Distinct Biomarkers of ANT Stimulation and Seizure Freedom in an Epilepsy Patient with Ambulatory Hippocampal Electrocorticography

Medication-refractory focal epilepsy poses a significant challenge, with approximately 30% of patients ineligible for surgery due to the involvement of eloquent cortex in the epileptogenic network. For such patients with limited surgical options, electrical neuromodulation represents a promising alternative therapy. In this study, we investigate the potential of non-invasive temporal interference (TI) electrical stimulation to reduce epileptic biomarkers in patients with epilepsy by comparing intracerebral recordings obtained before, during, and after TI stimulation, and to those recorded during low and high kHz frequency (HF) sham stimulation. Thirteen patients with symptoms of mesiotemporal epilepsy (MTLE) and implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130Hz (Δf), where the AM was delivered with lower frequency kHz carriers (1kHz + 1.13kHz), or higher frequency carriers (9kHz + 9.13kHz), targeting the hippocampus – a common epileptic focus and consequently stimulation target in MTLE.Our results show that TI stimulation yields a statistically significant decrease in interictal epileptiform discharges (IEDs) and pathological high-frequency oscillations (HFOs) – specifically Fast-ripples (FR) –, where the suppression is apparent in the hippocampal focus and propagation from the focus is reduced brain-wide. HF sham stimulation at 1kHz frequency also impacted the IED rate in the cortex, but without reaching the hippocampal focus. The HF sham effect diminished with increasing frequencies (2, 5, and 9kHz, respectively), specifically as a function of depth into the cortex. This depth dependence was not observed with the TI, independent of the employed carrier frequency (low or high kHz). Our findings underscore the possible application of TI in epilepsy, as an additional non-invasive brain stimulation tool, potentially offering opportunities to assess brain region responses to electrical neuromodulation before committing to a deep brain stimulation (DBS) or responsive neurostimulation (RNS) implant. Our results further demonstrate distinct biophysical differences between kHz and focal AM stimulation.Graphical Abstract

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Combination of or Transition between Deep Brain Stimulation and Responsive Neurostimulation for the Treatment of Drug-Resistant Epilepsy

Yang,

Skelton,

Isbaine

et al. 2024

Stereotact Funct Neurosurg

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Introduction: Neuromodulation is an important treatment modality for patients with drug-resistant epilepsy who are not candidates for resective or ablative procedures. However, randomized controlled trials and real-world studies reveal that a subset of patients will experience minimal reduction or even an increase in seizure frequency after neuromodulation. We describe our experience with patients who undergo a second intracranial neuromodulation procedure after unsatisfactory initial response to intracranial neuromodulation. Methods: We performed a retrospective chart review to identify all patients who had undergone deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) or responsive neurostimulation (RNS), followed by additional intracranial neuromodulatory procedures, with at least 12 months of follow-up. Demographic and clinical data, including seizure frequencies, were collected. Results: All patients had temporal lobe epilepsy. Six patients were treated with concurrent ANT DBS and temporal lobe RNS, and 3 patients transitioned between neuromodulation systems. Of the patients treated concurrently with ANT DBS and temporal lobe RNS, 5 of the 6 patients experienced additional reduction in seizure frequency after adding a second neuromodulation system. Of the patients who switched between neuromodulation modalities, all patients experienced further reduction in seizure frequency. Conclusions: For patients who do not experience adequate benefit from initial therapy with ANT DBS or temporal lobe RNS, the addition of a neuromodulation system or switching to a different form of neuromodulation may allow for additional reduction in seizure frequency. Larger studies will need to be performed to understand whether the use of multiple systems concurrently leads to improved clinical results in patients who are initially treatment resistant to neuromodulation.

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Distinct Biomarkers of ANT Stimulation and Seizure Freedom in an Epilepsy Patient with Ambulatory Hippocampal Electrocorticography

Cited by 3 publications

References 23 publications

Neurostimulation targeting the epileptic focus: Current understanding and perspectives for treatment

Neurostimulation targeting the epileptic focus: Current understanding and perspectives for treatment

Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation

Combination of or Transition between Deep Brain Stimulation and Responsive Neurostimulation for the Treatment of Drug-Resistant Epilepsy

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