EpiZode: Noninvasive Seizure Screening in Preclinical Models of Epilepsy There is an urgent need for research into treatment options for epilepsy and other seizure disorders. Animal models are increasingly used to understand disease mechanisms and to screen promising therapeutic approaches. Animal epilepsy model use typically requires expensive and labor-intensive experimentation, with invasive EEG measurements being the preferred method of validation. This severely limits the pace and scale of investigation. In models of acquired epilepsy, animals usually undergo treatment to induce status epilepticus? a period of unremitting seizure?followed by a latent period during which the brain rewires itself to generate spontaneously recurring seizures, the hallmark of chronic epilepsy. The duration of the latent period and the likelihood that an animal will develop epilepsy are both uncertain. Animals must be observed for weeks to confirm epilepsy before they are ready for experimentation. During this latent period, seizures are commonly documented by visual observation or video review, which are tedious and prone to error. A commercial system for automated noninvasive seizure detection would therefore be invaluable to epilepsy researchers. Signal Solutions, LLC, has developed piezoelectric sensor technologies for noninvasive, high-throughput behavioral monitoring in rodents. This is being used by sleep/circadian researchers around the world, and discriminates sleep from wakefulness with >90% accuracy. The Sunderam Lab at the University of Kentucky has further demonstrated that these piezo sensors can distinguish REM and NREM stages of sleep in mice. To address the needs of epilepsy researchers, we performed a Phase I STTR study to: 1. Test the feasibility of epilepsy onset detection in rodents using noninvasive piezo film sensors; 2. Validate piezo detections against simultaneous EEG recordings in rodents with epilepsy; and 3. Test the feasibility of using smaller profile piezo sensors and an infrared imager for seizure screening and verification. The study successfully confirmed the feasibility of these aims. In this Phase II STTR proposal, we will further develop methods for accurate noninvasive seizure screening in rodent models through the following objectives: 1. Develop algorithms for detection of both overt and subtle seizures using small form factor piezo sensors; 2. Send a prototype system out for beta testing on different animal models and refine the system based on feedback; 3. Develop and validate novel sensor configurations algorithms for accurate seizure detection and attribution in group-housed epileptic animals. The envisioned product is a turnkey system for convenient noninvasive seizure screening in small animal models of epilepsy in custom or commercial cages that minimizes the need for invasive and resource-intensive EEG analysis. Potential customers include academic research labs as well as labs in the pharmaceutical sector engaged in high-volume screening of antiepileptic drugs.
The development of drugs and other treatments for epilepsy depends heavily on laboratory animal studies in which their effect on seizures is measured. Seizures are rare and unpredictable, and monitoring animals for seizures in person or from video recordings is tedious; the alternative is to record brain signals, which requires invasive and expensive recordings using electrodes. A new noninvasive technology is proposed for detecting seizures in lab animals used for epilepsy research.
