Methotrexate-Induced Status Epilepticus (original) (raw)
Related papers
Blood, 1983
In acute lymphoblastic leukemia (ALL), central nervous system (CNS) prophylaxis with cranial irradiation plus 5 doses of intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity started to be recognized as CT scan abnormalities and neuropsychologic alterations, mainly in children. Two questions were analyzed in the present report: (1) Will further doses of i.t. methotrexate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse in patients treated early in remission with cranium irradiation plus i.t. MTX-DMT even more? (2) Is i.t. MTX-DMT given during induction and maintenance equally as effective as cranium irradiation plus i.t. MTX-DMT? A randomized study was designed to answer the first question. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count less than 50,000 was 11% (15 of 135 patients) and was 11% (17 of 150) in the untreated group. In patients with...
Blood, 1983
Between 1 972 and 1 979, 214 children with acute lymphoblastic leukemia and no evidence of central nervous system (CNS) disease prior to CNS prophylaxis were treated with 2400 rad cranial irradiation and concurrent intrathecal methotrexate. Only nine children developed CNS leukemia; five of them in the CNS only and four concurrently in the CNS and another site. Major acute effects of CNS prophylaxis were seizures in seven patients (3%). Sixty-nine children who had a minimum follow-up of 4 yr were evaluable for late effects of therapy. Small cataracts. incomplete regrowth of hair. and learning disabilities were noted. The latter occurred in 1 8% of patients. an incidence similar to that encountered in a normal community of ' leukoencephalopathy,'#{176}'7 and abnormal computed tomography ofthe brain.'02' We report on the efficacy and morbidity of CNSP with cranial irradiation and i.t. MTX in children with ALL treated at Children's Hospital Medical Center, Sidney Farber Cancer Institute and the Joint Center for Radiation Therapy between 1972 and 1979. MATERIALS AND METHODS Two-hundred twenty-seven children with untreated ALL ages I mo to 15 yr attained complete remission between
Nonconvulsive Status Epilepticus and Leucoencephalopathy After High-Dose Methotrexate
Journal of Clinical Oncology, 2011
A 58-year-old African-Caribbean woman with a medical history of controlled hypertension was admitted with sudden onset of expressive and receptive dysphasia; she was unable to read, write, or obey commands. She had a 3-month history of intermittent headaches. Initial computed tomography (CT) scan of brain was suggestive of a left middle cerebral infarct, but subsequent findings on a magnetic resonance imaging (MRI) scan were consistent with a neoplastic lesion in the left temporal lobe. Biopsy of this lesion showed high-grade B-cell non-Hodgkin's lymphoma. Whole-body staging CT scan showed no evidence of neoplastic disease elsewhere, but there was an incidental pulmonary embolism. Bone marrow aspirate and trephine were normal, and HIV test was negative. A craniotomy was performed with insertion of an Ommaya reservoir. She received two cycles of alternating intravenous and intrathecal methotrexate (MTX) with no complications. After the third cycle, she was admitted to her local hospital with pyrexia, dysphasia, and confusion. The admitting team suspected CNS infection, and treatment with antibiotics was commenced despite normal CSF examination. Subsequent CT imaging showed a decrease in the size of the lymphoma. On eventual transfer to the cancer center, her symptoms had completely resolved, and she went on to receive her fourth cycle of chemotherapy 1 week later than planned. One week after the fifth cycle of intravenous MTX, she was admitted again with recurrence of dysphasia, confusion, and intermittent fevers; however, there was no change in Glasgow Coma Scale score. Investigations including CSF analysis via Ommaya aspiration ruled out a septic cause. CT of brain showed resolution of the lymphoma. Neurologic opinion suggested she had possible clinical features of left temporal lobe dysfunction, and a subsequent electroencephalogram (EEG) was suggestive of nonconvulsive status epileptiucs (NCSE), which showed partial reversibility after intravenous diazepam. Figure 1 shows EEG tracings taken when the patient presented with dysphasia and confusion after the fifth cycle of MTX. The top tracing (Fig 1A) was taken 10 minutes before diazepam, showing changes in the highlighted left hemisphere leads. The middle tracing (Fig 1B) was taken immediately after 5 mg of intravenous diazepam and shows attenuation of epileptifrom activity. The bottom tracing (Fig 1C) shows a return to baseline appearance before diazepam. The top tracing also demonstrates the importance of distinguishing between epileptiform activities and blink artifact. MRI demonstrated diffuse T2W/fluid attenuation inversion recovery (FLAIR) signal hypersensitivity in the cerebral white matter of the left temporal lobe compatible with chemotherapy-induced leukoencephalopathy. There was no evidence of
