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)

A 74-year-old man developed progressive deafness and unsteady gait two years after gastrectomy for a gastric cancer. Neurological examination revealed an alert and intelligent Japanese male in no acute distress. The optic fundi were normal. The pupils and the extraocular muscles were normal, however, horizontal nystagmus was noted in right and left gaze. He showed marked bilateral deafness, and loss of caloric response bilaterally. No muscle atrophy nor weakness was noted. His gait was wide-based and ataxic. Tandem gait was impossible. Romberg sign was present. No cerebellar ataxia was noted in the finger-to-nose or the heel-to-knee test. No adiadochokinesis was noted. Hyperextensibility was noted in the lower extremities. Deep reflexes were normal in the upper limbs, and diminished in the lower extremities. Sensation was intact. He showed the jumbling phenomenon, and the disturbance of the righting reflex in the tilt-table examination. Neuroradiological as well as laboratory studies were unremarkable except for the high titer of CEA in the CSF. Four months after his admission, malignant tumor cells were found in the CSF. It seemed likely that he had completely lost bilateral vestibular and auditory functions caused by meningeal carcinomatosis. His disturbance of gait and station was apparently similar to cerebellar ataxic gait, however, he did not have limb ataxia. The cranial CT scans failed to show cerebellar atrophy. It was our impression that his motor disturbance was in all likelihood caused by the bilateral loss of vestibular functions, i.e., vestibular ataxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Vestibular ataxia caused by meningeal carcinomatosis]. 236 34

Acivicin is an investigational amino acid antitumor antibiotic currently being evaluated in Phase II clinical trials. In humans acivicin causes reversible, dose-limiting central nervous system (CNS) effects including somnolence, ataxia, personality changes, and hallucinations. We have observed and reported previously that acivicin-treated cats exhibit symptoms (ataxia, sedation, somnolence) resembling CNS toxicity reported in humans. We hypothesized that if acivicin uptake into brain were mediated by a saturable transport system common to endogenous amino acids, drug uptake and CNS toxicity might be blocked by elevation of normal amino acid concentrations in circulating plasma. To test this hypothesis, cats received constant-rate i.v. infusions of either saline or Aminosyn, 10% (a commercially available mixture of 16 amino acids not containing glutamine, glutamate, aspartate, or cysteine) for 4 h prior to and 18 h subsequent to administration of acivicin at a dose producing marked behavioral changes in control cats. Presence or absence of ataxia and sedation were noted at intervals after acivicin treatment. Results showed that Aminosyn infusion prevented CNS symptoms in six of eight cats. Subsequent experiments showed that acivicin levels in brain tissue of Aminosyn-treated cats were 13% of the drug levels in saline-infused cats. Acivicin levels in most peripheral tissues were also decreased significantly by Aminosyn infusion but not to the extent observed in brain. Decreased brain uptake was shown to be due to a combination of amino acid blockade of drug transport into that organ and of increased total body clearance of drug. Concomitant Aminosyn treatment did not alter the efficacy of acivicin in mice bearing L1210 leukemia or MX-1 human mammary carcinoma. Further studies demonstrated that a solution containing only four large neutral amino acids (leucine, isoleucine, phenylalanine, and valine) could also protect cats from acivicin-induced CNS toxicity, apparently without increasing acivicin total body clearance. However, a mixture of several other amino acids contained in Aminosyn (alanine, arginine, tyrosine, histidine, proline, serine, and glycine) failed to prevent CNS toxicity. We conclude that cotreatment with Aminosyn or a mixture of large neutral amino acids could protect cancer patients from acivicin-induced CNS toxicity without ablating antitumor efficacy.
Cancer Res 1990 Sep 01
PMID:Prevention of central nervous system toxicity of the antitumor antibiotic acivicin by concomitant infusion of an amino acid mixture. 238 52

Aminoglutethimide (AG) was administered as palliative therapy in 112 patients with metastatic breast cancer. In 36 patients, the dose level was 1000 mg/day; 76 patients received a dose level of 500 mg/day. Patients with brain or liver metastasis were excluded, as were patients with tumors determined to be negative for estrogen receptors. Objective regression was observed in 35 (31%) patients, with the duration of response ranging from 4 to 36 + months (mean, 12 months; median, 10 months). Response was observed in 11 of 31 (35%) patients with soft tissue metastasis; 16/59 (27%) patients with osseous metastasis; and 8 of 22 (36%) having visceral metastasis. In 93 patients with positive estrogen receptor (ER), 33 responded (35%), whereas in 19 patients with unknown ER status, two responded (11%). Response to previous treatment with tamoxifen (TAM) had occurred in 31 patients; of these, response to AG was noted in 11 (35%). Of 24 patients failing to respond to prior treatment with tamoxifen, four (17%) responded to subsequent therapy with AG. Thirteen patients had previously received combination chemotherapy, and response to AG was noted in two (15%). The side effects observed in this study included skin rash in ten patients, fever in eight, somnolence in three, weakness and dizziness in one, headache in one, insomnia in one, dyspnea in one, and ataxia in one. Treatment had to be discontinued in eight patients, due to the severity of the side effects. As expected, patients receiving AG at the lower dose level of 500 mg/day experienced fewer and less severe side effects than those treated with the higher dose. The response rate in the 1000 mg/day group was 10/36 (28%) and in the 500 mg/day group, it was 25/76 (33%). The lower dosage was better tolerated without apparent compromise in therapeutic efficacy.
Cancer 1989 May 01
PMID:Aminoglutethimide in patients with metastatic breast cancer. 246 35

