Abstracts

Rationale: Focal cortical epilepsy can be treated effectively with surgical removal of the epileptic focus but if the focus lies within or adjacent to important brain tissue neurologic deficits can occur. A less invasive surgical technique that reduces seizures with minimal damage to brain tissue is needed. Tightly-focused, femtosecond infrared laser pulses provide can produce precise cuts only micrometers in diameter to selective layers of the neocortex. Methods: We use femtosecond laser (Chinhook Ti:Sapphire Laser, 50-fs pulses; 800-nm wavelength; 1-kHz repetition rate; pulse energies up to 0.5 mJ) to produce sub-surface cortical incisions selectively to supragranular layers surrounding an epileptic focus in an acute 4-aminopyridine (4-AP, 0.5 µl ) rat seizure model. Results: Compared with sham animals in which ictal events occurred in all animals, femtosecond laser microtransection completely blocked all seizures in 20% of animals and ictal propagation in another 15%. In the remaining animals, seizure frequency was reduced by 2/3 and seizure propagation reduced by 1/3.  In those seizures that still propagated, it was delayed and reduced in amplitude. When the recording electrode was inside the partially isolated cube and the focus was on the outside, the results were even more striking.  Somatosensory responses were maintained but with reduced amplitude. Conclusions: Our data shows that just a single enclosing wall of laser cuts limited to supragranular layers led to a marked reduction in seizure initiation and propagation with preserved cortical function. Modifications of this concept may be a useful treatment for human epilepsy. Funding: Supported by: the AES seed grant (T.H.S), the NINDS R21 NS078644-01A1 (C.B.S&T.H.S), the Clinical and Translational Science Center (CTSC) Grant UL1 RR 024996 Pilot Grant (M.Z.&C.B.S), the Cornell University Ithaca-WCMC seed grant (M.Z.&C.B.S), and the Daedalus Fund for Innovation (T.H.S, C.B.S & M.Z).