Characterization of Fasciculation Potentials (FPs) in Amyotrophic Lateral Sclerosis (ALS) and Peripheral Nerve Hyperexcitability Syndromes (PNH)

This study is aimed at investigating the features of fasciculation potentials (FPs) in amyotrophic lateral sclerosis (ALS) and peripheral nerve hyperexcitability syndromes (PNH). Needle electrophysiologic examination (EMG) was performed for 5-15 muscles in the ALS and PNH patients. The spontaneous activity of fasciculations and fibrillations/sharp-waves (fibs-sw) was recorded. The distribution, firing frequency, and waveform parameters of FPs in muscles were calculated and compared. In total, 361 muscles in ALS patients and 124 muscles in PNH patients were examined, with the FP detection rates of 45.1% and 53.2%. Moreover, the ALS patients with the upper limb onset had the highest FP detection rate. Fasciculations occurred more frequently in the upper limbs than in the lower limbs in ALS and PNH. The detection rate of fibs-sw in the bulbar muscle was relatively low, which could be elevated when combining fibs-sw and FPs. Benign FPs in PNH were of smaller amplitude, shorter duration, and fewer phases/turns, compared with malignant FPs in ALS. The FP area in PNH was significantly smaller than that in ALS. The incidence of polyphasic FPs in ALS was distinctly greater than that in PNH. The firing frequency of FPs in PNH was higher than that in ALS. There was no significant difference in the amplitude, duration, phases and turns, and area of FPs between groups with and without fibs-sw in the muscles of normal strength in ALS. Conclusively, it is necessary to detect the FPs in the thoracic and bulbar muscles of patients suspected having ALS. FP parameters in ALS are significantly different from PNH.

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Prognosis of amyotrophic lateral sclerosis with cognitive and behavioural changes based on a sixty-month longitudinal follow-up

PLoS ONE ◽

10.1371/journal.pone.0253279 ◽

2021 ◽

Vol 16 (8) ◽

pp. e0253279

Author(s):

Shan Ye ◽

Pingping Jin ◽

Lu Chen ◽

Nan Zhang ◽

Dongsheng Fan

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Survival Time ◽

Progression Rate ◽

Behavioural Changes ◽

Significant Difference ◽

Long Term Follow Up ◽

Behaviour Changes ◽

Als Patients ◽

Lateral Sclerosis

Objective Approximately 50% of amyotrophic lateral sclerosis (ALS) patients have cognitive and behavioural dysfunction in varying degrees and forms. Previous studies have shown that cognitive and behavioural changes may indicate a poor prognosis, and cognitive function gradually deteriorates over the course of disease, but the results of different studies have been inconsistent. In addition, there are relatively limited long-term follow-up studies tracking death as an endpoint. The purpose of this study was to investigate the clinical prognostic characteristics of ALS patients with cognitive behavioural changes through long-term follow-up in a cohort. Methods A total of 87 ALS patients from 2014 to 2015 in the Third Hospital of Peking University were selected and divided into a pure ALS group, an ALS with behavioural variant of frontotemporal dementia (ALS-bvFTD) group, and an ALS with cognitive and behaviour changes group. All patients were followed up for 60 months. The main end point was death and tracheotomy. Results There was no significant difference in survival curve between pure ALS and ALS with cognitive and behavioural change group, but the survival time of ALS-bvFTD group was significantly lower than the other two groups (P < 0.001). For those who was followed up to the endpoint, the survival time of the ALS-bvFTD group was significantly shorter than that of the pure ALS group (t = 5.33, p < 0.001) or the ALS with cognitive and behaviour changes group (t = 4.25, p < 0.001). The progression rate of ALS Functional Rating Scale–Revised (FRS-R) scores from recruitment to endpoint was significantly faster in the ALS-bvFTD group than in the pure ALS group (z = 2.68, p = 0.01) or the ALS with cognitive and behavioural changes group (z = 2.75, p = 0.01). There was no significant difference in survival time (t = 0.52, P = 0.60) or FRS-R score progression rate (z = 0.31, p = 0.76) between the pure ALS group and the ALS with cognitive and behavioural changes group. The total Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) score was positively correlated with survival time (r = 0.38, p = 0.01). Conclusion ALS-bvFTD patients have shorter survival time. The total ECAS score may be correlated with survival time.

