Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighteen patients with advanced solid cancer were treated with daily 5'-dFUrd infusions given over 1 h on days 1-5 of a 4-week cycle. Nine patients received 3 g/m2 5'-dFUrd daily and another nine patients 5 g/m2. One patient on 5 g/m2 5'-dFUrd was not fully evaluable for tolerability due to early death (progressive disease) 4 weeks after the first cycle. A total of 48 cycles was given. The gastrointestinal and hematological toxicity was generally mild (grade 1-2). Central neurotoxicity (ataxia, unsteadiness, diplopia, dysarthria, sometimes confusion) was observed in 7 of 8 patients on 5 g/m2 5'-dFUrd leading to premature discontinuation of treatment in 3 patients (after 2 cycles). Only 3 of the 9 patients in the 3 g/m2 group had slight signs of cerebellopathy. Typically, the reversible neurological side effects started at the end of the 2nd week of a cycle. The serum elimination kinetics of 5'-dFUrd and its metabolites 5-FU and 5'-dFUH2 have been investigated in the serum and showed very low intra- and interindividual variations. Peak concentrations of the 5'-dFUrd at the end of the infusion approximated 500 mumol/l and 1000 mumol/l for the 3 g/m2 and 5 g/m2 group, respectively. The peak of the serum 5-FU was reached at the same time, the ratio 5-FU/5'-dFUrd being around 10%. The elimination half-life time for 5-FU was protracted by a factor of 2-3 compared with the direct injection of 5-FU. Monthly infusion of 5'-dFUrd 5 mg/m2 per day on days 1-5 lead to an unacceptable frequency and degree of neurological toxicity. Similar infusions of 5'-dFUrd 3 g/m2 per day on days 1-5 were well tolerated.
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PMID:Phase I/II tolerability/pharmacokinetic study with one-hour intravenous infusion of doxifluiridine (5'-dFUrd) 3 g/m2 VS 5 g/m2 QD x 5 per month. 294 31

Four different antineuronal autoantibodies have been identified in 23 of 47 patients with paraneoplastic cerebellar degeneration (PCD). The most common, an antibody against 34- to 38-kDa and 62- to 64-kDa protein antigens in the cytoplasm of Purkinje cells, was found in 18 patients. It is a highly specific marker for a severe stereotypical subacute pancerebellar syndrome of truncal and appendicular ataxia, dysarthria, and nystagmus in women with cancer (usually ovarian or breast carcinoma). Different anti-Purkinje cell antibodies (APCA) were found in 2 other patients with PCD. With two possible exceptions, an APCA was not found in patients with other neurological diseases, with cancer not associated with neurological symptoms, or in normal subjects. Antibodies reactive with neuronal nucleoproteins were identified in 3 other patients with PCD: an antibody that recognized 35- to 40-kDa neuronal antigens was found in 2 women with small-cell lung carcinoma, while an antibody in a woman with breast carcinoma identified 53- to 61-kDa and 79- to 84-kDa antigens. Detection of an antineuronal antibody in a patient without known cancer should prompt a careful search for a tumor at a site appropriate to the antibody type.
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PMID:Paraneoplastic cerebellar degeneration: clinical-immunological correlations. 323 56

Eleven patients with acquired cerebellar degeneration (10 of whom had paraneoplastic cerebellar degeneration [PCD]) were evaluated using neuropsychological tests and 18F-fluorodeoxyglucose/positron emission tomography to (1) quantify motor, cognitive, and metabolic abnormalities; (2) determine if characteristic alterations in the regional cerebral metabolic rate for glucose (rCMRGlc) are associated with PCD; and (3) correlate behavioral and metabolic measures of disease severity. Eighteen volunteer subjects served as normal controls. Although some PCD neuropsychological test scores were abnormal, these results could not, in general, be dissociated from the effects of dysarthria and ataxia. rCMRGlc was reduced in patients with PCD (versus normal control subjects) in all regions except the brainstem. Analysis of patient and control rCMRGlc data using a mathematical model of regional metabolic interactions revealed two metabolic pattern descriptors, SSF1 and SSF2, which distinguished patients with PCD from normal control subjects; SSF2, which described a metabolic coupling between cerebellum, cuneus, and posterior temporal, lateral frontal, and paracentral cortex, correlated with quantitative indices of cerebellar dysfunction. Our inability to document substantial intellectual impairment in 7 of 10 patients with PCD contrasts with the 50% incidence of dementia in PCD reported by previous investigators. Widespread reductions in PCD rCMRGlc may result from the loss of cerebellar efferents to thalamus and forebrain structures, a "reverse cerebellar diaschisis."
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PMID:The metabolic anatomy of paraneoplastic cerebellar degeneration. 326 71

