Neurophysiological indices for split phenomena: correlation with age and sex and potential implications in amyotrophic lateral sclerosis

Stefano Zoccolella; Giammarco Milella; Alessia Giugno; Vito Devitofrancesco; Rosaria Damato; Ludovica Tamburrino; Salvatore Misceo; Marco Filardi; Giancarlo Logroscino

doi:10.3389/fneur.2024.1371953

Neurophysiological indices for split phenomena: correlation with age and sex and potential implications in amyotrophic lateral sclerosis

Front Neurol. 2024 Mar 7:15:1371953. doi: 10.3389/fneur.2024.1371953. eCollection 2024.

Authors

Stefano Zoccolella^{1

2}, Giammarco Milella³, Alessia Giugno², Vito Devitofrancesco¹, Rosaria Damato¹, Ludovica Tamburrino^{2

3}, Salvatore Misceo¹, Marco Filardi^{2

3}, Giancarlo Logroscino^{2

3}

Affiliations

¹ Neurology Unit, San Paolo Hospital, Azienda Sanitaria Locale (ASL) Bari, Bari, Italy.
² Center for Neurodegenerative Diseases and the Aging Brain, University of Bari Aldo Moro at Pia Fondazione "Card. G. Panico", Tricase, Italy.
³ Department of Translational Biomedicine and Neurosciences (DiBraiN), University of Bari Aldo Moro, Bari, Italy.

Abstract

Background: Split phenomena (SP) are characterized by patterns of differential muscle wasting and atrophy, which are highly prevalent in amyotrophic lateral sclerosis (ALS) patients. Several neurophysiological indicators, including the split-hand index (SHI), split-leg index (SLI), and split-elbow index (SEI), have been proposed to assess SP. Nevertheless, their cutoff values and the impact of age and sex on these measures remain unclear.

Methods: We prospectively collected neurophysiological data from 300 healthy adult subjects. The following indices were measured from compound muscle action potentials (CMAPs): SHI [abductor pollicis brevis (APB_cmap) x first dorsal interosseous (FDI)_cmap/adductor digiti minimi (ADM_cmap)], SEI (BICEPS_cmap/TRICEPS_cmap), SLI (extensor digit brevis (EDB)_cmap/abductor Hallucis (AH)_cmap), and the neurophysiological ratios APB_cmap /ADM_cmap and FDI_cmap/ADM_cmap. Multiple linear regression analysis was used to investigate the association between age, sex, CMAPs, and neurophysiological indicators.

Results: The median SHI was 10.4, with a median APB_cmap/ADM_cmap ratio of 0.9 and a median FDI_cmap/ADM_cmap ratio of 1.2. The median SEI was 1.6 (IQR:1.1-2.4) and the median SLI was 0.7 (IQR:0.5-1.0). Negative associations were observed between age, most of the CMAPs, and all the neurophysiological indices, except for SLI. The male subjects exhibited significantly higher CMAP values for the first dorsal interosseous (FDI), biceps, and SHI compared to the female participants.

Conclusion: Our findings highlight the importance of age- and sex-adjusted normative data for SP indices, which could enhance their diagnostic accuracy and clinical utility in patients with ALS. The SL index appears to be the most reliable indicator, as it showed no significant association with age or sex.

Keywords: amyotrophic lateral sclerosis; neurophysiology; split elbow sign; split-hand; split-leg.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Regione Puglia and CNR for Tecnopolo per la Medicina di Precisione. D.G.R. n. 2117 of 21.11.2018 (CUPB84I18000540002) - C.I.R.E.M.I.C. (Research Center of Excellence for Neurodegenerative Diseases and Brain Aging) - University of Bari Aldo Moro.