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)

Dextromethorphan (DM), a widely used and well-tolerated centrally acting antitussive, has been tested in several clinical trials for its antiepileptic and neuroprotective properties. However, the use of DM in these new clinical indications requires higher doses than antitussive doses, which may therefore induce phencyclidine (PCP)-like side-effects (memory and psychotomimetic disturbances) through its metabolic conversion to the active metabolite dextrorphan (DX), a more potent PCP-like non-competitive antagonist at the N-methyl-D-aspartate (NMDA) receptor than DM. Thus, we compared the behavioural effects in rats of intraperitoneal administration of DM and DX on motor activity in an open field and on learning and memory in the Morris water maze. DM (20, 30, 40 mg/kg) produced a dose-dependent decrease in both locomotion and stereotyped behaviour with a slight ataxia for the highest dose. DX (20, 30, 40 mg/kg) induced a dose-dependent increase in locomotion and stereotypies (swaying, turning) with moderate ataxia. Assessments of learning and memory were performed with lower doses of DM (10, 20, 30 mg/kg) and DX (5, 10, 15 mg/kg) because of motivational deficits (40 mg/kg of DM, 20-40 mg/kg of DX) and motor disorders (30, 40 mg/kg of DX) in the cue learning procedure. DX (10, 15 mg/kg) impaired spatial learning with a long-lasting effect for the highest dose whereas 5 mg/kg of DX and DM (10-30 mg/kg) did not. Only 15 mg/kg of DX appeared to slightly impair working memory. DM (10-30 mg/kg) and DX (5-15 mg/kg) did not impair reference memory. Thus, the two antitussives DM and DX induced different behavioural effects suggesting sedative effects for DM and PCP-like effects for DX. However, PCP-like side-effects with DM remain possible through its metabolic conversion to DX, with very high doses and/or in extensive metabolizers and/or in aged subjects prone to cognitive dysfunction. Therefore, the identification of DM metabolism phenotype, an adapted prescription and a pharmacological modulation of the DM metabolism may avoid adverse effects.
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PMID:Dextromethorphan and dextrorphan in rats: common antitussives--different behavioural profiles. 979 51

Our objective was to investigate how cooling of the arm and vision influence pointing movements in healthy subjects and patients with cerebellar limb ataxia due to clinically proven multiple sclerosis. An infrared video motion analysis system was used to record the unrestricted, horizontal pointing movements toward a target under three different conditions involving a moving, stationary, or imaginary target; a visual, or acoustic trigger; and vision or memory guidance. All three tasks were performed before and after cooling the arm in ice water. Patients had more hypermetric and slower pointing movements than controls under all tested conditions. Patients also had significantly larger three-dimensional finger sway paths during the postural phase and larger movement angles of the wrist joint. Memory-guided movements were the most hypermetric recorded in both groups. Cooling of the limb had no effect on amplitude or peak velocity of the pointing movement in either group under all tested conditions, but significantly reduced the three-dimensional finger sway path during the postural phase in patients with limb ataxia. Cooling-induced reduction of the finger sway was largest in those patients with the largest finger sway before cooling. In conclusion, the cooling-induced reduction of the proprioceptive afferent inflow, most probably of group I spindle afferents, reduces postural tremor of patients with cerebellar dysfunction.
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PMID:Influence of visual and proprioceptive afferences on upper limb ataxia in patients with multiple sclerosis. 1022 13

An 18-year-old woman in her first pregnancy with hyperemesis gravidarum, presented dehydration, without hyponatremia. She was confused with profound disorientation, apathy, and drowsiness. She presented upbeating nistagmus on upward gaze and gate ataxia recognised as Wernicke's encephalopathy. Laboratory tests demonstrated hypokalemia, hypernatremia and aminotransferase elevation. The serum osmolality was 319 mOsm/kg and the water deficiency 2.73 l. The patient developed weakness in the four limbs, with hypotonicity, absence of tendon reflexes and showed bilateral Babinski signs. A T2 weighted sagittal cranial-magnetic resonance imaging revealed a high signal within mid-pons suggesting central pontine myelinolysis. In this case we highlight the absence of hyponatremia. Furthermore, the central pontine myelinolysis was probably secondary to hypokalemia, hypernatremia and hyperosmolality.
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PMID:[Central pontine myelinolysis induced by hyperemesis gravidarum]. 1041 97