We compared the severity of ataxic and spastic dysarthria with local cerebral metabolic rates for glucose (lCMRGlc) in 30 patients with olivopontocerebellar atrophy (OPCA). Perceptual analysis was used to examine the speech disorders, and rating scales were devised to quantitate the degree of ataxia and spasticity in the speech of each patient. lCMRGlc was measured with 18F-2-fluoro-2-deoxy-D-glucose and positron emission tomography (PET). PET studies revealed marked hypometabolism in the cerebellar hemispheres, cerebellar vermis, and brainstem of OPCA patients compared with 30 control subjects. With data normalized to the cerebral cortex, a significant inverse correlation was found between the severity of ataxia in speech and the lCMRGlc within the cerebellar vermis, cerebellar hemispheres, and brainstem, but not within the thalamus. No significant correlation was found between the severity of spasticity in speech and lCMRGlc in any of these structures. The findings support the view that the severity of ataxia in speech in OPCA is related to the functional activity of the cerebellum and its connections in the brainstem.
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PMID:Speech disorders in olivopontocerebellar atrophy correlate with positron emission tomography findings. 326 72

Aneurysm of the vein of Galen is a very rare disease. The authors present a case of secondary aneurysm of the vein of Galen which was confirmed by characteristic clinical symptoms, brain CT and angiographic findings. The patient was a 14-year-old right handed girl with intermittent headache, nausea, vomiting, dysphasia and gait disturbance. Neurologic examination revealed dysarthria, nasal voice, blurring of both margins of optic discs, truncal ataxia and dysdiadochokinesia. Sensory function was normal but right hemiparesis was seen. Roentgenogram of the skull revealed diffuse thinning of the calvarium, widening of sella turcica and erosion of clinoid processes. Computed tomogram of the brain showed dilatation of all ventricles and round hyperdense mass behind the third ventricle in the midline. The lesion was enhanced markedly and homogeneously. Left and right internal carotid angiograms showed arteriovenousmal-formation with drainage to the aneurysm of the vein of Galen.
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PMID:A case of aneurysm of the vein of Galen. 327 Oct 52

The clinical and pathological findings in 4 adults with cancer and opsoclonus were compared with those of 15 other patients described elsewhere. The clinical syndrome of paraneoplastic opsoclonus is characterized by the acute onset of opsoclonus and truncal ataxia, often accompanied by encephalopathy, myoclonus and a cerebrospinal fluid pleocytosis. Unlike most other paraneoplastic syndromes, the course is often remitting and relapsing. Neuropathological examination in 3 of our patients showed lymphocytic cuffing of occasional blood vessels throughout the central nervous system, associated with a mild, diffuse proliferation of microglia in 1 patient. Apart from a mild, patchy loss of Purkinje cells in 1 patient, there was no loss of neurons from the cerebellum, brainstem, cerebral hemispheres, or spinal cord. These patients differ from those with the more common paraneoplastic cerebellar degeneration by the predominance of truncal over limb ataxia, the presence of myoclonus, the absence of severe dysarthria, a tendency for remission, and the preservation of Purkinje cells.
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PMID:Opsoclonus, myoclonus, ataxia, and encephalopathy in adults with cancer: a distinct paraneoplastic syndrome. 335 11

