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)

Homozygous tottering (tg/tg) and compound heterozygous tottering/leaner (tg/tg(la)) mutant mice exhibit juvenile onset of three abnormal neurological phenotypes: (i) petit mal-like epilepsy; (ii) ataxia; and (iii) an intermittent myoclonus-like movement disorder. Homozygous leaner mice (tg(la)/tg(la)) exhibit early onset of ataxia (postnatal days 10-12), and also exhibit the myoclonus-like movement disorder and evidence of absence seizure activity; the myoclonus-like disorder is most evident in the first month of life, then diminishes in severity and frequency. The ultrastructure of the cerebellar molecular layer was examined in adult (six to eight months) and juvenile (20-25 days) mice of all three mutant genotypes. In mice of all three genotypes and both ages, Purkinje cell dendritic spines were observed to make multiple contacts with individual parallel fiber varicosities in all sections analysed. These multiple synaptic units were observed in both anterior and posterior vermis and hemispheres of the cerebellum, and ranged from two to nine spines/parallel fiber varicosity. Occasionally, one of the postsynaptic spines belonged to an ectopic spine emerging from the proximal region of a Purkinje cell dendrite. This increase in the multiple synaptic index of some parallel fiber varicosities was observed in juvenile tottering mice before the onset of the symptoms of the neurological disorders. This is highly suggestive that the onset of the neurological phenotype is not a primary cause of multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities in these mice, but on the contrary, that it could be the cause of the ataxic symptoms.
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PMID:An ultrastructural study of granule cell/Purkinje cell synapses in tottering (tg/tg), leaner (tg(la)/tg(la)) and compound heterozygous tottering/leaner (tg/tg(la)) mice. 1021 73

Rolling mouse Nagoya (rolling: tg(rol)) is a neurologic mutant mouse exhibiting severe ataxia. Two alleles of the rolling mutation, tottering (tg) and leaner(tg(la)), have been identified as mutations in the voltage-dependent calcium channel alpha1A subunit. No specific light and electron microscopic findings have been reported for the rolling mouse cerebellum except a decreased number of granule cells, while altered Purkinje cell/parallel fiber synapses have been observed in tottering and leaner cerebella. Rolling mouse cerebella were analyzed using anti-calbindin-D immunohistochemistry and transmission electron microscopy to investigate Purkinje cell morphology and synaptic contacts between Purkinje cell dendritic spines and parallel fiber varicosities. Multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities were frequently observed in rolling cerebella. The correlation between the presence of altered Purkinje cell synapses and ataxia in rolling mice warrants further investigation.
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PMID:Morphologic investigation of rolling mouse Nagoya (tg(rol)/tg(rol)) cerebellar Purkinje cells: an ataxic mutant, revisited. 1033 81

The pogo mouse is a new ataxic mutant derived from the Korean wild mouse. The pathological manifestations include difficulty in maintaining normal posture and the inability to walk straight. The ataxia becomes apparent at about 2 weeks of age. Electron microscopic studies of the pogo/pogo homozygous cerebellum, revealed that the ectopic spines emanating from the primary dendrite of Purkinje cells were observed. Major difference between pogo/pogo homozygous and non-affected pogo/+ heterozygous was the synaptic organization of the molecular layer. Parallel fiber varicosities were larger than normal and a single fiber often established synaptic contacts with up to four dendritic spines of a Purkinje cell. This correlation between the presence of altered synaptic organization in the cerebellum and ataxia in pogo/pogo mutant mice warrants further investigation.
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PMID:Abnormal synaptic organization between granule cells and Purkinje cells in the new ataxic mutant mouse, pogo. 1105 91

Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, which produces delayed neurotoxicity (OPIDN) in hens in 7-14 days. OPIDN is characterized by mild ataxia in its initial stages and severe ataxia or paralysis in about 3 weeks. It is marked by distal swollen axons, and exhibits aggregations of neurofilaments (NFs), microtubules, proliferated smooth endoplasmic reticulum, and multivesicular bodies. These aggregations subsequently undergo disintegration, leaving empty varicosities. Previous studies in this laboratory have shown an increased level of medium-molecular weight NF (NF-M) and decreased levels of high- and low-molecular weight NF (NF-H, NF-L) proteins in the spinal cord of DFP-treated hens. The main objective of this investigation was to study the effect of DFP administration on NF subunit levels when OPIDN is prevented or potentiated by pretreatment or post-treatment with phenylmethylsulfonyl fluoride (PMSF), respectively. Hens pretreated or post-treated with PMSF were killed 1, 5, 10, and 20 days after the last treatment. The alteration in NF subunit protein levels observed in DFP-treated hen spinal cords was not observed in protected hens. Estimation of NFs in the potentiation experiments, however, showed a different pattern of alteration in NF subunit levels. The results showed that an alteration in NF subunit levels in DFP-treated hens might be related to the development of OPIDN, since these changes were suppressed in PMSF-protected hens. However, results from PMSF post-treated hen spinal cords suggested that potentiation of OPIDN by PMSF was mediated by a mechanism different from that followed by DFP alone to produce OPIDN.
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PMID:Protein levels of neurofilament subunits in the hen central nervous system following prevention and potentiation of diisopropyl phosphorofluoridate (DFP)-induced delayed neurotoxicity(1). 1175 69

A neonatal ataxia syndrome was observed in Coton de Tulear dogs. Seven affected pups (32%; 7/22) of both genders came from 5 different litters with phenotypically normal parents. Neurologic examination revealed normal mental status, head titubation, intention tremors, and severe gait, stance, and ocular ataxia beginning at 2 weeks of age. One of the pups was able to walk with assistance, but most of the affected pups were unable to stand and used propulsive movements ("swimming") for goal-oriented activities. They frequently would fall to lateral recumbency with subsequent decerebellate posturing and paddling. Ocular motor abnormalities included fine vertical tremors at rest and saccadic dysmetria. The condition was nonprogressive at least until 4 months of age. No specific abnormalities were identified in routine laboratory screening of blood and urine. Cerebrospinal fluid (CSF) analysis was normal in 1 dog, and a mild increase in protein concentration was observed in a second dog. CSF organic and amino acid concentrations were within normal limits. Magnetic resonance imaging and computed tomography of the brain, electromyography, motor nerve conduction studies, and brain stem auditory-evoked potentials were within normal limits. Postmortem examinations were performed on 5 affected dogs between 2 and 4 months of age. Routine light microscopic and immunocytochemical examination of brain, spinal cord, peripheral nerve, and muscle did not disclose any gross or histologic lesions. Compared with the cerebellum from an age-matched normal dog, the cerebellum from an affected dog showed synaptic abnormalities, including loss of presynaptic terminals and organelles associated with parallel fiber varicosities within the molecular layer and increased numbers of lamellar bodies in Purkinje cells. An autosomal recessive trait affecting development of the cerebellum is suspected.
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PMID:Neonatal cerebellar ataxia in Coton de Tulear dogs. 1246 65

We report a case of tentorial dural arteriovenous fistula(dAVF)treated with transarterial and transvenous embolization using n-butyl-2-cyanoacrylate(NBCA). A 70-year-old man presented with dysarthria and trunk ataxia. Computed tomography(CT)on admission revealed right cerebellar hemorrhage. Right external carotid angiography demonstrated a tentorial dAVF fed by the marginal tentorial artery, petrosquamous branch of the middle meningeal artery, ascending pharyngeal artery, and artery of foramen rotundum. Right internal carotid angiography demonstrated a shunt fed by the meningohypophyseal trunk. The draining vein was the right basal vein with a varix, which drained into the straight sinus. Thin-slice axial images on magnetic resonance angiography demonstrated a shunt point located on the right tentorial incisura. The lesion was diagnosed as Cognard type IV tentorial dAVF. It was initially treated with transarterial embolization using 25% NBCA, which was injected into the marginal tentorial artery and the petrosquamous branch of the middle meningeal artery. However, owing to partial persistence of the shunt after the procedure, transvenous embolization using NBCA was performed. A microcatheter was navigated through the straight sinus into the basal vein, and a balloon catheter was also navigated to the confluence of the straight sinus and the basal vein to interrupt blood flow and prevent the NBCA from flowing back to the sinus. 80% NBCA was injected into the draining vein near the shunt point. Angiography performed immediately after the procedure revealed complete occlusion of the shunt, and postoperative CT showed no evidence of hemorrhage. Transvenous embolization of tentorial dAVF can be an effective method if a microcatheter can be safely advanced close to the shunt point.
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PMID:[A Case of Tentorial Dural Arteriovenous Fistula Treated with Transvenous Embolization Using NBCA]. 2879 Feb 16