Prognosis and Treatment of eizures in Children with Acute Lymphoblastic Leukemia

Abstract

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.

Temporal Lobe Epilepsy With Hippocampal Sclerosis in Acute Lymphoblastic Leukemia

“…Such events are triggered by acute treatment toxicity, which might be related to chemotherapeutic neurotoxicity, cranial radiation, metabolic complications, cerebral hemorrhage, CNS infection, cerebral vascular disorders, and leukemic infiltration. 2,3 Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is characterized by intractable epilepsy with complex partial seizures (CPSs) of temporal origin and temporal sclerosis and represents the final common pathway of several processes. 4 Early detection of MTLE-HS is important, because these children are likely candidates for brain surgery and have an excellent chance of a subsequent normal life.…”

Neurologic complications of chemotherapy for children with cancer

“…It is commonly used to treat many pediatric cancers, including ALL, lymphoma, and bone or soft tissue sarcomas. A pediatric ALL study incorporated a retrospective review of 127 children and demonstrated a 13% incidence rate (n=17) of seizures in this population [6]. Sixteen of these patients experienced seizures after receiving intrathecal methotrexate or subcutaneous L-asparaginase.…”

The Antiepileptic Drugs Phenobarbital and Carbamazepine Reduce Transport of Methotrexate in Rat Choroid Plexus by Down-Regulation of the Reduced Folate Carrier

“…We have demonstrated that hepatocellular Rfc1-mediated MTX influx is significantly reduced after treatment with a clinically relevant concentration of the antiepileptic drug (AED) PB or CBZ as a result of post-transcriptional down-regulation of the carrier protein (Halwachs et al, 2007). In childhood ALL, seizures represent a frequent clinical manifestation of MTX neurotoxicity particularly related to intrathecal MTX (Maytal et al, 1995). Besides, seizures due to metabolic disorders, cerebral infarction, or CNS infection have been observed (Maytal et al, 1995).…”

“…In childhood ALL, seizures represent a frequent clinical manifestation of MTX neurotoxicity particularly related to intrathecal MTX (Maytal et al, 1995). Besides, seizures due to metabolic disorders, cerebral infarction, or CNS infection have been observed (Maytal et al, 1995). As in these patients, comedication with AEDs is regularly required (Tibussek et al, 2006), we examined the contribution of Rfc1 to MTX transport at the blood-CSF barrier and investigated the effect of AEDs on Rfc1 uptake activity on the functional, transcriptional, and posttranscriptional level using the rat CP-like in vitro model Z310 (Zheng and Zhao, 2002;Shi et al, 2008).…”