Abstracts

Rationale: Seizures are seen in 8-13% of the children with ALL. In the great majority of the cases, they suffer of acute symptomatic seizures occuring during the induction and consolidation phases of the therapy. More rarely, patients develop a chronic seizure disorder. We describe four adult patients treated during childhood for ALL who later developed drug-resistant refractory epilepsies. Methods: This is a retrospective study of four patients with severe epilepsy refered to the outpatient clinic of the Montreal Neurological Hospital between 1996 and 2012. Patients' epilepsy history and clinical and laboratory features were reviewed and compared to similar cases described in the literature. Results: The four patients (all females; mean age, 25.7 yrs) were diagnosed with ALL before age 5 (range, 18mo to 4.5yr). They received standard chemotherapy protocols including intrathecal methotrexate in all, and two also received prophylatic whole-brain radiation. None of the patients experienced CNS complications including acute symptomatic seizures during induction or consolidation therapy, nor they developed leukemic CNS infiltration. There was no family history for seizures and, except for the hematological disease, personal antecedants were negative. One patient, who received whole-brain radiation, developed a drug-resistant temporal lobe epilepsy 8 years after the cessation of the ALL treatment, due to a left temporal lobe cavernous angioma. She became seizure-free after the lesion was removed. A second patient developed a severe epileptic disorder 6 years after the chemotherapy ended with EEG showing bilateral, diffuse or multifocal epileptic discharges. Brain MR and CT were normal. The two remaining patients presented with an intractable generalized epilepsy and clinical and EEG features of Lennox-Gastaut Syndrome, one starting at the end of a 3-yr maintenance therapy and the other 4 years after therapy (received prophylactic whole-brain radiation). They both had multiple calcifications on imaging studies (CT and MR) consistent with mineralizing microangiopathy. In these 3 patients, the seizures remained severe in spite of different antiepileptic drug polytherapies (n=3), VNS (n=2) and anterior callosotomy (n=1). The four patients developed cognitive decline preceding or following the epilepsy. Conclusions: Remote intractable seizures are a rare complication of pediatric ALL In many instances, chronic seizures are delayed sequelae resulting from a focal CNS damage (explained either by the disease or the treatment), leading to focal epilepsy. In other cases, seizures appear to result from a diffuse brain insult due to leukemic treatment given during a crucial phase of brain development, and leading to catastrophic multifocal or generalized epilepsy. Factors contributing to the appearance of such secondary severe generalized or diffuse seizure disorders are still unclear.