptoms and clinical characteristics. It is well established that they share a common pathologic and genetic background. Recently, mutations in profilin 1 gene (PFN1) have been identified in patients with familial ALS, suggesting a role for this gene in the pathogenesis of the disease. Based on this, we hypothesized that mutations in PFN1 might also contribute to FTLD disease. We studied a French cohort of 165 ALS/FTLD patients, without finding any variant. We conclude that mutations in PFN1 are not a common cause for ALS/FTLD in France. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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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.

Home tracheotomy mechanical ventilation in patients with amyotrophic lateral sclerosis: causes, complications and 1-year survival.

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Sancho, Jesús; Servera, Emilio; Díaz, José Luis; Bañuls, Pilar; Marín, Julio

2011-11-01

Home tracheotomy mechanical ventilation (HTMV) can prolong survival in patients with amyotrophic lateral sclerosis (ALS) when non-invasive ventilation (NIV) fails, but knowledge about HTMV is scarce. The aim of this study was to determine the causes of tracheotomy and the main issues of 1-year HTMV in a cohort of patients with ALS. A prospective study of all patients needing HTMV was performed in a referral respiratory care unit (RCU) from April 2001 to January 2010. Patients' informed decisions about HTMV were fully respected. Caregivers were trained and could telephone the RCU. Hospital staff made home visits. All patients (n=116) agreed to participate and a tracheotomy was needed for 76, mainly due to bulbar dysfunction. Of the 38 who had a tracheotomy, in 21 it was performed in an acute setting and in 17 as a non-emergency procedure. In 19 patients the tracheotomy was related to the inadequacy of mechanically assisted coughing (MAC) to maintain normal oxygen saturation. During HTMV, 19 patients required hospitalisation, 12 with respiratory problems. The 1-year survival rate was 78.9%, with a mean survival of 10.39 months (95% CI 9.36 to 11.43). Sudden death was the main cause of death (n=9) and only one patient died from respiratory causes. No predictive factors for survival were found. Besides NIV inadequacy, the ineffectiveness of mechanically assisted coughing appears to be a relevant cause of tracheotomy for patients with ALS with severe bulbar dysfunction. Patients choosing HTMV provided by a referral RCU could have a good 1-year survival rate, respiratory problems being the main cause of hospitalisation but not of death.

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

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.

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.

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.

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.

[Unexpected treatable dyspnea caused by intratracheal granuloma in an amyotrophic lateral sclerosis patient with mechanical ventilation].

Science.gov (United States)

Ishida, Shimon; Kimura, Fumiharu; Hosokawa, Takafumi; Satoh, Toshihiko; Furutama, Daisuke; Sugino, Masakazu

2007-09-01

Respiratory insufficiency is a problem that develops in nearly all people diagnosed with amyotrophic lateral sclerosis (ALS). A 46-year-old man with ALS, who had been in a bedridden state with tracheal ventilation support, complained of faintness and dyspnea. The airway pressure of the ventilator had increased, and bleeding from the trachea had occurred several times. A fiberoptic bronchoscopy showed granulation located on the anterior wall of the trachea and severe airway obstruction of the tracheostomy tube. Although a long tracheostomy tube had been intubated for the initial management of the tracheal granulation, a tumor on the posterior tracheal wall had relapsed and occluded the tracheal lumen. A self-expandable metallic airway stent was placed into the tracheal stenosis. After stenting, his symptoms of dyspnea and syncope imploved, and the increased airway pressure of the ventilator was normalized. We speculated that the tracheal granuloma had occurred due to a tracheal mucosal injury related to endotracheal suctioning. We should pay attention to complaints of dyspnea in ALS patients with tracheostomy and make a careful consideration to airway care including suction management.

MR imaging of multiple sclerosis in patients with negative cerebrospinal fluid

International Nuclear Information System (INIS)

Dooms, G.C.; Mathurin, P.; Cornelis, G.; Laterre, E.C.; Demeure, R.

1986-01-01

A prospective study was performed to assess the value of MR imaging for detecting demyelinating disease of the brain in 50 patients with clinically suspected multiple sclerosis but negative cerebrospinal fluid (CSF). The MR imaging examinations were performed with a superconducting magnet (Philips Gyroscan S15) operating at 0.5T. A multisection, double spin-echo technique was used in all cases (TR = 2,100 msec, TE = 50 and 100 msec). No abnormality was demonstrated in eight patients. In the others, lesions were usually located in the periventricular white matter (rounded masses and/or high signal intensity bands along the lateral ventricles), the brain stem and thalami (12 patients), and the cerebellum (6 patients). In conclusion, MR imaging appears to be an exquisite imaging modality for confirmation of clinically suspected multiple sclerosis in patients with negative CSF. However, it must include examination of the spinal cord when the brain examination is negative

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...

Strategies to reduce hyperthermia in ambulatory multiple sclerosis patients.

