Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gross and histopathological findings in the brain and spinal cord of five Alaskan Husky dogs with a novel incapacitating and ultimately fatal familial and presumed hereditary neurodegenerative disorder are described. Four dogs presented with neurological deficits before the age of 1 year (7-11 months) and one animal at 2.5 years old. Clinical signs in all dogs were of acute onset and included ataxia, seizures, behavioral abnormalities, blindness, facial hypalgesia and difficulties in prehension of food. In animals allowed to survive, the disease was static but with frequent recurrences. Pathological findings were limited to the central nervous system. Grossly visible bilateral and symmetrical cavitated foci were consistently present in the thalamus with variable extension into the caudal brain stem. Microscopic lesions were more widespread and included foci of bilateral and symmetrical degeneration in the basal nuclei, midbrain, pons and medulla, as well as multifocal lesions at the base of sulci in the cerebral cortex and in the gray matter of cerebellar folia in the ventral vermis. Neuronal loss with concomitant neuronal sparing, spongiosis, vascular hypertrophy and hyperplasia, gliosis, cavitation and transient mixed inflammatory infiltration were the main histopathological findings. In addition, a population of reactive gemistocytic astrocytes with prominent cytoplasmic vacuolation was noted in the thalamus. Lesions of this nature in this distribution within the neuroaxis have not been reported in dogs. The neuropathological findings resemble Leigh's disease/subacute necrotizing encephalomyelopathy of man. Neuronal sparing in conjunction with apparently transient astrocytic vacuolation point to the possible pathogenetic role of astrocytes in the evolution of these lesions. An inherited metabolic derangement of unknown nature is postulated as the cause of this breed-specific disorder.
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PMID:Alaskan Husky encephalopathy--a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome). 1091 20

Thiophene is a sulfur-containing heterocyclic hydrocarbon that has been detected in a number of environmental sources as various derivatives. Previous studies with rats have shown that thiophene induces selective degeneration of granule cells in the cerebellum, as observed with methyl mercury. To study the neurotoxicity of thiophene, Wistar rats received daily intramuscular injections of 0.2 mL thiophene for 3 days. Ataxia and convulsions were noted in all animals within 24 h after the final dose. Histologically, multiple foci of necrosis were observed in the cerebellum, predominantly in the granular layer. Neuronal damage was also found in the cerebral cortex, inferior colliculus and inferior olive. These findings suggest that thiophene causes widespread neuronal degeneration in rats and that the regional distribution of brain lesions induced by thiophene is different from that caused by methyl mercury poisoning.
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PMID:Thiophene, a sulfur-containing heterocyclic hydrocarbon, causes widespread neuronal degeneration in rats. 1121 Oct 52

A Japanese girl with peculiar leukoencephalopathy was reported. Following normal development until 1 year of age, she showed progressive neurological deterioration with ataxia, epilepsy, pyramidal tract signs and choreic movement. Serial brain computed tomographies (CTs) revealed markedly low density and progressive volume loss in whole white matter. In extensive laboratory investigations, the level of glycine in the urine was elevated. She died at the age of 4 years, and the neuropathological findings were comprised of severe extensive changes in cerebral and cerebellar white matter, such as marked rarefaction or cystic degeneration with axonal loss. The pontine central tegmental tracts were also affected. Neuronal loss was seen in the cerebellar cortex. These features were compatible with leukoencephalopathy with vanishing white matter, which was recently established as a clinical entity. To our knowledge, this is the first report of a non-Caucasian patient with this new type of leukoencephalopathy.
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PMID:A Japanese girl with leukoencephalopathy with vanishing white matter. 1122 33

There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia may result from dysfunction of voltage-gated sodium, potassium and calcium channels, or acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's syndrome, policystic kidney disease and Dent's disease, secretion disorders, e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision disorders, e.g., congenital stationary night blindness and total colour-blindness may also be linked to mutations in ion channels.
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PMID:Ion channels-related diseases. 1131 Sep 70

