Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate (MTX) is an indispensable antimetabolite for the treatment of oncological and immunological disorders in all age groups. Chronic leukoencephalopathy is a well know side effect of MTX, especially in conjunction with intrathecal administration and whole brain radio therapy. However, acute neurotoxicity with confusion, disorientation, seizures and focal deficits has also been reported. Because acute neurological symptoms in patients under chemotherapy for neoplastic disorders may have many reasons, MR-imaging is usually necessary to identify the underlying pathology. Apart from conventional sequences, diffusion-weighted imaging (DW-MRI) is frequently performed. We report on clinical and imaging findings of reversibly restricted diffusion in a patient with transient encephalopathy after intrathecal administration of MTX for recurrent acute lymphatic leukaemia.
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PMID:Transient encephalopathy after intrathekal methotrexate chemotherapy: diffusion-weighted MRI. 1593 17

Methotrexate (MTX)-induced neurotoxicity may occur after intrathecal or systemic administration at low, intermediate and high doses for the treatment of malignant or inflammatory diseases. The mechanisms of MTX neurotoxicity are not totally understood, and appear to be multifactorial. In this study we characterized a model of MTX-induced seizures in mice to evaluate the convulsive and toxic MTX properties. Additionally, the effect of MTX-induced seizures on the activity of glutamate transporters, as well as the anticonvulsant role of MK-801, DNQX and adenosine on glutamate uptake in brain slices was investigated . MTX induced tonic-clonic seizures in approximately 95% of animals and pre-treatment with MK-801, DNQX and adenosine prevented seizure in 80%, 62% and 50% of animals, respectively. Moreover, MTX leads 59% of mice to death, which was prevented in 100% and 94% when animals received MK-801 and DNQX, respectively. Glutamate uptake decreased by 20% to 30% in cortical slices after MTX-induced seizures. Interestingly, when seizures were prevented by MK-801, DNQX or adenosine, glutamate uptake activity remained at the same level as the control group. Thus, our results demonstrate the involvement of the glutamatergic system in MTX-induced seizures.
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PMID:Methotrexate induces seizure and decreases glutamate uptake in brain slices: prevention by ionotropic glutamate receptors antagonists and adenosine. 1696 42

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)+/-high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16-18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.
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PMID:Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children. 1717 Jul 21

We report a 7-year-old boy who unexpectedly developed a multi-drug resistant epilepsy with negative neuroimaging results, followed by the insidious appearance of linear localized scleroderma involving the right leg. When the boy was 16 and severely affected by epileptic encephalopathy, we have evaluated this case for the first time: his localized scleroderma had reached the right buttock and positive anti-nuclear antibody was the only positive laboratory test. Methotrexate administered for 12 months was ineffective in improving both the organization of his electroencephalographic pattern and seizure control, though seemed to stabilize the progression of linear scleroderma. This report suggests that neurological abnormality and extracranial scleroderma might represent two own distinct processes in a same patient.
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PMID:Longstanding epileptic encephalopathy and linear localized scleroderma: two distinct pathologic processes in an adolescent. 1827 99

Methotrexate is a common agent used in the management of hematological malignancies, but is often associated with the development of diverse central nervous system adverse events, such as seizures. We present a case of seizures after intrathecal administration of methotrexate, during the management of diffuse large B-cell lymphoma. There was complete resolution of the CNS lesions after chemotherapy along with the interval development of diffuse cerebral edema. We hypothesize that tumor lysis is the underlying mechanism of this untoward event, resulting in the corresponding clinical presentation.
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PMID:Intracranial tumor lysis and cerebral edema after administration of intrathecal methotrexate: a case report and discussion. 1984 78

Methotrexate (MTX) is an indispensable antimetabolite for the treatment of oncological and immunological disorders in all age groups. It can be administrated intravenously as well as intrathecally and may be used alone or in combination with other drugs. Chronic leukoencephalopathy is a well-known side effect of MTX, especially in conjunction with intrathecal administration. However, acute neurotoxicity with confusion, disorientation, seizures, and focal deficits may also be seen. This can clinically mimic stroke with restricted diffusion on MRI. However, unlike stroke, there is resolution of clinical and imaging findings within 1-4 weeks. We report two cases of transient leukoencephalopathy following intrathecal methotrexate, with complete clinical and radiological resolutions on follow-up.
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PMID:Transient leukoencephalopathy after intrathecal methotrexate mimicking stroke. 2124 92

