Authors :
Presenting Author: Daniela Maltais, BS – Mayo Clinic
Filip Mivalt, PhD – Mayo Clinic Rochester
Inyong Kim, Ph.D. – Mayo Clinic Rochester
Patrik Began, MS – Mayo Clinic
Jiwon Kim, BS – Mayo Clinic
Andre Duque Lopez, MD – Mayo Clinic
Veronika Krakorova, BS – Mayo Clinic
Nicholas Gregg, MD – Mayo clinic, Rochester, Minnesota
Daniel Montonye, D.V.M – Mayo Clinic
Chris Gow, D.V.M – Mayo Clinic
Kai Miller, MD, PhD – Mayo Clinic
Jamie J Van Gompel, MD – Mayo Clinic, Rochester MN, USA.
Doug Sheffield, VMD, PhD – Cadence Neuroscience Inc
Kent Leyde, MS – Cadence Neuroscience Inc
Vaclav Kremen, PhD – Mayo Clinic
Su-youne Chang, PhD – Mayo Clinic
Gregory Worrel, MD,PhD – Mayo Clinics
Rationale:
Mesial temporal lobe epilepsy (mTLE) is the most common type of drug-resistant focal epilepsy and is associated with mood, memory and sleep comorbidities. Deep brain stimulation (DBS) is an established therapy, but optimization is slow and infrequently results in long-term seizure freedom. Sleep impairments are common in people with epilepsy and can be exacerbated by DBS, possibly contributing to worse seizure control and comorbidities. Understanding the interplay between epilepsy, sleep, and DBS is clinically important.
We developed a kainic acid (KA)-induced porcine model of mTLE. Pigs are a convenient model to test next-generation implantable neural stimulation and recording (INSR) systems designed to optimize network targets and stimulation paradigms for humans. This model reproduced key pathological features of human mTLE, providing a preclinical platform for advancing and validating devices for classifying and monitoring seizures, interictal epileptiform spikes (IES), and behavior across sleep and wake states.
Methods:
Four lead constructs were placed targeting bilateral hippocampus (HPC) and anterior nucleus of thalamus (ANT) in 7 domestic pigs, under MRI stereotactic guidance. Intraoperative local field potentials (LFP) recordings before, during, and after KA injection to confirm status epilepticus. Electrode leads were connected to a 16-channel INSR device designed for humans after status epilepticus. Freely behaving pigs were chronically monitored by both 24/7 video and LFP INSR recordings, and data were evaluated with automated seizure, IES, and sleep-wake classifiers. Neuropathology was evaluated with Cresyl violet staining.
Results:
Intra-hippocampal KA infusion induced acute status epilepticus in all pigs, followed by key electrophysiological features of mTLE in the long-term INSR monitoring, including IES (7/7 pigs), and spontaneous seizures (5/7 pigs) with a range of semiologies (focal and generalized tonic-clonic convulsive seizures, and myoclonic jerks). HPC theta (4 – 8 Hz) power was higher during running and rapid eye movement (REM) sleep, compared to wakefulness. Non-REM sleep was characterized by increased delta (1 – 4 Hz) power, sleep spindles and K-complexes in cortical regions. HPC had strong LFP theta oscillations (4.53 ± 0.22 Hz) during wakefulness and REM sleep periods. Average NREM Stage 3 duration was 11.63 ± 2.25 minutes. IES rate/minute are increased during NREM sleep compared to REM and wakefulness (26.53 ± 19.99, 3.49 ± 4.82, 0.30 ± 0.39, p < 0.005).