Split phenomena in amyotrophic lateral sclerosis: Current evidences, pathogenetic hypotheses and diagnostic implications

Abstract

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease and has emerged among the disorders with the largest increasing incidence in Western countries. Although the diagnosis is based on clinical grounds, electromyography (EMG), and nerve conduction studies (NCS) play a crucial role to exclude other potential etiologies of lower motor neuron (LMN) dysfunction. Based on clinical grounds, a peculiar pattern of dissociated atrophy of the intrinsic hand and foot muscles, termed the “split-hand” (SH) and “split-leg” (SL) signs, has been described in a significant proportion of subjects with ALS, even at the early stages of the disease, when symptoms are focal. These signs are rare in neurological and non-neurological diseases other than ALS. In this review, we discussed current evidences concerning SH and SL signs, their pathogenetic hypotheses and neurophysiological findings. We also analyze whether SH and SL signs can be reliable markers in the differential diagnosis and in the prognosis of ALS.

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

“…In the present study, we examined the influence of age and sex on neurophysiological indicators of dissociated pattern of muscle wasting in a large cohort of adult participants with unremarkable neurological conditions. These neurophysiological indices play a critical role in the clinical and diagnostic work-up of patients with ALS and have been proposed as reliable measures for the differential diagnosis ( 1 ).…”

“…A striking manifestation of amyotrophic lateral sclerosis (ALS) is the preferential dysfunction of certain groups of muscles over others, despite receiving the same innervation, particularly in the intrinsic hand, the elbow, and the foot muscles. This phenomenon is termed the “split phenomenon” (SP) ( 1 ).…”

“…Over the years, several neurophysiological methods have attempted to assess and quantify the SP in patients with ALS. However, consensus remains elusive regarding which methods represent the most useful neurophysiological indicator of ALS ( 1 ).…”

“…In a recent meta-analysis, a cutoff value of 7.4 was proposed for the SHI in patients with a disease duration of 8–20 months ( 17 ). Several neurophysiological indices based on CMAP amplitudes of different muscles have been proposed for assessing the SH sign, with the most commonly used being APB CMAP /ADM CMAP and FDI CMAP /ADM CMAP (with cutoff values of 0.6 and 0.9, respectively) ( 1 , 8 , 14 , 16 , 18 ). Nonetheless, all the above-mentioned indices for the SH sign present several limitations, with the most important limitation being the confounding effect of aging on intrinsic hand amyotrophy ( 1 ).…”

“…Several neurophysiological indices based on CMAP amplitudes of different muscles have been proposed for assessing the SH sign, with the most commonly used being APB CMAP /ADM CMAP and FDI CMAP /ADM CMAP (with cutoff values of 0.6 and 0.9, respectively) ( 1 , 8 , 14 , 16 , 18 ). Nonetheless, all the above-mentioned indices for the SH sign present several limitations, with the most important limitation being the confounding effect of aging on intrinsic hand amyotrophy ( 1 ). Indeed, in a recent study on healthy subjects, Pechirra et al found that CMAPs of APB, FDI, and ADM decreased with age at approximately 0.8, 0.7, and 0.3 mV/year, respectively.…”