The toxicological characteristics of SM-5887 were evaluated in mice after a bolus intravenous injection, and compared with those of adriamycin (ADR). The acute toxic signs observed after SM-5887 administration were body weight decrease, ataxia, hair loss, and myelosuppression. They were qualitatively comparable to those induced by ADR. The 50% lethal dose values determined by 14-day observation after drug administration were in the range of 32 to 50 mg/kg for SM-5887 and 16 to more than 20 mg/kg for ADR in four strains of mice. The maximum tolerated doses (MTD) were estimated to be 25 mg/kg for SM-5887 and 12.5 mg/kg for ADR (no death or body weight loss of more than 3 g occurred). When 14-day survivors were further observed until 90 days after drug administration, ADR frequently and dose-independently showed delayed-type lethal toxicity at doses of more than 10 mg/kg, whereas SM-5887 did not. The myelosuppression of SM-5887 was more severe even at a half of the MTD than that of ADR at the MTD, but its recovery was more rapid than that after ADR. In addition, when the drugs were injected into the subplantar region of mouse hind paws, ADR induced a severe inflammatory reaction, whereas SM-5887 yielded only a slight one. The data suggest that toxic effects of SM-5887 are more reversible and more controllable than those of ADR.
Jpn J Cancer Res 1989 Jan
PMID:Toxicological aspects of a novel 9-aminoanthracycline, SM-5887. 249 62

The association of opsoclonus and malignant neoplasia is infrequent. The clinical and neuropathological data of two patients in whom opsoclonus and ataxia developed 7 and 11 months before the detection of a bronchial carcinoma are reported. Loss of Purkinje cells, edema of dentate nucleus and peridental demyelination were the most important neuropathological findings; neither carcinomatous metastases nor inflammatory signs were found in the brain. From the review of the pathological reports of paraneoplastic opsoclonus, the following conclusions can be drawn: the changes in the cerebellum are produced by the paraneoplastic cerebellar degeneration and are unrelated to the origin of opsoclonus, which has other anatomic substrates; paraneoplastic opsoclonus is a "remote effect" of cancer with an inflammatory basis, for which neurotoxic and immunological mechanisms have been hypothesized.
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PMID:Paraneoplastic opsoclonus: a neuropathologic study of two cases. 255 25

Sural nerve biopsy was done 7 cases of cancer patients associated with peripheral neuropathy. There were 3 cases of lung carcinoma and one each of pancreas adenoma, seminoma, sigmoid carcinoma and chondrosarcoma of the femur. The neurological features manifested themselves with sensory pattern of neuropathy associated with ataxia in one case, sensorimotor neuropathy in 3 cases, and idiopathic polyneuropathy, peripheral neuropathy with proximal myopathy and neuropathy with paraneoplastic cerebellar syndrome each in one case, 6 patients showed neuropathy before malignancy was discovered and only one patient had neuropathy after the onset of carcinoma. Sural nerve biopsy studied in all the 7 patients with light and electron microscope revealed no infiltration of carcinomatous cells in the sural nerve fascicles. There was severe loss of myelinated fibers and severely axonal degeneration in one patient. Another patient showed segmental demyelination (5.03 x 10(3)/mm2). There was evidence of both axonal degeneration and demyelination associated with moderate reduction in the number of the myelinated fiber density ranging from 1.02 to 4.35 x 10(3)/mm2. In 6 cases, mononuclear cells were seen in nerve fascicles under the electron microscope. The characteristic pathological findings, their relation with the duration and onset of the cancer and some ideas regarding the pathogenesis are discussed.
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PMID:[Carcinomatous neuropathy: clinical and pathologic findings of sural nerve biopsy in 7 cases]. 255 34

