Introduction Status epilepticus (SE) can result in irreversible brain injury. Brain MRI may provide some insights into the pathophysiological processes of brain injury implicated in SE. Corpus callosum is the important propagation pathway of ictal activity in SE. We describe the possible mechanism of the hemispheric brain injury following refractory SE. Case 18 months old young infant with known epilepsy, agenesis of corpus callosum, and partial trisomy 8q and partial monosomy 13q was admitted due to refractory SE. Barbiturate coma therapy with continuous midazolam infusion (20 ug/kg/min) terminated SE. At the time of cessation of SE, the patient had left hemispheric interictal spikes consistent with periodic lateralized epileptiform discharges ( PLEDs). After cessation of the SE, right hemiparesis was noted. Brain MRI taken 8 days after SE revealed diffuse swelling and diffusion restriction confined to the cerebral hemisphere, basal ganglia, thalamus, and midbrain on the left. Brain MRA did not revealed the evidence of cerebrovascular disorders. Serial brain MRIs showed gradual resolution of hemispheric swelling with resultant progressive hemispheric atrophy and ventricular enlargement. Two months later, patient still had moderate degree of hemiplegia. Conclusion This case illustrates irreversible one hemispheric brain injury following refractory SE in a patient with known epilepsy and agenesis of corpus callosum. We suggest that MRI changes are restricted to one cerebral hemisphere because the agenesis of corpus callosum limit the spread of ictal activity to the contralateral hemisphere. We also support the termination of PLEDs as an ideal treatment goal of refractory SE in order to avoid irreversible brain damage.