Methotrexate Induced Encephalopathy in Acute Lymphoblastic Leukemia in Omani Children
Hematology & Transfusion International Journal
Objectives: To investigate the incidence and clinical profile of methotrexate related encephalopathy in Omani children with pre-B Acute Lymphoblastic Leukemia (ALL). Methods: A retrospective cohort study of 8 children with Pre B Acute Lymphoblastic Leukemia who developed encephalopathy while being treated according to United Kingdome Research Council (UK MRC) ALL protocol during the period between 2005-2016. Demographic data, clinical presentation, diagnosis and treatment are discussed. Results: Eight children (4males,4females), 7 of them were above 10 years of age, with ALL treated according to intermediate risk UK MRC ALL protocol developed transient encephalopathy during treatment. Six children had one episode, one had two episodes, and last one had 3 episodes. All except one recovered completely within 24-96hours after symptomatic treatment. This one had extensive neurological involvement and took seven days to recover. All children had normal coagulation and thrombophilia studies. Four out of the 8 patients subsequently received intrathecal (IT) cytarabine instead of methotrexate without any neurotoxicity. The other 4 patients received further IT methotrexate. Three of these four had recurrence on re-challenge, while the fourth remained asymptomatic. Seven children with neurotoxicity had MRI findings of white matter changes. Six out of eight children are in complete remission while two died later following relapse. Conclusion: Methotrexate induced encephalopathy can occur after intrathecal methotrexate treatment especially in children older than 10 years of age. Diffusion weighted MRI is the currently available best diagnostic tool. Treatment of methotrexate neurotoxicity is mainly supportive and recovery is usually complete. Further studies are needed to understand the mechanism of neurotoxicity, risk factors, and to define the safe dose to prevent such neurotoxicity.
Methotrexate-related neurotoxicity in the treatment of childhood acute lymphoblastic leukemia
The Israel Medical Association journal: IMAJ
The addition of methotrexate to treatment protocols in children with acute lymphoblastic leukemia has been found beneficial in preventing central nervous system relapse. However, MTX itself may be associated with neurologic morbidities, the most significant of which is leukoencephalopathy. The present study describes the clinical spectrum of leukoencephalopathy, which ranges from a subclinical disease manifested only radiologically to a progressive, devastating encephalopathy. The interaction of MTX with other components of the treatment protocol is discussed, as is the effect of leucovorin. A summary is presented of the metabolic pathways that may be involved in the development of MTX toxicity. Researchers are still seeking a biochemical marker to aid in the determination of the amount of MTX that may be safely administered.
A Case of Methotrexate Neurotoxicity Presented as Status Epilepticus, Encephalopathy, and High Fever
Journal of Investigative Medicine High Impact Case Reports
High-dose methotrexate is used to treat a range of adult and childhood cancers including osteosarcoma. Significant neurotoxicity is reported in 1% to 4.5% of patients treated with high-dose methotrexate and can present in a wide variety of symptoms. We present a case of a 14-year-old boy with a recent diagnosis of osteosarcoma who presented to the emergency department with status epilepticus, altered mental status, and very high fever secondary to methotrexate neurotoxicity. We review current literature and discuss some controversies related to this state. We also describe high fever as one of the possible symptoms associated with this condition and suggest using specific magnetic resonance imaging sequence to uncover abnormal findings related to this state. Since high-dose methotrexate is not a rare treatment in this era, we believe that in addition to oncologists, emergency department and intensive care providers should be aware of the potential role of methotrexate in causing sig...
Indian pediatrics, 1996
To assess the incidence of isolated central nervous system (CNS) relapses in patients of acute lymphoblastic leukemia (ALL) treated with a protocol containing cranial irradiation and intrathecal methotrexate as CNS directed therapy. Prospective non randomized study. Department of Medical Oncology, Tata Memorial Hospital. 623 children of ALL on MCP 841. CNS relapse was diagnosed, if upon examination of the CSF, more than 50 cells/microliter were observed, or a count of 5 cells which were unequivocally lymphoblasts. The incidence of isolated CNS relapse was 1.75% with the use of this treatment. Age, sex, white blood cell count, platelet count, lactic dehydrogenase and immunophenotyping were not significantly related to isolated CNS relapse. A low incidence of isolated CNS relapse demonstrates the adequacy of the presymptomatic CNS therapy.