A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation.

Intracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.

Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Importance: Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. Objective: To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. Data Sources: PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Study Selection: Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. Main Outcome Measures: The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. Results: A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Conclusion and Relevance: Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

Insights into epileptogenesis from post-traumatic epilepsy.

Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies. The incidence of PTE after traumatic brain injury (TBI) depends on the severity of injury, approaching one in three in groups with the most severe injuries. The repeated seizures that characterize PTE impair neurological recovery and increase the risk of poor outcomes after TBI. Given this high risk of recurrent seizures and the relatively short latency period for their development after injury, PTE serves as a model disease to understand human epileptogenesis and trial novel anti-epileptogenic therapies. Epileptogenesis is the process whereby previously normal brain tissue becomes prone to recurrent abnormal electrical activity, ultimately resulting in seizures. In this Review, we describe the clinical course of PTE and highlight promising research into epileptogenesis and treatment using animal models of PTE. Clinical, imaging, EEG and fluid biomarkers are being developed to aid the identification of patients at high risk of PTE who might benefit from anti-epileptogenic therapies. Studies in preclinical models of PTE have identified tractable pathways and novel therapeutic strategies that can potentially prevent epilepsy, which remain to be validated in humans. In addition to improving outcomes after TBI, advances in PTE research are likely to provide therapeutic insights that are relevant to all epilepsies.

Complications and visual outcomes following surgical resection of pediatric optic pathway/hypothalamic gliomas: a systematic review and meta-analysis.

Pediatric optic pathway/hypothalamic gliomas (OPHG) pose challenges in treatment due to their location and proximity to vital structures. Surgical resection plays a key role in the management of OPHG especially when the tumor exhibits mass effect and causes symptoms. However, data regarding outcomes and complications of surgical resection for OPHG remains heterogenous. The authors performed a systematic review on pediatric OPHG in four databases: PubMed, EMBASE, Cochrane Library, and Google Scholar. We included studies that reported on the visual outcomes and complications of OPHG resection. A meta-analysis was performed and reported per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 26 retrospective studies were included. Seven hundred ninety-seven pediatric patients with OPHG undergoing surgical resection were examined. A diagnosis of NF1 was confirmed in 9.7%. Gross total resection was achieved in 36.7%. Intraorbital optic pathway gliomas showed a significantly higher gross total resection rate compared to those located in the chiasmatic/hypothalamic region (75.8% vs. 9.6%). Postoperatively, visual acuity improved in 24.6%, remained unchanged in 68.2%, and worsened in 18.2%. Complications included hydrocephalus (35.4%), anterior pituitary dysfunction (19.6%), and transient diabetes insipidus (29%). Tumor progression post-resection occurred in 12.8%, through a mean follow-up of 53.5 months. Surgical resection remains an essential strategy for treating symptomatic and large pediatric OPHG and can result in favorable vision outcomes in most patients. Careful patient selection is critical. Patients should be monitored for hydrocephalus development postoperatively and followed up to assess for tumor progression and adjuvant treatment necessity.

Thalamic stereoelectroencephalography for neuromodulation target selection: Proof of concept and review of literature of pulvinar direct electrical stimulation.

In patients with drug-resistant epilepsy (DRE) who are not candidates for resective surgery, various thalamic nuclei, including the anterior, centromedian, and pulvinar nuclei, have been extensively investigated as targets for neuromodulation. However, the therapeutic effects of different targets for thalamic neuromodulation on various types of epilepsy are not well understood. Here, we present a 32-year-old patient with multifocal bilateral temporoparieto-occipital epilepsy and bilateral malformations of cortical development (MCDs) who underwent bilateral stereoelectroencephalographic (SEEG) recordings of the aforementioned three thalamic nuclei bilaterally. The change in the rate of interictal epileptiform discharges (IEDs) from baseline were compared in temporal, central, parietal, and occipital regions after direct electrical stimulation (DES) of each thalamic nucleus. A significant decrease in the rate of IEDs (33% from baseline) in the posterior quadrant regions was noted in the ipsilateral as well as contralateral hemisphere following DES of the pulvinar. A scoping review was also performed to better understand the current standpoint of pulvinar thalamic stimulation in the treatment of DRE. The therapeutic effect of neuromodulation can differ among thalamic nuclei targets and epileptogenic zones (EZs). In patients with multifocal EZs with extensive MCDs, personalized thalamic targeting could be achieved through DES with thalamic SEEG electrodes.

Safety of Concomitant Cortical and Thalamic Stereoencephalography Explorations in Patients With Drug-Resistant Epilepsies.