Science.gov (United States)

Edlich, Richard F; Buschbacher, Ralph M; Cox, Mary Jude; Long, William B; Winters, Kathryne L; Becker, Daniel G

2004-01-01

Approximately 400,000 Americans have multiple sclerosis. Worldwide, multiple sclerosis affects 2.5 million individuals. Multiple sclerosis affects two to three times as many women as men. The adverse effects of hyperthermia in patients with multiple sclerosis have been known since 1890. While most patients with multiple sclerosis experience reversible worsening of their neurologic deficits, some patients experience irreversible neurologic deficits. In fact, heat-induced fatalities have been encountered in multiple sclerosis patients subjected to hyperthermia. Hyperthermia can be caused through sun exposure, exercise, and infection. During the last 50 years, numerous strategies have evolved to reduce hyperthermia in individuals with multiple sclerosis, such as photoprotective clothing, sunglasses, sunscreens, hydrotherapy, and prevention of urinary tract infections. Hydrotherapy has become an essential component of rehabilitation for multiple sclerosis patients in hospitals throughout the world. On the basis of this positive hospital experience, hydrotherapy has been expanded through the use of compact aquatic exercise pools at home along with personal cooling devices that promote local and systemic hypothermia in multiple sclerosis patients. The Multiple Sclerosis Association of America and NASA have played leadership roles in developing and recommending technology that will prevent hyperthermia in multiple sclerosis patients and should be consulted for new technological advances that will benefit the multiple sclerosis patient. In addition, products recommended for photoprotection by The Skin Cancer Foundation may also be helpful to the multiple sclerosis patient's defense against hyperthermia. Infections in the urinary tract, especially detrusor-external sphincter dyssynergia, are initially managed conservatively with intermittent self-catheterization and pharmacologic therapy. In those cases, refractory to conservative therapy, transurethral external

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.

A muscle ultrasound score in the diagnosis of amyotrophic lateral sclerosis.

Science.gov (United States)

Tsuji, Yukiko; Noto, Yu-Ichi; Shiga, Kensuke; Teramukai, Satoshi; Nakagawa, Masanori; Mizuno, Toshiki

2017-06-01

The aims of this study are to elucidate the frequencies and distribution of fasciculations using muscle ultrasound in patients with amyotrophic lateral sclerosis (ALS) and those with other conditions mimicking ALS, and subsequently to develop a novel fasciculation score for the diagnosis of ALS. Ultrasound of 21 muscles was performed to detect fasciculations in 36 consecutive patients suspected of having ALS. We developed a fasciculation ultrasound score that indicated the number of muscles with fasciculations in statistically selected muscles. A total of 525 muscles in 25 ALS patients and 231 in 11 non-ALS patients were analysed. Using relative operating characteristic and multivariate logistic regression analysis, we selected the trapezius, deltoid, biceps brachii, abductor pollicis brevis, abdominal, vastus lateralis, vastus medialis, biceps femoris, and gastrocnemius muscles for the fasciculation ultrasound score. The mean scores were higher in the ALS group than those in the non-ALS group (5.3±0.5vs. 0.3±0.7) (mean±SD); pdifferentiating ALS patients from non-ALS patients. The fasciculation ultrasound score can be a simple and useful diagnostic marker of ALS. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

[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.

[Neuropsychology of mildly disabled patients with relapsing-remitting multiple sclerosis].

Science.gov (United States)

Santiago Rolanía, Olga; Guàrdia Olmos, Joan; Arbizu Urdiain, Txomin

2006-02-01

Previous papers have mainly demonstrated the presence of cognitive impairment in patients with multiple sclerosis (MS), these changes have been traditionally associated with the later stages of the disease. In the current study, a comprehensive neuropsychological battery was administered to 216 relapsing-remitting MS patients with mild clinical disability (EDSSreproduction visual memory; and long term verbal memory of texts, and information processing speed. We also observed greeter incidence of depressive symptoms in patients. And a little relation of the cognitive deficits with the clinical variables in these phase of the disease.

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.

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).

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

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.)

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.)

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.)

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.)

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.

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

Science.gov (United States)

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

[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.

Profile of medical care costs in patients with amyotrophic lateral sclerosis in the Medicare programme and under commercial insurance.

Science.gov (United States)

Meng, Lisa; Bian, Amy; Jordan, Scott; Wolff, Andrew; Shefner, Jeremy M; Andrews, Jinsy

2018-02-01

To determine amyotrophic lateral sclerosis (ALS)-associated costs incurred by patients covered by Medicare and/or commercial insurance before, during and after diagnosis and provide cost details. Costs were calculated from the Medicare Standard Analytical File 5% sample claims data from Parts A and B from 2009, 2010 and 2011 for ALS Medicare patients aged ≥70 years (monthly costs) and ≥65 years (costs associated with disability milestones). Commercial insurance patients aged 18-63 years were selected based on the data provided in the Coordination of Benefits field from Truven MarketScan® in 2008-2010. Monthly costs increased nine months before diagnosis, peaked during the index month (Medicare: $10,398; commercial: $9354) and decreased but remained high post-index. Costs generally shifted from outpatient to inpatient and private nursing after diagnosis; prescriptions and durable medical equipment costs were much higher for commercial patients post-diagnosis. Patients appeared to progress to disability milestones more rapidly as their disease progressed in severity (14.4 months to non-invasive ventilation [NIV] vs. 16.6 months to hospice), and their costs increased accordingly (NIV: $58,973 vs. hospice: $76,179). For newly diagnosed ALS patients in the U.S., medical costs are substantial and increase rapidly and substantially with each disability milestone.