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Ectopic impulse generation in peripheral nerve hyperexcitability syndromes and amyotrophic lateral sclerosis

Clinical Neurophysiology ◽

10.1016/j.clinph.2018.01.061 ◽

2018 ◽

Vol 129 (5) ◽

pp. 974-980 ◽

Cited By ~ 9

Author(s):

Yu-ichi Noto ◽

Neil G. Simon ◽

Alexis Selby ◽

Nidhi Garg ◽

Kazumoto Shibuya ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Peripheral Nerve ◽

Impulse Generation ◽

Peripheral Nerve Hyperexcitability ◽

Lateral Sclerosis

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Brainstem Involvement in Amyotrophic Lateral Sclerosis: A Combined Structural and Diffusion Tensor MRI Analysis

Frontiers in Neuroscience ◽

10.3389/fnins.2021.675444 ◽

2021 ◽

Vol 15 ◽

Author(s):

Haining Li ◽

Qiuli Zhang ◽

Qianqian Duan ◽

Jiaoting Jin ◽

Fangfang Hu ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Correlation Analysis ◽

Disease Severity ◽

Structural Changes ◽

Diffusion Tensor ◽

Healthy Controls ◽

Significant Difference ◽

Als Patients ◽

And Diffusion ◽

Lateral Sclerosis

IntroductionThe brainstem is an important component in the pathology of amyotrophic lateral sclerosis (ALS). Although neuroimaging studies have shown multiple structural changes in ALS patients, few studies have investigated structural alterations in the brainstem. Herein, we compared the brainstem structure between patients with ALS and healthy controls.MethodsA total of 33 patients with ALS and 33 healthy controls were recruited in this study. T1-weighted and diffusion tensor imaging (DTI) were acquired on a 3 Tesla magnetic resonance imaging (3T MRI) scanner. Volumetric and vertex-wised approaches were implemented to assess the differences in the brainstem’s morphological features between the two groups. An atlas-based region of interest (ROI) analysis was performed to compare the white matter integrity of the brainstem between the two groups. Additionally, a correlation analysis was used to evaluate the relationship between ALS clinical characteristics and structural features.ResultsVolumetric analyses showed no significant difference in the subregion volume of the brainstem between ALS patients and healthy controls. In the shape analyses, ALS patients had a local abnormal surface contraction in the ventral medulla oblongata and ventral pons. Compared with healthy controls, ALS patients showed significantly lower fractional anisotropy (FA) in the left corticospinal tract (CST) and bilateral frontopontine tracts (FPT) at the brainstem level, and higher radial diffusivity (RD) in bilateral CST and left FPT at the brainstem level by ROI analysis in DTI. Correlation analysis showed that disease severity was positively associated with FA in left CST and left FPT.ConclusionThese findings suggest that the brainstem in ALS suffers atrophy, and degenerative processes in the brainstem may reflect disease severity in ALS. These findings may be helpful for further understanding of potential neural mechanisms in ALS.

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Ultrasound versus electromyography for the detection of fasciculation in amyotrophic lateral sclerosis: systematic review and meta-analysis

Radiologia Brasileira ◽

10.1590/0100-3984.2019.0055 ◽

2020 ◽

Vol 53 (2) ◽

pp. 116-121

Author(s):

Márcio Luís Duarte ◽

Wagner Iared ◽

Acary Souza Bulle Oliveira ◽

Lucas Ribeiro dos Santos ◽

Maria Stella Peccin

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Diagnostic Accuracy ◽

Latin American ◽

Detection Rate ◽

Meta Analysis ◽

Cochrane Library ◽

Detection Rates ◽

Examination Time ◽

The Cochrane Library ◽

Lateral Sclerosis

Abstract The objective of this study was to determine the diagnostic accuracy of ultrasound and electromyography for the detection of fasciculation in patients with amyotrophic lateral sclerosis and to compare detection rates between the two methods. By searching the Cochrane Library, MEDLINE, Excerpta Medica, and Latin-American and Caribbean Health Sciences Literature databases, we identified studies evaluating the diagnostic accuracy and fasciculation detection rates of ultrasound and electromyography. The Quality Assessment of Diagnostic Accuracy Studies, version 2, and RTI item bank tools were used for the evaluation of methodological quality. Ultrasound, for 10 s or 30 s, had a higher detection rate than did electromyography in all muscles evaluated. The overall detection rate (in patients) did not differ significantly between ultrasound for 10 s and ultrasound for 30 s. The accuracy of ultrasound for 10 s was 70% in muscles and 85% in patients. The accuracy of ultrasound for 30 s was 82% in patients. Ultrasound provided detection rates superior to those achieved with electromyography, independent of the examination time and muscles evaluated.

