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)

Paraneoplastic syndromes, or the remote effects of cancer on the nervous system, can result in significant functional impairment. One syndrome in particular, paraneoplastic subacute cerebellar degeneration (PSCD), may be severely disabling. Patients with PSCD can experience severe ataxia resulting in an inability to ambulate or perform their activities of daily living. Little has been written about the value of rehabilitation in cases of paraneoplastic syndrome. We report the case of a 51-year-old woman with PSCD who experienced improvements in all functional activities after comprehensive inpatient rehabilitation. She has maintained her improved functional status after discharge; her case is testimony to the value of rehabilitation in paraneoplastic syndrome.
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PMID:Paraneoplastic subacute cerebellar degeneration: functional improvement and the role of rehabilitation. 812 92

Carcinoid tumor is regarded as a tumor with low grade malignancy, mostly originating from the gastrointestinal tract with little danger of metastasis. The authors encountered a very rare case of bronchial carcinoid tumor that had multiple metastasis to the intracranial space. The characteristics of radiological and hormonal examinations of this tumor are reported and discussed. The patient was a 73-year-old woman who gradually developed unsteadiness in walking and somnolence in daytime one month prior to admission. Those symptoms were aggravated and she began to vomit. On admission, neurological examination showed slight ataxia of left upper and lower extremities and dominant truncal ataxia. Chemical and hormonal examinations of blood and urine showed, gastrin was 230 pg/ml (37-172), ACTH was 67 pg/ml (< 60), serotonin was 565 ng/ml (53-200), and urinary 5-HIAA was 9.9 mg/day (0.8-4.8). Tumor markers (CEA, AFP, HGG, NSE) were all negative. Radiological examinations (chest X-P, CT scan) of her lung demonstrated a 3 x 3 cm tumor mass adjacent to the hilum of the left lower lobe. CT-scan of the head demonstrated cystic tumor in the vermis of the cerebellum (3 x 3 cm), the right posterior parietal lobe and the right temporal lobe. The wall of each tumor was enhanced by contrast medium. T1 weighted MRI demonstrated the walls of cystic tumors as iso intensity and the contents as low and high intensity with niveau formation. Little edema was recognized around the tumors. The wall of each cystic tumor was enhanced by Gd-DTPA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Bronchial carcinoid tumor with multiple brain metastasis]. 816 99

Immunotoxins have been suggested as possible therapeutic agents in patients with leptomeningeal carcinomatosis. The pharmacokinetics, stability, and toxicity of immunotoxins injected into the i.t. space were examined in rats and rhesus monkeys. Monoclonal antibodies specific for the human (454A12 and J1) and rat (OX26) transferrin receptors were coupled to recombinant ricin A chain. In monkeys, the maximally tolerated dose of the anti-human transferrin receptor immunotoxin (454A12-rRA) was a dose that yielded a nominal cerebrospinal fluid (CSF) concentration of approximately 1.2 x 10(-7) M. In rats, the 10% lethal dose (LD10) of the anti-human transferrin receptor immunotoxin was a dose yielding a nominal CSF concentration of 8.8 x 10(-7) M whereas the LD10 of the anti-rat transferrin receptor immunotoxin (OX26-rRA) was a dose yielding a nominal CSF concentration of 1.2 x 10(-7) M. Thus, the species-relevant antibody resulted in toxicity at a concentration one-seventh that of the immunotoxin with the irrelevant antibody. A comparison of the area under the concentration curve at the LD10 for rats with the area under the concentration curve at the maximally tolerated dose in monkeys and humans shows that the species-relevant immunotoxin was a better predictor of the toxic dose of the anti-transferrin receptor immunotoxin in humans than the irrelevant immunotoxin. The pharmacokinetics of the 454A12-rRA immunotoxin within the CSF of monkeys showed a biphasic clearance with an early-phase half-life of 1.4 h and a late phase half-life of 10.9 h. The clearance was 4.4 ml/h or approximately twice the estimated clearance due to bulk flow of CSF. Loss by degradation was ruled out because immunoblot analysis showed that the immunotoxin was stable for up to 24 h after administration. Possible losses in addition to sampling include diffusion into brain tissue and transcapillary permeation. The apparent volume of distribution was 10.1 ml or approximately three-fourths the total CSF volume of the monkey. Dose limiting toxicity corresponded with the selective elimination of Purkinje cells in both rats and monkeys and was manifested clinically as ataxia and lack of coordination. The onset of ataxia in monkeys occurred within 5 days and, in the more mild form, was reversible with time. There was evidence of only minimal inflammation within the CSF, and there were no signs of systemic toxicity. Immunotoxins injected into the subarachnoid space may have potential for treatment of leptomeningeal carcinomatosis.
Cancer Res 1993 Aug 15
PMID:Pharmacokinetics and toxicology of immunotoxins administered into the subarachnoid space in nonhuman primates and rodents. 833 87

