Split hand in amyotrophic lateral sclerosis: A systematic review and meta-analysis

Highlight

• Half of ALS patients might present split hand according to quantitatively summarized results.

• APB/ADM_CMAP of ALS patients was significantly lower than healthy controls.

• SI_CMAP had good performance in diagnosis of ALS.

Abstract

Objective

To investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS).

Methods

PubMed, EMBASE, OVID and other databases were searched systematically up to March 2021 for relevant reports about the split hand syndrome. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. In our study, AA_CMAP was calculated by AA_CMAP = APB_CMAP/ADM_CMAP and split-hand index (SI) was calculated by SI_CMAP = (APB_CMAP × FDI_CMAP)/ADM_CMAP. The mean differences (MD) in APB/ADM_CMAP and SI_CMAP between patients with ALS and control group were calculated (APB the abductor pollicis brevis muscle; ADM the abductor digiti minimi muscle; CMAP compound muscle action potentials). Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI) for SI_CMAP.

Results

Pooled results of five studies including 339 patients showed that 50% (95%CI: 35%–65%) of patients with ALS presented split hand. APB/ADM_CMAP in patients with ALS was significantly lower than healthy population (MD: −0.38, 95%CI: −0.48, −0.28). SI_CMAP in patients with ALS was significantly lower than healthy controls (MD: −5.87, 95%CI: −6.28, −5.46) and neuromuscular controls (MD: −5.60, 95%CI: −5.78, −5.42). Receiver operating characteristic curve analysis showed that the AUC was 0.860 [95%CI: 0.808, 0.911] for SI_CMAP. The sensitivity and specificity for SI_CMAP were 78% and 81% (cut-off value: 5.2–11.8), respectively.

Conclusion

Half of ALS patients might show split hand sign. SI_CMAP could be a potential biomarker in the diagnosis of ALS.

Introduction

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by relentlessly progressive skeletal muscle paralysis [1]. The incidence of ALS was between 0.6 and 3.8 per 100 000 person-years, and continuously increased in the past few years [2]. The survival duration from symptoms onset to death or invasive respiratory support was between 24 and 50 months [3], [4]. Although several diagnostic criteria have been suggested by WFN (the World Federation of Neurology) and IFCN (International Federation of Clinical Neurophysiology) [5], more reliable biomarkers are still needed.

Split hand is a specific pattern of dissociated hand muscle atrophy, characterized by preferential weakness and wasting of the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) muscles with relative sparing of the abductor digiti minimi muscle (ADM) [6]. Since first reported by Wilbourn et al. in the 1994 [7], split hand has been believed to be a characteristic sign in ALS and helpful to diagnose ALS. However, data of the frequency of split hand in ALS patients are currently scarce [8]. Increasingly studies have been done to explore the diagnostic accuracy of indices regarding split hand including APB/ADM ratio (AA) and split-hand index (SI) using compound muscle action potentials (CMAP) while no consensus has been reached. Other types of split signs were also reported to be potential biomarkers for the diagnosis of ALS [9], [10], which might even show higher sensitivity and specificity.

Therefore, the aim of this study is to summarize the frequency of split hand in patients with ALS and compare the AA and SI using CMAP (AA_CMAP and SI_CMAP) between patients with ALS and controls. We also explored the diagnostic accuracy of SI_CMAP though receiver operating characteristic (ROC) analysis. Our results might provide the new and comprehensive evidence of the application of SI in clinical practice.