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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pyrrolizidine alkaloids are among the most significant plant chemicals causing disease in animals and humans. After absorption from the gut, the compounds are converted to electrophilic pyrroles in the liver which, apart from causing damage to this organ, may escape to cause injury to extraheptic tissues such as the lungs, heart, and kidneys. A group of compounds more recently found to be associated with neurotoxicity are various polyhydroxyalkaloids which are able to interfere with polysaccharide metabolism. They are able to inhibit lysosomal monosaccharidases by virtue of their structural resemblance to the transition state of particular sugar molecules. The resulting lysosomal storage diseases have pathology identical to that of the respective congenital and heritable lysosomal storage diseases which occur in animals and humans. Consumption of cycad plants by cattle may cause a neurotoxicity characterised mainly by a posterior sensory ataxia. In recent years, cycads are considered to be a risk factor for a spectrum of progressive neuro degenerative diseases of humans in the Western Pacific region. The known toxins in the plant are the methylazoxymethanol glycosides which are hepatotoxic and carcinogenic, and the neurotoxic non-protein amino acid beta-methylaminoalanine. A plant carcinogen which can be of great abundance in the nutritional environment is the illudine norsesquiterpene glucoside ptaquiloside which is found in bracken fern. This is the only plant carcinogen which causes natural outbreaks of bladder and/or intestinal cancer in livestock. Many legumes contain phytooestrogens, notably isoflavones. Consumption of these compounds at high levels by sheep can cause extensive lesions of the genitalia of females and castrated males.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Directly toxic effects of plant chemicals which may occur in human and animal foods. 758 21

A historical group of 45 children (4-18 years) and adults (18-39 years) with classical galactosemia had deficits of cognitive function that were variable and not related to the age at diagnosis or to severity of illness at presentation. There was a trend for patients to score highest on visual processing tasks. The standardized tests of speech and memory skills fell within the same range as the Broad Cognitive Ability score, indicating that the speech and language deficits may be part of a more global set of cognitive impairments. Scores on the Beery Visual Motor Integration and Block Design Tests fell in approximately the same range as other cognitive abilities. In addition, there was a high incidence of abnormality detected on MRI and 12 patients had neurologic symptoms that included ataxia, tremor and dysmetria. These abnormalities did not correlate with the age at diagnosis, severity of illness at presentation or scores on cognitive testing. The pathophysiology of neurologic and neuropsychologic impairments remains unknown. Since these appear to be unrelated to the duration of galactose exposure, other factors impacting on outcome need to be understood so that strategies can be developed to improve what appears to be a global impairment of cognitive function.
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PMID:Cognitive functioning, neurologic status and brain imaging in classical galactosemia. 767 58

We report on a 13-year-old girl with late infantile neuronal ceroid lipofuscinosis (NCL) in whom PET scanning with [18F]-2-fluoro-2-deoxy-D-glucose ([18F]/FDG) was performed. Early psychomotor development was normal. At the age of 2 years, neurological signs such as hypotonia and incoordination appeared, followed by visual failure and ataxia. At the age of 4, funduscopic examination showed macular degeneration and papillary atrophy. At the age of 9, myoclonic jerks were observed; subsequently, generalized seizures together with failing vision, mental deterioration, and visual and auditory hallucinations appeared. Brain MRI showed severe cortical and subcortical atrophy. A skin biopsy detected the presence of 'finger-print' inclusions in the cytoplasm of smooth muscle fibers. Late infantile NCL (Jansky-Bielschowsky disease) was diagnosed. FDG/PET revealed a severe reduction of metabolism in all the cortical and subcortical structures. A regional analysis of the distribution of the tracer revealed marked bilateral hypometabolism, particularly in calcarine, lateral, occipital, and temporal cortices and in the thalamus.
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PMID:Positron emission tomography in neuronal ceroid lipofuscinosis (Jansky-Bielschowsky disease): a case report. 757 68

