The 6-min walk test as a new outcome measure in Amyotrophic lateral sclerosis

Abstract One of the issues highlighted in amyotrophic lateral sclerosis (ALS) clinical trials is the lack of appropriate outcome measures. The aim of this multicentric study was to evaluate the 6-min walk test (6MWT) as tool to monitor the natural history of a cohort of ALS patients followed up over a 6-month interval. Forty-four ambulant patients were assessed at baseline and after 1, 3 and 6 months. Eight out of forty-four lost the ability to walk before the end of the study. The 6MWT and the objective measures linked to motor function, such as 10 m walking test (10MWT) and Time-up and go (TUG), the ALSFRS-R and the ALSFRS-R items 7–9 showed a good responsiveness to change over the 6-month interval. There was a strong correlation between 6 and 10MWT, TUG, ALSFRS-R, ALSFRS-R items 7–9 and FVC% at baseline. There was no correlation with Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and Modified Borg Scale (MBS). The Δ of 6MWT from T0 to T6 significantly correlated with the Δs of 10MWT and TUG. There was no correlation with the Δs of ALSFRS-R, ALSFRS-R items 7 9, ECAS, MBS and FVC%. The discordance between changes of the 6MWT and ALSFRS-R at 6 month highlights the different content validity among these instruments. The concordance among 6MWT, 10MWT and TUG indicates that the 6MWT is an objective, sensitive and robust tool to measure motor performances in a longitudinal setting. The main limitations of our study were the small sample size and the high percentage of patients (18%) lost at follow-up. Therefore, further studies on larger cohorts, and exploring the relation between 6MWT and need of ventilator support or survival could strengthen our results.

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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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Impact of Percutaneous Endoscopic Gastrostomy (PEG) on the Evolution of Disease in Patients with Amyotrophic Lateral Sclerosis (ALS)

Nutrients ◽

10.3390/nu13082765 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2765

Author(s):

Juan J. López-Gómez ◽

María D. Ballesteros-Pomar ◽

Beatriz Torres-Torres ◽

Begoña Pintor-De la Maza ◽

María A. Penacho-Lázaro ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Percutaneous Endoscopic Gastrostomy ◽

Anthropometric Parameters ◽

Endoscopic Gastrostomy ◽

Frequent Event ◽

The Mean ◽

Als Patients ◽

Prevalent Symptom ◽

Lateral Sclerosis

Dysphagia is a highly prevalent symptom in Amyotrophic Lateral Sclerosis (ALS), and the implantation of a percutaneous endoscopic gastrostomy (PEG) is a very frequent event. The aim of this study was to evaluate the influence of PEG implantation on survival and complications in ALS. An interhospital registry of patients with ALS of six hospitals in the Castilla-León region (Spain) was created between January 2015 and December 2017. The data were compared for those in whom a PEG was implanted and those who it was not. A total of 93 patients were analyzed. The mean age of the patients was 64.63 (17.67) years. A total of 38 patients (38.8%) had a PEG implantation. An improvement in the anthropometric parameters was observed among patients who had a PEG from the beginning of nutritional follow-up compared to those who did not, both in BMI (kg/m2) (PEG: 0 months, 22.06; 6 months, 23.04; p < 0.01; NoPEG: 0 months, 24.59–23.87; p > 0.05). Among the deceased patients, 38 (40.4%) those who had an implanted PEG (20 patients (52.6%) had a longer survival time (PEG: 23 (15–35.5) months; NoPEG 11 (4.75–18.5) months; p = 0.01). A PEG showed a survival benefit among ALS patients. Early implantation of a PEG produced a reduction in admissions associated with complications derived from it.

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Epidemiology of Amyotrophic Lateral Sclerosis: A Population-Based Study in Israel

Neuroepidemiology ◽

10.1159/000448921 ◽

2016 ◽

Vol 47 (2) ◽

pp. 76-81 ◽

Cited By ~ 6

Author(s):

Clara Weil ◽

Neta Zach ◽

Shay Rishoni ◽

Varda Shalev ◽

Gabriel Chodick

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Health Maintenance Organization ◽

