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)

Twenty-three leukemic children were studied prospectively to detect chronic effects of therapy. All patients received CNS prophylaxis, including 2400 R cranial irradiation, and intermittent maintenance therapy with intravenous methotrexate, cyclophosphamide and cytosine arabinoside. Neurologic symptoms were observed in 12 patients, all of whom had intermittent limping and mild incoordination, between the 10th and 18th month of maintenance therapy. Five of the 12 sustained seizures and four of these had subsequent abnormalities in motor, perceptual, behavioral or language development. Three school-aged children have learning disability and perceptual-motor defects. Studies of CSF folate and MTX content are presented but not helpful in delineating the etiology of these neurologic symptoms.
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PMID:Chronic neurologic disturbance in childhood leukemia. 106 30

Chemotherapy with high-dose methotrexate (HD-MTX) is often associated with acute neurotoxicity. We determined whether the altered neuronal function after HD-MTX [such as the reduced regional cerebral metabolic glucose rate (rCMRGlc) and slow electroencephalographic pattern] affects the sensitivity of the CNS to centrally acting drugs: the depressant phenobarbital, which reduces rCMRGlc, and the analeptic agent pentylenetetrazol (PTZ), which elevates rCMRGlc. Adult male Sabra rats received an i.v. infusion of MTX, 0.51 mg/min, to induce neurotoxicity or saline solution for 24 hr. Subsequently, MTX-treated and control groups were infused in one experiment with phenobarbital until loss of the righting reflex and in the second experiment with PTZ until the onset of maximal seizures. HD-MTX did not affect the infused hypnotic dose or serum, brain, and cerebrospinal fluid concentrations of phenobarbital at the onset of anesthesia. The convulsive dose and PTZ concentrations in the serum and brain at the onset of maximal seizures were significantly higher in the HD-MTX-treated animals. These outcomes indicate that HD-MTX and the reduced rCMRGlc that follows this treatment do not contribute to the hypnotic action of phenobarbital. On the other hand, treatment with HD-MTX exhibited anticonvulsant properties as evidenced by the reduced CNS sensitivity to PTZ-induced seizures.
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PMID:High-dose methotrexate does not affect the pharmacodynamics of phenobarbital hypnotic action but decreases the central nervous system (CNS) sensitivity to pentylenetetrazol-induced maximal seizures in rats. 144 29

20 patients with malignant brain tumors in childhood were treated according to a regimen which included initial surgery, preradiation chemotherapy and subsequent irradiation. The chemotherapy consisted of alternating cycles of high-dose methotrexate (12 g/m2) and "8 drugs in 1 day" (Bleyer, 1983). Each cycle was to be given up to six times, as tolerated. The diagnoses were medulloblastoma in 10 cases, astrocytoma in 5 cases, ependymoma and PNET in 2 patients each, and malignant mesenchymoma in 1 case. 15 patients were previously untreated, 5 patients experienced relapse after a different first line therapy and a longer time interval. 8 patients are in continuous complete remission for 13 to 54 months. The toxicity upon the bone marrow, the kidney and the inner ear was tolerable. Long lasting emesis contributed a marked problem to the patients but did not cause abbreviation of the therapy. The neurotoxicity was notably mild. Three episodes of generalized seizures were seen without subsequent sequelae, four cases of peripheral neuropathy were attributable to vincristine. A leukoencephalopathy was neither detected on clinical grounds nor on neuroradiological imaging. Therapy related deaths were not seen. We conclude that the combination of HD-MTX and "8 in 1" markedly contributes to the intensification of the chemotherapy for malignant brain tumors in childhood. In the setting as preradiation chemotherapy the toxicity is tolerable.
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PMID:[High dosage methotrexate in combination with "8 in 1" in therapy of pediatric grade III/IV brain tumors]. 158 54

Neurological disorders, such as seizures, are not infrequently associated with anti-leukemic therapy. It has been hypothesized that a disrupted peptidergic transmission between neurons could be the cellular basis of the neurological dysfunction. Since endogenous opioids have been recently found to alter neuronal function and possess anticonvulsant properties, the cerebrospinal fluid (CSF) immunoreactive beta-endorphin levels in children with Acute Lymphoblastic Leukemia (ALL) during chemotherapy and cranial irradiation have been studied. Twenty-seven children, 2 at low, 20 at medium and 5 with high risk ALL, undergoing prophylactic treatment for meningeal leukemia, entered the study. Sequential lumbar punctures with introduction of MTX combined with oral prednisone therapy were performed; each lumbar puncture sample was collected and assayed for immunoreactive beta-endorphin. All the patients studied showed a biphasic profile of the peptide with the minimum levels reached during the induction (days 14-28) and the maximum levels detected at the end of the intensification chemotherapy (days 49-55). In the 3 groups the beta-endorphin decrease corresponded to the period of prednisone therapy; the increase was concomitant with the suspension of oral glucocorticoids. 3 patients showed tonic-clonic seizures which coincided with the lowest cerebrospinal fluid beta-endorphin levels and, in the follow-up, 13 out of 27 patients displayed EEG abnormalities. From these findings a relationship between cerebrospinal fluid beta-endorphin concentrations and neuronal excitability in patients with ALL can be suggested. It is also evidenced that oral glucocorticoid therapy has profound inhibitory effects on central beta-endorphin levels.
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PMID:Immunoreactive beta-endorphin levels in cerebrospinal fluid of children with acute lymphoblastic leukemia: relationship with glucocorticoid therapy and neurological complications. 253 Nov 80

