Reverse Split Hand as a Neurophysiological Hallmark of Spinal Muscular Atrophy

Abstract

Objective: Motor unit number estimation (MUNE) methods are crucial for estimating lower motor neuron loss in motor neuron diseases. The MScanFit MUNE (MScanFit) is a novel method that estimates MUNE values from compound motor action potential (CMAP) scans, demonstrating high sensitivity and reproducibility in detecting motor unit loss in amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). In this study, we aimed to characterize the pattern of motor unit loss in the hand intrinsic muscles of SMA patients compared to ALS patients and healthy controls (HC) using MScanFit MUNE. Methods: Patients diagnosed with ALS, adult SMA patients, and HC were prospectively enrolled. MScanFit examinations were performed on the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles. To focus on the different patterns of motor neuron degeneration in the intrinsic hand muscles, the ratio of CMAP amplitude of APB to ADM (CMAP ratio) and the ratio of MUNE values of APB to those of the ADM muscle (MUNE ratio) were calculated. Results: The study included 46 ALS patients, 16 SMA patients, and 23 HC. MScanFit MUNE revealed distinct patterns of motor unit degeneration in SMA patients, notably more severe in the ADM than in the APB muscle, indicating a "reverse" split-hand phenomenon. Both CMAP and MUNE ratios demonstrated high diagnostic accuracy in distinguishing ALS from SMA, with the MUNE ratio performing better. Conclusions: MScanFit MUNE is a valuable tool for exploring distinct patterns of motor neuron degeneration in patients with different types of motor neuron diseases.

Keywords: MScanFit MUNE; amyotrophic lateral sclerosis; reverse split hand; spinal muscular atrophy.

Figure 1

(A): Group comparisons were implemented using the Kruskal–Wallis test. The CMAP ratio was significantly higher in SMA patients than in controls (p = 0.017) and ALS patients (p < 0.001), and it was lower in ALS patients than in controls (p = 0.014). The MUNE ratio was higher in SMA patients than in both ALS patients and controls (p < 0.001), and it was lower in ALS patients than in controls (p = 0.047). (B): General linear models adjusted for age. The CMAP ratio was significantly higher in SMA patients than in ALS patients and healthy controls (p < 0.001), but it was not significantly different between ALS patients and controls (p = 0.199). The MUNE ratio was significantly higher in SMA patients than in ALS patients and controls (p < 0.001), while it was not different between ALS patients and controls (p = 0.89). The LSMUP ratio was significantly lower in SMA patients than in ALS patients (p = 0.014) and showed a trend toward significance compared to controls (p = 0.05) (B).

Figure 2

ROC curve analysis to determine the AUC and cut-off values for both CMAP and MUNE ratios for distinguishing between ALS and SMA patients. CMAP ratio: AUC = 0.871 (95% CI: 0.779–0.963), sensitivity = 93.8%, specificity = 69.6%, and cut-off = 0.79 (p < 0.001). MUNE ratio: AUC = 0.931 (95% CI: 0.867–0.995), sensitivity = 93.8%, specificity = 71.7%, and cut-off = 0.69 (p < 0.001).

Figure 3

MUNE values of the APB muscle in a healthy control (A), an ALS patient (B), and a SMA subject (C). MUNE values of the ADM muscle in a healthy control (D), an ALS patient (E), and a SMA subject (F). On the horizontal axis, the stimulus current (mA) is displayed; on the vertical axis, the CMAP amplitude (mV) is displayed. Note the reverse pattern in the SMA patient, with MUNE 63 in the APB vs. MUNE 15 in the ADM muscle.