Localized and multisystem nocardiosis is an opportunistic disease that occurs commonly in immunocompromised patients. Rarely, it is also seen in immunocompetent individuals. The most common disease sites include lung, skin and central nervous system. We report a case of 73 years old man who is a known case of rheumatoid arthritis for more than 15 years and was on Methotrexate and Prednisolone. Now presented with generalized tonic clonic seizures. His Magnetic Resonace Imaging (MRI) scan showed a ring enhancing lesion with mild surrounding oedema in right posterior parietal cortex. Based on the finding, the most probable diagnosis of cerebral abscess was suggested. Patient underwent right sided craniotomy with aspiration of abscess. Serum Gram staining showed branching Gram-positive rods, and serum culture showed colonies of Nocardia Asteroides. He was started on Sulfamethoxazole-Trimethoprim. On follow-up examination, the patient showed marked improvement clinically and was discharged in stable condition on long term antibiotic therapy. This case highlights the importance of including nocardia on the differential diagnosis especially in patients who present with abnormal MRI scan findings that mimic tuberculoma or neoplastic disease. Clinical awareness of this condition could expedite the diagnostic process and help improve morbidity and mortality.
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PMID:Cerebral nocardiosis. 2220 50

Acute lymphoblastic leukemia (ALL) is one of the most common malignancies of childhood, which is treated with high doses of methotrexate (MTX), as it crosses the blood-brain barrier and can be administered intravenously and via intrathecal route to eradicate leukemic cells from central nervous system (CNS). Additionally, high doses of MTX not only prevent CNS recurrence but also hematologic relapses. Although, standard treatment protocol for ALL includes multimodality therapy, MTX is usually associated with neurotoxicity and affects periventricular deep white matter region. Methotrexate-induced 'acute toxic leukoencephalopathy' has varying clinical manifestations ranging from acute neurological deficit to seizures or encephalopathy. Diffusion weighted magnetic resonance imaging (DW-MRI) is widely available and routinely used in clinical practice to identify acute stroke and also to distinguish acute stroke from non-stroke like conditions. We report a local teenage Chinese girl who developed 2 discrete episodes of left upper and lower limb weakness with left facial nerve paresis after receiving the 2 nd and 3 rd cycle of high dose of intravenous and intrathecal methotrexate, without having cranial irradiation. After each episode of her neurological deficit, the DW-MRI scan showed focal restricted diffusion in right centrum semiovale. Her left sided focal neurological deficit and facial nerve paresis almost completely subsided on both these occasions within 3 days of symptom onset. Follow-up DW-MRI, after her neurological recovery, revealed almost complete resolution of previously noted restricted diffusion in right centrum semiovale, while the lesion was not evident on concurrent T2W (T2-weighted) and FLAIR (Fluid-Attenuated Inversion recovery) sequences, nor showed any post contrast enhancement on post gadolinium enhanced T1W (T1-weighted) sequences. No residual neurological deficit or intellectual impairment was identified on clinical follow up over a 2 year period.
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PMID:Methotrexate-induced acute toxic leukoencephalopathy. 2284 79

Intrathecal therapy with cytarabine is widely used in the treatment of acute lymphocytic leukemia. We report the first case of accidental intrathecal cytarabine overdose in an adult patient. Overdose of intrathecal chemotherapy has been reported to cause severe neurological damage including seizures, coma and death. Methotrexate levels can help guide intrathecal dosing of methotrexate, but no such test is commercially available for cytarabine. There are no standardized treatment recommendations for the management of this medical emergency. Intrathecal methotrexate overdose has been variously treated with cerebrospinal fluid drainage or exchange. Ventriculo-lumbar perfusion, steroids and leucovorin have also been used. It seems crucial to quickly remove as much drug as possible from the cerebrospinal fluid. Our patient was successfully treated with large-volume cerebrospinal fluid aspiration through an Ommaya reservoir. She did not suffer any significant immediate or late complications at 4 months of follow-up.
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PMID:Successful large-volume cerebrospinal fluid aspiration for an accidental overdose of intrathecal cytarabine. 2346 68

A 12-year-old Saudi girl, known case of T-cell leukemia with CNS relapse. She was diagnosed 2 years ago. Multiple cycles of chemotherapy had been used (Fludarabine, Cytarabine, Methotrexate, Cyclosporine, and Mercaptopurine). She was admitted electively for cord blood transplantation. Afterward, she developed visual, and behavioral change followed by seizure.
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PMID:A child with leukemia and behavioral changes. 2473 15


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