Healthcare Services ◽

Population Based ◽

Annual Incidence ◽

Health Maintenance ◽

High Prevalence ◽

Als Patients ◽

Lateral Sclerosis

Background: Globally, the annual incidence and prevalence of amyotrophic lateral sclerosis (ALS) are estimated at 1.9 and 4.5 per 100,000 population, respectively. This study is aimed at describing the epidemiology of ALS in Israel in a real-world setting. Methods: A retrospective study was performed using the databases of Maccabi Healthcare Services (MHS), a 2-million-member health maintenance organization in Israel. The study included all MHS adults diagnosed with ALS between 1997 and 2013. In 2013, characteristics of ALS patients were compared to those of age-sex-matched patients without ALS. Survival after ALS diagnosis was assessed until death and until tracheostomy or death (follow-up through 2014). Results: In 2013 (n = 158), the prevalence of ALS was 8.1 per 100,000 population in MHS. In 1997-2013, a total of 375 ALS patients were diagnosed, corresponding to an average annual incidence of 1.8 per 100,000 population in MHS. The median survival from diagnosis to death was 3.5 years (95% CI 2.9-4.1), with approximately 28% surviving at least 10 years. Median tracheostomy-free survival was 2.5 years (95% CI 2.1-2.9). Conclusions: Results suggest that there is a relatively high prevalence of ALS in Israel. Further research is needed to investigate factors that may contribute to the survival of patients with ALS in Israel.

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Validation of the Six Minute Walk Test (6MWT) in Ambulatory Amyotrophic Lateral Sclerosis (ALS) Patients (P01.107)

Neurology ◽

10.1212/wnl.78.1_meetingabstracts.p01.107 ◽

2012 ◽

Vol 78 (Meeting Abstracts 1) ◽

pp. P01.107-P01.107

Author(s):

M. Sanjak ◽

V. Langford ◽

S. Holsten ◽

J. Bockenek ◽

E. Bravver ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Walk Test ◽

Six Minute Walk Test ◽

Als Patients ◽

Minute Walk ◽

Lateral Sclerosis

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Telemedicine for management of patients with amyotrophic lateral sclerosis through COVID-19 tail

Neurological Sciences ◽

10.1007/s10072-020-04783-x ◽

2020 ◽

Author(s):

Alessandro Bombaci ◽

◽

Gianmarco Abbadessa ◽

Francesca Trojsi ◽

Letizia Leocani ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Neurological Diseases ◽

Healthcare Systems ◽

Digital Tools ◽

Social Restriction ◽

Containment Measures ◽

Life Threatening ◽

Als Patients ◽

Lateral Sclerosis

Abstract Over the last months, due to coronavirus disease (COVID-19) pandemic, containment measures have led to important social restriction. Healthcare systems have faced a complete rearrangement of resources and spaces, with the creation of wards devoted to COVID-19 patients. In this context, patients affected by chronic neurological diseases, such as amyotrophic lateral sclerosis (ALS), are at risk to be lost at follow-up, leading to a higher risk of morbidity and mortality. Telemedicine may allow meet the needs of these patients. In this commentary, we briefly discuss the digital tools to remotely monitor and manage ALS patients. Focusing on detecting disease progression and preventing life-threatening conditions, we propose a toolset able to improve ALS management during this unprecedented situation.

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Changes in Retinal OCT and Their Correlations with Neurological Disability in Early ALS Patients, a Follow-Up Study

Brain Sciences ◽

10.3390/brainsci9120337 ◽

2019 ◽

Vol 9 (12) ◽

pp. 337 ◽

Cited By ~ 5

Author(s):

Pilar Rojas ◽

Rosa de Hoz ◽

Ana I. Ramírez ◽

Antonio Ferreras ◽

Elena Salobrar-Garcia ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Rating Scale ◽