Acrylamide intoxication produces peripheral neuropathy characterized by weakness and ataxia in both humans and experimental animals. Previous studies on animals of different ages and species indicate that the longest and largest nerves are affected earlier with the major pathology in the terminal parts of axons, i.e., distal axonopathy. However, several issues have remained elusive; for example, what are the earliest pathological changes? An equally intriguing question is whether younger animals are more susceptible to acrylamide than older animals. To address these issues, we compared the vulnerability to acrylamide of 3- and 8-week-old mice. These mice were intoxicated with acrylamide in drinking water (400 ppm). The sequence of intoxication could be categorized into three stages. In the initial stage, there was no visible weakness or ataxia. The only noticeable changes were poor performance on the rota-rod test and swelling of motor nerve terminals. Obvious weakness and ataxia of hindlimbs developed gradually (here designated as the early stage). The weakness and ataxia progressed at variable speeds in mice of different ages, and eventually the forelimbs (quadriparesis) were affected in the late stage. Each stage appeared earlier in 3-week-old mice than in 8-week-old mice (7.1 +/- 1.1 vs 15.6 +/- 4.0 days, P < 0.01 for the early stage; and 15.3 +/- 2.1 vs 31.7 +/- 6.0 days, P < 0.01 for the late stage). The progression of neurological deficits was also faster in the younger mice (7.2 +/- 1.8 vs 16.3 +/- 4.2 days, P < 0.01). Pathological changes in the distal parts of motor nerves innervating hindfoot muscles were evaluated by combined cholinesterase histochemistry and immunocytochemistry for neuronal markers to demonstrate motor nerve terminals and neuromuscular junctions simultaneously. In the initial stage, there was axonal swelling in motor nerve terminals. As acrylamide intoxication continued, axonal swelling extended into junctional folds and into the intramuscular nerves, which resulted in Wallerian-like degeneration. Our results indicate that younger mice show a much higher susceptibility to acrylamide intoxication, and pathological changes precede neurological symptoms.
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PMID:Age-dependent acrylamide neurotoxicity in mice: morphology, physiology, and function. 1044 16

A case report is presented of an electrophysiologic recovery from vitamin E-deficient neuropathy after treatment with water-soluble vitamin E in a patient with chronic hepatobiliary disease. The patient was a 64-year-old man who had experienced progressive difficulty in ambulation, with ataxia, over the previous 3 years. The symptoms were associated with pain, tingling sensation in the extremities, and reduced fine motor activity. The patient had chronic hepatobiliary disease, with recurrent cholangitis and external drainage of bile acid through a T-tube for more than 20 years. Vitamin E level was barely detectable (<0.5 mg/L). Sensory conduction was absent in both sural nerves. Other sensory and motor conduction studies in the upper and lower extremities showed decreased amplitude. The patient was treated with water-soluble vitamin E. After 4 months of therapy, his ambulation function improved, but pain and tingling sensation in both hands remained. Sensory nerve action potentials appeared in both sural nerves, and amplitudes of other sensory nerves were increased. In a second follow-up study after 9 months, all of the evaluated parameters in the nerve conduction studies, as well as the vitamin E level, were normal. The authors conclude that vitamin E-deficient neuropathy is reversible and electrophysiologic recovery can occur with water-soluble vitamin E therapy.
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PMID:Electrophysiologic recovery after vitamin E-deficient neuropathy. 1045 75

Two rare cases of Wernicke's encephalopathy (WE) in non-alcoholic patients on hemodialysis (HD) are reported. They presented with the clinical triad of WE (ophthalmoplegia, ataxia and disturbance of consciousness) and intravenous administration of thiamine led to complete elimination of these manifestations. Reduced plasma thiamine levels prior to the administration confirmed the diagnosis of WE. Interestingly, a reduction in plasma thiamine levels by about half was seen in one of the patients on HD, suggesting that thiamine, a water-soluble vitamin, can be depleted with HD. In the literature, nine HD-dependent patients have been reported to develop WE, seven of whom were diagnosed postmortem. Their premortem diagnoses included uremic encephalopathy, dysequilibrium syndrome and dialysis dementia, which can often complicate HD and present symptoms similar to those of WE. We therefore emphasize that WE, even though a rare complication, should be suspected in all patients on HD who present with at least one of the clinical triad of WE.
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PMID:Wernicke's encephalopathy associated with hemodialysis: report of two cases and review of the literature. 1046 8

