Acute to Subacute Atraumatic Entrapment Neuropathies in Patients With CMT1A: A Report of a Distinct Phenotypic Variant of CMT1A.

Zhiyong Chen,Corrine Kang,Sonia Davila,Weng Khong Lim,Josiah Y H Chai,Peng-Soon Ng,Kalpana Prasad,Shermyn X M Neo,Ziqun Phua,Michelle M Li,Karine S S Tay,Kamal Verma,Jasmine S Koh,Monica Saini

doi:10.3389/fneur.2022.826634

Abstract

Charcot-Marie-Tooth type 1A (CMT1A) is typically characterised as a childhood-onset, symmetrical, length-dependent polyneuropathy with a gradual progressive clinical course. Acute to subacute neurological deterioration in CMT1A is rare, and has been reported secondary to overlap pathologies including inflammatory neuropathy. We identified two patients with CMT1A who presented with acute to subacute, atraumatic, entrapment neuropathies as an initial symptom. A superimposed inflammatory neuropathy was excluded. Both patients had a diffuse demyelinating polyneuropathy, with markedly low motor nerve conduction velocities (<20 m/s). In both patients, we demonstrated symptomatic and asymptomatic partial conduction blocks at multiple entrapment sites. Nerve ultrasound findings in our patients demonstrated marked diffuse nerve enlargement, more pronounced at non-entrapment sites compared to entrapment sites. We discuss ways to distinguish this condition from its other differentials. We propose pathophysiological mechanisms underlying this condition. We propose that CMT1A with acute to subacute, atraumatic, entrapment neuropathies to be a distinct phenotypic variant of CMT1A.

Highlights

Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant, demyelinating polyneuropathy caused by a 1.4 Mb duplication on chromosome 17p11.2
We report two patients with CMT1A who presented with acute to subacute asymmetric neuropathy with electrophysiological features suggestive of entrapment neuropathy [focal demyelination]
No congruent history of compression or minor trauma was evident, and a superimposed inflammatory neuropathy was excluded. As such clinical presentations may be confused with chronic inflammatory demyelinating polyneuropathy [chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)], or overlap hereditary and inflammatory demyelinating neuropathy, we evaluate the role of ancillary investigations, such as nerve ultrasound, in the diagnosis of this clinical entity, suggest strategies to avoid misdiagnosis, with the aim of avoiding unnecessary immunosuppressive therapy for patients with this unique clinical syndrome

Summary

INTRODUCTION

CMT1A is an autosomal dominant, demyelinating polyneuropathy caused by a 1.4 Mb duplication on chromosome 17p11.2 It is the commonest form of Charcot-Marie-Tooth (CMT) disease. We report two patients with CMT1A who presented with acute to subacute asymmetric neuropathy with electrophysiological features suggestive of entrapment neuropathy [focal demyelination]. No congruent history of compression or minor trauma was evident, and a superimposed inflammatory neuropathy was excluded. As such clinical presentations may be confused with chronic inflammatory demyelinating polyneuropathy [CIDP], or overlap hereditary and inflammatory demyelinating neuropathy, we evaluate the role of ancillary investigations, such as nerve ultrasound, in the diagnosis of this clinical entity, suggest strategies to avoid misdiagnosis, with the aim of avoiding unnecessary immunosuppressive therapy for patients with this unique clinical syndrome.

METHODS

DISCUSSION

Findings

ETHICS STATEMENT