Split Hand Syndrome is a characteristic finding in amyotrophic lateral sclerosis (ALS) where there is preferential denervation and wasting of the thenar muscles and first dorsal interossei muscle compared to the hypothenar muscles. This pattern, known as split hand syndrome, has high specificity for ALS. The syndrome is thought to be due to greater use and oxidative stress of the affected muscles as well as differences in motor axon membrane properties. It represents an early, primarily cortical lesion in ALS and assessment of pincer grip strength may prove useful for early diagnosis of ALS.

1. Split Hand Syndrome in
Amyotrophic Lateral Sclerosis
Ade Wijaya, MD
- February 2021 -

2. Introduction
 Amyotrophic lateral sclerosis (ALS) is a
neurodegenerative disorder in which
there is preferential loss of both the
upper and lower motor neurons
 At clinical onset, manifestations appear
rather focal, resulting in bulbar, cervical
or lumbar phenotypes, then spreads
contiguously from the site of origin,
becoming diffuse and resulting in
complex motor deficits
Kiernan MC, Vucic S, Cheah BC, et al Amyotrophic lateral sclerosis. Lancet 2011;377:942–55
Ravits JM, La Spada AR . ALS motor phenotype heterogeneity, focality, and spread: deconstructing motor neuron degeneration. Neurology 2009;73:805–11.

3. Split Hand Syndrome
 Wilbourn, 1990 observe thenar
muscles and first dorsal interossei
muscle are frequently and
substantially more denervated than
the hypothenar muscles in ALS
 1996  Split Hand Syndrome
Wilbourn AJ . Electrodiagnostic evaluation of the patient with possible ALS. In: Belsh JM, Schiffman PL, eds. Amyotrophic lateral sclerosis. Armonk, NY:
Futura Books, 1996:183.
Wilbourn AJ. The “split hand syndrome”. Muscle Nerve 2000;23:138.
Wilbourn AJ. Dissociated wasting of medial and lateral hand muscles with motor neuron disease. Can J Neurol Sci 1994;21(Suppl 2):S9.

4. Differential Diagnosis
 Autosomal dominant distal spinal muscular
atrophy
 Spinocerebellar ataxia type 3 (Machado–
Joseph disease)
 Juvenile muscular atrophy
 Spinal and bulbar muscular atrophy (SBMA).
 Thenar wasting from a cervical rib and band
 Spondylotic cord compression
 Compression of the deep motor branch of the
ulnar nerve
 Carpal tunnel syndrome
 C8 root lesion
Eisen A, Kuwabara S. The split hand syndrome in amyotrophic lateral sclerosis. Journal of Neurology, Neurosurgery & Psychiatry. 2012 Apr 1;83(4):399-403.

5. Diagnostic Value
 Sensitivity (52%)
 High specificity (95%)
Kuwabara S, Sonoo M, Komori T, et al; Tokyo Metropolitan Neuromuscular Electrodiagnosis Study Group. Dissociated small hand muscle atrophy in
amyotrophic lateral sclerosis: frequency, extent, and specificity. Muscle Nerve 2008;37:426–30.

6. Physiology
 In humans, use of the APB muscle is
greater than that of the ADM, which
could render the former muscles
(involved in split hand syndrome)
subject to greater oxidative stress
Kuwabara S, Mizobuchi K, Ogawara K, et al. Dissociated small hand muscle involvement in amyotrophic lateral sclerosis detected by motor unit number
estimates. Muscle Nerve 1999;22:870–3.
Voermans NC, Schelhaas HJ, Munneke M, et al . Dissociated small hand muscle atrophy in aging: the 'senile hand' is a split hand. Eur J Neurol 2006;13:1381–4

7. Physiology
 It has been suggested that the split hand
may be explained by differences in
membrane properties among motor
axons innervating the APB, FDI and
ADM.
 These findings suggest that motor axons
with physiologically greater persistent
sodium currents—namely ALS-like—may
be more vulnerable and more readily die
in ALS, and this may contribute to the
development of split hand
Bae JS, Sawai S, Misawa S, et al. Differences in excitability properties of FDI and ADM motor axons. Muscle Nerve 2009;39:350–4.

8. Physiology
 The thenar complex together with the
FDI is responsible for precision or
‘pincer grip’, which is the main clinical
deficit of the split hand syndrome
 This would support the concept that
the split hand deficit, and maybe ALS,
are primarily cortical in origin
Vucic S, Kiernan MC . Novel threshold tracking techniques suggest that cortical hyperexcitability is an early feature of motor neuron disease. Brain 2006;129:2436–46
Eisen A, Kim S, Pant B . Amyotrophic lateral sclerosis (ALS): a phylogenetic disease of the corticomotoneuron? Muscle Nerve 1992;15:219–24.

9. Eisen A, Kuwabara S. The split hand syndrome in amyotrophic lateral sclerosis. Journal of Neurology, Neurosurgery & Psychiatry. 2012 Apr 1;83(4):399-403.

10. Summary
 The split hand is a useful clinical clue to
the early diagnosis of ALS
 The split hand of ALS is predominantly
due to a corticomotneuronal lesion.
Nevertheless, lower motor neuronal
(anterior horn cell) and motor axonal
components are likely to also contribute
 Measures of pincer grip integrity, yet to
be developed for ALS, may prove to be
the earliest and most robust
documentation of the deficit.

11. THANK YOU