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)

Infants with macrocephaly, young children with acute disease resembling encephalitis, and children with truncal hypotonia, ataxia, or dystonia may be affected by glutaric aciduria type I (GA 1, glutaryl-CoA-dehydrogenase deficiency), a not-so-rare autosomal recessive neurometabolic disease. Well-known features of GA1 are fronto-temporal brain atrophy with macrocephaly and acute encephalopathic episodes with striatal necrosis followed by dystonia, but some patients develop motor disease without overt crises and other biochemically affected individuals remain asymptomatic. Biochemical and molecular characterization is available and allows post- and prenatal diagnosis. The pathogenesis of fronto-temporal atrophy, macrocephaly, and basal ganglia necrosis is still not understood, and there is no close correlation between biochemical parameters and clinical outcome. There is, however, evidence suggesting that carnitine supplementation and anticatabolic treatment of intercurrent illness may arrest or prevent neurological deterioration, while the role of limitation of dietary lysine and tryptophane is not yet clear. Although pathogenetic aspects are poorly understood, the natural course of glutaric aciduria type 1 can be changed by early diagnosis and treatment. Coordinated research is needed to understand the pathogenesis of brain toxicity, to define the role of dietary therapy, and to explore the possibility of neonatal screening.
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PMID:Glutaric aciduria type 1 (glutaryl-CoA-dehydrogenase deficiency): advances and unanswered questions. Report from an international meeting. 939 91

Between May 1982 until January 1997 we investigated 200 patients suspected for normal pressure hydrocephalus (NPH) by performing an intrathecal infusion test. According to our experiences gait ataxia is the leading symptom of NPH. Regarding dementia we could not find a significant difference compared to cerebral atrophy. Bladder incontinence can be characterised as a symptom of late-stage NPH. The complete Hakim trias should not be overestimated in differential diagnostic considerations. Graduation of NPH and cerebral atrophy after the results of the infusion test in an early and late stage enables prognostic evaluation of the course of disease. Patients with NPH in an early stage report in the follow-up on an improvement of their symptoms after shunt operation (65 percent of patients), whereas 50 percent of the patients with late stage NPH were improved. The computer-aided infusion test allows secure differentiation between patients with NPH and those with cerebral atrophy.
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PMID:[Psychophysiology, signs and symptoms of disease the course of normal pressure hydrocephalus]. 958 78

We presented a case of Creutzfeldt-Jakob disease (CJD) associated with ocular dipping (OD). A 65-year-old woman was hospitalized with two months history of progressive ataxia and mental deterioration. On admission, she was bed-ridden and stuporous with rigidity of the four limbs. Her both eyes were noted to deviate downward slowly from midpossition, taking 1 to 3 seconds to reach the nadir and rapidly returned to midpossition. It was felt that these abnormal eye movements are compatible with OD. Findings of EOG were compatible with that of typical OD. Electroencephalogram obtained a few months later revealed periodic synchronous discharge. Magnetic resonance imaging of the brain which had demonstrated mild cerebral atrophy in the beginning subsequently revealed full-brown cerebral atrophy. Hence, she was diagnosed of having CJD. There has been no report of CJD associated with OD. The OD was observed to last as long as 110 days. When the above described abnormal eye movements were noted, there was no signs indicative of brain stem dysfunction present. Therefore, we feel that the present case suggest that a diffuse cerebral dysfunction involving the cerebral cortex and basal ganglia may underlie in the development of OD.
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PMID:[Creutzfeldt-Jakob disease associated with ocular dipping--a case report]. 959 17

