Leaving tissue associated with infrequent intracranial EEG seizure onsets is compatible with post-operative seizure freedom.

Identify seizure onset electrodes that need to be resected for seizure freedom in children undergoing intracranial electroencephalography recording for treatment of medically refractory epilepsy. All children undergoing intracranial electroencephalography subdural grid electrode placement at the Children's Hospital of Philadelphia from 2002-2008 were asked to enroll. We utilized intraoperative pictures to determine the location of the electrodes and define the resection cavity. A total of 15 patients had surgical fields that allowed for complete identification of the electrodes over the area of resection. Eight of 15 patients were seizure free after a follow up of 1.7 to 8 yr. Only one seizure-free patient had complete resection of all seizure onset associated tissue. Seizure free patients had resection of 64.1% of the seizure onset electrode associated tissue, compared to 35.2% in the not seizure free patients (p=0.05). Resection of tissue associated with infrequent seizure onsets did not appear to be important for seizure freedom. Resecting ≥ 90% of the electrodes from the predominant seizure contacts predicted post-operative seizure freedom (p=0.007). The best predictor of seizure freedom was resecting ≥ 90% of tissue involved in majority of a patient's seizures. Resection of tissue under infrequent seizure onset electrodes was not necessary for seizure freedom.

Promotion of proliferation in the developing cerebral cortex by EphA4 forward signaling.

Eph receptors are widely expressed during cerebral cortical development, yet a role for Eph signaling in the generation of cells during corticogenesis has not been shown. Cortical progenitor cells selectively express one receptor, EphA4, and reducing EphA4 signaling in cultured progenitors suppressed proliferation, decreasing cell number. In vivo, EphA4(-/-) cortex had a reduced area, fewer cells and less cell division compared with control cortex. To understand the effects of EphA4 signaling in corticogenesis, EphA4-mediated signaling was selectively depressed or elevated in cortical progenitors in vivo. Compared with control cells, cells with reduced EphA4 signaling were rare and mitotically inactive. Conversely, overexpression of EphA4 maintained cells in their progenitor states at the expense of subsequent maturation, enlarging the progenitor pool. These results support a role for EphA4 in the autonomous promotion of cell proliferation during corticogenesis. Although most ephrins were undetectable in cortical progenitors, ephrin B1 was highly expressed. Our analyses demonstrate that EphA4 and ephrin B1 bind to each other, thereby initiating signaling. Furthermore, overexpression of ephrin B1 stimulated cell division of neighboring cells, supporting the hypothesis that ephrin B1-initiated forward signaling of EphA4 promotes cortical cell division.