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.

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

Assessment of the upper motor neuron in amyotrophic lateral sclerosis.

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

2016-07-01

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

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...

Usability of eyetracking computer systems and impact on psychological wellbeing in patients with advanced amyotrophic lateral sclerosis.

Science.gov (United States)

Linse, Katharina; Rüger, Wolfgang; Joos, Markus; Schmitz-Peiffer, Henning; Storch, Alexander; Hermann, Andreas

2018-05-01

Restrictions in communicative abilities are well known in patients with amyotrophic lateral sclerosis (ALS), but only few approaches in terms of evaluation of supportive technologies have been made. We aimed to assess the use and perceived usability of eye-tracking computer devices (ETCS) of severely impacted patients with ALS in an independent, direct manner and relate it to psychological well-being. ETCS enable active communication and social participation in the quadriplegic and anarthric disease state. Therefore, ETCS-based versions of widely used psychosocial questionnaires (ADI-12, SeiQoL-DW, WHO-5) as well as structured questions on communicative functioning and ETCS usage were developed to assess ALS patients, their next of kin and professional caregivers. Eleven patients (ALSFRS-R: 5.3 ± 5.9; ALS duration: 6.5 ± 3.8 years, range 1‒12; 82% invasively ventilated), nine next of kin and 10 professional caregivers could be assessed. Patients reported a mean use of their personal ETCS of 9.1 h per d (range 0.5‒16), with a high user satisfaction, preservation of communicative abilities and subjective indispensability of the ETCS. ETCS use was associated with higher psychological well-being. Next of kin and professional caregivers also nominated some critical aspect, which remains to be clarified. Our results strengthen the evidence that preserved mental autonomy influences psychological well-being in ALS and might even modify disease course and end-of-life-decisions in ALS.

Healthcare professionals' views on the provision of gastrostomy and noninvasive ventilation to amyotrophic lateral sclerosis patients in England, Wales, and Northern Ireland.

Science.gov (United States)

Ruffell, Tamatha O; Martin, Naomi H; Janssen, Anna; Wijesekera, Lokesh; Knights, Catherine; Burman, Rachel; Oliver, David J; Al-Chalabi, Ammar; Goldstein, Laura H

2013-01-01

Gastrostomy and noninvasive ventilation (NIV) are recommended interventions for the management of symptoms associated with amyotrophic lateral sclerosis (ALS). This study aimed to quantify the views of a range of healthcare professionals (HCPs) on the provision of these interventions in the United Kingdom. A total of 177 HCPs participated in an online survey. Significant differences were found between medical and allied HCPs' views on: whether HCPs adhere to policy and accept legal constraints when it comes to making gastrostomy available to people with ALS; the impressions that HCPs receive of the way patients and caregivers understand the effects of gastrostomy and NIV on symptoms and quality of life; and the challenges HCPs face when caring for patients who have refused gastrostomy. More widely available guidelines for the provision of gastrostomy and advice on the best way to impart information to patients and caregivers about gastrostomy and NIV appear to be needed.

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.

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…

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.

Clinical features and lifestyle of patients with amyotrophic lateral sclerosis in Campania: brief overview of an Italian database

Directory of Open Access Journals (Sweden)

Francesca Trojsi

2012-01-01

Full Text Available BACKGROUND: Physical activity and occupational exposures appeared to play a relevant role in pathogenesis of amyotrophic lateral sclerosis (ALS, a neurodegenerative disease of unknown origin. MATERIALS AND METHODS: We aimed to make an overview of the clinical characteristics and lifestyle (occupation and sport of a population of 395 patients with ALS from Campania, in southern Italy. RESULTS: ALS onset resulted anticipated of about 11 years in industry workers, whilst the more frequent site of onset among farmers was upper limbs. Compared to non-athletes, athletes, particularly soccer players, showed a 7 years anticipation of ALS onset, with higher mortality after 5 years. DISCUSSION AND CONCLUSIONS: We suggest that subjects genetically prone to abnormal response to hypoxia during strenuous physical activity or exposed to neurotoxic agents, such as athletes, farmers or industry workers, might present increased risk to develop ALS. Future case-control and follow-up studies on our population should be implemented to deepen the present results.

The processing of actions and action-words in amyotrophic lateral sclerosis patients.