We reviewed the records of 127 consecutive pediatric patients with acute lymphoblastic leukemia (ALL) to determine the incidence, timing, etiologies, and recurrence rate of seizures in this population. Patients with ALL and seizures were identified retrospectively by review of the records of all pediatric ALL patients who were diagnosed and treated during the years 1983 through March 1993 in a large tertiary-care hospital. Seventeen patients (13%) developed one or more seizures. In 16 patients, seizures occurred during antileukemic treatment, and in almost all of them seizures were related to intrathecal methotrexate (IT MTX) or subcutaneous L-asparaginase treatment. One patient who developed a seizure while not receiving chemotherapy had a history of cerebral infarctions. In 8 patients, (47%), the initial seizure episode was associated with a cerebral lesion. One or more seizures recurred in 6 patients. Four of these patients had an isolated recurrence, in 3 patients < or = 3 months and in 1 patient < or = 6 months after the initial event. Two patients (12%) with static encephalopathy and neurological deficits developed a chronic seizure disorder. There is a significant risk of acute symptomatic seizures in pediatric ALL patients. Most seizures in these patients occur during the acute treatment phase and are most frequently related to side effects of chemotherapy. The long-term recurrence risk is low; recurrence occurs most often in patients with evidence of cerebral structural lesions and neurological deficits. Long-term antiepileptic drug (AED) therapy should be restricted to such patients.
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PMID:Prognosis and treatment of seizures in children with acute lymphoblastic leukemia. 763 3

The sequence of chemotherapy administered prior to cranial irradiation rather than the more traditional order of radiation followed by chemotherapy is currently being evaluated. This rodent study was designed to assess the sequencing of radiation therapy and chemotherapy administered with osmotic blood-brain barrier disruption (BBBD). Drug delivery and acute toxicity were evaluated. Two clinically relevant chemotherapy regimens were given with BBBD: intraarterial methotrexate (MTX, 1 g/m2), or a combination of intraarterial carboplatin (200 mg/m2) and i.v. etoposide (200 mg/m2). In a randomized protocol, the standard rodent model of 2000 cGy as a single fraction using parallel opposed portals was administered 30 days prior to, concurrent with (24 h prior), or 30 days after these two chemotherapeutic regimens. A total of 72 animals was evaluated in this study. The administration of external beam radiation therapy either prior to or concurrent with the administration of a high molecular weight marker 14C-labeled dextran 70 (Mr 70,000), or a low molecular weight marker 3H-labeled MTX (Mr 456) resulted in a statistically significant (P < 0.01) decrease in drug delivery when compared to animals not receiving cranial irradiation. Seizures were observed in 26% of the animals that received radiation prior to the administration of intraarterial MTX after BBBD. It did not matter whether the radiotherapy was administered 30 days prior to or concurrent with MTX. Seizures were not seen in any other group. The mortality in animals receiving radiotherapy 30 days prior to chemotherapy was significantly (P = 0.03) higher than the mortality in control animals receiving chemotherapy after osmotic BBBD, but no radiation. Drug delivery was significantly decreased when the animals received prior radiotherapy; the administration of radiation prior to MTX with BBBD resulted in an increased incidence of seizures, and there was a significant increase in mortality when cranial irradiation was given 30 days prior to chemotherapy administered with BBBD. With regard to delivery and toxicity, chemotherapy with BBBD administered prior to radiotherapy may have advantages over the other sequences utilizing chemotherapy and cranial irradiation.
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PMID:Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: the issue of sequence. 981 39

An episode of subacute encephalopathy after the infusion of a moderate dose of methotrexate (1500 mg/m2) (MTX) is reported in a young adult with metastastic gastric cancer. Weakness of the right arm, focal seizures, lethargy and confusion appeared on day 10. High signal intensity in periventricular white matter was observed on T2-weighted magnetic resonance imaging. Symptoms resolved spontaneously and completely after 48 h. We believe that this represents an unusual case of moderate-dose MTX-induced neurotoxicity in a patient with gastric cancer, which has not previously been reported.
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PMID:Subacute encephalopathy after combination chemotherapy including moderate-dose methotrexate in a patient with gastric cancer. 1032 35

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