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An in-depth analysis of phosphorylated tau in amyotrophic lateral sclerosis post-mortem motor cortex and cerebrospinal fluid

10.1101/2020.12.30.20248944 ◽

2021 ◽

Author(s):

Tiziana Petrozziello ◽

Ana C. Amaral ◽

Simon Dujardin ◽

Sali M.K. Farhan ◽

James Chan ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Cortex ◽

Molecular Mechanisms ◽

Rating Scale ◽

Phosphorylated Tau ◽

Post Mortem ◽

Significant Difference ◽

Depth Analysis ◽

Als Patients ◽

Lateral Sclerosis

AbstractAlthough the molecular mechanisms underlying amyotrophic lateral sclerosis (ALS) are not yet fully understood, recent studies have described alterations in tau protein in both sporadic and familial ALS. However, it is unclear whether alterations in tau contribute to ALS pathogenesis. Here, we leveraged the ALS Knowledge Portal and Project MinE data sets and identified specific genetic variants clustering within the microtubule-binding domain of MAPT, which were unique to ALS cases. Furthermore, our analysis in a large post-mortem cohort of ALS and control motor cortex demonstrates that although there was no significant difference in the presence of phosphorylated tau (pTau) neuropil threads and neurofibrillary tangles between the two groups, pTau-S396 and pTau-S404 mis-localized to the nucleus and synapses in ALS. This was specific to the C-terminus phosphorylation sites as there was a significant decrease in pTau-T181 in ALS synaptoneurosomes compared to controls. Lastly, while there was no change in total tau or pTau-T181 in ALS CSF, there was a decrease in pTau-T181:tau ratio in ALS CSF, as previously reported. Importantly, CSF tau levels were increased in ALS patients diagnosed with bulbar onset ALS, while pTau-T181:tau ratio was decreased in ALS patients diagnosed with both bulbar and limb onset. Additionally, there was an inverse correlation between tau levels in the CSF and the revised ALS functional rating scale (ALSFRS-R) as well as a correlation between pTau-T181:tau ratio and ALSFRS-R. While there were no longitudinal alterations in tau, pTau-T181 and pTau-T181:tau ratio, there was an increase in the rate of ALSFRS-R decline per month associated with increases in tau levels. This decline was also inversely correlated with increases in pTau-T181 in relation to tau levels. Taken together, our findings demonstrate that, like Alzheimer’s disease, hyperphosphorylated tau is mis-localized in ALS and that decreases in CSF pTau-T181 may serve as a biomarker in ALS.

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Clinical Tests for Predicting Fallers Among Ambulatory Patients with Amyotrophic Lateral Sclerosis: A Preliminary Cohort Study

Journal of Neuromuscular Diseases ◽

10.3233/jnd-210730 ◽

2021 ◽

pp. 1-8

Author(s):