A prospective long-term semiquantitative evaluation of the results of ventral intermediate-posterior ventral oral nucleus thalamotomy on the different aspects of dystonia was made in 29 patients with secondary disease, 12 with nonfamilial, eight with (non-Jewish) familial, and seven with atypical DMD. The effect of disease progression, even in secondary patients, on surgical outcome was reviewed. Thalamotomy resulted in a long-term improvement in limb function of more than 25% to 50% in 23% of the patients, over 50% in 34% of patients, but midline features responded poorly. Manual dexterity was little changed in secondary cases because of underlying paralysis but improved 38% in cases of DMD. Involvement of neck and trunk, of three to four limbs, and progressive disease prognosticated for a poorer result, but phasic and tonic, familial, and nonfamilial dystonia respond equally well and age at surgery made no difference. Significant complications in 29 secondary cases included one death 31 days postoperative, one case of worsened hemiparesis, two cases of worsened dysarthria, two cases of worsened locomotion, one case of hydrocephalus requiring shunting, and one case of need for permanent tracheotomy. In 27 cases of typical and atypical DMD, there were two instances of hemiparesis, two of significant speech deterioration, three of hand ataxia, one of postoperative seizures, and one of hydrocephalus requiring shunting for an overall significant morbidity rate of 21%. The limiting factor in treating secondary dystonia is the underlying spastic paralysis but that in DMD is the relentless postoperative progression. The overall results of this study are remarkably similar to those of other published series: a quarter of the patients improved by 25% to 50%, a quarter to a third by more than 50%. The analysis of effect on specific features of the disease may be useful in the future for predicting outcome in a particular patient.
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PMID:Thalamotomy in generalized dystonia. 340 May 14

The author depicts a psycholinguistic technique aimed at the identification in the speech of patients with impaired cerebellum of the same signs of ataxia which can be detected in their hand movements. The diagnostic significance of the technique was tested in 3 clinical groups of patients: with multiple sclerosis (Group 1), neurosurgical diseases of the cerebellum (Group 2), and with olivopontocerebellar atrophy (Group 3). The findings obtained suggest that the psycholinguistic technique may be used for the early diagnosis of neurosurgical diseases of the cerebellum, detection of residual focal lesions, diagnosis of multiple sclerosis and its individual clinical forms, as well as for the pathogenetic validation of the restorative training of patients with cerebellar dysarthria.
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PMID:[Focal cerebellar lesions and psycholinguistic methods for their diagnosis]. 342 76

High-dose cytarabine (HDARAC) therapy is an effective regimen in treating refractory leukemias. A typical regimen is cytarabine 3 g/m2 iv over one to three hours q 12h for a total of 8 to 12 doses. This case report illustrates the neurotoxicity unique to HDARAC. The patient received two cycles of HDARAC over the course of a ten-week period. During the first treatment, dysarthria and ataxia were seen after completion of the patient's eighth and final dose of HDARAC. These symptoms resolved over a period of five days. Six weeks later a more severe syndrome of dysarthria and ataxia developed during a second cycle of treatment. These symptoms worsened over 24 hours despite discontinuation of therapy, then gradually decreased in severity but persisted until his death two months later. The neurotoxicity seen with HDARAC is dose-related and has occurred in up to 60 percent of treated patients. The incidence of cerebellar toxicity approaches 30 percent, with irreversible ataxia reported in up to 16.7 percent. Because the cerebellar toxicity may be worsened by continuation of therapy after initial onset of symptoms, prompt termination of HDARAC is recommended.
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PMID:Cytarabine-induced cerebellar syndrome: case report and literature review. 347 Jan 73

A male patient was suspected as olivo-ponto-cerebellar atrophy from the clinical and computed tomographic features at 34 years of age. Afterwards, his dysarthria and limb ataxia were slowly and steadily worsened. He was finally bed-ridden and unresponsive, and died of hyperpyrexia and general wasting at 37 years of age. It was noted that laboratory investigation gave lower values of urinary 17-ketosteroids and 17-hydroxycorticosteroids in comparison with those of normal subjects. Pathological investigation in autopsy showed that he had pathological features consistent with adrenoleukodystrophy accompanying the olivo-ponto-cerebellar atrophy; diffuse demyelination in the cerebrocerebellear white matter, distorted architecture and cytoplasmic striations in the adrenal cortex, and in addition, a pseudosystemic degeneration of the olivo-ponto-cerebellar system and subcortical gray matter.
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PMID:An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: I. Clinical and pathological studies. 347 76


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