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We present a case of a woman who reported to the emergency unit due to recurrent episodes of severe headache and collapse. MRI examination revealed no relevant findings apart from small meningioma of the right parietal region. The patient was diagnosed with epilepsy and received outpatient treatment, which was changed due to poor toleration. A follow-up MRI was performed which revealed an isolated, focal lesion of the splenium of the corpus callosum. The patient underwent extensive laboratory testing and antiseizure medications were started again. Another MRI indicated substantial regression of the splenium of the corpus callosum (SCC) lesion. Both the complete clinical image and results of the diagnostic evaluation spoke in favor of cytotoxicity of the corpus callosum associated with anti-epileptic drug treatment. Pathologies involving the corpus callosum include congenital, demyelination, infection, neoplasm, trauma and vascular changes. Isolated, non-specific lesions of the splenium of corpus callosum usually indicate multiple sclerosis; however, other pathologies should be considered. Anti-epileptic drugs may evoke cytotoxic lesions of the corpus callosum (CLOCCs). [ABSTRACT FROM AUTHOR]