P Value ◽

Ophthalmological Examination ◽

Fiber Layer ◽

Neurological Disability ◽

Als Patients ◽

Lateral Sclerosis ◽

Visual Changes

Background: To compare early visual changes in amyotrophic lateral sclerosis (ALS) patients with healthy controls in a baseline exploration, to follow-up the patients after 6 months, and to correlate these visual changes with neurological disability. Methods: All patients underwent a comprehensive neurological and ophthalmological examination. A linear mixed analysis and Bonferroni p-value correction were performed, testing four comparisons as follows: Control baseline vs. control follow-up, control baseline vs. ALS baseline, control follow-up vs. ALS follow-up, and ALS baseline vs. ALS follow-up. Results: The mean time from the diagnosis was 10.80 ± 5.5 months. The analysis of the optical coherence tomography (OCT) showed: (1) In ALS baseline vs. control baseline, a macular significantly increased thickness of the inner macular ring temporal and inferior areas; (2) in ALS follow-up vs. ALS baseline, a significant macular thinning in the inner and outer macular ring inferior areas; (3) in ALS follow-up vs. ALS baseline, a significant peripapillary retinal nerve fiber layer (pRNFL) thinning in the superior and inferior quadrants; and (4) ALS patients showed a moderate correlation between some OCT pRNFL parameters and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score. Conclusion: The OCT showed retinal changes in patients with motoneuron disease and could serve as a complementary tool for studying ALS.

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Longitudinal Timed Up and Go Assessment in Amyotrophic Lateral Sclerosis: A Pilot Study

European Neurology ◽

10.1159/000516772 ◽

2021 ◽

pp. 1-5

Author(s):

Eglė Sukockienė ◽

Ruxandra Iancu Ferfoglia ◽

Antoine Poncet ◽

Jean-Paul Janssens ◽

Gilles Allali

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Pilot Study ◽

Walking Ability ◽

University Hospitals ◽

Timed Up And Go ◽

Progressive Loss ◽

Bulbar Onset ◽

Als Patients ◽

Lateral Sclerosis

Progressive loss of walking ability in amyotrophic lateral sclerosis (ALS) has been scarcely studied as a potential predictive factor for survival in motor neuron disease. We aimed to assess the progression of gait decline and its association with mortality in ALS using the Timed Up and Go test (TUG). Patients were followed up prospectively at the Centre for ALS and Related Disorders in Geneva University Hospitals between 2012 and 2016. The TUG was performed at baseline and subsequent evaluations occurred every 3 months. At inclusion, patients were classified as unable to perform the TUG, “slow TUG” (>10.6 s), and “fast TUG” (≤10.6 s). In total, 68 patients with ALS (mean ± SD age: 68.6 ± 11.9 years; 50% female) were included. Baseline TUG was negatively correlated with the total ALSFRS-R score (r = −0.63, p < 0.001). At baseline, ALS patients with bulbar onset performed the TUG faster (9.9 ± 3.7 s) than the non-bulbar ones (17.3 ± 14.9 s, p = 0.008). Thirty of 68 (44%) patients died by the end of the follow-up period. The TUG performance at the first visit did not predict mortality. While we did not find any association with mortality in ALS and gait quantification, the TUG was feasible in a majority of ALS patients, was correlated with functional status, and could be of interest in the follow-up of non-bulbar ALS patients.

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The Profile of Amyotrophic Lateral Sclerosis in Natives of Western Himalayas: Hospital-Based Cohort Study

Journal of Neurosciences in Rural Practice ◽

10.4103/jnrp.jnrp_8_18 ◽

2018 ◽

Vol 09 (03) ◽

pp. 305-311

Author(s):

Sachin Sondhi ◽

Sudhir Sharma ◽

S. S. Kaushal ◽

Ayushi Mehta ◽

Vikas Banayal

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Clinical Characteristics ◽

Western Himalayas ◽

Duration Of Symptoms ◽

Female Ratio ◽

Bulbar Onset ◽

Als Patients ◽

Lateral Sclerosis ◽

Limb Onset

ABSTRACT Background: Despite the disabling nature of amyotrophic lateral sclerosis (ALS), there are no contemporary data on clinical characteristics available from rural hilly states from India. Thus, the present study aimed at reporting clinical profile in ALS patients from natives of Western Himalayas. Materials and Methods: A total of 32 patients of ALS were enrolled over a period of 1 year (2013–2014) in the present study. The demographic profile, clinical characteristics, and risk factors were systematically recorded, and these patients were followed for 1 year. Results: The mean age of ALS patients was 53 ± 15.88 (23–90 years). Maximum number of patients of both limb onset and bulbar onset were in the age group of 40–49 years Figure 1. Male to female ratio was 1.46. Limb-onset was seen in 23 (72%) and bulbar-onset in 9 (28%) of patients. Bulbar-onset was more common in females as compared to males. Mean duration of symptoms were 19.06 ± 24 months (range 4–120 months). None of the studied risk factor showed statistically significant association with outcome of the disease. No familial association was found. The most common site of weakness was upper limb distal weakness. Definite ALS was seen in 13 (40.6%) patients. Mean ALS functional rating scale (ALSFRS) at presentation is 35.7 ± 7.9. All patients were started on riluzole. Mean ALSFRS at 9-month follow-up was 32.9 ± 7.4. After 1 year of follow up, 5 out of 32 patients died and among them, 4 were of limb onset and 1 was of bulbar onset ALS. Mean age at death in males was 66 ± 16 years and in females was 56.33 ± 24.8 years; mean survival in these patients was 25 months. Conclusion: This present study highlights following findings: (1) Male preponderance is less common in our patients as compared to earlier reports from India. Bulbar onset is more common in elderly (age >60 years) females. (2) As per previous reports from India, when compared to Western population present study supports the fact of the younger age of onset and longer duration of symptoms and slow course of disease in Indian patients.

