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

Seizure. 2025 Dec:133:261-267. doi: 10.1016/j.seizure.2025.11.008. Epub 2025 Nov 6.

Abstract

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.

Keywords: Anti-seizure medications (ASMs); Cytotoxic lesions of the corpus callosum (CLOCCs); Epilepsy; Treatment discontinuation.

Publication types

  • Systematic Review

MeSH terms

  • Anticonvulsants* / adverse effects
  • Anticonvulsants* / therapeutic use
  • Corpus Callosum* / diagnostic imaging
  • Corpus Callosum* / drug effects
  • Corpus Callosum* / pathology
  • Epilepsy* / diagnostic imaging
  • Epilepsy* / drug therapy
  • Female
  • Humans
  • Magnetic Resonance Imaging

Substances

  • Anticonvulsants