Science.gov (United States)

Papeo, Liuba; Cecchetto, Cinzia; Mazzon, Giulia; Granello, Giulia; Cattaruzza, Tatiana; Verriello, Lorenzo; Eleopra, Roberto; Rumiati, Raffaella I

2015-03-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with prime consequences on the motor function and concomitant cognitive changes, most frequently in the domain of executive functions. Moreover, poorer performance with action-verbs versus object-nouns has been reported in ALS patients, raising the hypothesis that the motor dysfunction deteriorates the semantic representation of actions. Using action-verbs and manipulable-object nouns sharing semantic relationship with the same motor representations, the verb-noun difference was assessed in a group of 21 ALS-patients with severely impaired motor behavior, and compared with a normal sample's performance. ALS-group performed better on nouns than verbs, both in production (action and object naming) and comprehension (word-picture matching). This observation implies that the interpretation of the verb-noun difference in ALS cannot be accounted by the relatedness of verbs to motor representations, but has to consider the role of other semantic and/or morpho-phonological dimensions that distinctively define the two grammatical classes. Moreover, this difference in the ALS-group was not greater than the noun-verb difference in the normal sample. The mental representation of actions also involves an executive-control component to organize, in logical/temporal order, the individual motor events (or sub-goals) that form a purposeful action. We assessed this ability with action sequencing tasks, requiring participants to re-construct a purposeful action from the scrambled presentation of its constitutive motor events, shown in the form of photographs or short sentences. In those tasks, ALS-group's performance was significantly poorer than controls'. Thus, the executive dysfunction manifested in the sequencing deficit -but not the selective verb deficit- appears as a consistent feature of the cognitive profile associated with ALS. We suggest that ALS can offer a valuable model to study the relationship between

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.

Energy requirement assessed by doubly-labeled water method in patients with advanced amyotrophic lateral sclerosis managed by tracheotomy positive pressure ventilation.

Science.gov (United States)

Ichihara, Noriko; Namba, Kazuyoshi; Ishikawa-Takata, Kazuko; Sekine, Kazunori; Takase, Mitsunori; Kamada, Yuko; Fujii, Seigo

2012-10-01

This study aimed to clarify the energy requirement in patients with amyotrophic lateral sclerosis (ALS) undergoing tracheostomy positive pressure ventilation with tracheostomy. Total energy expenditure (TEE) was measured in 10 hospitalized bedridden ALS patients using the doubly-labeled water (DLW) method. The mean TEE/day and TEE/fat- free mass estimated by DLW method were 934 ± 201 kcal/day and 34.8 ± 5.5 kcal/kg/day, respectively. The mean TEE/resting metabolic rate (RMR) was 0.85 when RMR was estimated by the Harris-Benedict equation, 0.91 by Dietary Reference Intake (DRI), and 0.97 by Ganpule's equation using fat-free mass (FFM). The ratios of TEE to measured RMR were 1.05, 1.15 and 1.23 in three patients. In conclusion, multiplying measured RMR by 1.1 to 1.2 is considered to be appropriate to estimate energy need. However, because it is difficult to measure RMR directly in a clinical setting, an appropriate equation for estimating RMR for ALS patient should be developed.

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.

Interplay of upper and lower motor neuron degeneration in amyotrophic lateral sclerosis.

Science.gov (United States)

de Carvalho, Mamede; Poliakov, Artiom; Tavares, Cristiano; Swash, Michael

2017-11-01

We studied motor unit recruitment to test a new method to identify motor unit firing rate (FR) variability. We studied 68 ALS patients, with and without upper neuron signs (UMN) in lower limbs, 24 patients with primary lateral sclerosis (PLS), 13 patients with spinal cord lesion and 39 normal subjects. All recordings were made from tibialis anterior muscles of normal strength. Subjects performed a very slight contraction in order to activate 2 motor units in each recording. 5-7 motor unit pairs were recorded in each subject. Mean consecutive differences (MCD) were calculated for each pair of potentials. The mean MCD for each muscle was estimated as the mean from the total number of pairs recorded. Ap valuemotor unit in a pair of units was markedly reduced in PLS, and in subjects with spinal cord lesions. These results support a lower threshold and reduced FR fluctuation in spinal motor neurons of spastic patients. This method can be developed for detection of UMN lesions. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

MRI of the intracranial corticospinal tracts in amyotrophic and primary lateral sclerosis

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Peretti-Viton, P.; Brunel, H.; Daniel, C.; Salazard, B.; Salamon, G. [Dept. of Neuroradiology, Hopital de la Timone, Marseille (France); Azulay, J.P.; Trefouret, S.; Pouget, J.; Serratrice, G. [Dept. of Neurology and Neuromuscular Diseases, Hopital de la Timone, Marseille (France); Viton, J.M. [Dept. of Physical Medicine and Rehabilitation, Hopital de la Timone, Marseille (France); Flori, A. [Medical Informatics Dept., Hopital Nord, Marseille (France)

1999-10-01

Our aim was to investigate the corticospinal tracts (CST) in motor neurone disease, using MRI, and to correlate findings with clinical data. We studied 31 patients with amyotrophic (ALS) and eight with primary lateral sclerosis (PLS). The signal from the CST was classified into four grades on T2-weighted images, and compared to T2-weighted images of 37 age-matched control subjects. No abnormalities were seen in the CST on T1-weighted images and were rarely evident on proton-density weighting. Variable high signal in the CST was found on T2-weighted images in 35 patients, and in 29 control subjects. Our grades 0 and 1 were more frequent in control subjects, grades 2 and 3 more frequent in patients. We found no correlation between the high signal and clinical data, including the duration of the illness. We therefore conclude that this technique is neither sensitive nor specific except in grade 3 which is quite specific for ALS. In half the patients we found atrophy of the superior parietal gyrus, which merits further study. (orig.)