Brainstem tumors arise in portions of the rhombencephalon and mesencephalon. Some authorities include diencephalic tumors in this group. We have reviewed our clinical experience of 69 children (less than 21 years of age) with brainstem tumors evaluated and treated at Duke University Medical Center (DUMC) from 1960 to 1986. There were 19 patients with group 1 tumors (thalamus, third ventricle region, or midbrain) and 50 with group II tumors (pons, medulla oblongata). The common presenting signs and symptoms were ataxia, headache, motor loss, and cranial nerve palsies. The most commonly employed diagnostic imaging studies were air examinations and CT. Preradiotherapy confirmation of malignancy was obtained in five group I patients (astrocytoma, 4; germinoma, 1) and 8 group II patients (astrocytoma, 3; anaplastic astrocytoma, 2; glioblastoma multiforme, 3). All patients received radiotherapy. The 5-year survival rate for the entire population was 40%. The survival rate for group I patients was significantly better than that observed for group II patients. In the 50 group II patients neither patient sex nor age nor presence of cranial nerve palsies nor pretreatment CT scan findings nor field size influenced survival. A long duration of symptoms positively influenced survival. The vast majority of tumor recurrences were within the radiation field. Half of the patients had either stable or improved Karnofsky status 6 months following completion of irradiation. The management strategy for childhood brainstem tumors is discussed.
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PMID:Selection of a management strategy for pediatric brainstem tumors. 270 33

When a patient with cancer develops a brain metastasis, death is usually imminent, but aggressive treatment in some patients with limited or no systemic disease yields long-term survival. In such patients, delayed deleterious effects of therapy are particularly tragic. We report 12 patients who developed delayed complications of whole brain radiotherapy (WBRT) given as sole treatment (4 patients) or in combination with surgical resection (8 patients). Within 5 to 36 months (median, 14) all patients developed progressive dementia, ataxia, and urinary incontinence causing severe disability in all and leading to death in 7. No patient had tumor recurrence when neurologic symptoms began. Cortical atrophy and hypodense white matter were identified by CT in all. Contrast-enhancing lesions were seen in 3 patients; 2 of the lesions yielded radionecrosis on biopsy. Autopsies on 2 patients revealed diffuse chronic edema of the hemispheric white matter in the absence of tumor recurrence. Corticosteroids and ventriculoperitoneal shunt offered significant but incomplete improvement in some patients. The total dose of WBRT was only 2,500 to 3,900 cGy, but daily fractions of 300 to 600 cGy were employed. We believe that these fractionation schedules, several of which are used commonly, predispose to delayed neurologic toxicity, and that more protracted schedules should be employed for the safe and efficacious treatment of good-risk patients with brain metastases. The incidence of WBRT-induced dementia was only 1.9 to 5.1% in the 2 populations reviewed here; however, this underestimates the incidence because only severely affected patients could be identified from chart review.
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PMID:Radiation-induced dementia in patients cured of brain metastases. 272 74

T-cell lymphoma may involve the CNS as either a primary or secondary neoplasm. This report describes 8 patients with either primary or secondary T-cell malignancies in the CNS. Five patients presented with symptoms and signs of CNS disease that included seizures, visual impairment, cranial nerve palsies, sensory and motor deficits, gait ataxia, and paraparesis. Three of them had primary parenchymal CNS lymphoma, and 2 had epidural lymphoma that originated in adjacent bone marrow. Three patients were neurologically asymptomatic, but had leptomeningeal tumor and focal parenchymal infiltration at postmortem examination. Histologically, 4 lymphomas were large cell, 3 were mixed large and small cell, and 1 could not be classified by the working formulation for non-Hodgkin's lymphomas. The clinical and pathologic manifestations of T-cell lymphoma in the CNS may be diverse. This report demonstrates that neurologic abnormalities may be the presenting signs of either primary CNS or systemic T-cell lymphoma.
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PMID:T-cell lymphoma in the CNS: clinical and pathologic features. 278 32

We report a case of primary position downbeating nystagmus due to an occult breast carcinoma in a 57-year-old woman with progressive oscillopsia and truncal ataxia. Acute nausea and vomiting precipitated hospitalization. Magnetic resonance imaging of the brain was normal, though a sterile mononuclear cerebrospinal fluid pleocytosis was present. Search for an occult malignancy disclosed an adenocarcinoma of the breast. Radical mastectomy and oral corticosteroid therapy did not alter the clinical course of the paraneoplastic syndrome in our patient. Primary position downbeating nystagmus is an uncommon manifestation of an occult malignancy. Our report and review of the literature suggests that investigations necessary for the diagnosis of occult malignancies of the lung, breast, uterus, and ovary be included in the search for cryptic causes of downbeating nystagmus.
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PMID:Paraneoplastic downbeating nystagmus. A sign of occult malignancy. 285 13


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