Feasibility, Safety, and Performance of Full-Head Subscalp EEG Using Minimally Invasive Electrode Implantation.

BACKGROUND AND OBJECTIVES: Current practice in clinical neurophysiology is limited to short recordings with conventional EEG (days) that fail to capture a range of brain (dys)functions at longer timescales (months). The future ability to optimally manage chronic brain disorders, such as epilepsy, hinges upon finding methods to monitor electrical brain activity in daily life. We developed a device for full-head subscalp EEG (Epios) and tested here the feasibility to safely insert the electrode leads beneath the scalp by a minimally invasive technique (primary outcome). As secondary outcome, we verified the noninferiority of subscalp EEG in measuring physiologic brain oscillations and pathologic discharges compared with scalp EEG, the established standard of care. METHODS: Eight participants with pharmacoresistant epilepsy undergoing intracranial EEG received in the same surgery subscalp electrodes tunneled between the scalp and the skull with custom-made tools. Postoperative safety was monitored on an inpatient ward for up to 9 days. Sleep-wake, ictal, and interictal EEG signals from subscalp, scalp, and intracranial electrodes were compared quantitatively using windowed multitaper transforms and spectral coherence. Noninferiority was tested for pairs of neighboring subscalp and scalp electrodes with a Bland-Altman analysis for measurement bias and calculation of the interclass correlation coefficient (ICC). RESULTS: As primary outcome, up to 28 subscalp electrodes could be safely placed over the entire head through 1-cm scalp incisions in a ∼1-hour procedure. Five of 10 observed perioperative adverse events were linked to the investigational procedure, but none were serious, and all resolved. As a secondary outcome, subscalp electrodes advantageously recorded EEG percutaneously without requiring any maintenance and were noninferior to scalp electrodes for measuring (1) variably strong, stage-specific brain oscillations (alpha in wake, delta, sigma, and beta in sleep) and (2) interictal spikes peak-potentials and ictal signals coherent with seizure propagation in different brain regions (ICC >0.8 and absence of bias). DISCUSSION: Recording full-head subscalp EEG for localization and monitoring purposes is feasible up to 9 days in humans using minimally invasive techniques and noninferior to the current standard of care. A longer prospective ambulatory study of the full system will be necessary to establish the safety and utility of this innovative approach. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/study/NCT04796597.

Designing next-generation subscalp devices for seizure monitoring: A systematic review and meta-analysis of established extracranial hardware.

Implantable brain recording and stimulation devices apply to a broad spectrum of conditions, such as epilepsy, movement disorders and depression. For long-term monitoring and neuromodulation in epilepsy patients, future extracranial subscalp implants may offer a promising, less-invasive alternative to intracranial neurotechnologies. To inform the design and assess the safety profile of such next-generation devices, we estimated extracranial complication rates of deep brain stimulation (DBS), cranial peripheral nerve stimulation (PNS), responsive neurostimulation (RNS) and existing subscalp EEG devices (sqEEG), as proxy for future implants. Pubmed was searched systematically for DBS, PNS, RNS and sqEEG studies from 2000 to February 2024 (48 publications, 7329 patients). We identified seven categories of extracranial adverse events: infection, non-infectious cutaneous complications, lead migration, lead fracture, hardware malfunction, pain and hemato-seroma. We used cohort sizes, demographics and industry funding as metrics to assess risks of bias. An inverse variance heterogeneity model was used for pooled and subgroup meta-analysis. The pooled incidence of extracranial complications reached 14.0%, with infections (4.6%, CI 95% [3.2 - 6.2]), surgical site pain (3.2%, [0.6 - 6.4]) and lead migration (2.6%, [1.0 - 4.4]) as leading causes. Subgroup analysis showed a particularly high incidence of persisting pain following PNS (12.0%, [6.8 - 17.9]) and sqEEG (23.9%, [12.7 - 37.2]) implantation. High rates of lead migration (12.4%, [6.4 - 19.3]) were also identified in the PNS subgroup. Complication analysis of DBS, PNS, RNS and sqEEG studies provides a significant opportunity to optimize the safety profile of future implantable subscalp devices for chronic EEG monitoring. Developing such promising technologies must address the risks of infection, surgical site pain, lead migration and skin erosion. A thin and robust design, coupled to a lead-anchoring system, shall enhance the durability and utility of next-generation subscalp implants for long-term EEG monitoring and neuromodulation.