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Facial onset sensory and motor neuronopathy

Neurology Clinical Practice ◽

10.1212/cpj.0000000000000834 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000000834 ◽

Cited By ~ 1

Author(s):

Eva M.J. de Boer ◽

Andrew W. Barritt ◽

Marwa Elamin ◽

Stuart J. Anderson ◽

Rebecca Broad ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Dna Binding Protein ◽

Behavioral Changes ◽

Genetic Mutations ◽

Sensory Disturbances ◽

New Finding ◽

History Of ◽

Autoimmune Pathogenesis ◽

Lateral Sclerosis

Purpose of reviewTo improve our clinical understanding of facial onset sensory and motor neuronopathy (FOSMN).Recent findingsWe identified 29 new cases and 71 literature cases, resulting in a cohort of 100 patients with FOSMN. During follow-up, cognitive and behavioral changes became apparent in 8 patients, suggesting that changes within the spectrum of frontotemporal dementia (FTD) are a part of the natural history of FOSMN. Another new finding was chorea, seen in 6 cases. Despite reports of autoantibodies, there is no consistent evidence to suggest an autoimmune pathogenesis. Four of 6 autopsies had TAR DNA-binding protein (TDP) 43 pathology. Seven cases had genetic mutations associated with neurodegenerative diseases.SummaryFOSMN is a rare disease with a highly characteristic onset and pattern of disease progression involving initial sensory disturbances, followed by bulbar weakness with a cranial to caudal spread of pathology. Although not conclusive, the balance of evidence suggests that FOSMN is most likely to be a TDP-43 proteinopathy within the amyotrophic lateral sclerosis–FTD spectrum.

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TDP–43, Protein Aggregation, and Amyotrophic Lateral Sclerosis

US Neurology ◽

10.17925/usn.2010.05.02.35 ◽

2010 ◽

Vol 05 (02) ◽

pp. 35 ◽

Cited By ~ 3

Author(s):

Edor Kabashi ◽

Paul N Valdmanis ◽

Hussein Daoud ◽

Véronique V Belzil ◽

Patrick A Dion ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neurons ◽

Inclusion Bodies ◽

Missense Mutations ◽

Cellular Models ◽

Truncating Mutation ◽

C Terminus ◽

History Of ◽

Als Patients ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disorder and the third most common neurodegenerative cause of adult death after Alzheimers and Parkinsons diseases. TAR DNA binding protein (TDP-43) has been found to be a major component of inclusion bodies in motor neurons of ALS patients. Inclusion bodies are protein aggregates considered a pathological hallmark of neurodegeneration. Our group and eight independent research groups screened TDP-43 for mutations. Overall, 19 missense mutations and one truncating mutation were identified only in ALS patients. These mutations were not found in a considerable number of controls sequenced in several independent studies. Ten of these mutations were found in patients with a family history of ALS. To further support a pathogenic role, the mutations segregated with the disease in three families, including one family with a significant logarithm of odds (LOD) score. Nineteen of these 20 mutations are located in the C-terminus of the TDP-43 protein. These mutations could disrupt several of the already known functions of TDP-43, including nuclear localization, exon splicing, and RNA and heterogenous ribonucleoprotein particle (hnRNP) binding, or could introduce a novel gain of function that is toxic to motor neurons. In the future, animal and cellular models using these mutations should elucidate the role of TDP-43 mutations in ALS pathogenesis and could provide new means to test pharmaceutical compounds for this neurological disease.

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