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Circumscribing Laser Cuts Attenuate Seizure Propagation in a Mouse Model of Focal Epilepsy
Seth Lieberman1,2, Daniel A Rivera1, Ryan Morton1
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853, USA.
Abstract:
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 ≈20-µm 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.
Insights
This study demonstrates a novel neurosurgical technique for epilepsy. Precisely targeted laser cuts effectively reduced seizure frequency and propagation in mice, offering a promising new treatment for intractable focal cortical epilepsy.
Area of Science:
- Neuroscience
- Neurosurgery
- Epilepsy Research
Background:
- Partial onset epilepsy originates focally and can become medically refractory.
- Neurosurgery is an option but may cause neurological deficits.
- Seizures spread via horizontal connections in cortical layers II/III.
Purpose of the Study:
- To investigate the efficacy of targeted sub-surface cuts in blocking seizure propagation.
- To assess the safety and functional impact of this novel neurosurgical approach.
Main Methods:
- Focal neocortical epilepsy was induced in a mouse model.
- Sub-surface cuts were created around seizure foci using femtosecond laser pulses.
- Electrophysiological recordings monitored seizure activity and propagation over 3-12 months.
Main Results:
- Cuts reduced seizure frequency by 87% in most animals.
- Seizure propagation to distant electrodes decreased significantly (5% vs. 80% in controls).
- Minimal collateral damage, a small scar, and temporary cortical blood flow reduction were observed.
Conclusions:
- Targeted laser cuts effectively inhibit seizure spread in a mouse model of focal cortical epilepsy.
- This technique shows promise for preserving function while treating intractable epilepsy.
- Further research may lead to a novel, minimally invasive neurosurgical treatment.