MRI of the intracranial corticospinal tracts in amyotrophic and primary lateral sclerosis

International Nuclear Information System (INIS)

Peretti-Viton, P.; Brunel, H.; Daniel, C.; Salazard, B.; Salamon, G.; Azulay, J.P.; Trefouret, S.; Pouget, J.; Serratrice, G.; Viton, J.M.; Flori, A.

1999-01-01

Our aim was to investigate the corticospinal tracts (CST) in motor neurone disease, using MRI, and to correlate findings with clinical data. We studied 31 patients with amyotrophic (ALS) and eight with primary lateral sclerosis (PLS). The signal from the CST was classified into four grades on T2-weighted images, and compared to T2-weighted images of 37 age-matched control subjects. No abnormalities were seen in the CST on T1-weighted images and were rarely evident on proton-density weighting. Variable high signal in the CST was found on T2-weighted images in 35 patients, and in 29 control subjects. Our grades 0 and 1 were more frequent in control subjects, grades 2 and 3 more frequent in patients. We found no correlation between the high signal and clinical data, including the duration of the illness. We therefore conclude that this technique is neither sensitive nor specific except in grade 3 which is quite specific for ALS. In half the patients we found atrophy of the superior parietal gyrus, which merits further study. (orig.)

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

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...

Motoneuron firing in amyotrophic lateral sclerosis (ALS

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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.

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)…

Intellectual function and radiological images in patients with amyotrophic lateral sclerosis. Special reference to single photon emission computed tomography images

International Nuclear Information System (INIS)

Ichikawa, Hiroo; Kanda, Mikio; Fukui, Toshiya; Sugita, Koujiro

1994-01-01

To clarify cognitive decline in amyotrophic lateral sclerosis (ALS), we compared cognitive and motor signs with neuroradiological features, with special reference to single photon emission computed tomography (SPECT), in 23 patients with ALS. Of these 23 patients, five demented patients (ALS-D) showed a decrease in voluntary speech output, abnormal behavior or character change. SPECT images in these patients were specifically characterized by marked uptake reduction in the frontal lobes. ALS patients with normal mentality (ALS-N) showed either a normal pattern or non-specific patchy uptake reduction on SPECT, but never showed the diffuse frontal uptake reduction that was observed in ALS-D patients. None of the ALS-N patients showed cognitive decline or frontal uptake reduction during the follow-up period of up to 29 months. There was no relation in either ALS-D or ALS-N patients between the degree of tracer uptake reduction and clinical features of ALS including severity and duration of illness. Clinical and neuroradiological features in ALS-D patients were compatible with those of 'frontal lobe dementia'. ALS-D patients may compose a distinct group because cognitive decline is unlikely to occur in ALS-N patients with a long clinical course. ALS-D patients may be differentiated from other non-demented ALS patients in the early clinical course by the characteristic diffuse frontal uptake reduction on SPECT. (author)

Intellectual function and radiological images in patients with amyotrophic lateral sclerosis. Special reference to single photon emission computed tomography images

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Ichikawa, Hiroo; Kanda, Mikio; Fukui, Toshiya; Sugita, Koujiro [Showa Univ., Tokyo (Japan). School of Medicine

1994-10-01

To clarify cognitive decline in amyotrophic lateral sclerosis (ALS), we compared cognitive and motor signs with neuroradiological features, with special reference to single photon emission computed tomography (SPECT), in 23 patients with ALS. Of these 23 patients, five demented patients (ALS-D) showed a decrease in voluntary speech output, abnormal behavior or character change. SPECT images in these patients were specifically characterized by marked uptake reduction in the frontal lobes. ALS patients with normal mentality (ALS-N) showed either a normal pattern or non-specific patchy uptake reduction on SPECT, but never showed the diffuse frontal uptake reduction that was observed in ALS-D patients. None of the ALS-N patients showed cognitive decline or frontal uptake reduction during the follow-up period of up to 29 months. There was no relation in either ALS-D or ALS-N patients between the degree of tracer uptake reduction and clinical features of ALS including severity and duration of illness. Clinical and neuroradiological features in ALS-D patients were compatible with those of `frontal lobe dementia`. ALS-D patients may compose a distinct group because cognitive decline is unlikely to occur in ALS-N patients with a long clinical course. ALS-D patients may be differentiated from other non-demented ALS patients in the early clinical course by the characteristic diffuse frontal uptake reduction on SPECT. (author).

