Abstract
The clinical phenomenon of a split hand, dominant muscle atrophy in the thenar as compared to the hypothenar complex, has been used to support the theory of primary cortical degeneration in amyotrophic lateral sclerosis. However, the same phenomenon, both clinically and electrophysiologically, was observed in three diseases with a second but not first motor neuron affection: autosomal dominant spinal muscular atrophy, spinocerebellar ataxia type 3, and juvenile muscular atrophy. Neurogenic loss in a split hand distribution points to a spinal instead of cortical origin.
The term split hand, first coined by Willbourn et al.,1 refers to a type of hand muscle atrophy in which the muscles of the lateral aspect of the hand (first dorsal interosseus and thenar) are more affected than those of the medial aspect (hypothenar). Willbourn et al. described the split hand in the context of amyotrophic lateral sclerosis (ALS) and stated that, although not limited to ALS, this phenomenon seems to be specific for anterior horn disease.2 However, as the thenar and hypothenar complex have the same segmental supply and a different cortical presentation, others suggested that this pattern of muscle wasting is of cortical origin.3 As such, the dissociation of hand muscle wasting is considered to confirm the theory of cortical dysfunction with anterograde degeneration as the initial step in the pathogenesis of ALS. We wondered whether the split hand is also observed in disorders that are known to be characterized by lower motor neuron degeneration in the absence of cortical degeneration. Therefore, we performed nerve conduction studies in patients with autosomal dominant distal spinal muscular atrophy (DSMA), spinocerebellar ataxia type 3 (SCA-3), and juvenile muscular atrophy (JMA).
Methods.
Patients.
All five affected members of a three-generation family with DSMA, five consecutive patients with SCA-3, and three patients with JMA participated in the study. Each patient was subjected to a thorough neurologic and electrophysiologic examination.
Nerve conduction studies.
Nerve conduction studies were recorded with a Medelec Synergy EMG system (Oxford Medical Instruments). Skin temperature was maintained at 34 °C and limbs were warmed if necessary. Compound muscle action potentials (CMAP) of the thenar and hypothenar complexes were evoked by supramaximal peripheral stimulation of the median and ulnar nerves. One patient with SCA-3 (data not shown) with neurophysiologic evidence of a carpal tunnel syndrome was excluded.
Statistics.
Analysis was done using binomial distribution statistics.
Results.
The five members of the DSMA family showed a mild disease severity and slow progression, with lower limb predominance. Dissociated hand muscle wasting was evident in four of five members of the DSMA family.
The phenotype of the five patients with SCA-3 was characterized by a late onset (40 to 60 years), slow progression, cerebellar ataxia, cramps, fasciculations, and muscle atrophy. A split hand pattern of muscle atrophy was present in four of five patients with SCA-3.
The clinical course of the three (male) patients with JMA was characterized by an insidious onset, slow progression, and, ultimately, stabilization of disease. Dominant muscle atrophy in the thenar as compared to the hypothenar complex was present in two patients with JMA. One patient with JMA showed a reverse pattern of muscle wasting, with sparing of the thenar and prominent involvement of the hypothenar muscles. Intriguingly, this patient showed lower focal cervical cord atrophy on cervical MRI.
In four of five subjects with DSMA, in all patients with SCA-3, and in two patients with JMA, the electrically evoked hypothenar CMAP was larger than the thenar CMAP (table).
Table 1 Clinical features and nerve conduction studies in five patients of a three-generation family with autosomal dominant DSMA, in five patients with SCA-3, and in three patients with JMA
Concerning a total population of 13 patients, there was a binomial distribution and a prior probability of 0.5 (no significant difference in the thenar as compared to the hypothenar CMAP in normal controls), with 13 trials and two failures: p = 0.0111 (one-tailed sign test).
Discussion.
Our results support the theory that a dissociation of hand muscle atrophy, in which the thenar muscles are more affected than the hypothenar muscles, is an important clinical feature that localizes the lesion to the anterior horn. Greater thenar than hypothenar involvement is also seen in patients with T1 root involvement and in patients with lower trunk plexus involvement. However, the indefinite onset with slow progression over years in the absence of pain or sensory symptoms makes the possibility of additional radicular or plexus involvement unlikely.
DSMA, SCA-3, and JMA are clinically and genetically very different disorders. Still, distal muscle atrophy and motor neuron degeneration is a common feature in all. Autosomal dominant DSMA is a rare, genetically heterogeneous lower motor neuron disorder that may be difficult to distinguish clinically from type II Charcot-Marie-Tooth disease.4 SCA-3 or Machado-Joseph disease (MJD) is an autosomal dominant cerebellar ataxia caused by CAG trinucleotide repeat expansions in the MJD/SCA-3 gene.5 The phenotype of the five patients with SCA-3 studied here is compatible with a SCA-3 subtype (subtype III)6 in which late onset, slow progression, cramps, fasciculations, and muscle atrophy are typical features and degeneration of anterior horn cells a common neuropathologic finding.7 JMA is a focal amyotrophy with unilateral or asymmetric bilateral wasting of C7-Th1 innervated muscles.8 Whereas some studies suggest that JMA is an intrinsic motor neuron disease,9 others favor the view that the disorder results from mechanical distortion of the cervical spinal cord due to neck flexion during growth.10
Because the pathophysiologic mechanisms of DSMA, SCA-3, and JMA are presumably very different, the observation of a split hand in these diseases weakens the theory of the cortical origin of degeneration in ALS and supports the theory of an intrinsic vulnerability of spinal motor neurons subserving the thenar complex.
- Received April 28, 2003.
- Accepted August 13, 2003.
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