Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy

In partial onset epilepsy, seizures arise focally in the brain and often propagate. Patients frequently become refractory to medical management, leaving neurosurgery, which can cause neurologic deficits, as a primary treatment. In the cortex, focal seizures spread through horizontal connections in layers II/III, suggesting that severing these connections can block seizures while preserving function. Focal neocortical epilepsy is induced in mice, sub-surface cuts are created surrounding the seizure focus using tightly-focused femtosecond laser pulses, and electrophysiological recordings are acquired at multiple locations for 3-12 months. Cuts reduced seizure frequency in most animals by 87%, and only 5% of remaining seizures propagated to the distant electrodes, compared to 80% in control animals. These cuts produced a modest decrease in cortical blood flow that recovered and left a approximate to 20-mu m wide scar with minimal collateral damage. When placed over the motor cortex, cuts do not cause notable deficits in a skilled reaching task, suggesting they hold promise as a novel neurosurgical approach for intractable focal cortical epilepsy. Blocking the spread of epileptic seizures in the brain can provide symptomatic relief for patients. Tightly-focused infrared femtosecond laser pulses can produce micrometer-sized cuts deep inside tissue. In an in vivo mouse model of focal epilepsy, these cuts are used to isolate the seizure-prone cortex by severing connections in cortical layers II-IV, without injuring the overlying tissue and blood vessels, leading to dramatic reductions in seizure propagation. image