In classic galactosemia, long-term neurologic sequelae can include low cognitive functioning and a curious neurologic syndrome with tremors, dysmetria, and ataxia. An abnormal white-matter signal on cerebral magnetic resonance imaging (MRI) is present in almost all patients; some have mild cerebral or cerebellar atrophy and focal white-matter lesions. The present study was undertaken to assess the integrity of myelinated pathways by recording somatosensory evoked potentials. Results were correlated with age at diagnosis, severity of illness, age at evoked potentials, neurologic examination, MRI studies and cognitive outcome as measured by the Woodcock-Johnson Revised Standard Cognitive Battery. Evoked potentials were abnormal in 17 (28%) of 60 patients who had median nerve, and 26 (77%) of 34 patients who had posterior tibial nerve studies. Abnormalities of the central rather than the peripheral nervous system were most common. Evoked potentials correlated with severity of presenting symptoms (P = .011), age at evoked potential testing (P = .029), and presence of focal white-matter lesions on MRI (P = .049). Results of neurophysiologic testing showed no correlation with the Woodcock-Johnson Battery. Patients with classic galactosemia may have abnormal conduction along myelinated pathways that is associated with other central deficits. Myelin, which contains galactose, may be adversely affected in this inborn error of metabolism.
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PMID:Abnormal somatosensory evoked potentials in patients with classic galactosemia: correlation with neurologic outcome. 776 75

A 25-year-old woman suffered from hyperemesis gravidarum when she was seven weeks pregnant. Since her vomiting continued, she received intravenous dextrose and electrolytes without thiamine in a hospital. One month later, she developed gait disturbance, followed by confusion and dysarthria. On admission to our department, she was confusional and had ataxic dysarthria. Spontaneous and gaze evoked nystagmus was present. Limb coordination was bilaterally ataxic. Based on her clinical course and symptoms, she was diagnosed as having Wernicke's encephalopathy. From the admission day, intravenous infusion of vitamin B1 (600 mg/day) was started. A few days later, her consciousness and limb ataxia began to improve. However, truncal ataxia and polyneuropathy became evident. Eight weeks after onset, she developed Korsakoff's psychosis such as anterograde and retrograde amnesia, disorientation and confabulation. We administered large amounts of corticosteroid (methylprednisolone 500 mg/day) in order to reduce brain edema or stabilize the impaired blood-brain barrier. Soon after, her psychosis began to improve gradually. She recovered remarkably from the psychosis, but she was left with persistent nystagmus, mild ataxic gait and polyneuropathy. The present case suggests that corticosteroid may have the beneficial effect on Wernicke-Korsakoff syndrome.
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PMID:[Beneficial effect of steroid pulse therapy on Wernicke-Korsakoff syndrome due to hyperemesis gravidarum]. 795 22

In a retrospective study 134 galactosaemic patients, born between 1955 and 1989 in the Federal Republic of Germany were traced and their long-term outcome evaluated. We investigated 83 galactosaemic patients (78 homozygotes, 5 compound heterozygotes) by clinical, psychometric and laboratory testing; 31 patients were evaluated by medical history, the remaining 20 patients had died due to sequelae of the underlying disease. In 48 out of 78 classical galactosaemia patients galactose-free therapy had been started before the 15th day, in 19 between days 15 and 56 and in 11 patients after the 56th day. Physical findings revealed that puberty was delayed in 1 out of 18 males and 6 out of 11 females. Neurological abnormalities included ataxia (n = 6), intention tremor (n = 11) and microcephaly (n = 10). Speech abnormalities were found in 43 out of 66 patients over 3 years of age and disturbance of visual perception and/or arithmetic deficits in 29. Intelligence declined with age, i.e., a DQ or IQ less than 85 was found in 4 out of 34 patients less than 6 years of age (12%), in 10 out of 18 between 7 and 12 years (56%) and in 20 out of 24 older than 12 years (83%). Metabolite patterns (RBC galactose-1-phosphate and UDP-galactose, plasma and urinary galactitol) did not correlate with DQ or IQ. Dietary compliance was good in almost all patients. Compound heterozygotes (n = 5) had normal mental and growth development and all laboratory parameters were in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term outcome in 134 patients with galactosaemia. 844 4