BACKGROUND AND OBJECTIVES: Intracranial electrophysiology of thalamic nuclei has demonstrated involvement of thalamic areas in the propagation of seizures in focal drug-resistant epilepsy. Recent studies have argued that thalamus stereoencephalography (sEEG) may aid in understanding the epileptogenic zone and treatment options. However, the study of thalamic sEEG-associated hemorrhage incidence has not been investigated in a cohort study design. In this article, we present the largest retrospective cohort study of sEEG patients and compare hemorrhage rates between those with and without thalamic sEEG monitoring. METHODS: Retrospective chart review of clinical and epilepsy history, electrode implantation, rationale, and outcomes was performed for 76 patients (age 20-69 years) with drug-resistant epilepsy who underwent sEEG monitoring at our institution (2019-2022). A subset of 38% of patients (n = 30) underwent thalamic monitoring of the anterior thalamic nucleus (n = 14), pulvinar nucleus (n = 25), or both (n = 10). Planned perisylvian orthogonal sEEG trajectories were extended to 2- to 3-cm intraparenchymally access thalamic area(s).The decision to incorporate thalamic monitoring was made by the multidisciplinary epilepsy team. Statistical comparison of hemorrhage rate, type, and severity between patients with and without thalamic sEEG monitoring was made. RESULTS: Our approach for thalamic monitoring was not associated with local intraparenchymal hemorrhage of thalamic areas or found along extended cortical trajectories, and symptomatic hemorrhage rates were greater for patients with thalamic coverage (10% vs 0%, P = .056), although this was not found to be significant. Importantly, patients with perisylvian electrode trajectories, with or without thalamic coverage, did not experience a higher incidence of hemorrhage (P = .34). CONCLUSION: sEEG of the thalamus is a safe and valuable tool that can be used to interrogate the efficacy of thalamic neuromodulation for drug-resistant epilepsy. While patients with thalamic sEEG did have higher incidence of hemorrhage at any monitoring site, this finding was apparently not related to the method of perisylvian implantation and did not involve any trajectories targeting the thalamus.

Supraspinal control of motoneurons after paralysis enabled by spinal cord stimulation.

Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

SUPRASPINAL CONTROL OF MOTONEURONS AFTER PARALYSIS ENABLED BY SPINAL CORD STIMULATION.

Spinal cord stimulation (SCS) restores motor control after spinal cord injury (SCI) and stroke. This evidence led to the hypothesis that SCS facilitates residual supraspinal inputs to spinal motoneurons. Instead, here we show that SCS does not facilitate residual supraspinal inputs but directly triggers motoneurons action potentials. However, supraspinal inputs can shape SCS-mediated activity, mimicking volitional control of motoneuron firing. Specifically, by combining simulations, intraspinal electrophysiology in monkeys and single motor unit recordings in humans with motor paralysis, we found that residual supraspinal inputs transform subthreshold SCS-induced excitatory postsynaptic potentials into suprathreshold events. We then demonstrated that only a restricted set of stimulation parameters enables volitional control of motoneuron firing and that lesion severity further restricts the set of effective parameters. Our results explain the facilitation of voluntary motor control during SCS while predicting the limitations of this neurotechnology in cases of severe loss of supraspinal axons.

Challenging Cortical Explorations in Difficult-to-Localize Seizures: The Rationale and Usefulness of Perisylvian Paralimbic Explorations With Orthogonal Stereoelectroencephalography Depth Electrodes.

BACKGROUND AND OBJECTIVE: Stereoelectroencephalography (SEEG) is an invasive monitoring method designed to define and localize the epileptogenic zone (EZ) and explore the putative network responsible for the electroclinical seizures using anatomo-functional-electroclinical correlations. When indicated by semiology in selected patients, exploration of both limbic and paralimbic (PL) regions is indispensable. However, the PL cortex is located in deep and highly vascularized areas in proximity to the anterior Sylvian fissure and middle cerebral artery branches. Thus, those explorations are considered surgically challenging because of the multilobar location and fear of hemorrhagic events. Here, we discuss and illustrate the rationale and SEEG methodology approach in usefulness of exploring the PL regions using standard orthogonal SEEG depth electrode trajectories with the Talariach reference system. METHODS: We retrospectively studied PL exploration from a cohort of 71 consecutive SEEG procedures from Nov 2019 to Nov 2022 and identified 31 patients who underwent PL trajectories. RESULTS: In 31 patients, there were 32 SEEG trajectories, and no major complications were observed. PL electrodes were consistently implanted in the C10/D10 coordinates of the Talariach reference coordinates. The most common confirmed EZ in our cohort was mesio-temporal (45%), followed by temporo-perisylvian regions (16%), ventromedial frontal (13%), and mesio-lateral temporal regions (13%). The PL contacts were involved in the EZ in 10 patients (32%). Of 31 patients, 25 underwent resective surgery, and 19 obtained Engel 1 outcome with a mean follow-up of 25 months (range 12-41 months) after surgery. CONCLUSION: The orthogonal perisylvian PL trajectories are feasible and useful in sampling multiple PL regions with single-electrode trajectories. In patients with perisylvian seizures, sampling PL structures may contribute to an improved understanding of seizure propagation and the optimal anatomic demarcation of the EZs in this surgically challenging region.

