1/6. X-linked adrenoleukodystrophy with olivopontocerebellar atrophy.X-linked adrenoleukodystrophy (X-ALD) is a rare neurological disorder characterized by adrenal, gonadal and nervous system dysfunction. patients usually develop spinal cord degeneration with involvement of the cerebral white matter. While a spinocerebellar variant has been described, the selective involvement of cerebellar white matter is very rare. We report the case of a patient affected by X-ALD whose clinical and magnetic resonance imaging (MRI) results resembled olivopontocerebellar atrophy. He was a 29-year-old mentally retarded man, who began to complain of slowly progressive gait ataxia after an 8-year history of Addison's disease. Serial MRI revealed marked cerebellar atrophy involving the inferior cerebellar vermis and brainstem, but sparing the supratentorial white matter. The diagnosis of X-ALD was confirmed by elevated levels of very long-chain fatty acids in the serum. After 2 years follow-up, the patient developed spastic paraparesis. The patient represents an unusual clinical presentation of X-ALD, as further confirmed by the MRI results. Consequently, cerebellar symptoms should be considered as a clinical presentation of X-ALD. Early recognition of this rare disorder would be useful for genetic counselling and therapy.- - - - - - - - - - ranking = 1keywords = adrenoleukodystrophy (Clic here for more details about this article) |
2/6. An autopsy case of mitochondrial encephalomyopathy with prominent degeneration in olivo-ponto-cerebellar system.We describe a sporadic case of adult-onset, complex I deficiency mitochondrial encephalomyopathy (MEM), the clinical and pathological features of which failed to fit any of the known subgroups of MEM, such as kearns-sayre syndrome, mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes or myoclonus epilepsy with ragged-red fibers. Clinically, this patient had only progressive cerebellar ataxia, generalized muscle weakness and hearing loss. The principal finding at autopsy was degeneration of the olivo-ponto-cerebellar system. This case suggests that mitochondrial disease could underlie some cases of olivo-ponto-cerebellar atrophy.- - - - - - - - - - ranking = 5.8911179607893E-7keywords = complex (Clic here for more details about this article) |
3/6. Olivopontocerebellar atrophy with retinal degeneration. A clinical and ocular histopathologic study.The ocular histopathologic and electron microscopic findings were determined in eyes obtained at autopsy from twins with dominant olivopontocerebellar atrophy (OPCA) and retinal degeneration (OPCA type III). On light microscopy, a retinal degeneration that involved primarily the photoreceptor layer was present and appeared to start in the macular area and spread to involve the peripheral fundus. The retinal pigment epithelium was variably hypopigmented and hyperpigmented. On electron microscopy, osmiophilic, multimembranous, and complex lipofuscin inclusions were present in conjunctival cells, keratocytes, lens epithelium, iris and ciliary body fibrocytes, occasional outer retinal cells, and retinal pigment epithelial cells. The twins' father and an older sister were also affected and had classic neurologic and ophthalmologic abnormalities. The similarities were noted between the clinical and ultrastructural findings between OPCA type III and the neuronal ceroid lipofuscinoses.- - - - - - - - - - ranking = 5.8911179607893E-7keywords = complex (Clic here for more details about this article) |
4/6. An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: I. Clinical and pathological studies.A male patient was suspected as olivo-ponto-cerebellar atrophy from the clinical and computed tomographic features at 34 years of age. Afterwards, his dysarthria and limb ataxia were slowly and steadily worsened. He was finally bed-ridden and unresponsive, and died of hyperpyrexia and general wasting at 37 years of age. It was noted that laboratory investigation gave lower values of urinary 17-ketosteroids and 17-hydroxycorticosteroids in comparison with those of normal subjects. Pathological investigation in autopsy showed that he had pathological features consistent with adrenoleukodystrophy accompanying the olivo-ponto-cerebellar atrophy; diffuse demyelination in the cerebrocerebellear white matter, distorted architecture and cytoplasmic striations in the adrenal cortex, and in addition, a pseudosystemic degeneration of the olivo-ponto-cerebellar system and subcortical gray matter.- - - - - - - - - - ranking = 1keywords = adrenoleukodystrophy (Clic here for more details about this article) |
5/6. An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: II. Lipid biochemical studies.Different portions with or without demyelination or degeneration of formalin-fixed brain tissues of a patient with adrenoleukodystrophy and a control subject were applied to analyses of lipids, particularly sphingolipids and cholesteryl ester. Demyelinated area of the white matter in the occipital lobe showed marked decrease in cerebroside and sulfatide except for sphingomyelin and, conversely an accumulation of cholesteryl ester, whereas un-demyelinated white matter in the frontal lobe showed no abnormalities in lipids. Abnormalities of lipids in degenerated lateral nuclei of the thalamus were not so remarkable as the demyelinated white matter, whereas apparently normal dorsomedial nuclei of the thalamus showed no abnormalities in lipids. With regard to the fatty acid composition of abnormal lipids in the demyelinated white matter, all sphingolipids of cerebroside, sulfatide, and sphingomyelin showed remarkable reduction of their longer chain fatty acids and, conversely a significant increment of shorter chain fatty acids. However, these fatty acids in the degenerated lateral nuclei of the thalamus were not so different from those in the undemyelinated and apparently normal areas as well as in control brain. The fatty acids of cholesteryl ester contained mainly C18:1 and C16 acids, and very long chain fatty acids, namely fatty acids with chain length more than 22 carbons, by about 22% of the total fatty acids. In view of the analytical results of the fatty acid composition of brain lipids, it was inconceivable that this ALD patient brain showed especially the accumulation of very long chain fatty acids, and that the biochemical defect in this disease was related to the abnormal oxidation of very long chain fatty acids in peroxisomes. However, the neuropathological findings of demyelination, reactive astrocytosis, and massive infiltration of foam cells well correlated with the abnormalities in myelin lipids and the accumulation of cholesteryl ester. Also, the lower values of urinary 17-ketosteroid and 17-hydroxycorticosteroid suggested that the failure of ACTH to stimulate corticoid secretion seemed to indicate the relationship between the adrenocortical insufficiency and the affected areas of the central nervous system.- - - - - - - - - - ranking = 1keywords = adrenoleukodystrophy (Clic here for more details about this article) |
6/6. autoantibodies to glutamate receptor subunit GluR2 in nonfamilial olivopontocerebellar degeneration.We describe a 63-year-old man with a 5-year history of progressive sporadic olivopontocerebellar atrophy (OPCA) who exhibits high serum titers of IgM autoantibodies to the neuronal glutamate receptor subunit GluR2. immunohistochemistry revealed intense staining of mouse cerebellar purkinje cells and cells in the pontine nuclei and olivary complex. Glutamate receptor currents were activated in a subset of cultured mouse neurons by an anti-GluR2 IgM fraction, and they were blocked by the competitive AMPA-type glutamate receptor antagonist CNQX and by a synthetic peptide to a specific epitope region of GluR2 (AA 369-393). The patient was treated with nine courses of plasmapheresis with little improvement of symptomatology. However, IgM titers to GluR2 decreased approximately 8-fold and the serum functional activity decreased proportionally. These findings may suggest a role for autoimmunity to glutamate receptors in the pathophysiology of certain forms of progressive nervous system degeneration.- - - - - - - - - - ranking = 5.8911179607893E-7keywords = complex (Clic here for more details about this article) |