Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Side effects on the central nervous system by antileukemic treatment have been well known for a long time. We report on 2 patients suffering from a severe encephalopathy during antileukemic therapy. Furthermore the results of cerebral computer tomography in 50 children with acute leukemia have been analysed. In 21 patients morphological findings were evident. Four patients had CCT-changes already before the beginning of their treatment. Initially in 2 patients leukemic cerebral infiltrations were detected. The importance of the computer tomography for the detection of cerebral affections by disease and treatment is demonstrated.
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PMID:[Encephalopathy in leukemia treatment in children]. 189 52

Fludarabine phosphate (NSC 312878), an adenosine deaminase resistant analogue of 9-beta-D-arabinofuranosyladenine, has entered clinical trials. Eleven patients with acute leukemia in relapse received 14 courses of fludarabine phosphate as a 5-day continuous infusion administered at doses of 40 to 100 mg/m2/day. Toxicity was characterized by uniform myelosuppression, as well as occasional nausea, vomiting, and hepatotoxicity. Three episodes of metabolic acidosis and lactic acidemia were noted. In addition, three patients suffered neurotoxicity. Two of these three patients had a severe neurotoxicity syndrome characterized by blindness, encephalopathy, and coma. Neither patient recovered neurological function. Neuropathological findings at autopsy were characterized by a diffuse, necrotizing leukoencephalopathy which was most severe in the occipital lobes. The medullary pyramids and posterior columns were also severely affected. This sporadic fatal neurotoxicity was observed only at doses greater than 40 mg/m2/day. The maximum tolerated dose for a 5-day infusion of fludarabine phosphate is thus 40 mg/m2/day.
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PMID:Fludarabine phosphate (NSC 312878) infusions for the treatment of acute leukemia: phase I and neuropathological study. 242 88

Nine patients with Budd-Chiari syndrome (BCS) were treated by a portal systemic shunt. One had thrombosis of the superior mesenteric vein (SMV) and another had complete obstruction of the retrohepatic inferior vena cava (IVC). All other patients had a marked stenosis of the retrohepatic IVC with caval pressure ranging from 12 to 24 mmHg (mean: 17 mmHg). Seven patients had an interposition mesocaval shunt using an autologous jugular vein. The patient with a thrombosed SMV had a portoatrial shunt. The patient with an obstructed IVC had a cavoatrial shunt after an erroneous portacaval shunt had failed to relieve ascites. There were no operative deaths and no major postoperative complications. One patient died 19 months after operation of acute leukemia complicating polycythemia rubra vera. All other patients were alive and well 8 months to 6 years after operation. None of them had encephalopathy. These results suggest several comments: Portal systemic shunts are a good treatment for BCS and have a low operative risk. The mesocaval shunt is an efficient procedure, even when there is stenosis of the IVC with high caval pressure; shunts to the right atrium should be performed only in the case of complete obstruction or inaccessibility of the IVC. The long-term prognosis is excellent, except in patients with potential malignancies. Therefore, portal systemic shunts should be indicated early in patients with symptomatic BCS.
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PMID:Results of portal systemic shunts in Budd-Chiari syndrome. 396 96

We evaluated the CNS complications in 118 adults with acute leukemia who received IV high-dose Ara-C therapy. Fourteen (12%) had cerebellar signs, encephalopathy, seizures, or leukoencephalopathy. Symptoms usually occurred within 24 hours after the last treatment. Patients receiving a cumulative dose in excess of 24 g/m2 had more severe or irreversible symptoms. After lower cumulative doses, symptoms often resolved even though treatment was continued. The incidence of CNS complications of high-dose Ara-C is acceptable and is potentially reversible if appropriate precautions are taken.
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PMID:Central nervous system toxicity with high-dose Ara-C. 403 29

The Central Nervous System has often been classified as a "drug sanctuary" as most anticancer drugs do not achieve effective penetration of the blood-brain barrier. With more effective systemic chemotherapy programs (especially in acute leukemia in children), the incidence of meningeal tumor involvement has increased. Even though a number of systemically administered agents might be used in treating the CNS, only three have been used intrathecally with good clinical results: the antimetabolites methotrexate (MTX) and cytosine arabinoside (Ara-C) and the alkylating derivative thiophosphoramide (thio-TEPA). Drug distribution in the CSF which is injected by lumbar puncture does not generally allow for delivery of effective quantities of drug to the cisternae nor the ventricles. Thus direct intraventricular injection via a subcutaneously implanted (Ommaya) reservoir is necessary to achieve adequate drug levels in the higher CNS cavities. The peak ventricular concentration of MTX, which was administered by Ommaya reservoir, at a dose of 15mg/m2, was 2.5 +/- 0.9 X 10(-4)M, and remained as a level of 10(-6)M for 72 hours with a half-life of 10.5 hours. During an intravenous 6 hour-infusion at a dose of 750-3,000mg/m2, MTX concentration in CSF reached 8.2 X 10(-7)M to 2.7 X 10(-6)M. The drug content in CSF had a linear concentration related to the drug level in plasma. Intrathecal MTX and Ara-C frequently cause symptoms of meningeal irritation. Occasionally cases of weakness and paralysis and rare instances of severe encephalopathy may occur. The best established causes of these symptoms is high concentration of these drugs in the CSF, or prolonged exposure of the brain to low CSF concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pharmacokinetics of intrathecal chemotherapy and clinical problems]. 643 96