Five women are presented with a subacute pure pancerebellar syndrome of ataxia and dysarthria to emphasize that this illness may occur without anti-Purkinje-cell or anti-Yo antibodies, or associated systemic cancer. The syndrome evolved over weeks or less and stabilized in four of the patients. Three had had a preceding infection and one, a rash, but there was no inflammatory response in the spinal fluid. Over the 5-year period during which these patients appeared in an individual general neurology practice, there was only one patient with paraneoplastic cerebellar degeneration. Despite the association of this syndrome with cancer, particularly in women, clinicians will still commonly confront the idiopathic variety.
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PMID:Seronegative, non-neoplastic acute cerebellar degeneration. 835 Oct 20

A 3-year-old girl received conventional-dose external beam posterior fossa irradiation (5400 cGy in 30 fractions over 40 days) for good-risk medulloblastoma. Soon thereafter, she experienced an extraneural (occipital scar, cervical lymph nodes) and central nervous system (CNS) recurrence. Intensive cisplatin and cyclophosphamide chemotherapy led to rapid disappearance of the extraneural disease. Methotrexate was administered via a ventricular reservoir. After 2 months of chemotherapy, CNS toxicity progressed rapidly from ataxia to paraplegia to quadriplegia to central respiratory failure. Radiographic scans and autopsy material revealed brain stem necrosis. This unusual toxicity raises concern about the safety of aggressive systemic chemotherapy and intrathecal therapy, when given after conventional radiotherapy.
Cancer 1993 Jun 15
PMID:Fatal brain stem necrosis after standard posterior fossa radiation and aggressive chemotherapy for metastatic medulloblastoma. 850 76

Since the discovery of the biologically active platinum complexes 30 years ago, 2 agents have become widely established in clinical oncology practice. Both cisplatin and carboplatin are platinum(II) complexes with 2 ammonia groups in the cis- position. However, they differ in their solubility, chemical reactivity, dichloride or alicyclic oxygenated leaving groups, pharmacokinetics and toxicology. Cisplatin causes severe renal tubular damage and reduces glomerular filtration, and requires concurrent saline hydration and mannitol diuresis to eliminate potentially lethal and unacceptable damage to the kidneys. Carboplatin, at conventional doses, causes no decrease in glomerular filtration and only minor transient elevations in urinary enzymes. Cisplatin is the most emetic cancer drug in common use, while nausea and vomiting associated with carboplatin are moderately severe. Serotonin release from enterochromaffin gut mucosal cells and stimulation of serotonin 5-HT3-receptors mediates acute emesis. Selective inhibitors of the 5-HT3-receptor protect against cisplatin- and carboplatin-induced nausea and vomiting. Peripheral neurotoxicity is the most dose-limiting problem associated with cisplatin. Loss of vibration sense, paraesthesia and sensory ataxia comes on after several treatment cycles. Carboplatin, however, is relatively free from peripheral neurotoxicity. Audiometry shows cisplatin-induced ototoxicity in 75 to 100% of patients, which may be associated with tinnitus and hearing loss. Ototoxicity is rare with conventional dose carboplatin therapy. Monitoring hearing with audiograms may identify early signs before significant impairment occurs. Cisplatin causes mild haematological toxicity to all 3 blood lineages. Haematological toxicity is dose-limiting for carboplatin, with thrombocytopenia being a greater problem than leucopenia. Although carboplatin is not toxic to the kidney, renal function markedly affects the severity of carboplatin-induced thrombocytopenia. The major clearance mechanism of cisplatin is irreversible binding in plasma and tissues, while carboplatin is cleared by glomerular filtration. Metabolism of cisplatin to aqua, amino acid and protein species is extensive, whereas carboplatin exists mainly as the free unchanged form. Strong relationships between carboplatin renal clearance, glomerular filtration rate, area under the plasma concentration-time curve (AUC) of filterable platinum and severity of thrombocytopenia have prompted dose adjustment according to renal function. New analogues such as JM216 offer the potential advantages of oral administration and few nonhaematological toxicities. Analogues based on the diaminocyclohexane ligand have encountered problematic neurotoxicity.
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PMID:Comparative adverse effect profiles of platinum drugs. 857 96