Triggered Seizures for Ictal SPECT Imaging: A Case Series and Feasibility Study.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

Deep Brain Stimulation of the Central Lateral and Ventral Posterior Thalamus for Central Poststroke Pain Syndrome: Preliminary Experience.

OBJECTIVE: The beneficial effects of thalamic deep brain stimulation (DBS) at various target sites in treating chronic central neuropathic pain (CPSP) remain unclear. This study aimed to evaluate the effectiveness of DBS at a previously untested target site in the central lateral (CL) thalamus, together with classical sensory thalamic stimulation (ventral posterior [VP] complex). MATERIALS AND METHODS: We performed a monocentric retrospective study of a consecutive series of six patients with CPSP who underwent combined DBS lead implantation of the CL and VP. Patient-reported outcome measures were recorded before and after surgery using the numeric rating scale (NRS), short-form McGill pain questionnaire (sf-MPQ), EuroQol 5-D quality-of-life questionnaire, and Beck Depression Inventory. DBS leads were reconstructed and projected onto a three-dimensional stereotactic atlas. RESULTS: NRS-but not sf-MPQ-rated pain intensity-was significantly reduced throughout the follow-up period of 12 months compared with baseline (p = 0.005, and p = 0.06 respectively, Friedman test). At the last available follow-up (12 to 30 months), three patients described a more than 50% reduction. Two of the three long-term responders were stimulated in the CL (1000 Hz, 90 µs, 3.5-5.0 mA), whereas the third preferred VP complex stimulation (50 Hz, 200 µs, 0.7-1.2 mA). No persistent procedure- or stimulation-associated side effects were noted. CONCLUSIONS: These preliminary findings suggest that DBS of the CL might constitute a promising alternative target in cases in which classical VP complex stimulation does not yield satisfactory postoperative pain reduction. The results need to be confirmed in larger, prospective series of patients.

Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor.

OBJECTIVE: The objective of this study was to obtain individual clinical and neuroimaging data of patients undergoing deep brain stimulation (DBS) for essential tremor (ET) from 5 different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS: We analyzed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (for 12 months) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data were used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS: Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement >50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural connectivity-based cerebellothalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a >50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION: Our multicenter ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of DBS in the future. ANN NEUROL 2022;91:602-612.

Required growth facilitators propel axon regeneration across complete spinal cord injury.

Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after injury1-3, but efficient reversal of this regrowth failure remains elusive4. Here we show that three factors that are essential for axon growth during development but are attenuated or lacking in adults-(i) neuron intrinsic growth capacity2,5-9, (ii) growth-supportive substrate10,11 and (iii) chemoattraction12,13-are all individually required and, in combination, are sufficient to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents. We reactivated the growth capacity of mature descending propriospinal neurons with osteopontin, insulin-like growth factor 1 and ciliary-derived neurotrophic factor before SCI14,15; induced growth-supportive substrates with fibroblast growth factor 2 and epidermal growth factor; and chemoattracted propriospinal axons with glial-derived neurotrophic factor16,17 delivered via spatially and temporally controlled release from biomaterial depots18,19, placed sequentially after SCI. We show in both mice and rats that providing these three mechanisms in combination, but not individually, stimulated robust propriospinal axon regrowth through astrocyte scar borders and across lesion cores of non-neural tissue that was over 100-fold greater than controls. Stimulated, supported and chemoattracted propriospinal axons regrew a full spinal segment beyond lesion centres, passed well into spared neural tissue, formed terminal-like contacts exhibiting synaptic markers and conveyed a significant return of electrophysiological conduction capacity across lesions. Thus, overcoming the failure of axon regrowth across anatomically complete SCI lesions after maturity required the combined sequential reinstatement of several developmentally essential mechanisms that facilitate axon growth. These findings identify a mechanism-based biological repair strategy for complete SCI lesions that could be suitable to use with rehabilitation models designed to augment the functional recovery of remodelling circuits.