Nine children treated for acute leukemia or lymphosarcoma developed subacute encephalopathy starting with listlessness, depression and impairment of speech. Walking difficulties, ataxia, spasticity and sphincter disorders developed later. Transient intracranial hypertension and abnormal movements respectively developed in two patients. EEG frontal slow waves, raised CSF protein, abnormal white matter radioisotope uptake and CT scan hypodensity with patchy contrast enhancement were evident at the onset. Later, dilated ventricles and calcification appeared in the younger patients. Post-mortem neuropathological studies of three patients disclosed predominantly perivascular myelin loss in areas of white matter necrosis, abnormalities of small vessels and numerous axonal swellings. The spinal cord showed secondary degeneration of the corticospinal tracts. Analysis of the aetiological factors in this series points to the prevailing danger of cranial radiotherapy, probably increased by the young age of patients and by associated drug administration.
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PMID:Necrotising leukoencephalopathy complicating treatment of childhood leukaemia. 669 15

The case of a 42 years old man who had a monoblastic acute leukemia treated by a bone-marrow graft is described. The patient died of a cerebral toxoplasmosis and a cerebral computed tomography done two days before is correlated with anatomopathologic slices done in the same planes than the computed tomagraphy examination. There is a good correlation between necrotic abceded areas and hypodense areas accompanied by serpiginous fixations of contrast media. The immunocompromised patient is very favorable for the development of a cerebral toxoplasmosis. CT, while not specific, has the advantage to suspect the diagnosis which must be discussed with other oportunistic infections, leukemic infiltrates, methotrexate encephalopathy, progressive multifocal encephalopathy, and small infarcts.
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PMID:[Tomodensitometric aspects of a case of intracranial toxoplasmosis in an immunosuppressed patient]. 687 18

We treated 13 adult patients with acute leukemia or chronic myelocytic leukemia (CML) in blast phase using succinylated Acinetobacter glutaminase-asparaginase (SAGA) administered on a daily dose schedule. SAGA reduced the peripheral blast count in two patients with acute lymphoblastic leukemia and two with blastic CML; however, no patient achieved either complete or partial remission. Marked central nervous system toxic effects (encephalopathy and coma) were observed, limiting treatment in patients whose disease appeared responsive; this effect finally prompted early discontinuance of the trial. Other toxic effects observed included nausea, hyperglycemia, and respiratory alkalosis. Hypersensitivity reactions to the enzyme were not seen. Pharmacologic analyses showed that prolonged blood glutamine depletion was achieved only by daily enzyme administration; however, we noted the importance of performing amino acid analysis on blood which was deproteinized immediately following phlebotomy. Our results demonstrate excessive central nervous system toxicity when glutaminase-asparaginase is administered on a daily schedule. Because of this effect, we propose that future trials of similar enzymes be limited to short courses of enzyme therapy, possibly with the addition of antimetabolites or amino acid analogs, which could enhance the antitumor effect without increasing toxicity.
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PMID:Clinical evaluation of succinylated Acinetobacter glutaminase-asparaginase in adult leukemia. 704 29

We routinely perform echo-planar diffusion-weighted sequences in all brain magnetic resonance (MR) imaging studies. When three children undergoing chemotherapy for acute leukemia presented with seizures, conventional MR images demonstrated what appeared to be acute, posterior, parasagittal infarcts. However, diffusion-weighted images were normal. These MR imaging findings were consistent with those of hypertensive encephalopathy. Early recognition and treatment of minimal hypertension in these patients allows reversal of encephalopathy.
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PMID:Hypertensive encephalopathy: complication in children treated for myeloproliferative disorders--report of three cases. 1071 35

We studied clinical features of immunosuppressive (cyclosporine, tacrolimus) associated encephalopathy in bone marrow transplant patients. 378 cases of allogeneic bone marrow transplant recipients over fifteen years old of chronic and acute leukemia (CML, ANLL, ALL) (n = 311), myelodysplastic syndrome (MDS) (n = 42) and severe aplastic anemia (SAA) (n = 25) were investigated. Immunosuppressive associated encephalopathy occurred in 12 cases. The rate of incidence was significantly higher in SAA and MDS (7 cases) than in leukemia. The cases which showed typical radiological abnormality in MRI were limited in SAA and hypoplastic MDS. 10 cases died, which revealed worse than an overall survival rate of recipients without immunosupressive-associated encephalopathy. 5 of 7 cases in SAA and MDS had taken cyclosporine as treatment of the disease before bone marrow transplantation and that might influence the incidence of encephalopathy.
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PMID:[Immunosuppressive-associated encephalopathy in bone marrow transplant recipients]. 1527 97


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