Charcot–Marie–Tooth disease and neuroinflammation

Abstract

AbstractPatients with the misdiagnosis or co‐occurrence of Charcot–Marie–Tooth disease (CMT) and inflammatory neuropathies have been reported previously. Both CMT and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have similar clinical features, including flaccid weakness in four limbs with areflexia, demyelinating neurophysiological features and pathological demyelination. However, the symptoms of CIDP progress for several weeks or months, and typical CIDP shows proximal and distal muscle weakness. In contrast, CMT progresses for several decades and presents distal‐dominant muscle weakness, which is called length‐dependent neuropathy. On neurophysiological evaluation, CMT had been considered to show “uniform conduction slowing.” However, a recent study showed that CMT could show non‐uniform conduction abnormalities, which resemble inflammatory neuropathies. Furthermore, the incidence of inflammatory neuropathy in CMT is estimated to be higher than that in the general population. CMT1A with CIDP was the most common, followed by CMTX1 with CIDP and CMT1A with Guillain–Barré syndrome. Some patients showed macrophage‐associated demyelination or mononuclear cell infiltrations in their nerves. Most patients responded to immune therapies at least partly. The pathophysiology in such patients has not yet been elucidated. However, the involvement of the immune system in the development of demyelination in CMT was established by experimental animal studies, and vulnerability to immune abnormalities is suggested in abnormal myelin.