CMT X exercise at high altitudes

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Charcot-Marie-Tooth Disease Type X at high altitudes - from Medscape

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Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy

and the most common inherited neurologic disorder, affecting

approximately 150,000 people in the United States. The disease was first

described in 1886 by 3 physicians, Jean-Marie-Charcot, Pierre Marie, and

Henry Tooth.

CMT is usually inherited in an autosomal dominant pattern with high

penetrance, but approximately 15% of patients with CMT have an X-linked

form (CMTX) that is related to mutations in the connexin 32 gene.

Although this gene is expressed in both the central and peripheral

nervous system, the clinical features of CMTX have been defined

previously as strictly peripheral.

Shy and colleagues[8] presented 2 patients with CMTX who developed

transient clinical evidence of brain dysfunction shortly after

exercising at high altitudes. The symptoms included ataxia, dysarthria,

and limb weakness. Brain MRI showed symmetric white matter

hyperintensities on T2-weighted images in the centrum semiovale that

were posterior-predominant. The lesions did not enhance on

postgadolinium images. Several months later, the MRI findings

disappeared in conjunction with neurologic recovery. The lesions were

associated with an increase in magnetization transfer ratio, the

opposite of what is typically seen in multiple sclerosis.

These cases provide evidence that CMTX includes a brain disorder that is

characterized by a vulnerability to developing an acute, transient

neurologic illness after exercising at high altitudes. The investigators

speculated that the mutations in CMTX cause brain disease by reducing

ion channel function in oligodendrocytes and astrocytes during metabolic

stress. These cases force the rethinking of CMT as strictly a peripheral

nerve disorder and may open a new line of investigation toward

uncovering the pathophysiology of these diseases.