Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease

Henry L. Paulson, James Y. Garbern, Timothy F. Hoban, Karen M. Krajewski, Richard A. Lewis, Kenneth H. Fischbeck, Robert I. Grossman, Robert Lenkinski, John A. Kamholz, Michael E. Shy

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136 Scopus citations


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 fseveral 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.

Original languageEnglish (US)
Pages (from-to)429-434
Number of pages6
JournalAnnals of Neurology
Issue number4
StatePublished - Oct 1 2002

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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