We report an unusual cause of periodic lateralized epileptiform discharges (PLEDs) in a young man with a long history of multiple sclerosis. Two exacerbations of multiple sclerosis, 3 years apart, were complicated by complex partial status epilepticus. After each episode, serial electroencephalograms revealed PLEDs (right frontal PLEDs in the first episode and right frontotemporal and bifrontal PLEDs in the second one), which resolved within 2 weeks. With the first episode, magnetic resonance imaging revealed an enhancing white matter lesion in the right frontal area, which improved after 3 weeks. We concluded that in each instance an exacerbation of multiple sclerosis caused the seizures.