Dissociated leg muscle atrophy in amyotrophic lateral sclerosis/motor neuron disease: the ‘split-leg’ sign

Abstract

Disproportionate muscle atrophy is a distinct phenomenon in amyotrophic lateral sclerosis (ALS); however, preferentially affected leg muscles remain unknown. We aimed to identify this split-leg phenomenon in ALS and determine its pathophysiology. Patients with ALS (n = 143), progressive muscular atrophy (PMA, n = 36), and age-matched healthy controls (HC, n = 53) were retrospectively identified from our motor neuron disease registry. We analyzed their disease duration, onset region, ALS Functional Rating Scale-Revised Scores, and results of neurological examination. Compound muscle action potential (CMAP) of the extensor digitorum brevis (EDB), abductor hallucis (AH), and tibialis anterior (TA) were reviewed. Defined by CMAPEDB/CMAPAH (SIEDB) and CMAPTA/CMAPAH (SITA), respectively, the values of split-leg indices (SI) were compared between these groups. SIEDB was significantly reduced in ALS (p < 0.0001) and PMA (p < 0.0001) compared to the healthy controls (HCs). SITA reduction was more prominent in PMA (p < 0.05 vs. ALS, p < 0.01 vs. HC), but was not significant in ALS compared to the HCs. SI was found to be significantly decreased with clinical lower motor neuron signs (SIEDB), while was rather increased with clinical upper motor neuron signs (SITA). Compared to the AH, TA and EDB are more severely affected in ALS and PMA patients. Our findings help to elucidate the pathophysiology of split-leg phenomenon.

MND Phenotypes Differentiation: The Role of Multimodal Characterization at the Time of Diagnosis

“…In accordance with the observation of similar onset features, we further found similar degrees of overall functional impairment (ALSFRS-r scores) in pLMN and ALS cases, a result which is largely in line with previous studies of both flail limb and PMA phenotypes [ 13 , 16 ].…”

“…Conversely, compared to ALS, pLMN cases exhibited greater right lower limb muscular weakness as well as less severe total and regional UMN burden. One factor possibly accounting for the severe lower limbs involvement observed in pLMN cases is the so-called split-leg phenomenon, an uneven atrophy recently found to be more prominent in PMA than in ALS cases [ 16 ] and postulated to be largely influenced by peripheral pathophysiological mechanisms. Notably, this measure was further predictive of more severe functional impairment at the end of the study period, suggesting either a potential role of this feature in identifying those pLMN cases more likely to convert to classic ALS phenotypes, or simply a significant impact of lower limb muscular weakness on the course of functional status in pLMN syndromes.…”

Evaluation of Amyotrophic Lateral Sclerosis-Induced Muscle Degeneration Using Magnetic Resonance-Based Relaxivity Contrast Imaging (RCI)

“…The heterogeneity could be attributed to varying degrees of muscle atrophy within individual ALS patients and the respective contrast mechanisms of each imaging approach. It has been hypothesized that some of the more active muscle groups such as the Tibialis Anterior have a higher atrophy rate [25]. At the time of imaging, the extent of muscle atrophy for each muscle group could be different due to the time elapsed between disease onset and imaging timepoint(s) in the study population.…”

Split-hand and split-limb phenomena in amyotrophic lateral sclerosis: pathophysiology, electrophysiology and clinical manifestations

“…29 Notwithstanding the different clinical observations, most authors agree that unlike the 'split-hand syndrome', 'split leg' is primarily a neurophysiological phenomenon. [25][26][27][28][29]…”