Koshiro Haruyama ◽

Michiyuki Kawakami

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Regression Analysis ◽

Gait Speed ◽

Linear Regression Analysis ◽

Lower Limbs ◽

Outcome Variable ◽

Functional Reach Test ◽

Als Patients ◽

Lateral Sclerosis ◽

Ankle Dorsiflexors

Background: Few studies have examined falls and their predictors in patients with amyotrophic lateral sclerosis (ALS). Objective: The aim of this study was to survey fall incidence and to identify variables predicting the presence or absence of falls occurring within 3 months after discharge of patients with ALS from hospital. Methods: The following variables were evaluated in 14 patients with ALS: timed up and go test (TUG), functional reach test, 10-m comfortable gait speed, single-leg stance time, manual muscle test (MMT) scores for the lower limb, total modified Ashworth scale score for the lower limbs, fear of falling, and pull test score. The primary outcome variable was the occurrence of a fall within 3 months after discharge. The fall rate was calculated based on fall record forms. The specific circumstances of each fall were also recorded. Univariate and multiple regression analyses were used to identify fall predictors. Results: Seven of the 14 ALS patients (50%) experienced a fall within 3 months. Five fallers reported experiencing a fall that had caused injury, and three reported experiencing a fall that had required a hospital visit. Univariate logistic regression analysis identified TUG time, gait speed and MMT of the ankle dorsiflexors as factors associated with falls (p = 0.02–0.04). Multiple linear regression analysis of fall numbers identified age and TUG time as predictor models (p = 0.03). Conclusion: TUG time and MMT of ankle dorsiflexors may help predict falls in ALS patients. Validation studies in larger cohorts are needed.

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Open Randomized Clinical Trial on JWSJZ Decoction for the Treatment of ALS Patients

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/347525 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 6

Author(s):

Weidong Pan ◽

Xiaojing Su ◽

Jie Bao ◽

Jun Wang ◽

Jin Zhu ◽

...

Keyword(s):

Clinical Trial ◽

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

Control Group ◽

Efficacy And Safety ◽

Significant Difference ◽

Als Patients ◽

And Control ◽

Lateral Sclerosis ◽

Basic Treatment

Objective. To investigate the efficacy and safety of the traditional Chinese medicine Jiawei Sijunzi (JWSJZ) decoction for the treatment of patients with amyotrophic lateral sclerosis (ALS).Methods. Forty-eight patients with ALS were divided into a JWSJZ group (n=24) and a control group (n=24) using a randomized number method. Together with the basic treatment for ALS, JWSJZ decoction was added to the treatment regimen of patients in the JWSJZ group or Riluzole was administered to the control group for 6 months. Neurologists evaluated the treated and control patients using the ALS functional rating scale (ALSFRS) before, 3 and 6 months after starting the additional treatments.Results. The ALSFRS scores in both groups were lower 3 and 6 months after treatment than before. There was a significant difference at 6 months after treatment between the subgroups of patients with ALS whose limbs were the initial site of attack. No serious adverse effects were observed in the JWSJZ group.Conclusion. JWSJZ decoction may be a safe treatment for ALS, and may have delayed the development of ALS, especially in the subgroup of patients in whom the limbs were attacked first when compared with Riluzole treatment.

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Electrophysiological Characterization of C9ORF72-Associated Amyotrophic Lateral Sclerosis: A Retrospective Study

European Neurology ◽

10.1159/000505777 ◽

2019 ◽

Vol 82 (4-6) ◽

pp. 106-112 ◽

Cited By ~ 1

Author(s):

Antoine Pegat ◽

Françoise Bouhour ◽

Kevin Mouzat ◽

Christophe Vial ◽

Benoit Pegat ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Sensory Neuropathy ◽

Mean Values ◽

Cognitive Domains ◽

Sensory Conduction ◽

Significant Difference ◽

The Mean ◽

Electrophysiological Characterization ◽

Als Patients ◽

Lateral Sclerosis

Objective: C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS). The aim of the present study was to determine whether C9ORF72-associated ALS (C9-ALS) patients present distinctive electrophysiological characteristics that could differentiate them from non C9ORF72-associated ALS (nonC9-ALS) patients. Methods: Clinical and electrodiagnostic data from C9-ALS patients and nonC9-ALS patients were collected retrospectively. For electroneuromyography, the mean values of motor conduction, myography, and the mean values of sensory conduction were considered. Furthermore, the proportion of ALS patients with electrophysiological sensory neuropathy was determined. Results: No significant difference was observed between 31 C9-ALS patients and 22 nonC9-ALS patients for mean motor conduction and myography. For sensory conduction analyses, mean sensory conduction was not significantly different between both groups. In total, 38% of C9-ALS patient and 21% of nonC9-ALS patients presented electrophysiological sensory neuropathy (p = 0.33). In C9-ALS patients with electrophysiological sensory neuropathy, 80% (8/10) were male and 67% (6/9) presented spinal onset compare to 25% (4/16, p = 0.014) male and 25% (4/16, p = 0.087) with spinal onset in those without electrophysiological sensory neuropathy. Conclusion: Although not different from nonC9-ALS, these results suggest that sensory involvement is a frequent feature of C9-ALS patients, expanding the phenotype of the disease beyond the motor and cognitive domains.

