A case is presented of a woman with a history of daily persistent head pressure and dizziness who developed a cytotoxic lesion of the splenium of the corpus callosum after an acute withdrawal of chronic acetazolamide treatment and then, in quick succession, a CSF pressure/volume drop with a lumbar puncture. This is the first documentation that rapid alterations of CSF pressure/volume may trigger cytotoxic lesions in the central nervous system.