Neuronal ceroid lipofuscinoses are a group of rare neurodegenerative disorders that are characterised by an accumulation of autofluorescent lipopigments in neurons and extraneuronal tissues. We report on a 4-year-old boy who presented with an acute onset of seizures followed by rapid psychomotor deterioration, ataxia, and visual failure. Photic stimulation at 1 to 3 Hz elicited discrete spike and wave discharges in the electroencephalogram, which were diminished at a higher frequency of stimulation. The electroretinogram was extinct. Magnetic resonance imaging of the brain showed generalised cerebral and cerebellar atrophy. Electron microscopic examination of lymphocytes and samples of muscle and skin revealed characteristic curvilinear inclusion bodies. To our knowledge, this is the first case of late infantile neuronal ceroid lipofuscinosis to be reported in a Hong Kong Chinese patient.
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PMID:Classic late infantile neuronal ceroid lipofuscinosis in a Chinese patient. 1140 82

Neuronal intranuclear inclusions (NIIs) found in CAG/polyglutamine-expansion disorders contain both expanded polyglutamine and the gene product without the CAG repeat. The gene product containing expanded polyglutamine has, therefore, been considered to be a major component of NIIs. In this immunohistochemical study, we showed recruitment of ataxin-2, ataxin-3 and TATA box binding protein (TBP) into NIIs of the pontine neurons of spinocerebellar ataxia type (SCA) 1, SCA2, SCA3 and dentatorubral-pallidoluysian atrophy brains. Triple-labeling immunofluorescence demonstrated colocalization of ataxin-2 and ataxin-3 in NIIs containing expanded polyglutamine, irrespective of the disease examined. These in vivo findings indicate that polyglutamine proteins recruited into NIIs are not restricted to their expanded form. Among these proteins, recruitment of ataxin-2 was least frequent in every case examined, suggesting that the rate of recruitment partly depends on the protein transported into NIIs. Because other proteins lacking polyglutamine motif were not detected in NIIs, it is suggested that the presence of polyglutamine is a prerequisite for these proteins to be recruited into nucleus and to form NIIs. Interaction between expanded and non-expanded polyglutamine may play roles during these processes.
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PMID:Non-expanded polyglutamine proteins in intranuclear inclusions of hereditary ataxias--triple-labeling immunofluorescence study. 1156 29

We report a 58-year-old man with slowly progressive muscle atrophy and weakness in the four extremities, accompanying cerebellar ataxia and sensory impairment of all modalities. He was a product of consanguineous marriage. His neurological manifestations began in childhood. He was admitted to our hospital because of marked abdominal distension and pretibial edema with hypoalbuminemia and hyperlipidemia. Neuroimaging studies showed marked atrophy of the cerebellum and spinal cord. Nerve conduction studies presented with slowing and sural nerve biopsy revealed demyelination with onion-bulbs. Abdominal distension was interpreted to be caused by chronic idiopathic intestinal pseudo-obstruction (CIIP), leading to protein-losing gastroenteropathy and hypalbuminemia caused by the CIIP. He died of DIC by myelodysplasic syndrome and DIC, two years later. Postmortem study demonstrated with severe loss of anterior horn cells and gliosis in the spinal cord. The Clarke's column was also affected. There was symmetrical degeneration in the dorsal column and corticospinal tracts. The cerebellum showed atrophy of molecular layer, prominent loss of Purkinje's cells and sparse granular cell layer, but no obvious change in the dentate nucleus. Neuronal loss in the dorsal root ganglia was remarkable. There were no alternations in the cerebral cortex, striatum, thalamus, subthalamic nucleus, and pontine nucleus, except for mild changes in substantia nigra and inferior olivary nucleus. This case was clinically suspected either of variant of Friedreich's ataxia or an early onset ataxia associated with hypoalbuminemia (EOAHA), although marked autonomic dysfunction was atypical. But the postmortem study, demonstrated with marked neuronal loss in anterior horn cells and cerebellan cortex and rather suggested an independent category of this case.
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PMID:[An autopsy case of atypical Friedreich's ataxia with chronic idiopathic intestinal pseudo-obstruction]. 1180 52