Microstimulation of human somatosensory cortex evokes task-dependent, spatially patterned responses in motor cortex.

The primary motor (M1) and somatosensory (S1) cortices play critical roles in motor control but the signaling between these structures is poorly understood. To fill this gap, we recorded - in three participants in an ongoing human clinical trial (NCT01894802) for people with paralyzed hands - the responses evoked in the hand and arm representations of M1 during intracortical microstimulation (ICMS) in the hand representation of S1. We found that ICMS of S1 activated some M1 neurons at short, fixed latencies consistent with monosynaptic activation. Additionally, most of the ICMS-evoked responses in M1 were more variable in time, suggesting indirect effects of stimulation. The spatial pattern of M1 activation varied systematically: S1 electrodes that elicited percepts in a finger preferentially activated M1 neurons excited during that finger's movement. Moreover, the indirect effects of S1 ICMS on M1 were context dependent, such that the magnitude and even sign relative to baseline varied across tasks. We tested the implications of these effects for brain-control of a virtual hand, in which ICMS conveyed tactile feedback. While ICMS-evoked activation of M1 disrupted decoder performance, this disruption was minimized using biomimetic stimulation, which emphasizes contact transients at the onset and offset of grasp, and reduces sustained stimulation.

Internal states as a source of subject-dependent movement variability are represented by large-scale brain networks.

Humans' ability to adapt and learn relies on reflecting on past performance. These experiences form latent representations called internal states that induce movement variability that improves how we interact with our environment. Our study uncovered temporal dynamics and neural substrates of two states from ten subjects implanted with intracranial depth electrodes while they performed a goal-directed motor task with physical perturbations. We identified two internal states using state-space models: one tracking past errors and the other past perturbations. These states influenced reaction times and speed errors, revealing how subjects strategize from trial history. Using local field potentials from over 100 brain regions, we found large-scale brain networks such as the dorsal attention and default mode network modulate visuospatial attention based on recent performance and environmental feedback. Notably, these networks were more prominent in higher-performing subjects, emphasizing their role in improving motor performance by regulating movement variability through internal states.

Added value of corpus callosotomy following vagus nerve stimulation in children with Lennox-Gastaut syndrome: A multicenter, multinational study.

OBJECTIVE: Lennox-Gastaut syndrome (LGS) is a severe form of epileptic encephalopathy, presenting during the first years of life, and is very resistant to treatment. Once medical therapy has failed, palliative surgeries such as vagus nerve stimulation (VNS) or corpus callosotomy (CC) are considered. Although CC is more effective than VNS as the primary neurosurgical treatment for LGS-associated drop attacks, there are limited data regarding the added value of CC following VNS. This study aimed to assess the effectiveness of CC preceded by VNS. METHODS: This multinational, multicenter retrospective study focuses on LGS children who underwent CC before the age of 18 years, following prior VNS, which failed to achieve satisfactory seizure control. Collected data included epilepsy characteristics, surgical details, epilepsy outcomes, and complications. The primary outcome of this study was a 50% reduction in drop attacks. RESULTS: A total of 127 cases were reviewed (80 males). The median age at epilepsy onset was 6 months (interquartile range [IQR] = 3.12-22.75). The median age at VNS surgery was 7 years (IQR = 4-10), and CC was performed at a median age of 11 years (IQR = 8.76-15). The dominant seizure type was drop attacks (tonic or atonic) in 102 patients. Eighty-six patients underwent a single-stage complete CC, and 41 an anterior callosotomy. Ten patients who did not initially have a complete CC underwent a second surgery for completion of CC due to seizure persistence. Overall, there was at least a 50% reduction in drop attacks and other seizures in 83% and 60%, respectively. Permanent morbidity occurred in 1.5%, with no mortality. SIGNIFICANCE: CC is vital in seizure control in children with LGS in whom VNS has failed. Surgical risks are low. A complete CC has a tendency toward better effectiveness than anterior CC for some seizure types.

