Cytotoxic lesions of the corpus callosum related to epilepsy or anti-seizure medications: a systematic review

Background: Cytotoxic lesions of the corpus callosum (CLOCCs) are unusual MRI findings in epilepsy patients, often related to sudden anti-seizure medication (ASM) discontinuation or seizures. We reviewed the data of patients with epilepsy and/or under ASMs who developed CLOCCs, defining their clinical course focusing on therapies and intercurrent seizures. Methods: A systematic review was performed including articles reporting on adult and pediatric patients who developed a CLOCC following ASMs modification and/or related to epilepsy. Results: 80 patients from 45 studies were included (44 females), 19 (24%) pediatric patients and 61 (76%) adults. 86% lesions were classified as Starkey A. CLOCCs were related to ASM withdrawal in 27 (34%) patients, seizure activity in 23 (29%), seizure activity with concomitant ASM variation in 18 (23%), ASM initiation in 5 (6%), ASM switch in 3 (4%) cases. The most frequent ASMs used in the sample were carbamazepine (30), phenytoin (14) and lamotrigine (13) however, non-sodium-channel blockers, e.g., levetiracetam (9) and valproate (8) were reported. CLOCCS regressed in a median time of 15 days (interquartile range [IQR]=14-25) in pediatric patients and 42 days (IQR=28-120) in adults (p<0.01). Conclusion: CLOCCS are associated to sudden ASM modification or seizures. Regression time may vary widely and seems to be faster in children; moreover, non-sodium channel blockers are an increasingly recognized association.