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A Phase 2A randomized, double-blind, placebo-controlled pilot trial of GM604 in patients with Amyotrophic Lateral Sclerosis (ALS Protocol GALS-001) and a single compassionate patient treatment (Protocol GALS-C)

F1000Research ◽

10.12688/f1000research.10519.1 ◽

2017 ◽

Vol 6 ◽

pp. 230 ◽

Cited By ~ 6

Author(s):

Mark Kindy ◽

Paul Lupinacci ◽

Raymond Chau ◽

Tony Shum ◽

Dorothy Ko

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Pilot Trial ◽

Disease Onset ◽

Treatment Protocol ◽

Double Blind ◽

Insulin Receptor Tyrosine Kinase ◽

Double Blind Placebo ◽

Significant Difference ◽

Als Patients ◽

Lateral Sclerosis

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that lacks effective treatment options. Genervon has discovered and developed GM604 (GM6) as a potential ALS therapy. GM6 has been modeled upon an insulin receptor tyrosine kinase binding motoneuronotrophic factor within the developing central nervous system. Methods This was a 2-center phase 2A, randomized, double-blind, placebo-controlled pilot trial with 12 definite ALS patients diagnosed within 2 years of disease onset. Patients received 6 doses of GM604 or placebo, administered as slow IV bolus injections (3x/week, 2 consecutive weeks). Objectives were to assess the safety and efficacy of GM604 based on ALSFRS-R, FVC and selected biomarkers (TDP-43, Tau and SOD1, pNFH). This report also includes results of compassionate treatment protocol GALS-C for an advanced ALS patient. Results Definite ALS patients were randomized to one of two treatment groups (GM604, n = 8; placebo, n = 4). 2 of 8 GM604-treated patients exhibited mild rash, but otherwise adverse event frequency was similar in treated and placebo groups. GM604 slowed functional decline (ALSFRS-R) when compared to a historical control (P = 0.005). At one study site, a statistically significant difference between treatment and control groups was found when comparing changes in respiratory function (FVC) between baseline and week 12 (P = 0.027). GM604 decreased plasma levels of key ALS biomarkers relative to the placebo group (TDP-43, P = 0.008; Tau, P = 0.037; SOD1, P = 0.009). The advanced ALS patient in compassionate treatment demonstrated improved speech, oral fluid consumption, mouth suction with GM604 treatment and biomarker improvements. Conclusions We observed favorable shifts in ALS biomarkers and improved functional measures during the Phase 2A study as well as in an advanced ALS patient. Although a larger trial is needed to confirm these findings, the present data are encouraging and support GM604 as an ALS drug candidate.

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Basophilic peripheral nerve inclusions in patient with L144F SOD1 amyotrophic lateral sclerosis

Vojnosanitetski pregled ◽

10.2298/vsp210717097a ◽

2021 ◽

pp. 97-97

Author(s):

Dejan Aleksic ◽

Stojan Peric ◽

Sanja Milenkovic ◽

Milena Jankovic ◽

Vidosava Rakocevic-Stojanovic ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Peripheral Nerve ◽

Motor Neurons ◽

Peripheral Nerves ◽

Periodic Acid ◽

Limb Weakness ◽

Periodic Acid Schiff ◽

The Central Nervous System ◽

Als Patients ◽

Lateral Sclerosis

Introduction. Histopathological findings of various inclusions were reported in the central nervous system of amyotrophic lateral sclerosis (ALS) patients, but not in the peripheral nerves. Case report. Our patient was a 66-year-old man with lower limb weakness later involvement of upper limbs, and loss of sphincter control. Neurological examination showed affection of both upper and lower motor neurons. He had paresthesia of the left side of his body and socks-distribution numbness. Histopathology of the sural nerve and genetic report showed basophilic periodic acid-Schiff (PAS)-positive intra-axonal inclusions and heterozygous L144F mutation in the exon 5 of the SOD1 gene. Conclusion. It seems that presence of the basophilic peripheral nerve inclusions may suggest diagnosis of SOD1 positive ALS.

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