In the cases described by Rapin and colleagues the first findings were visual impairment with cherry-red macular spots, similar to those seen in Tay-Sachs disease and less consistently in GM1 gangliosidosis, Niemann-Pick disease, and metachromatic leukodystrophy. In one case, there was severe episodic pain in the hands, legs, and feet during hot weather, reminiscent of Fabry disease. Polymyoclonus followed within a few years and, together with cerebellar ataxia, disabled the patients. Mental function remained relatively normal. Liver and spleen were not enlarged, but storage material was found in the Kupffer cells, neurons of the myenteric plexus, and cerebral neurons, and presumably in cerebellar and retinal neurons.
The cases reported by Thomas and colleagues were young adults, all members of one generation, who had developed dysarthria, intention myoclonus, cerebellar ataxia, and cherry-red macular lesions. Like the cases of Rapin and coworkers, the heredity was autosomal recessive. There was urinary excretion of sialylated oligosaccharides and a sialidase deficiency in cultured fibroblasts. The two patients described by Tsuji and associates (1982) are noteworthy in that they were of age 50 and 30 years. In addition to the macular lesions, polymyoclonia, and cerebellar ataxia, there were gargoyle-like facial features, corneal opacities, and vertebral dysplasia. These patients also had a neuraminidase (partial beta-galactosidase) deficiency.
This progressive degeneration of the cerebellar-dental efferent system was originally described by Ramsay Hunt under the title of dyssynergia cerebellaris myoclonica but no has an uncertain meaning. It was classified as Ramsay Hunt syndrome type 1 to distinguish from the more common herpes zoster oticus syndrome that also carries his name. It probably should be considered a rare form of spinocerebellar ataxia. The onset is in late childhood; both sexes are vulnerable, and it probably has more than one cause. In Hunt’s case, a progressive ataxia was accompanied by a striking degree of action myoclonus. Seizures are infrequent, and the intellect is relatively preserved. The neurons of the dentate nuclei and their ascending and descending brainstem axons gradually disappear. Berkovic and associates studied 84 cases of polymyoclonus, 13 of which conformed to the Hunt syndrome. Of these, 9 proved to have a mitochondrial encephalomyopathy. However, there are other reports (Tassinari et al) in which muscle biopsies showed no mitochondrial abnormalities. In the series of 30 cases reported by Marsden and coworkers (1990) the onset was usually before the age of 21 years. Cortical electrographic discharges were found to precede each myoclonic twitch (cortical myoclonus). A biochemically supported diagnosis could not be made in nearly half of their cases.
Another mitochondrial disorder, the myoclonic epilepsy ragged red fiber (MERRF) disease, begins in the second decade or later with myoclonus and ataxia and enters into the differential diagnosis of this group of diseases. The mitochondrial diseases as a group are considered in the last part of this chapter.
Epilepsies of Hereditary Metabolic Disease (See Chap. 15)