异环磷酰胺引起的脑病:15例临床观察及文献回顾

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Objectives.-Based on both our experience and a review of the literature,we propose some recommendations for the management of this complication.Patients a nd methods.-We report 15 encephalopathy cases in non-brain tumor patients,wh ich occurred between January 1987 and March 2002 in children from 2 to 17 years old,treated for solid tumors at the Institut Gustave Roussy.Ifosfamide was adm inistered at a posology between 5.4 and 15 g/m 2/course,associated with other a ntimitotics such as actinomycin D,etoposide or vincristine.Results.-Six pati ents experienced a grade III neurological toxicity according to the NCI classifi cation,which developed as excess drowsiness lasting up to 36 hours.Six other p atients developed grade IV neurotoxicity,including two comas resolving within 4 days and four short generalized convulsions.Three other children experienced g rade II drowsiness.Brain MRIs were normal and EEG showed an aspecific encephalo pathy tracing.This early central neurotoxicity appeared right from the first ad ministration,and occurred immediately after the first injection or during the s econd or third day of treatment.It was most often reversible,usually 3 to 5 da ys after the last ifosfamide administration.Five patients were administered a t reatment with Methylene Blue with a demonstrable efficacy in only one case.No d eath or neurological sequelae have been noted.Ifosfamide has been renewed after the neurological accident in 7 of those patients.Only 1 of those 7 patients de veloped grade IV neurotoxicity during the next course of treatment.In 2 of thos e 7 children,Methylene Blue was used in a prophylacticway.No neurological diso rders have been noted during the next courses of treatment.Discussion.-In the literature,the following are described as risk factors for ifosfamide encephal opathy:advanced pelvic disease,previous cisplatyl treatment and renal failure.We have not found any of these predisposing factors in our series,but three of the fifteen patients had severe neurotoxicity associated with Vincristin during previous treatments.Conclusion.-Facing a clinical diagnosis of ifosfamide en cephalopathy,it is recommended to discontinue administration of ifosfamide and inject by intravenous route 50 mg Methylene Blue every 4 hours until the symptom atology recedes.The rechallenge of Ifosfamide is not contra-indicated and shou ld be performed under prophylactic treatment with Methylene Blue by intravenous route at the dose of 50 mg every 6 hours. Objectives.-Based on both our experience and a review of the literature, we propose some recommendations for the management of this complication. Patients a nd methods. -We report 15 encephalopathy cases in non-brain tumor patients, wh ich occurred between January 1987 and March 2002 in children from 2 to 17 years old, treated for solid tumors at the Institut Gustave Roussy. Ifosfamide was admistered at a posology between 5.4 and 15 g / m2 / course, associated with other atimitotics such as actinomycin D, etoposide or vincristine. Results.-Six pati ents experienced a grade III neurological toxicity according to the NCI classifi cation, which developed as excess drowsiness lasting up to 36 hours. and four short generalized convulsions. Three other children experienced g rade II drowsiness. Brain MRIs were normal and EEG showed an aspecific encephalo pathy tracing. This early central neurotoxicity appear ed right from the first ad ministration, and occurred immediately after the first injection or during the second or third day of treatment. It was most often reversible, usually 3 to 5 da ys after the last ifosfamide administration. Five patients were administered at reatment with Methylene Blue with a demonstrable efficacy in only one case. No d eath or neurological sequelae has been observed. Ifosfamide has been renewed after the neurological accident in 7 of those patients. Ofly 1 of those 7 patients de veloped grade IV neurotoxicity during the next course of treatment. 2 in thos e 7 children, Methylene Blue was used in a prophylactic path. No neurological dis rders have been noted during the next courses of treatment. Discussion. - In the literature, the following are described as risk factors for ifosfamide encephal opathy: advanced pelvic disease, previous cisplatyl treatment and renal failure. We have not found any of these predisposing factors in our series, but three of the fifteen patients had severe neurotoxicity associated with Vincristin during previous treatments. Confluence - Facing a clinical diagnosis of ifosfamide en cephalopathy, it is recommended to discontinue administration of ifosfamide and inject by intravenous route 50 mg Methylene Blue every 4 hours until the symptom atology recedes. of Ifosfamide is not contra-indicated and shou ld be performed under prophylactic treatment with Methylene Blue by intravenous route at the dose of 50 mg every 6 hours.
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