Hippocampal atrophy is now routinely detected in MRI studies of patients at the onset of seizures and during presurgical evaluation for intractable temporal lobe epilepsy (TLE). The classic lesion of hippocampal sclerosis (HS) was described in 1880 by Sommer. Subsequent postmortem and surgical pathologic studies revealed that patterns of neuronal loss in TLE are considerably more diverse than the “classic” lesion, are frequently bilateral, are sometimes limited to the hilus of the dentate gyrus without prominent loss in CA1 (endfolium sclerosis), and may involve all hippocampal subfields.1 Neuronal loss in the epileptic hippocampus is accompanied by sprouting and reorganization of surviving synaptic connections, essentially rewiring hippocampal circuits.2–4 As surgical resection of the sclerotic rewired hippocampus and temporal lobe is frequently curative in cases with unilateral alterations, it has been presumed that more extensive bilateral hippocampal circuit rewiring may contribute to seizure susceptibility and influence prognosis. In this issue of Neurology ®, a postmortem study by Thom et al.5 revealed that synaptic reorganization is frequently bilateral and appears to be a long-term, essentially permanent hippocampal …