Correlation between weakness and axonal loss in patients with CMT1A

Abstract

We have developed a protocol to measure the progression of disability in patients with Charcot Marie Tooth (CMT) disease, particularly CMT1 over a several year period. Because CMT1 is a chronic disease, the natural history of changes occurring in such a brief period are not well understood, making clinical trials for CMT1 patients difficult to evaluate. We hypothesize that weakness in CMT1 correlates with axonal loss secondary to the abnormalities in Schwann cell myelin gene expression, which cause the disease. To test this hypothesis, we elected to carefully evaluate CMT patients by various modalities to measure strength, sensory loss, and axonal loss and demyelination and to compare these modalities to determine whether they correlated with findings on clinical examination. As suspected, patient weakness correlates more with secondary axonal loss than with demyelination, even though the primary abnormality in CMT1 is demyelination.