The translational asymmetry of corpus callosotomy: Two literatures that answered different questions

Corpus callosotomy is an established palliative operation for drug-resistant epilepsy dominated by drop attacks, and it is performed in three extents: anterior, usually of the anterior two-thirds; total, in one or two stages; and selective posterior, which preserves the genu and rostral body. Meta-analysis finds no difference between them in overall seizure reduction, a difference in drop attack control favoring the posterior approach, and a graded difference in disconnection syndrome, but there has never been a prospective head-to-head comparison, and the optimal extent of section remains undefined. A search of PubMed, Embase, and the Web of Science Core Collection identified 62 experimental studies in which the corpus callosum or another forebrain commissure was sectioned with an epilepsy-related outcome, spanning 1948-2026 across six species and every major seizure model. This literature is neither absent nor recent. What it has almost never done is vary the extent of section: the few studies that varied it took the laterality of kindling transfer or of interictal synchrony as the endpoint, never seizure control and never cognitive cost. No study compares the three extents against a common outcome; none models the selective posterior operation as it is defined clinically; none randomizes between extents; and none combines graded disconnection with time-locked bilateral electrophysiology, diffusion-based verification of the fibers divided, and a behavioral read-out in the same animals. The effect of section is also bidirectional: focal seizures may intensify through loss of transcallosal inhibition, and in the pentylenetetrazol model callosal section paradoxically facilitates convulsions, which limits chemoconvulsant preparations. The asymmetry between the clinical and experimental literatures is therefore one of method rather than of volume or attention: the two answered different questions, and the question the clinical field now asks requires a manipulation the experimental literature has never performed. PLAIN LANGUAGE SUMMARY: Surgeons can treat severe epilepsies by cutting the bundle of fibers that joins the two halves of the brain, but they do not agree on how much of it to cut. We searched three databases and found 62 animal studies of this operation going back to 1948. Almost none of them compared different amounts of cutting, and none looked at the newest version of the operation. Answering the surgeons' question will require a new kind of animal experiment rather than more reading of the old ones.