Neuropsychiatric symptoms of hyperammonaemia include alterations of mood and personality, cognitive impairment, ataxia, convulsions and coma. The nature and severity of CNS dysfunction depend upon the aetiology and degree of hyperammonaemia, its acuteness of onset and the age of the patient. Neuropathological studies reveal Alzheimer type II astrocytosis in the adult hyperammonaemic patient, whereas hyperammonaemia in the infant resulting from congenital urea cycle disorders or Reye syndrome is accompanied by cerebral atrophy, neuronal loss and cerebral oedema. Several electrophysiological and biochemical mechanisms have been proposed to explain the deleterious effects of ammonia on CNS function. Such mechanisms include direct effects of the ammonium ion on excitatory and inhibitory neurotransmission and a deficit in cerebral energy metabolism due to ammonia-induced inhibition of alpha-ketoglutarate dehydrogenase. In addition, ammonia has been shown to interfere with normal processes of uptake, storage and release of various neurotransmitters. Ammonia disrupts monoamine storage, inhibits the high-affinity uptake of glutamate by both astrocytic and neuronal elements and activates 'peripheral-type' benzodiazepine receptors leading to the potential synthesis of neuroactive steroids in brain. On the basis of these actions, it has been proposed that ammonia disrupts neuron-astrocyte trafficking of amino acids and monoamines in brain. The increased formation of brain glutamine in hyperammonaemic syndromes could be responsible for the phenomenon of brain oedema in these disorders. Therapies aimed at either decreasing ammonia production in the gastrointestinal tract or increasing ammonia removal by liver or skeletal muscle are the mainstay in the prevention and treatment of the CNS consequences of hyperammonaemia. New therapeutic approaches aimed at correction of the neurotransmitter and cerebral energy deficits in these syndromes could hold promise for the future.
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PMID:Effects of hyperammonaemia on brain function. 968 41

We report a 73-year-old woman who presented progressive motor clumsiness, cortical sensory loss, and focal parietal lobe atrophy. She was well until one year prior to the present admission when she suffered from what appeared to be mild Fisher syndrome from which she showed excellent recovery. However, soon she noted a gradual onset of difficulty in hand movements and in the recognition of objects by hands. Neurologic examination revealed an alert and well oriented Japanese woman without dementia. Cranial nerves were unremarkable. Although, she did not have aphasia, apraxia, or agnosia, she showed marked clumsiness in skilled hand movements such as using chopsticks, hand writing, and buttoning. She had no motor weakness, ataxia, rigidity, or spasticity. Deep tendon reflexes were symmetrically diminished. Sensory examination revealed cortical sensory loss such as disturbances of two point discrimination, weight sensation, and stereotactic sensations. Her motor clumsiness appeared to be caused by her cortical sensory loss. MRI revealed marked focal atrophy in the bilateral parietal lobe, particularly in the postcentral gyrus and the adjacent association areas. Recently, neurodegenerative disorders with focal brain atrophy such as corticobasal degeneration, Pick's disease, and dementia of frontal lobe type have been reported, however, our patient does not fit to any of these known disorders nor clinical features are distinctly different from Alzheimer's disease. Our patient may be another example of progressive cerebral degeneration with emphasis on the parietal cortex.
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PMID:[A patient with focal bi-parietal atrophy presenting motor clumsiness and cortical sensory loss]. 971 Nov 23

Twenty-six patients suffering from autosomal dominant cerebellar ataxia type I were subjected to a genotype-phenotype correlation analysis using molecular genetic assignment to the genetic loci for spinocerebellar ataxia type 1, 2 or 3 (SCA1, SCA2, SCA3) and MRI-based volumetry of posterior fossa structures and basal ganglia nuclei. There was significant atrophy of the cerebellum and brainstem in all three SCA mutations compared with a group of 31 age- and sex-matched controls. Comparison between the SCA groups showed that cerebellar and brainstem atrophy was more severe in SCA2 than in SCA1 and SCA3. Putaminal and caudate volume was reduced only in SCA3, but not in SCA1 and SCA2. A set of three morphological criteria was defined that enabled us to assign all SCA2 and SCA3 patients correctly to the underlying genotype. In contrast, these criteria did not distinguish SCA1 from SCA2 and SCA3. Regression analysis failed to reveal a significant association between CAG repeat length and the volumes of the respective brain structures in any of the SCA mutant types. The present data provide in vivo evidence that SCA2 and SCA3 lead to distinct patterns of brain atrophy, while the atrophy changes in SCA1 overlap with both SCA2 and SCA3.
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PMID:Autosomal dominant cerebellar ataxia type I. MRI-based volumetry of posterior fossa structures and basal ganglia in spinocerebellar ataxia types 1, 2 and 3. 976 57