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

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

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....

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.

Relationship between respiratory failure and plasma noradrenaline levels in amyotrophic lateral sclerosis.

Science.gov (United States)

Yamashita, A; Koike, Y; Takahashi, A; Hirayama, M; Murakami, N; Sobue, G

1997-08-01

We evaluated plasma noradrenaline (NA) levels at test and during head-up tilt test in 20 patients with sporadic amyotrophic lateral sclerosis (ALS). Their fasting plasma NA levels ranged from 195 to 4227 pg/ml. The average plasma NA level was 483 pg/ml in five ambulatory patients, 341 in two wheelchair-bound patients, 1264 in 11 bedridden patients, and 208 in two respirator-dependent patients whose disability grading was the worst among the four groups. Arterial carbon dioxide (PCO2) was evaluated as a measure of respiratory function. The coefficient of correlation between PCO2 and plasma NA was r = 0.654 (p respiratory failure or lower motor neuron dysfunction may relate to the elevation of plasma NA levels. In the two bedridden patients, plasma NA levels and heart rate at rest increased significantly as the disease progressed. Cardiovascular responses to head-up tilting were normal. These data suggest that the elevation of plasma NA levels may be related to progression of respiratory failure and lower motor neuron dysfunction. In conclusion, sympathetic hyperactivity in ALS is considered to be not primary, but secondary to somatic motor disabilities and respiratory failure.

Multi-parametric spinal cord MRI as potential progression marker in amyotrophic lateral sclerosis.

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El Mendili, Mohamed-Mounir; Cohen-Adad, Julien; Pelegrini-Issac, Mélanie; Rossignol, Serge; Morizot-Koutlidis, Régine; Marchand-Pauvert, Véronique; Iglesias, Caroline; Sangari, Sina; Katz, Rose; Lehericy, Stéphane; Benali, Habib; Pradat, Pierre-François

2014-01-01

To evaluate multimodal MRI of the spinal cord in predicting disease progression and one-year clinical status in amyotrophic lateral sclerosis (ALS) patients. After a first MRI (MRI1), 29 ALS patients were clinically followed during 12 months; 14/29 patients underwent a second MRI (MRI2) at 11±3 months. Cross-sectional area (CSA) that has been shown to be a marker of lower motor neuron degeneration was measured in cervical and upper thoracic spinal cord from T2-weighted images. Fractional anisotropy (FA), axial/radial/mean diffusivities (λ⊥, λ//, MD) and magnetization transfer ratio (MTR) were measured within the lateral corticospinal tract in the cervical region. Imaging metrics were compared with clinical scales: Revised ALS Functional Rating Scale (ALSFRS-R) and manual muscle testing (MMT) score. At MRI1, CSA correlated significantly (Pleg ALFSRS-R scores. One year after MRI1, CSA predicted (Pleg ALSFRS-R subscore. From MRI1 to MRI2, significant changes (PDTI metrics predicted ALS disease progression. Cord atrophy was a better biomarker of disease progression than diffusion and MTR. Our study suggests that multimodal MRI could provide surrogate markers of ALS that may help monitoring the effect of disease-modifying drugs.

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

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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…

Factors affecting the diagnostic delay in amyotrophic lateral sclerosis.

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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.

FET Proteins TAF15 and EWS Are Selective Markers that Distinguish FTLD with FUS Pathology from Amyotrophic Lateral Sclerosis with "FUS" Mutations

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Neumann, Manuela; Bentmann, Eva; Dormann, Dorothee; Jawaid, Ali; DeJesus-Hernandez, Mariely; Ansorge, Olaf; Roeber, Sigrun; Kretzschmar, Hans A.; Munoz, David G.; Kusaka, Hirofumi; Yokota, Osamu; Ang, Lee-Cyn; Bilbao, Juan; Rademakers, Rosa; Haass, Christian; Mackenzie, Ian R. A.

2011-01-01

Accumulation of the DNA/RNA binding protein fused in sarcoma as cytoplasmic inclusions in neurons and glial cells is the pathological hallmark of all patients with amyotrophic lateral sclerosis with mutations in "FUS" as well as in several subtypes of frontotemporal lobar degeneration, which are not associated with "FUS" mutations. The mechanisms…

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...

Marital status is a prognostic factor in amyotrophic lateral sclerosis.

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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.

Vascular endothelial growth factor and amyotrophic lateral sclerosis: the interplay with exercise and noninvasive ventilation.