Wernicke's encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine (vitamin B1)-deficiency. WE is most commonly seen among patients with alcohol abuse, and thiamine deficiency is here caused by several factors, among others inadequate diet, insufficient gastrointestinal absorption and enzymatic abnormalities. The syndrome, however, is also seen among non-alcoholic, undernourished patients, e.g. certain patients with cancer or AIDS. The diagnosis WE has traditionally been given when the triad of confusion, ataxia and ophthalmoplegia was present. However, it should be recognised, that these three symptoms are not always present at the same time, partly because the mental symptoms often dominate and cloud, possible ocular abnormalities and ataxia. The syndrome is, according to the author's opinion, still underdiagnosed. The treatment of WE, consisting of large doses of intravenous thiamine, is effective and safe, and therefore it is important to be aware of WE among risk-patients, especially among patients with alcohol abuse, and to institute treatment with intravenous thiamine at the slightest suspicion.
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PMID:[Wernicke's encephalopathy]. 863 25

Case Report on a Breast Cancer Patient: A description of medical history, diagnosis and therapy of a patient with breast cancer is presented. The patient showed primary symptoms of vertigo and truncal and gait ataxia. The cause of this cerebellar disorder was a paraneoplastic cerebellar degeneration (PCD) characterized by anti-Purkinje cell antibodies (anti-Yo) directed against specific epitops shared by Purkinje and tumour cells. The presence of these antibodies in some patients suggests an autoimmune mechanism, although their role in pathogenesis has not been established. Usually malignancies of the breast and the ovaries are associated with anti-Yo positive PCD. The intensive search for the underlying neoplasma led to the identification of a malignant tumour of the right breast. Tumour excision of subsequent immunosuppressive treatment resulted in a progression of PCD. Antibody titers remained nearly unchanged during the course of the disease.
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PMID:[Paraneoplastic cerebellar degeneration: case report of a patient with breast carcinoma]. 868 88

We reviewed the records and radiologic studies of eight patients who developed new focal neurologic abnormalities while receiving interleukin-2 (IL2)-based immunotherapy for malignancy or HIV infection. Initial confusion and delirium in the patients evolved into coma, ataxia, hemiparesis, seizures, and cortical syndromes including aphasia, apraxia, and cortical blindness. Imaging studies showed multiple white and gray matter lesions with a predilection for the occipital poles, centrum semiovale, and cerebellum. After cessation of IL2 treatment, seven patients improved to normal or near-normal neurologic function paralleled by resolution of the lesions on scans. One patient improved only minimally. Possible etiologies for the lesions include an IL2-induced cerebral vasculopathy, a direct toxic effect of IL2, or immunologically mediated damage.
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PMID:Multiple cerebral lesions complicating therapy with interleukin-2. 875 14

A 50-year-old man was admitted to our hospital because of slowly progressing ataxia. After the neurological examination and after observation of the clinical course, paraneoplastic cerebellar degeneration was suspected. Extensive examination revealed a malignant tumor in the right upper lobe of the lung. Immunoblotting with rat cerebellum revealed a 68 KDa protein in the patient's serum, which suggested that paraneoplastic cerebellar degeneration was caused by an auto-antibody. Anti-cancer drugs and radiation therapy were begun 4 months after the onset of symptoms. After 4 months of therapy, the lung cancer had shrunk, but the neurological symptoms had become more severe.
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PMID:[Small-cell carcinoma of the lung with paraneoplastic cerebellar degeneration]. 877 84


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