By Kimberly Pargeon, MD
Assistant Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Pargeon reports no financial relationships relevant to this field of study.
SYNOPSIS: The authors report the preliminary findings for an implantable ambulatory intracranial recording device for seizure detection in 15 subjects. One of the primary findings was that spike rate significantly changed prior to seizures in nine of 15 subjects. Six of these subjects showed a significant decrease in spiking prior to ictal onset, whereas the remaining three showed a significant increase in spiking and these three subjects had the best seizure prediction results.
SOURCE: Karoly PJ, Freestone DR, Boston R, et al. Interictal spikes and epileptic seizures: Their relationship and underlying rhythmicity. Brain 2016;139:1066-1078.
With the growing concern for sudden unexpected death in epilepsy patients (SUDEP) and other comorbidities associated with intractable epilepsy, one of the latest trends in epilepsy research is seizure prediction and detection. With it, there has been a proliferation of so-called seizure detection devices, particularly ones that can be worn or used at home. Many of these devices focus on physiological changes, such heart rate changes, electrical activity in muscle, and galvanic skin resistance changes.1 Since many at risk for SUDEP have nocturnal seizures, pressure mats, as well as video and infrared devices, have been used. So-called seizure alert dogs also have been reported, although data are mixed. More recently, there have been collaborations with many companies for “wearable” devices, such as watches.2 The concern for many of these devices is that there may be some false positives and that not all of the detected events require evaluation or treatment.
The present study focuses on an implantable intracranial device for spike and seizure detection, which is not commercially available in the United States. Seattle-based NeuroVista makes the device, which is being tested clinically in Australia. The device is composed of two intracranial leads implanted subdurally and unilaterally in the seizure onset zone based on scalp electroencephalogram .3 These are connected to a telemetry unit placed subcutaneously under the clavicle. The telemetry unit sends data via a wireless signal to a handheld device, which can produce signals, either audio or visual, to indicate whether the patient has a low, medium, or high likelihood of having a seizure.
For the initial study, 15 patients with medically refractory partial epilepsy, having two to 12 partial seizures per month, were enrolled and implanted from three centers in Melbourne, Australia, from March 2010 to June 2011.3 During the data collection phase, spikes were identified using a complicated algorithm for automated spike detection, which erred of the side of over-detection, and were validated with expert review of randomly selected one-hour segments. Seizures were identified using a previously validated automated seizure detection algorithm, subjects’ seizure diaries, and device audio recordings, all of which were then verified by expert investigators.
One of the primary findings was that nine of 15 subjects showed a significant change in spike rate prior to seizures, suggesting a relationship between spiking and seizure activity. However, for three of these patients, the spike rate increased, and for the remaining six, the spike rate decreased. The three patients who had the increased spike rate also had the best seizure prediction results. In addition, subjects with high rates of seizures did not necessarily demonstrate high rates of interictal spiking. Thus, the authors could not conclude that spikes directly promoted or inhibited seizure activity, but suggested that seizures and spikes likely share some common regulatory mechanisms. This was further supported by another key finding, which suggested common circadian variations affecting both spikes and seizures, particularly related to sleep for many patients. Other cyclic patterns were noted and, interestingly, the only subject to show a monthly cycle for spike rate was male, while four of the female subjects showed peaks at intervals of less than a month, usually between 1 to 3 weeks. In general, the relationship between spikes and seizures appeared to be subject-specific.
COMMENTARY
Although the authors have produced some promising initial results, use of this device for seizure detection and prediction may be limited for several reasons. First, in reviewing the original paper by Cook et al, all patients had a refractory partial onset epilepsy with a localized epileptic onset zone,1 whereas many patients at risk for SUDEP have poorly controlled convulsive seizures, which can be from either from partial or generalized epilepsies. Second, this device, which is not approved in the United States, is invasive, costly, and requires implantation of electrodes in the epileptic onset zone, which needs to be clearly localized. Thus, in a patient with poorly localized or lateralized epilepsy, it may be of limited usefulness. The authors also report that the relationship between spikes and seizures was subject-specific, so the spiking pattern prior to seizures would need to be individually determined to improve seizure prediction and would vary across individual patients. In fact, the limited data from this study suggest that those with increased spiking prior to seizures may be the most ideal candidates for implantation of this device as a seizure detector.
REFERENCES
- Jory C, Shankar R, Coker D, et al. Safe and sound? A systematic literature review of seizure detection methods for personal use. Seizure 2016;36:4-15.
- van Andel J, Thijs RD, de Weerd A, et al. Non-EEG based ambulatory seizure detection designed for home use: What is available and how will it influence epilepsy care? Epilepsy Behav 2016;57:82-89.
- Cook MJ, O’Brien TL, Berkovic SF, et al. Prediction of seizure likelihood with a long-term, implanted seizure advisory system in patients with drug-resistant epilepsy: A first-in-man study. Lancet Neurol 2013;12:563-571.
The authors report the preliminary findings for an implantable ambulatory intracranial recording device for seizure detection in 15 subjects. One of the primary findings was that spike rate significantly changed prior to seizures in nine of 15 subjects. Six of these subjects showed a significant decrease in spiking prior to ictal onset, whereas the remaining three showed a significant increase in spiking and these three subjects had the best seizure prediction results.
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