Stereoelectroencephalography-guided laser ablation in neocortical epilepsy: Electrophysiological correlations and outcome.

OBJECTIVE: We aimed to study the correlation between seizure outcomes in patients with drug-resistant epilepsy (DRE) who underwent laser interstitial thermal therapy (LITT) and stereoelectroencephalographic electrophysiologic patterns with respect to the extent of laser ablation. METHODS: We retrospectively analyzed 16 consecutive DRE patients who underwent LITT. A seizure onset zone (SOZ) was obtained from multidisciplinary patient management conferences and again was confirmed independently by two epileptologists based on conventional analysis. SOZs were retrospectively divided into localized, lobar and multilobar, and nonlocalized onset types. A posteriori-predicted epileptogenic zone (PEZ) was identified using the previously developed "EZ fingerprint" pipeline. The completeness of the SOZ and PEZ ablation was compared and correlated with the duration of seizure freedom (SF). RESULTS: Of 16 patients, 11 had an a posteriori-identified PEZ. Three patients underwent complete ablation of SOZ with curative intent, and the other 13 with palliative intent. Of three patients with complete ablation of the SOZ, two had concordant PEZ and SOZ and achieved 40- and 46-month SF without seizure recurrence. The remaining patient, without any PEZ identified, had seizure recurrence within 1 month. Six of 13 patients with partial ablation of the SOZ and PEZ achieved mean seizure freedom of 19.8 months (range = 1-44) with subsequent seizure recurrence. The remaining seven patients had partial ablation of the SOZ without the PEZ identified or ablation outside the PEZ with seizure recurrence within 1-2 months, except one patient who had 40-month seizure freedom after ablation of periventricular heterotopia. SIGNIFICANCE: Only complete ablation of the well-restricted SOZ concordant with the PEZ was associated with long-term SF, whereas partial ablation of the PEZ might lead to SF with eventual seizure recurrence. Failure to identify PEZ and ablation limited to the SOZ often led to 1-2 months of SF.

Tessellation of artificial touch via microstimulation of human somatosensory cortex.

When we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations - their location and spatial extent - from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant's hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multichannel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.

Operative Technique and Nuances for the Stereoelectroencephalographic (SEEG) Methodology Utilizing a Robotic Stereotactic Guidance System.

The SEEG methodology has gained favor in North America over the last decade as a means of localizing the epileptogenic zone (EZ) prior to epilepsy surgery. Recently, the application of a robotic stereotactic guidance system for implantation of SEEG electrodes has become more popular in many epilepsy centers. The technique for the use of the robot requires extreme precision in the pre-surgical planning phase and then the technique is streamlined during the operative portion of the methodology, as the robot and surgeon work in concert to implant the electrodes. Herein is detailed precise operative methodology of using the robot to guide implantation of SEEG electrodes. A major limitation of the procedure, namely its heavy reliance on the ability to register the patient to a preoperative volumetric magnetic resonance image (MRI), is also discussed. Overall, this procedure has been shown to have a low morbidity rate and an extremely low mortality rate. The use of a robotic stereotactic guidance system for the implantation of SEEG electrodes is an efficient, fast, safe, and accurate alternative to conventional manual implantation strategies.

Predicting posttraumatic epilepsy using admission electroencephalography after severe traumatic brain injury.

OBJECTIVE: Posttraumatic epilepsy (PTE) develops in as many as one third of severe traumatic brain injury (TBI) patients, often years after injury. Analysis of early electroencephalographic (EEG) features, by both standardized visual interpretation (viEEG) and quantitative EEG (qEEG) analysis, may aid early identification of patients at high risk for PTE. METHODS: We performed a case-control study using a prospective database of severe TBI patients treated at a single center from 2011 to 2018. We identified patients who survived 2 years postinjury and matched patients with PTE to those without using age and admission Glasgow Coma Scale score. A neuropsychologist recorded outcomes at 1 year using the Expanded Glasgow Outcomes Scale (GOSE). All patients underwent continuous EEG for 3-5 days. A board-certified epileptologist, blinded to outcomes, described viEEG features using standardized descriptions. We extracted 14 qEEG features from an early 5-min epoch, described them using qualitative statistics, then developed two multivariable models to predict long-term risk of PTE (random forest and logistic regression). RESULTS: We identified 27 patients with and 35 without PTE. GOSE scores were similar at 1 year (p = .93). The median time to onset of PTE was 7.2 months posttrauma (interquartile range = 2.2-22.2 months). None of the viEEG features was different between the groups. On qEEG, the PTE cohort had higher spectral power in the delta frequencies, more power variance in the delta and theta frequencies, and higher peak envelope (all p < .01). Using random forest, combining qEEG and clinical features produced an area under the curve of .76. Using logistic regression, increases in the delta:theta power ratio (odds ratio [OR] = 1.3, p < .01) and peak envelope (OR = 1.1, p < .01) predicted risk for PTE. SIGNIFICANCE: In a cohort of severe TBI patients, acute phase EEG features may predict PTE. Predictive models, as applied to this study, may help identify patients at high risk for PTE, assist early clinical management, and guide patient selection for clinical trials.

