N.P.3 08 Contribution of the nerve biopsy in hereditary peripheral neuropathies

Abstract

Most cases of hereditary peripheral neuropathies (HPN) are now diagnosed by molecular biology, but the peripheral nerve biopsy (PNB) is still contributory in a few atypical cases. On the basis of a 30-year-experience of PNB, we wish to illustrate histopathological features which may inform the molecular biologist toward a specific genetic abnormality. A whole nerve biopsy is performed on the superficial peroneal or the sural nerve. Each case is prepared for light and electron microscopy (EM). On paraffin sections, small amyloid deposits scattered in the endoneurium, or intra-axonal polyglucosan bodies, can occasionally be disclosed. Semi-thin sections sometimes exhibit features of hypermyelination, i.e. tomaculae, or onion-bulb formations (OBF) indicating previous episodes of primary demyelination. EM is more informative, as it reveals nerve fiber modifications characteristic of certain types of HPN. Tomaculae correspond to hereditary neuropathy to pressure palsy, which presents in certain cases as acute symmetrical polyneuropathy, but tomaculae can also be the prominent feature in certain cases of Charcot-Marie-Tooth (CMT) disease type 1b. Other CMT1b families exhibit mainly features of uncompacted myelin lamellae. Myelin outfoldings are rarely observed and point to a recessive form, CMT4. Prominent OBF are present in every case of CMT1a and also in rare cases of chronic inflammatory demyelinating polyneuropathy (CIDP). Atypical OBF, mainly made of thin remnants of basal lamina are only observed in CMT infantile cases, so-called Dejerine-Sottas disease. Intra-axonal filament accumulation, with sometimes giant axons are seen in recessive cases, CMT4. Macrophage-associated demyelination is mainly observed in CIDP cases, but can reveal genuine cases of CMT1a presenting with a concurrent auto-immune inflammatory process. Occasionally, EM can disclose storage material in ceroid lipofuscinosis, adrenoleukodystrophy or Tangier’s disease. PNB can reveal familial pathology in pseudo-sporadic cases of any age and orientate molecular genetics investigation in rare cases.