Temporal Lobe Epilepsy With Hippocampal Sclerosis in Acute Lymphoblastic Leukemia

Abstract

Of 71 acute lymphoblastic leukemia survivors at our hospital over the past 10 years, 2 children developed mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). This is the first report to describe the clinical course of MTLE-HS observed longitudinally by EEG and MRI. Patient 1 experienced a seizure during chemotherapy involving intrathecal methotrexate. Postseizure MRI suggested methotrexate encephalopathy or leukemic invasion. Anticonvulsant therapy was initiated; subsequent EEGs and MRIs revealed normal results. Three years after chemotherapy, a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. Five years after chemotherapy, the patient developed MTLE-HS comprising complex partial seizures, typical temporal spikes on EEG, and hippocampal sclerosis (HS). Patient 2 did not experience seizures during chemotherapy. Four years later, the patient started experiencing complex partial seizures, and a diffuse, irregular spike-and-wave pattern was observed on interictal EEG. A clinical picture of MTLE-HS developed 2 years later. In both patients, nonspecific EEG abnormalities (ie, diffuse, irregular spike-and-wave activity) preceded the appearance of HS on MRI by 2 years, suggesting an insidious advance of HS during the latent period. Such atypical EEG findings may indicate MTLE-HS during follow-up of leukemia patients. MTLE-HS develops several years after an initial precipitating incident such as prolonged seizures, central nervous system infection, and brain trauma. In our cases, the initial precipitating incident may have been chemotherapy and/or prolonged seizures. Thus, MTLE-HS associated with leukemia may not be as rare as generally believed. A large cohort study of late neurologic complications is warranted. Pediatrics 2013;132:e252-e256

Drug resistant epilepsy with mesial temporal sclerosis as possible late neurological complication in two AML survivors after stem cell transplantation

“…Similar speculation for postulation was also described by Fasano et al in 2008 [1] and Yoshida et al in 2013 [7] . Yet there is no data available regarding the association of dose of intrathecal medication use and seizure activity.…”

“…Table C.1 summarises the demographics, diagnosis, use of intrathecal chemotherapy and application of cranial irradiation in the patients. Table C.2 summarises the features of epilepsy including seizure types, use of anti-seizure medications and neurological outcomes [2] , [3] , [4] , [5] , [6] , [7] .…”

MR imaging findings in some rare neurological complications of paediatric cancer

“…Hippocampal sclerosis is a neuropathological condition with severe neuronal cell loss and gliosis in the hippocampus, specifically in the cornu ammonias area 1 and subiculum of the hippocampus. Although hippocampal sclerosis is generally associated with biphasic seizures of the infantile period, cerebritis, head trauma and perinatal brain injury, there are also some reports of hippocampal sclerosis in patients with haematological malignancy [ 40 ]. Various factors are thought to underlie the sclerosis seen in haematological malignancies, such as neurotoxicity due to methotrexate or cyclosporine, radiation exposure and bone marrow transplantation.…”

Mer tyrosine kinase promotes the survival of t(1;19)-positive acute lymphoblastic leukemia (ALL) in the central nervous system (CNS)

“…Current CNS-targeted therapy is highly unspecific and can have side effects such as seizures, leukoencephalopathy, and late neurodevelopmental sequelae. [16][17][18] These reasons make evident that diagnostic and prognostic markers predicting CNS disease are needed. Furthermore, targeted therapies in the CNS niche are important for further optimization of ALL therapy.…”