The ASPCA National Animal Poison Center managed 29 cases of ingestion of commercially available macadamia nuts in dogs during a 5-y period. Clinical signs included, from most to least, weakness, depression, vomiting, ataxia, tremor, hyperthermia, abdominal pain, lameness, stiffness, recumbency, and pale mucous membranes. The onset of clinical signs was reported as < 12 h in 79% of the cases. The duration of clinical signs for the majority of cases was < 24 h. The amount of macadamia nuts ingested was estimated in 72% of the calls with a mean of 11.7 g/kg bw. In an attempt to reproduce the syndrome, 4 dogs were gavaged with 20 g macadamia nuts/kg bw in a water slurry. The experimentally dosed dogs developed weakness, manifested by the inability to rise 12 h after dosing, mild central nervous system depression, vomiting, and hyperthermia, with rectal temperatures up to 40.5 C. Mild elevations in serum triglycerides and serum alkaline phosphatase were detected. Lipase values peaked sharply at 24 h and returned to normal by 48 h after dosing. Other serum biochemical and electrolyte determinations were unremarkable. Serum lipoprotein electrophoresis determinations were unchanged from baseline. The mechanism of the syndrome is unknown. All field and experimental dogs recovered uneventfully within 1 to 2 d whether treated by a veterinarian or not.
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PMID:Weakness, tremors, and depression associated with macadamia nuts in dogs. 1067 81

A comparative study of the toxic effects of extracts from stem bark, leaf and seed kernel of yellow oleander (Thevetia peruviana) in albino rats was carried out. Male and female albino rats weighing 150-200 g were administered crude aqueous extracts of stem bark, leaf and seed kernel of the plant by intraperitoneal injection or exposed to baits prepared with the dry extracts of the plant parts. The control groups either received distilled water by injection, or were fed non-poisoned baits. Extracts from all the plant parts were toxic, and produced marked poisoning symptoms that culminated in death. Poisoning symptoms manifested earlier (10 min after treatment) in rats administered aqueous kernel extracts intraperitoneally as against 45 min to several hours in rats poisoned by ingestion of toxicant. Poisoning symptoms indicated serious cardiac, neuromotor and mental malfunctioning, and manifested as tachycardia, arrhythmia, paralysis, ataxia and disorientation. The lethal dose was lowest (507 mg/kg) with the concentrated aqueous kernel extract (CAKE), and highest (5700 mg/kg) with the bait formulated using 40% of the kernel meal - FKM(B). Rats treated by injection with aqueous kernel extract (AKE) died faster within 10 h, than those with the aqueous leaf or stem bark extracts that died after 260 h. No mortality or abnormal behavioural changes were observed among animals in the control groups.
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PMID:Toxicological studies on stem bark, leaf and seed kernel of yellow oleander (Thevetia peruviana). 1068 14

Oral administration of N-[4-(3-ethoxy-2-hydropropoxy)phenyl] acrylamide (EHA) induced selective granule cell destruction in the granular layer of the cerebellar cortex together with neurological signs, such as delayed righting reflex, gait or truncal ataxia, and convulsion. Neuropathologically, it caused multifocal granule cell destruction with nuclear pyknosis and spongiosis of the neuropile in the granular layer. Other neurons, including Purkinje cells, were spared. Ultrastructurally, damaged granule cells showed aggregation of nuclear chromatin and cytoplasmic edema, but cytoplasmic organelles were preserved. The brain uptake index of 14C-labeled EHA was similar to that of H2O. When EHA was added to rat cerebellar tissue cultures, only the granule cells showed nuclear pyknosis, aggregation of nuclear chromatin, and karyorrhexis with cytoplasmic swelling. These granule cells were positive for DNA fragmentation by the TUNEL method. These results suggest that EHA permeates the blood vessel wall and directly affects the cerebellar granule cells, resulting in selective granule cell apoptosis.
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PMID:N-[4-(3-ethoxy-2-hydropropoxy)phenyl] acrylamide selectively induces apoptosis of cerebellar granule cells in vivo and in vitro in rats. 1078 30

An improved understanding of its physiology has led to better therapeutic use of vitamin E in recent years. It is a physiological membrane bound antioxidant, protecting cell membrane lipids from oxidant damage by free redicals. Cholestatic liver disease, abetalipoproteinemia and ataxia with vitamin E deficiency are the common deficiency states where vitamin E is of definite therapeutic value, while reports of unproven benefits abound in literature. Vitamin E status of the body can be assessed by serum levels and various functional studies. The new water soluble form, tocopherol polyethylene glycol succinate (TPGS), is therapeutically superior to the standard oral forms available. Details of physiology and therapeutic application of the vitamin are discussed.
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PMID:Vitamin E updated. 1082 96


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