Distal infantile neuroaxonal dystrophy - a new familial variant with perineuronal argyrophilic bodies

We report on two sisters with an infantile onset of dyskinetic movements, t onic spasms, seizures and apneic spells. The condition deteriorated to a hy potonic "burnt out" stage by the age of 3 years in the older sister and to a stable dyskinetic condition by the age of 2.5 years in the younger one. A skin biopsy from the older sister revealed myelinated nerve fibers crowded with neurofilaments. The extensive investigation for neurometabolic disord er, magnetic resonance imaging of the brain, and ophthalmological and neuro physiological examinations were not especially revealing. The older sister died at the age of 3 years. The autopsy revealed no apparent loss of nerve cells in the brain and no sign of storage disease. However, silver-stained coarse granules, immunopositive for neurofilament polypeptide, were found a round nerve cell bodies in the cortex and in the basal ganglia. Electron mi croscopy revealed perineuronal membrane-bound profiles filled with filament s. Silver-stained axonal torpedoes were found in the cerebellum, but there were no spheroids. The substantia. nigra, the locus ceruleus and the nucleu s basalis of Meynert showed extensive perineuronal. and perivascular swelli ng. Homovanillic acid was severely reduced, while 5-hydroxy-indoleacetic ac id and hydroxymethylphenyl glycol were normal in the cerebrospinal fluid of the severely affected, autopsied case. The two cases are considered to rep resent a new form of infantile neuroaxonal dystrophy, characterized by the degeneration of perineuronal terminals in the cerebral cortex and in the ba sal ganglia, as well as by axonal degeneration in the cerebellum and periph eral nerves.