Abstracts

Rationale: For many patients, focally initiated cortical epilepsy is largely intractable, leaving surgical treatment as a last option. Resection of the seizure focus will stop seizures but frequently leads to other neurological deficits such as stroke. A less invasive technique, multiple subpial transections (MST), uses a mechanical hook to produce a series of incisions in the epileptic tissue, with the goal of disrupting neural connections that facilitate seizure propagation. This procedure is performed manually and, as a result, cuts are difficult to control and can often lead to collateral damage. A more controlled and reliable solution to preventing seizure propagation is desired in order to surgically treat focal epilepsy with few undesired consequences. The development of femtosecond laser technology allows for extremely precise and localized cuts below the cortical surface, all while producing minimal collateral damage. We propose the use of femtosecond laser pulses as a light scalpel to produce incisions around the epileptic focus and stop seizure propagation. Methods: We use a rat model of focal epilepsy in which 4-aminopyridine (4- AP), a seizure-inducing drug, is locally injected into the cortical tissue. First, femtosecond laser pulses are tightly focused into the brain to produce multiple 750 by 750 μm box cuts at depths ranging from 200 μm to 800 μm below the brain surface. Through a glass micropipette, 4-AP is injected within the box of cuts to induce seizures and record local field potential (LFP), while another distant electrode is implanted outside the box to record LFP. If the laser cuts are effective, we expect seizure activity to be contained to the focal region within the cuts and not propagate outwards to the distant electrode. Results: In sham experiments where no box cuts were made, seizures were seen to propagate to the distant electrode 100% of the time (n = 2 rats; 18 seizures). When box cuts were produced, the number of seizures seen to propagate was significantly reduced, with approximately 54% of seizures reaching the distant electrode (n = 13 rats; 90 seizures; p < 0.0005). Additionally, in those seizures that continued to propagate after cuts, we observed a significant delay in arrival of seizure activity at the distant electrode. For sham experiments, mean seizure delay was found to be 0.3390 ± 0.0875 seconds (n = 15 seizures). Cuts increased the mean delay of seizure onset at the distant electrode to 9.505 ± 1.985 seconds (n = 49 seizures; p < 0.02). This indicates that cuts that did not completely block seizure propagation were still able to delay the spread of activity beyond the focus. Conclusions: This work provides evidence that femtosecond laser incisions are capable of blocking seizure propagation beyond a focal region. Preliminary evidence also suggests that these cuts do not disrupt normal neural functionality. While much work remains, these results provide strong initial support for the potential of femtosecond laser incisions as a precise and controlled therapy for partial epilepsy.