Stroke-Like Episodes in Charcot-Marie-Tooth X1 (CMTX1) Disease

Abstract

Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of disorders best known for causing inherited forms of peripheral neuropathy. History of CMT disease is not considered relevant in patients presenting with acute central neurologic manifestations of acute stroke. The case described here should alert clinicians to the possibility of transient stroke-like episodes in young patients suffering from CMTX1, X‐linked variant of CMT. Case description: A 21-year-old man presented to our emergency department with acute onset dysarthria, right facial weakness and right hemiparesis, which started 2 hours before his admission. He was treated with intravenous thrombolysis with a suspected diagnosis of acute ischemic stroke with full resolution of symptoms. The following day he experienced another stroke-like episode of acute onset of dysarthria and left facial weakness that resolved within 3 hours. The patient underwent stroke in the young work-up which was normal. MRI of the brain showed symmetric, non-enhancing areas of restricted diffusion in the corona radiata bilaterally and corpus callosum, also demonstrated on T2/fluid-attenuated inversion recovery (FLAIR) sequences. Clinical and familial investigations resulted in diagnosing CMTX1, X‐linked variant of CMT. Discussion: This case illustrates that CMTX1 disease can have central nervous system (CNS) manifestations that could mimic stroke-like neurological deficits with pathological MRI findings. The prognosis of the CNS phenotype of CMTX1 is usually good, with spontaneous resolution without permanent deficits. Promptly identifying the disease is vital to avoid unnecessary investigation and potentially harmful therapeutic intervention. Interoduction: Charcot-Marie-Tooth (CMT) disease is a group of inherited disorders affecting the motor and sensory nerves of the peripheral nervous system. It is characterized by progressive weakness and atrophy of distal muscles, there are musculoskeletal changes such as high arched feet (pes cavus), and loss of deep tendon reflexes [1]. Five main types of CMT, with multiple subtypes, are described in most classification systems, and more than 60 causative genes are currently known. X-linked Charcot-Marie-Tooth disease type 1 (CMTX1) is an X-linked disease. This is the second most common form of CMT, accounting for 10-15% of cases. It is caused by mutations in the gap junction protein beta 1 (GJB1) gene located on chromosome Xq13.1, encoding connexin-32 (Cx32) [2,3]. Cx32 is normally expressed in Schwann cells, oligodendrocytes, and astrocytes, where it is thought to provide a pathway for the diffusion of small molecules and ions directly across the myelin sheath [4]. Most Cx32 mutations cause inability to form functional gap junctions. Electrophysiologically, CMTX1 shows mixed Nirit Lev et.all / Stroke-Like Episodes in Charcot-Marie-Tooth X1 (CMTX1) Disease 5300 International Journal of Medical Science and Clinical Invention, vol. 08, Issue 03, March 2021 A B features of a demyelinating and axonal polyneuropathy [1]. In addition to the common peripheral presentation of CMT, CMTX1 has been reported to have transient central nervous system manifestations [5]. Here, we describe a CMTX1 patient who experienced recurrent episodes of transient central nervous system (CNS) dysfunction associated with white matter abnormalities on magnetic resonance imaging (MRI) of the brain. Figure1. MRI of the brain demonstrating symmetric large confluent FLAIR (A) and T2-weighted images (B) hyperintensities in the white matter. FLAIR= fluidattenuated inversion recovery. Figure2. T2-weighted images of MRI of the brain demonstrated hyperintense signal in the splenium of the