The diagnostic significance of clinical, neurophysiologic, and neuroradiologic findings in 13 patients with infantile neuroaxonal dystrophy (INAD) was evaluated at the National Neurological Institute, Milan, Italy. Symptoms and signs of psychomotor regression presented between 6 months and 2 years of age. The clinical course was typical in 9 patients, with rapid motor and mental deterioration: it was atypical in 4 showing a slower rate of progression. Late neurologic features included optic atrophy and vision failure in 8, nystagmus in 3, and spastic or areflexic tetraparesis with axial hypotonia and distal contractures in all patients. EMG signs of chronic denervation, EEG fast activity, and abnormal visual evoked potentials occurred in all patients during the course of the disease. NCS became abnormal and consistent with axonal sensorimotor peripheral neuropathy in 9. All patients had histologic evidence of spheroids on skin biopsy. Characteristic MRI abnormalities were cerebellar atrophy, first involving the inferior vermis and later the cortex, with hyperintense signal on T2-weighted images, and hypointensity in the pallida and substantia nigra. a-N-acetyl-galactosaminidase leukocyte activity was normal in 10 patients tested. [1]

COMMENT. The diagnostic criteria for INAD are as follows: 1) spheroids on skin biopsy; 2) onset before 3 years; 3) psychomotor deterioration, with symmetric pyramidal tract signs and truncal hypotonia; and 4) progression to spastic tetraparesis, blindness, and dementia by the age of 4 years. Atypical cases may occur, with slower progression beginning between 7 and 12 years after a stable course resembling static encephalopathy, and hypotonic-areflexic tetraparesis with cerebellar signs, but without spasticity and signs of pyramidal dysfunction. The disease has greater clinical vartiability than previously recognized. MRI findings can be helpful in diagnosis, with early involvement and atrophy of the cerebellar vermis. The pallidal involvement in 2 of the above series suggests an overlap with the radiologic findings in Hallervorden-Spatz disease. A biochemical or molecular marker has not been uncovered.