We report a 65-year-old woman with paraneoplastic cerebellar degeneration (PCD) who showed reduced cerebellar metabolism with preserved blood flow. She was admitted to Gunma University Hospital because of progressive gait and speech disturbances. Neurologic examination revealed nystagmus, dysphagia, explosive speech, reduced muscle tone in limbs, and marked truncal and limb ataxia, and mild hypesthesia in hands and feet. Cranial MRI demonstrated slight cerebellar atrophy. Laboratory findings disclosed high levels of serum CA19-9 and other tumor markers, and positive anti-Yo antibody, indicating that she had PCD. A specimen obtained from an axillary lymph node revealed metastasis of poorly differentiated adenocarcinoma, although systemic and vigorous checkup failed to find its origin. Cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured using positron emission tomography (PET) 15 months after the onset. CMRO2 was clearly decreased in the cerebellum, while CBF was almost normal. Moreover, PET with 2 18F-fluoro-2-deoxy-D-glucose (FDG) revealed that glucose metabolism was also reduced in the cerebellum. Single photon emission tomography using 99mTc-ethyl cysteinate dimer (ECD) showed a normal blood flow pattern in the whole brain. These results indicated that uncoupling of circulation and metabolism in the cerebellum of this patient. There are several reports showing uncoupling of cerebral perfusion and metabolism in ischemic disorders, encephalitis, mitochondrial diseases, brain tumors, epilepsy and Gaucher disease, although its pathophysiology is not elucidated. Because anti-Yo antibody evidently gives a suppressive influence on the cerebellar neurons, understanding the way the autoantibody acts may give a clue to the mechanism of reduced cerebellar metabolism with preserved perfusion in PCD.
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PMID:[Uncoupling of cerebellar blood flow and metabolism in paraneoplastic cerebellar degeneration: report of a case]. 936 81

A T --> G mutation at position 8993 in human mitochondrial DNA is associated with the syndrome neuropathy, ataxia, and retinitis pigmentosa and with a maternally inherited form of Leigh's syndrome. The mutation substitutes an arginine for a leucine at amino acid position 156 in ATPase 6, a component of the F0 portion of the mitochondrial ATP synthase complex. Fibroblasts harboring high levels of the T8993G mutation have decreased ATP synthesis activity, but do not display any growth defect under standard culture conditions. Combining the notions that cells with respiratory chain defects grow poorly in medium containing galactose as the major carbon source, and that resistance to oligomycin, a mitochondrial inhibitor, is associated with mutations in the ATPase 6 gene in the same transmembrane domain where the T8993G amino acid substitution is located, we created selective culture conditions using galactose and oligomycin that elicited a pathological phenotype in T8993G cells and that allowed for the rapid selection of wild-type over T8993G mutant cells. We then generated cytoplasmic hybrid clones containing heteroplasmic levels of the T8993G mutation, and showed that selection in galactose-oligomycin caused a significant increase in the fraction of wild-type molecules (from 16 to 28%) in these cells.
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PMID:Oligomycin induces a decrease in the cellular content of a pathogenic mutation in the human mitochondrial ATPase 6 gene. 1009 18

The nucleotide pair (np) 7472 insC mitochondrial DNA mutation in the tRNA(Ser)(UCN) gene is associated with sensorineural deafness, combined in some individuals with a wider syndrome including ataxia and myo-clonus. Previous studies in osteosarcoma cell cybrids revealed only a mild respiratory defect linked to the mutation. We have investigated the biochemical and molecular consequences of the mutation, using a panel of seven osteosarcoma cell cybrids containing 100% mutant mtDNA, plus two cybrids carrying 100% wild-type mtDNA from the same patient. The mutation is associated with a mild growth deficit in selective (galactose) medium that is only significant in combination with a reduced mtDNA copy number, suggesting a mechanism that might modulate clinical phenotype. The mutation results in a 65% drop in the steady-state level of tRNA(Ser)(UCN), but causes at most only a very mild and quantitative abnormality of mitochondrial protein synthesis, associated with modest hypersensitivity to doxycyclin. No evidence for a specific defect in aminoacylation was obtained, and unlike the case with the np 7445 mutation, the pattern of RNA processing of light strand transcripts of the ND6 region was not systematically altered. Comparing the np 7472 and np 7445 mutant phenotypes in cultured cells suggests that sensorineural deafness can result from a functional insufficiency of mitochondrial tRNA(Ser)(UCN), to which some cells of the auditory system are especially vulnerable.
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PMID:Molecular phenotype of the np 7472 deafness-associated mitochondrial mutation in osteosarcoma cell cybrids. 1054 8

We report the case of a patient who experienced a postoperative Wernicke encephalopathy 8 days after a left hepatectomy performed for metastasis related to a rectal cancer. During the six months before surgery the patient lost 10 kg of weight (15%). Moreover, in the postoperative period the patient received exclusively 5% dextrose solution intravenously. On the 8th postoperative day, an alteration of consciousness, a vertical nystagmus and an ataxia led to consider the diagnosis of thiamine deficiency that was then established by the decrease in the transcetolase activity of the red blood cells. Vitamin B1 supply improved the clinical status rapidly and completely. This observation allows to review aetiologies and clinical forms of thiamine shortage. In addition, it stresses the detection of exposed patients and the prevention methods.
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PMID:[Postoperative encephalopathies: thiamine deficiency, an unrecognized etiology]. 1123 77


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