Risk factors for early-onset seizures in acute ischemic stroke include anterior circulation stroke, infarction of the cerebral cortex, large infarct size, and ischemic-to-hemorrhagic transformation. We define stroke-onset seizures as seizures occurring within 2 hours of stroke onset. A 64-year-old woman presented with top of the basilar artery syndrome-thalamic infarction occurred first and midbrain infarction 12 days later. She manifested stroke-onset seizures during midbrain infarction, which was heralded by stupor. Within 2 hours of the onset of stupor, she had a clonic seizure of the lower extremities, electroencephalography (EEG) revealed nonconvulsive status epilepticus, and an episode of convulsive movements of all extremities was recorded on video and on EEG. Continuous EEG recording showed epileptiform discharges that would appear, disappear, and reappear over a 3-week period. It took 3 weeks and 4 antiepileptic drugs to fully suppress cortical hyperexcitability, perhaps because injury to some midbrain structures resulted in global lowering of the seizure threshold. The most important risk factor for stroke-onset seizures appears to be posterior circulation stroke, particularly brainstem infarction. The difference in risk profile between stroke-onset seizures and other forms of early-onset seizures suggest that their pathophysiology is not exactly the same. Focusing some of the research spotlight on stroke-onset seizures can help us better understand their unique clinical, electrographic, radiologic, and pathophysiologic features.