Mutations in the EPM2A gene encoding a dual-specificity phosphatase (laforin) cause Lafora disease (LD), a progressive and invariably fatal epilepsy with periodic acid-Schiff-positive (PAS+) cytoplasmic inclusions (Lafora bodies) in the central nervous system. To study the pathology of LD and the functions of laforin, we disrupted the Epm2a gene in mice. At two months of age, homozygous null mutants developed widespread degeneration of neurons, most of which occurred in the absence of Lafora bodies. Dying neurons characteristically exhibit swelling in the endoplasmic reticulum, Golgi networks and mitochondria in the absence of apoptotic bodies or fragmentation of DNA. As Lafora bodies become more prominent at 4-12 months, organelles and nuclei are disrupted. The Lafora bodies, present both in neuronal and non-neural tissues, are positive for ubiquitin and advanced glycation end-products only in neurons, suggesting different pathological consequence for Lafora inclusions in neuronal tissues. Neuronal degeneration and Lafora inclusion bodies predate the onset of impaired behavioral responses, ataxia, spontaneous myoclonic seizures and EEG epileptiform activity. Our results suggest that LD is a primary neurodegenerative disorder that may utilize a non-apoptotic mechanism of cell death.
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PMID:Targeted disruption of the Epm2a gene causes formation of Lafora inclusion bodies, neurodegeneration, ataxia, myoclonus epilepsy and impaired behavioral response in mice. 1201 6

IP3 is an important second messenger to release Ca2+ from internal store. IP3receptor (IP3R) works as an IP3 induced Ca2+ release channel and requires IP3 and Ca2+ as coagoinist. We found IP3R is involved in fertilization, meiosis and mitosis by using a specific antibody. We further found that IICR is essential for determination of dorsoventral axis formation. Neuronal type 1 IP3R-deficient mice generated by a gene-targeting technique exhibit a significant reduction of birth rate and abnormal behavior (ataxia and seizure). Long-term depression of the cerebellum was blocked in the type 1 IP3R-deficient mice. Long-term potentiation (LTP) of CA1 hippocampus was enhanced but depotentiation and LTP suppression was reduced in IP3R1-deficient mice. These evidences suggest that IICR is involved in neuronal plasticity. The coupling mechanism between ER Ca2+ stores and plasma membrane store-operated channels is crucial to Ca2+ signaling. Recently we found that IP3R interacts with the TRP3 Ca2+ channel on the plasma membrane and functional coupling of IP3R to TRP3 channel is important for store operated Ca2+ entry. Recently we found that IP3R is involved in determination of polarity and input specificity of activity-induced synaptic modification.
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PMID:[IP3 receptor, a Ca2+ oscilator--role of IP3 receptor in development and neural plasticity]. 1249 67

Neuronal voltage-gated calcium channels (VGCCs) are critical to numerous cellular functions including synaptogenesis and neurotransmitter release. Mutations in individual subunits of VGCCs are known to result in a wide array of neurological disorders including episodic ataxia, epilepsy, and migraines. The characterization of these disorders has focused on channel function within the brain. However, a defect in the retina-specific alpha1F subunit of an L-type VGCC results is a loss of visual sensitivity or the incomplete form of X-linked congenital stationary night blindness (CSNB2). Based on the electroretinographic phenotype of these patients this channel type is localized to the axon terminal of photoreceptor cells and results in a loss of signal transmission from photoreceptors to bipolar cells. A mouse with a deletion of the beta2 subunit of VGCCs in the central nervous system was recently shown to have a similar phenotype as CSNB2 patients. The identification of the role of VGCCs in this disorder highlights the potential association of other VGCC mutations with retinal disorders. The study of the role of these channels in normal retinal function may also be elucidated by the characterization of retinal structure and visual function in the numerous knockout, transgenic, and naturally occurring mouse mutants currently available.
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PMID:Using mutant mice to study the role of voltage-gated calcium channels in the retina. 1259 37


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