Neuropathology of Charcot-Marie-Tooth and related disorders

The peripheral nervous system (PNS), with all its branches and connections, is so complex that it is impossible to study all components at the light or electron microscopic level in any individual case; nevertheless, in certain diseases a simple nerve biopsy may suffice to arrive at a precise diagnosis. Structural changes of the PNS in neuropathies of the Charcot-Marie-Tooth (CMT) type and related disorders comprise various components of the PNS. These include peripheral motor, sensory, and autonomous neurons with their axons, Schwann cells, and myelin sheaths in the radicular and peripheral nerves as well as satellite cells in spinal and autonomous ganglia. Astrocytes, oligodendroglial cells, and microglial cells around motor neurons in the anterior horn and around sensory neurons in other areas of the spinal cord are also involved. In addition, connective tissue elements such as endoneurial, perineurial, and epineurial components including blood and lymph vessels play an important role. This review focuses on the cellular components and organelles involved, that is, myelin sheaths, axons with their micro-tubules and neurofilaments; nuclei, mitochondria, endoplasmic reticulum, and connective tissue including the perineurium and blood vessels. A major role is attributed to recent progress in the pathomorphology of various types of CMT1, 2,4, CMTX, and HMNSL, based on light and electron microscopic findings, morphometry, teased fiber studies, and new immunohisto-chemical results such as staining of certain periaxin domains in CMT4F.