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Carilho, Rita; de Carvalho, Mamede; Swash, Michael; Pinto, Susana; Pinto, Anabela; Costa, Júlia

2014-04-01

We evaluated plasma vascular endothelial growth factor (VEGF) levels in patients with amyotrophic lateral sclerosis (ALS) with reference to the effects of respiratory failure, noninvasive ventilation (NIV), and exercise. We studied plasma VEGF levels in 83 ALS patients, 20 healthy controls, and 10 patients with other disorders. There were 4 groups of ALS patients: G1, 27 patients without respiratory problems; G2, 14 patients stabilized on nocturnal NIV; G3, 30 patients presenting with respiratory failure; G4, 12 patients on an aerobic exercise protocol. VEGF plasma levels did not differ significantly between ALS patients and controls, or between ALS groups. In G3, the mean VEGF levels increased 75% during NIV. In G4, the mean VEGF level increased by 300% during the exercise program. VEGF levels did not change during the course of the disease. VEGF levels in ALS depend on changes in ventilation and exercise but are probably not affected by the disease process itself. Copyright © 2013 Wiley Periodicals, Inc.

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

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

2013-02-17

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. The ALS registry Swabia started in October 2010 with both, the retrospective (01.10.2008-30.09.2010) and prospective (from 01.10.2010) collection of ALS cases, in a target population of 8.6 million persons in Southern Germany. In addition, a population based case-control study was implemented based on the registry that also included the collection of various biological materials.Retrospectively, 420 patients (222 men and 198 women) were identified. Prospectively data of ALS patients were collected, of which about 70% agreed to participate in the population-based case-control study. All participants in the case-control study provided also a blood sample. The prospective part of the study is ongoing. The ALS registry Swabia has been implemented successfully. In rare diseases such as ALS, the collaboration of registries, the comparison with external samples and biorepositories will facilitate to identify risk factors and to further explore the potential underlying pathophysiological mechanisms.

Comparison of optical coherence tomography findings and visual field changes in patients with primary open-angle glaucoma and amyotrophic lateral sclerosis.

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Liu, Ziyuan; Wang, Hongli; Fan, Dongsheng; Wang, Wei

2018-02-01

Recent studies revealing genetic connection of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis (ALS) have received particular attention. Exploring the evidence for common pathogenesis of these two progressive neurological disorders may assist in understanding the mechanism and searching for new treatment. Retinal nerve fiber layer (RNFL) defect and corresponding visual field (VF) impairment are well known neuropathy signs in glaucoma. In our study, thickness of certain retinal layer in ALS patients was analyzed to detect ganglion cell's soma and axon, and for first time visual field was examined for ALS. The correlation of retinal involvement and ALS progression were also investigated. The results were compared with those of POAG. The study may provide new knowledge for these two neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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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.

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

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

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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

[Management and treatment of respiratory failure associated with amyotrophic lateral sclerosis].

Science.gov (United States)

Danel-Brunaud, V; Perez, T; Just, N; Destée, A

2005-04-01

In amyotrophic lateral sclerosis (ALS), respiratory muscle involvement is highly predictive of survival and quality of life (QOL). There is compelling evidence that non invasive ventilation (NIV) prolongs survival by several months and improves QOL more than any other currently available treatment. Frequent testing of pulmonary function and regular evaluations are recommended since 1999 by the American Academy of Neurology in order to take appropriate treatment decisions. There are numerous tests available to evaluate respiratory status in ALS and it is important to know their sensitivity and specificity to recognize clinical risk situations. Some recent data suggest that sniff nasal pressure and maximal inspiratory pressure (MIP) can be performed reliably by most ALS patients and are more sensitive to decrements in inspiratory muscle strength than spirometry or arterial blood gasometry. Airway obstruction caused by ineffective coughing is the principal cause of intolerance to NIV. Several factors other than respiratory muscle strength may affect pulmonary function: postural changes, nutritional status, infectious disease, drugs. The neurologist has to coordinate multidisciplinary care, with attention to individual patient preferences, and with a frank and compassionate discussion between the patient, the family, the physicians and the caregivers.

The use of subcutaneous glycopyrrolate in the management of sialorrhoea and facilitating the use of non-invasive ventilation in amyotrophic lateral sclerosis.

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Cooper-Knock, Johnathan; Ahmedzai, Sam H; Shaw, Pamela

2011-11-01

Sialorrhoea is a recognized complication of bulbar amyotrophic lateral sclerosis (ALS) that leads to an increased risk of potentially harmful aspiration and often prevents patients from tolerating non-invasive ventilation (NIV). A case of treatment-resistant sialorrhoea in bulbar ALS is described where subcutaneous glycopyrrolate was effective without significant side-effects. The patient went on to markedly increase the length of time she could tolerate NIV each night.

[The advance in the research and therapeutic trials of amyotrophic lateral sclerosis].

Science.gov (United States)

Moriwaka, F; Tashiro, K

2000-12-01

The research concerning with the pathogenesis of amyotrophic lateral sclerosis (ALS) has been in steady progress in the last 10 years, including discovery of SOD mutation in familial ALS. Riluzole, by its inhibiting excitatory amino acid release, is the only drug, which has been demonstrated the neuroprotective activity in the randomised double-blind placebo-controlled clinical trials in patients with ALS, although many other clinical therapeutic trials for ALS patients has been carried out. We discussed the clinical trials being the under way, especially SR57746A, (1-[2-(naphth-2-yl)ethy]-4-(3-trifluoromethyl phenyl)-1, 2, 5, 6-tetrahydro-pyridine, hydrochloride), a non-peptide compound which has been shown to exhibit a wide range of neurotrophic effects both in vitro and in vivo, and its phase II study in Japan and two kinds of phase III studies ongoing in the United States, Canada and Europe. We also introduced the clinical guideline for practice and care of ALS patients proposed by American Academy of Neurology, expecting to establish clinical guideline to be applicable to Japanese cases.

