Persistent uncrossed corticospinal connections in patients with intractable focal epilepsy

Corticospinal connections may be bilateral at birth, but a predominantly unilateral and crossed pattern develops by the toddler years. Acquired injury can alter the normal development of laterality such that uncrossed corticospinal connections persist, particularly if the injury is early in life and involves the motor system. Whether other developmental insults, such as childhood epilepsy, affect the development of crossed laterality in the motor system is unknown, although this topic has relevance for understanding the broader impact of epilepsy on brain development. Accordingly, in a cohort of children with intractable focal epilepsy, we tested by neuronavigated transcranial magnetic stimulation (nTMS) whether childhood epilepsy is associated with persistent uncrossed corticospinal connections. Specifically, we hypothesized that in contrast to early-life neuroclastic corticospinal tract injury that induces preservation of uncrossed corticospinal connections in the contralesional hemisphere, uncrossed corticospinal connections will be preserved in the epileptic hemisphere where the corticospinal tract is intact, but overstimulated by ongoing seizures and epileptic interictal discharges. Motor cortex mapping was performed by nTMS as part of a clinical presurgical evaluation, and the analysis was limited to patients with radiographically intact motor cortices and corticospinal tracts. Given that foot motor cortex representation is often bilateral, we focused on the lateralization for the tibialis anterior muscle cortical motor representation and its relation to the seizure focus. We demonstrate preserved uncrossed corticospinal connections for the tibialis anterior region of the hemisphere affected by the epilepsy. These findings indicate a pathologically preserved immature motor lateralization in patients with epilepsy and suggest that developmental processes associated with hemispheric lateralization are affected by epilepsy.