DEAFENING SILENCE: NOVEL ANTIEPILEPTIC TREATMENT FOR MEDICALLY REFRACTORY PARTIAL-ONSET EPILEPSY
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Epilepsy afflicts about 50 million people in the world. There are two major types ofseizures: global seizures which are characterized by seizure activity in both hemispheres of the brain at the same time and focal seizures which are characterized by seizure activity initiating in a localized portion of the brain and propagating out to larger regions. The primary treatment for epilepsy is antiepileptic drugs which either fail initially or become medically refractory in 45% of focal epilepsy cases. Unfortunately, the primary alternative is invasive neurosurgical resection that can leave patients with neurologic deficits. Therefore, there is a need for new minimally invasive treatment option. This thesis presents a new laser neurosurgical approach that significantly reduces seizure initiation and propagation. Recent studies have shown that seizures mainly propagate using layer-specific lateral connections in the cortex. Therefore, it was hypothesized that if just these connections were severed, we could block seizures while maintaining normal brain activity. Here, we demonstrate that a tightly focused, femtosecond-duration infrared laser can ablate tissue with micrometer precision and block 95% of seizure propagation while significantly reducing seizure initiation. The laser cuts only caused a minor drop in global brain blood flow that returns to baseline within days, a microscopic scar with minimal collateral damage, and has almost no effect on behavior when attempting a complex reaching task with laser cuts in the motor cortex. Ultimately, these results support future investigation into the clinical efficiency and further development of this neurosurgical technique for possible use in humans. Further, we discuss another alternative treatment strategy for epilepsy. In conjunction with Open Source Instruments, we develop a new wireless electrophysiological recording device with closed-loop optogenetic stimulation, to record and block seizures before they occur. First, we developed an electrophysiological recording device and an optogenetically stimulating device separately to test the technology before combining into one device. The devices were able to record and optogenetically stimulate behavior for 5 weeks. The fully assembled device is still in development but with the promising results thus far we are close to recording seizures, interpreting the information with the onboard computing, and optogenetically modulating the neural activity to stop the epileptiform events.
226 pagesSupplemental file(s) description: Movie S4.4, Movie S4.3, Movie S4.2, Movie S4.1.
Ablation; Epilepsy; Femtosecond infrared ablation; Focal seizure; Laser; Optogenetics
Fetcho, Joseph R.; Nowak, Linda M.; Cummings, Bethany P.
Biomedical and Biological Sciences
Ph. D., Biomedical and Biological Sciences
Doctor of Philosophy
Attribution 4.0 International
dissertation or thesis
Except where otherwise noted, this item's license is described as Attribution 4.0 International