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

Amyotrophic Lateral Sclerosis Presenting Respiratory Failure as the Sole Initial Manifestation

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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.

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.

Characterization of Patients with Amyotrophic Lateral Sclerosis attending the Muscular Dystrophy Association-Supported Clinics in Puerto Rico.

Science.gov (United States)

Deliz, Brenda; Ramos, Kathya; Pérez, Cynthia M

2018-03-01

To evaluate the sociodemographic characteristics and clinical and functional profile of amyotrophic lateral sclerosis (ALS) patients evaluated at Puerto Rico's Muscular Dystrophy Association-supported (MDA) clinics. A retrospective review of 76 medical records of ALS patients evaluated at any of four MDA-sponsored clinics in Puerto Rico. The mean age of diagnosis was 57.4 ± 11.1 yrs. Most of the patients (52.3%) were women. The majority of the cases were sporadic (48.7%). Over 40% of the patients were diagnosed at one year or earlier. Patients with initial upper extremity involvement (63.2%) were diagnosed earlier (≤ 6 months) than any of the others. The most common presentation of the disease overall was lower extremity weakness (34.2%), which was followed by a bulbar presentation (31.6%). There was a marked difference between men and women in disease presentation, with bulbar involvement in 75% of the women. This study characterized a sample of ALS patients in Puerto Rico who are receiving services at the MDA-sponsored clinics. Puerto Rican patients have similarities with published data from the United States and other countries, including: sporadic pattern, initial symptoms in extremities, and time to diagnosis. Major differences are that the disease was more common in women than in men and that a higher than expected percentage of patients presented with bulbar onset. This may partly account for the overall predominance of the disease in women over men as found in our study, since the bulbar presentation has been reported to be more common in women. Studies with a greater number of patients are needed to determine whether our findings are reproducible. This study will serve as a basis for designing future analytic studies regarding etiology or the factors that might modulate disease progression.

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

Science.gov (United States)

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

2015-03-01

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 secretion clearance. Non-invasive ventilation (NIV) is the first choice in treating respiratory insufficiency in ALS as it improves sleep-related symptoms, quality of life and life expectancy. Nevertheless, NIV is not always effective, probably due to bulbar dysfunction or anatomical abnormalities. As a result, tracheostomy ventilation (TV) may become necessary. In this case report, we present a 60-year-old female with ALS, for whom it was not possible to provide a sufficient tidal volume with NIV. A chin lift was performed while the patient was awake to see if a more anterior jaw position would lead to an increased tidal volume. As this was the case, a mandibular advancement device (MAD) was fabricated. With a combination of a MAD and NIV, the upper airway obstructions were overcome and a good ventilation and adherence to therapy were seen. When there is the presumption of airway obstructions in combination with an ineffective NIV, we advise to perform a chin lift to assess whether the obstructions can be overcome by a more anterior jaw position. If that is the case, NIV may be combined with MAD to establish effective ventilation and avoid the use of TV.

Clinical recognition and management of amyotrophic lateral sclerosis: the nurse's role.

Science.gov (United States)

Clarke, Kathie; Levine, Todd

2011-08-01

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, causes a progressive wasting and loss of the upper and lower motor neurons that facilitate the movement of body parts. At onset, ALS patients may show symptoms such as muscle weakness, atrophy, hyperreflexia, or bulbar symptoms such as dysphagia or dysarthria. Deterioration progresses rapidly, and the later stages of ALS are characterized by severely limited mobility and respiratory failure, which is the primary cause of death. There is no specific diagnostic test for ALS, and there are a number of other conditions that may resemble ALS, making a diagnosis difficult. The variability of the initial presentation combined with the broad differential diagnosis may result in significant delays in diagnosis or, in some cases, misdiagnosis, which in turn have a negative impact on patient outcomes. There is no cure for ALS; however, many of the symptoms are treatable, and the physical and psychological symptoms are best managed through the efforts of a coordinated, multidisciplinary team. Nurses play a critical role in the clinical management of ALS and may be involved in coordinating the activities of the team, facilitating treatment, and helping patients and caregivers in making informed treatment and end-of-life decisions. Drug therapy for ALS is currently limited to riluzole; however, patients may be treated with a number of nonpharmacologic methods on the basis of their symptoms. A number of other treatment modalities, such as stem-cell-based therapy or gene therapy, and an array of neuroprotective clinical trials are currently under development for the treatment of ALS. Nurses may also have a key role in these various ALS studies.

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.

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 ...

Factors related to respiration influencing survival and respiratory function in patients with amyotrophic lateral sclerosis: a retrospective study.