Rationale:
The control of seizures achieved by neurostimulation may be improved by 1) characterization and targeting of patient specific circadian and multiday rhythms of seizure risk, in other words when to stimulate, and 2) efficient screening and identification of optimal stimulation parameters, or how to stimulate. A new generation of implantable devices, with sensing, stimulation and continuous iEEG telemetry may address these issues. We report on iEEG biomarkers from a patient implanted with a next generation system with bilateral anterior thalamic nuclei (ANT) stimulation and continuous iEEG recordings from the hippocampi (Hc) and ANT.
Method:
Ms. A is a 59-year-old woman with bilateral temporal lobe epilepsy, status post implantation of the investigational Medtronic RC+S system (rechargeable implantable neural sense & stimulation device with 4 independent 4 contact leads). RC+S provides electrical stimulation to 16 contacts and continuous sensing and iEEG telemetry from 4 dynamically selectable channel pairs. Ms. A has had ANT stimulation and continuous full bandwidth Hc iEEG recording since November, 2019. She has been treated with multiple stimulation parameters, including low (7 Hz) and high frequency (145 Hz) ANT stimulation. Response to stimulation was gauged by iEEG biomarkers including seizure and interictal epileptiform discharges (IED) rates. Circadian and multiday IED rhythms were measured with causal and non-causal finite impulse response (FIR) filters, and a causal moving average filter—frequency, phase, and amplitude data were assessed with the Hilbert transform analytic signal. Circular statistics measured the phase preference of seizures relative to IED rhythms.
Results:
Ms. A had circadian and multiday (approximately 11-day) oscillations in IED rates at baseline (no or low stimulation); seizure occurrences had a phase preference for circadian (Rayleigh test P-value=2.5x10-5; non-causal FIR) and 11-day (P< 1x10-5) rhythms (Fig. 1). Seizures had lesser but statistically significant phase preference for circadian and multiday IED oscillations using both causal filters. There was an abrupt reduction in IEDs for stim intensity 5V with associated dissipation of circadian and multiday oscillation power compared to baseline (P< 1x10-5), and no such change was seen 4V (Fig. 1) (pulse width 200 msec). There was a non-significant reduction in seizure rate for the relatively short duration stim was 5V.
Conclusion:
Chronic ANT DBS and continuous Hc iEEG recordings from a patient with temporal lobe epilepsy indicates that ANT DBS can modulate circadian and multiday patterns of seizure risk. An apparent stimulation threshold effect was seen with reduction in IEDs for stimulation 5V that was not seen with amplitudes 4V. Long-term follow-up in a larger cohort of subjects is needed to assess the broader applicability of this finding. A new generation of implanted sense and stim devices that identify ictal and interictal iEEG biomarkers may accelerate screening and identification of optimal stim parameters, enable chronotherapy, and transform neurostimulation therapy for patients with epilepsy.
Funding:
:AES Research & Training Fellowship for Clinicians; R01-NS92882, UH2&3-NS95495, K23-NS112339; Epilepsy Foundation Epilepsy Innovation Institute ‘My Seizure Gauge’
FIGURES
Figure 1