The brains of two patients with Lesch-Nyhan syndrome (LNS) were studied. The concentration of dopamine was decreased in the caudate nucleus of LNS patients. Immunohistochemical methods revealed that the dopamine (DA) D1 and D2 receptor and methionine-enkephalin immunoreactivities (IRs) were increased in the putamen, and less significantly in the caudate nucleus. The D1 and D2 receptor IRs of the cingulate cortex, the tryptophan-hydroxylase IR in the dorsal nucleus of the midbrain, as well as the substance P and methionine-enkephalin IRs of the nociception-conducting structures, including the periaqueductal gray and spinal trigeminal nucleus, were not changed. Tyrosine-hydroxylase IR was not decreased in the substantia nigra of the LNS patients. Therefore, the cause of the decreased dopaminergic activity in LNS may not be involved in the production of tyrosine hydroxylase in the substantia nigra. Developmental abnormalities due to the DA defect at an early age might exist in the postsynaptic structure in the striatum.

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Alexander disease is a leukodystrophy that is neuropathologically characterized by the presence of numerous Rosenthal fibers in astrocytes. Recently, mutations in the gene encoding glial fibrillary acidic protein (GFAP) were identified in patients with Alexander disease. We sequenced the GFAP gene of a Japanese girl who presented with typical symptoms of Alexander disease but in whom the diagnosis was not proven by histopathology. We identified a missense mutation, R239C, which is identical to the mutation previously reported to be most frequent. As was the case in previously described patients, our patient was also heterozygous for the de novo mutation. Interestingly, despite the fact that this is a de novo mutation, R239C was found to be common in different ethnic groups, implying that the site is a "hot spot" for mutagenesis. Molecular genetic analysis now makes the antemortem diagnosis of Alexander disease possible.

References1. Leigh RJ, Robinson DA, Zee DS. A hypothetical explanation for periodic alternating nystagmus: instability in the optokinetic-vestibular system. Ann NY Acad Sci 1981;374:619 -635. 2. Baloh RW, Honrubia V, Konrad HR. Periodic alternating nystagmus. Brain 1976;99:11-26. 3. Davis DG, Smith JL. Periodic alternating nystagmus: a report of eight cases. Am J Ophthalmol 1971;72:757-762. 4. Keane JR. Periodic alternating nystagmus with downward beating nystagmus: a clinicoanatomical case study of multiple sclerosis. Arch Neurol 1974;30:399 -402. 5. Dow ER, Anastasio TJ. Induction of periodic alternating nystagmus in intact goldfish by sinusoidal rotation. Neuroreport 1997;8:2755-2759. 6. Wearne S, Raphan T, Cohen B. Control of spatial orientation of the angular vestibuloocular reflex by the nodulus and uvula.Dentatorubral pallidoluysian atrophy (DRPLA) is an autosomal dominant disease that has a wide variety of clinical symptoms. 1 There is a correlation between age at onset and clinical symptoms. Progressive myoclonus epilepsy (PME) is a usual feature of juvenile DRPLA; but late adult DRPLA patients usually experience cerebellar ataxia and hyperkinetic involuntary movements such as choreoathetosis, often without myoclonus or epilepsy. 2 We report two unrelated patients with infantile DRPLA. Patient 1. The patient is a 4-year-old boy and the second child of healthy, nonconsanguineous Japanese parents without a family history of neurologic diseases. His father is 39 years old and his mother is 35 years old. He has a healthy 8-year-old brother. There were no major problems in the neonatal periods. He developed normally until age 6 months when his mother noticed decreased activity. At age 1 year, he could stand with support; but he began to regress slowly and became irritable. At age 2 years, he had difficulty controlling his head and swallowing, sometimes showing dystonic posture. Choreoathetosis of the limbs appeared and became prominent. At age 2 years 7 months, he had tonic convulsions. Various antiepileptic drugs did not control the convulsions.He was no longer able to fix or follow, but had light perception and normal optic fundus. Nystagmus was not noted. Muscle tone was variable, and deep tendon reflexes were exaggerated. Plantar response was absent. Oral dyskinesia, severe choreoathetosis, and dystonia were continuously seen. Myoclonus was not present.Laboratory examination including lysosomal enzyme activities, organic and amino acid analysis, and the level of lactate and pyruvate, were unremarkable. Histologic examination of the biopsied skin and muscle revealed no abnormalities.MRI of the brain showed atrophy of the cerebrum and cerebellum, brain stem, and delayed myelination ( figure, A and B).Patient 2. The patient is a 2-year-old girl and the second child of healthy, nonconsanguineous Japanese parents. Her father is 46 years old and her mother is 37 years old. Her 10-year-old brother has epilepsy and mild mental retardation. Her birth and development up to age 4 months were normal, but she could no...

Eleven orally fed (group A) and 14 tube‐fed patients (group B) with severe disabilities and neurological disorders were compared to determine whether selenium (Se) deficiency is present in patients undergoing long‐term tube feeding, and to examine if Se supplementation has beneficial effects on their cardiac function. Assessments of Se intake, serum levels of Se, and cardiac‐function analysis including chest X‐ray, electrocardiography (ECG), and M‐mode echocardiography (UCG) were made. For group B, the effect of Se supplementation on cardiac function was assessed. Statistical significance was determined using Mann‐Whitney U test and Wilcoxon signed‐rank test. Deficiencies of Se were found in group B. ECG abnormalities were more common in group B than group A. UCG showed a lower ejection fraction, a lower mean rate of circumferential fiber shortening corrected by heart rate, and a lower diastolic velocity of the left‐ventricular posterior walls in group B than in group A. In group B, Se supplementation resulted in normalized serum Se levels, partial improvement of ECG abnormalities, and an increase of cardiac functions on UCG. It is thought that Se has beneficial effects on the myocardium of chronically tube‐fed patients. Se supplementation is recommended in this population.

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