Cases reported "Neurotoxicity Syndromes"

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1/5. ammonia induced encephalopathy from valproic acid in a bipolar patient: case report.

    valproic acid is widely used as a mood stabilizer. We report a case of an adult with bipolar disorder taking therapeutic doses of valproic acid, who presented to the emergency department with coma related to hyperammonemia as a complication of valproic acid treatment. valproic acid was discontinued which resulted in rapid clinical recovery. valproic acid induced coma was likely related to a urea cycle enzymopathy. Clinicians should consider hyperammonemia in all patients who present with coma and other mental status changes while on valproic acid. In such patients, ammonia level should be obtained in addition to liver function tests.
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2/5. methylene blue for the treatment and prophylaxis of ifosfamide-induced encephalopathy.

    ifosfamide (IFOS) is used in cancer treatment. ifosfamide-induced encephalopathy (IIE) can result in treatment delay or discontinuation as well as morbidity and mortality. Cases using methylene blue (MB) in acute and prophylactic treatments are discussed. For acute use, marked central nervous system (CNS) improvement occurred within 24h of MB administration. For prophylactic use, the severity of the symptoms decreased significantly compared with previous treatment cycles, and enabled patients to continue further IFOS therapy. MB has potential use in both the acute treatment and prophylaxis of IIE.
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3/5. Prophylactic treatment of known ifosfamide-induced encephalopathy for chemotherapy with high-dose ifosfamide?

    We report about a case of advanced Ewing sarcoma in a 30-year-old woman. Initial treatment was started according to the Euro-Ewing 99 protocol. During the initial therapy, an ifosfamide-induced encephalopathy occurred as status epilepticus. Because of cerebral toxicity, the following chemotherapies went without ifosfamide. During final radiotherapy multiple lung metastasis were diagnosed. After two cycles of chemotherapy with cyclophosphamide and topotecan (no response), left thoracotomy, and palliative pneumectomy, the patient was transferred to our ward for further treatment. Undergoing two cycles of chemotherapy with ifosfamide 4 g/m(2) intravenously for 3 consecutive days followed by high-dose chemotherapy (HDCT) according to the ice-regimen (ifosfamide 2 g/m(2), carboplatin 200 mg/m(2), and etoposide 2 x 100 mg/m(2) intravenously for 6 consecutive days), and peripheral blood stem cell transplantation (PBSCT), complete remission was achieved. Under preventive therapy with methylene blue, thiamin, and glucose 5% infusions, no encephalopathy occurred.
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4/5. Reversible coma secondary to cefepime neurotoxicity.

    OBJECTIVE: To describe a case of cefepime neurotoxicity associated with acute renal failure that resulted in nonconvulsive status epilepticus. CASE SUMMARY: A 66-year-old woman with acute myeloid leukemia had fever on the third day of the initial chemotherapy cycle. Empiric antibiotic treatment with cefepime 2 g every 8 hours was started; fluconazole and vancomycin were subsequently added due to the persistence of fever. Ten days after initiation of cefepime, the patient developed acute renal failure followed by altered consciousness (glasgow coma scale 6) associated with nonconvulsive status epilepticus. Cefepime was discontinued. Epileptiform activity in the electroencephalogram disappeared with clonazepam, and the patient regained consciousness 48 hours after cefepime withdrawal. DISCUSSION: Acute renal impairment combined with the use of cefepime may account for nonconvulsive status epilepticus. An objective causality assessment revealed that the adverse event was probably due to cefepime. Cefepime's neurotoxic effects derive from high serum concentrations resulting from decreased renal clearance, increased unbound antibiotic, and blood-brain barrier dysfunction during uremia. CONCLUSIONS: The combination of cefepime treatment and acute renal failure may induce drug-related neurotoxicity. Nonconvulsive status epilepticus frequently passes unnoticed in severely ill patients without a history of epilepsy. This disorder should be included in the list of potential causes of coma. In this patient, early detection of nonconvulsive status epilepticus and withdrawal of the antibiotic resulted in full recovery.
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5/5. Intermediate dose 5-fluorouracil-induced encephalopathy.

    As an acute neurotoxicity, high dose 5-fluorouracil (5-FU)-induced encephalopathy is well-known, but encephalopathy associated with lower dose is rarely reported. Here, we report a case of a male with anal cancer who was treated with 5-FU 1000 mg/m(2), continuous infusion for 5 days q4 weeks. At the second and the fourth cycles of chemotherapy, sudden confusion, cognitive dysfunction and disorientation occurred during 5-FU infusion. They were accompanied by hyperammonemia in the absence of focal neurological deficits or structural abnormalities. These symptoms completely disappeared and the serum ammonia level returned to normal after discontinuation of 5-FU and conservative care. In order to investigate a possible deficit of dihydropyrimidine dehydrogenase (DPD), we checked its mRNA level before and after treatment using real-time PCR. The patient's pre-treatment level was 80% compared with reference group, and it was elevated up to 187% of initial after 5-FU treatment, implying that that his encephalopathy may be 5-FU catabolite type rather than DPD deficiency. In conclusion, we report that encephalopathy can develop even with the dose of 5-FU lower than ever reported, and it should be considered as a differential diagnosis for proper management.
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