CMT Type X and Altitude Research

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1: Ann Neurol 2002 Oct;52(4):429-34

Transient central nervous system white matter abnormality in X-linked

Charcot-Marie-Tooth disease.

son HL, Garbern JY, Hoban TF, Krajewski KM, RA, Fischbeck KH,

Grossman RI, Lenkinski R, Kamholz JA, Shy ME.

Department of Neurology, University of Iowa, Iowa City, IA.

X-linked Charcot-Marie-Tooth disease (CMTX) is a hereditary

demyelinating neuropathy caused by mutations in the connexin 32 (Cx32)

gene. Cx32 is widely expressed in brain and peripheral nerve, yet

clinical manifestations of CMTX mainly arise from peripheral neuropathy.

We have evaluated two male patients with CMTX who on separate occasions

developed transient ataxia, dysarthria, and weakness within 3 days of

returning from ski trips at altitudes above 8,000 feet. Magnetic

resonance imaging studies in both patients showed nonenhancing,

confluent, and symmetrical white matter abnormalities that were more

pronounced posteriorly and that resolved over several months. Magnetic

transfer images in one patient demonstrated increased magnetization

transfer ratios distinct from that seen in demyelination or edema. Both

patients returned to their normal baseline within 2 to 3 weeks. These

cases suggest that CMTX patients are at risk for developing an acute,

transient, neurological syndrome when they travel to places at high

altitudes and return to sea level. Cx32 mutations may cause central

nervous system dysfunction by reducing the number of functioning gap

junctions between oligodendrocytes and astrocytes, making both cells

more susceptible to abnormalities of intercellular exchange of ions and

small molecules in situations of metabolic stress.