Background:Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients’ homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is... Show moreBackground:Telemedicine (TM) contributes to bridge the gap between healthcare facilities and patients’ homes with neuromuscular disease (NMD) because of mobility issues. However, its deployment is limited due to difficulties evaluating subtle neurological signs such as mild weakness or sensory deficits. The COVID-19 pandemic has disrupted healthcare delivery worldwide, necessitating rapid measures implementation by health care providers (HCPs) to protect patients from acquiring SARS-CoV-2 while maintaining the best care and treatment.Objectives:Given the challenges faced by remote healthcare assistance of NMD patients, we aim to evaluate the use of TM in NMD during the COVID-19 pandemic.Methods:Based on the Model for Assessment-of-Telemedicine-Applications (MAST), we conducted a survey amongst clinicians of the ERN EURO NMD (European-Reference-Network-for-Rare-Neuromuscular-Diseases).Results:Based on 42 responses over 76 expected ones, our results show that the COVID-19 pandemic significantly increased the number of HCPs using TM (from 60% to 100%). The TM types most used during the COVID-19 period are teleconsultation and consultation by phone, particularly in the context of symptoms worsening in NMD patients with COVID-19 infection. Most European HCPs were satisfied when using TM but as a complementary option to physical consultations. Many responses addressed the issue of technical aspects needing improvement, particularly for elderly patients who need caregivers’ assistance for accessing the TM platform.Conclusions:TM has been essential during COVID-19, but its use still presents some limitations for NMD patients with cognitive deficits or for first-time diagnosis. Thus, TM should be used as complement to, rather than substitute, for face-to-face consultations. Show less
IMPORTANCE Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.OBJECTIVE To identify the genetic... Show moreIMPORTANCE Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.OBJECTIVE To identify the genetic variants associated with juvenile ALS.DESIGN, SETTING, AND PARTICIPANTS In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.MAIN OUTCOMES AND MEASURES De novo variants present only in the index case and not in unaffected family members.RESULTS Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p. Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.CONCLUSIONS AND RELEVANCE These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene. Show less
We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS... Show moreWe examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.Keywords: amyotrophic lateral sclerosis; frontotemporal dementia; huntingtin; repeat expansions; whole-genome sequencing.Published by Elsevier Inc. Show less
