Non-invasive fasciculation assessment of gastrocnemius failed to show diagnostic or prognostic utility in ALS

Objectives: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder, affecting both upper and lower motor neurons. High-density surface electromyography is a non-invasive measure of muscle fasciculations, a phenomenon prevalent early in the disease. Previous studies highlighted the clinical importance of these measures from the biceps brachii muscle. Our study aimed to investigate the diagnostic and prognostic value of the medial gastrocnemius muscle. Methods: We performed a retrospective study of 49 ALS and 25 control participants. Means comparisons, logistic regression, receiver operating characteristic analysis, Kaplan-Meier analysis, and a multilevel Cox model were used to determine the predictive utility of fasciculation potential (FP) parameters including FP frequency, median amplitude, and amplitude dispersion. Results: FP parameters demonstrated a poor ability to differentiate between ALS and controls, with ROC analysis producing areas under the curve between 0.58 and 0.63. Furthermore, there was no association between FP parameters and ALS prognosis in the Cox model. Conclusions: FP parameters from the medial gastrocnemius muscle are not useful for the diagnosis or prognosis of ALS patients. Significance: Our results highlight the poor clinical utility of fasciculation quantification in the medial gastrocnemius muscle. Future studies should focus on recordings from more clinically relevant muscles earlier in the disease. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement JB acknowledges funding from Medical Research Council and Motor Neurone Disease Association (Lady Edith Wolfson Clinical Research Training Fellowship; MR/P000983/1) Sattaripour Charitable Foundation UK Dementia Research Institute National Institute for Health and Care Research (Academic Clinical Lectureship program). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from Research Ethics Services in the North of Scotland (ref: 15/NS/0103), East Midlands (ref: 17/EM/0221), and Yorkshire and the Humber (ref: 19/YH/0164). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.