MELAS syndrome is typically characterized by normal early development and childhood-onset recurrent neurologic deficits (stroke-like episodes), seizures, short stature, lactic acidosis, and ragged red fibers on muscle biopsy specimens. It is usually, but not invariably, associated with the A3243G point mutation in the mitochondrial DNA tRNALeu(UUR) gene. We report 3 unrelated children with the A3243G mutation who presented with severe psychomotor delay in early infancy. One patient's clinical picture was more consistent with Leigh syndrome, with apneic episodes, ataxia, and bilateral striatal lesions on brain magnetic resonance imaging (MRI). The second patient had generalized seizures refractory to treatment and bilateral occipital lesions on brain MRI. The third child had atypical retinal pigmentary changes, seizures, areflexia, and cerebral atrophy on brain MRI. All patients had several atypical features in addition to early onset: absence of an acute or focal neurologic deficit, variable serum and cerebrospinal fluid lactate levels, lack of ragged red fibers in muscle biopsy specimens. The proportion of mutant mtDNA in available tissues was relatively low (range, 5% to 51% in muscle; 4% to 39% in blood). These observations further extend the phenotypic expression of the A3243G "MELAS" mutation. Our findings confirm previous observations that there is poor correlation between abundance of mutant mtDNA in peripheral tissues and neurologic phenotype. This suggests that other factors contribute to the phenotypic expression of this mutation.
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PMID:Infantile encephalopathy associated with the MELAS A3243G mutation. 1035 36

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun
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PMID:[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning]. 1050 96

Between May 1982 and January 1997 we investigated 200 patients for normal pressure hydrocephalus (NPH) by performing an intrathecal infusion test. 168 patients (84%) presented with the clinical syndrome of gait ataxia, dementia and urinary incontinence, the so called Adams triad. In 107 patients (54%) the diagnosis of a NPH could be confirmed. Of these, 102 patients (95%) underwent a shunt operation. In a follow-up (7 month and 3 years later) we interviewed the patients or their relatives about the progression of the disease. At those time intervals we could evaluate the improvement after shunt operation or infusion test. In our experience gait ataxia is the guiding sign of NPH. Regarding dementia we could not find a significant difference compared to cerebral atrophy. Urinary incontinence can be characterized as a symptom of late stage NPH. The complete Adams triad should not be overestimated in differential diagnostic considerations. Subdivision of NPH into an early stage and a late stage allows one to conclude prognostic evaluations about the course of the disease. Patients with an early stage NPH reported at the follow-up an improvement of their symptoms after shunt operation in 65 percent and those with a late stage NPH in 50 percent. The computer aided infusion test allows a safe differentiation between patients with NPH and those with cerebral atrophy.
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PMID:Signs, symptoms and course of normal pressure hydrocephalus in comparison with cerebral atrophy. 1055 Jun 47

Novel efficient and aggressive treatment protocols for primary CNS lymphomas have resulted in an increasing number of long term survivors. Follow up data show that in a substantial fraction of these patients, treatment benefits are overshadowed by neurotoxic sequelae. Neurotoxicity especially affects the older age group, presenting as cognitive dysfunction, ataxia or dementia as a consequence of leukoencephalopathy and brain atrophy. The combination of radiotherapy and chemotherapy seems to be particularly hazardous, though data are too sparse to draw any definite conclusions yet. Long term follow up of patients included in clinical studies therefore should not only evaluate survival or time to tumour progression, but also serial neuropsychometric evaluation and quality of life assessment.
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PMID:Neurologic sequelae of treatment of primary CNS lymphomas. 1056 34


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