Hereditary neuralgic amyotrophy. Clinical, genetic, electrophysiological and histopathological studies

Clinical, genetic, electrophysiological and histopathological studies in a four-generation family with hereditary neuralgic amyotrophy (HNA) are described. Clinically two kinds of attack could be distinguished: (1) the classical type with pain and weakness lasting for weeks to months, leaving atrophy and sometimes residual weakness; 2) attacks consisting of recurrent pain and weakness lasting for a few days and occurring about once a week for several months, also resulting in persisting atrophy and weakness. Genetically a strong association was found between HNA and hypotelorism, probably due to pleiotropism of one single gene. Close linkage with any of 29 genetic markers was not present. The electrophysiological findings indicated that a local process in the brachial plexus, possibly demyelination or a conduction block, was the primary pathophysiological mechanism. Nevertheless, the sural nerve of the index case, biopsied 5 months after the onset of an attack, showed a decreased number of myelinated nerve fibres per cross-sectional area. Apparently, other parts of the peripheral nervous system may be affected subclinically in an attack of brachial plexopathy. The central and peripheral nervous system of his mother, 30 years after her last attack of HNA, showed only nonspecific changes. Tomacula were not seen in either case. HNA and hereditary liability to pressure palsies (HLPP) are distinctly different disorders.