Personalised virtual brain models in epilepsy.

Individuals with drug-resistant focal epilepsy are candidates for surgical treatment as a curative option. Before surgery can take place, the patient must have a presurgical evaluation to establish whether and how surgical treatment might stop their seizures without causing neurological deficits. Virtual brains are a new digital modelling technology that map the brain network of a person with epilepsy, using data derived from MRI. This technique produces a computer simulation of seizures and brain imaging signals, such as those that would be recorded with intracranial EEG. When combined with machine learning, virtual brains can be used to estimate the extent and organisation of the epileptogenic zone (ie, the brain regions related to seizure generation and the spatiotemporal dynamics during seizure onset). Virtual brains could, in the future, be used for clinical decision making, to improve precision in localisation of seizure activity, and for surgical planning, but at the moment these models have some limitations, such as low spatial resolution. As evidence accumulates in support of the predictive power of personalised virtual brain models, and as methods are tested in clinical trials, virtual brains might inform clinical practice in the near future.

Association of Posttraumatic Epilepsy With Long-term Functional Outcomes in Individuals With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVE: Nearly one-third of patients with severe traumatic brain injury (TBI) develop posttraumatic epilepsy (PTE). The relationship between PTE and long-term outcomes is unknown. We tested whether, after controlling for injury severity and age, PTE is associated with worse functional outcomes after severe TBI. METHODS: We performed a retrospective analysis of a prospective database of patients with severe TBI treated from 2002 through 2018 at a single level 1 trauma center. Glasgow Outcome Scale (GOS) was collected at 3, 6, 12, and 24 months postinjury. We used repeated-measures logistic regression predicting GOS, dichotomized as favorable (GOS 4-5) and unfavorable (GOS 1-3), and a separate logistic model predicting mortality at 2 years. We used predictors as defined by the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) base model (i.e., age, pupil reactivity, and GCS motor score), PTE status, and time. RESULTS: Of 392 patients who survived to discharge, 98 (25%) developed PTE. The proportion of patients with favorable outcomes at 3 months did not differ between those with and without PTE (23% [95% Confidence Interval [CI]: 15%-34%] vs 32% [95% CI: 27%-39%]; p = 0.11) but was significantly lower at 6 (33% [95% CI: 23%-44%] vs 46%; [95% CI: 39%-52%] p = 0.03), 12 (41% [95% CI: 30%-52%] vs 54% [95% CI: 47%-61%]; p = 0.03), and 24 months (40% [95% CI: 47%-61%] vs 55% [95% CI: 47%-63%]; p = 0.04). This was driven by higher rates of GOS 2 (vegetative) and 3 (severe disability) outcomes in the PTE group. By 2 years, the incidence of GOS 2 or 3 was double in the PTE group (46% [95% CI: 34%-59%]) compared with that in the non-PTE group (21% [95% CI: 16%-28%]; p < 0.001), while mortality was similar (14% [95% CI: 7%-25%] vs 23% [95% CI: 17%-30%]; p = 0.28). In multivariate analysis, patients with PTE had lower odds of favorable outcome (odds radio [OR] 0.1; 95% CI: 0.1-0.4; p < 0.001), but not mortality (OR 0.9; 95% CI: 0.1-1.9; p = 0.46). DISCUSSION: Posttraumatic epilepsy is associated with impaired recovery from severe TBI and poor functional outcomes. Early screening and treatment of PTE may improve patient outcomes.

POTENTIATION OF CORTICO-SPINAL OUTPUT VIA TARGETED ELECTRICAL STIMULATION OF THE MOTOR THALAMUS.

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for new therapies aimed at improving volitional muscle activation. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby potentiating motor output. To test this hypothesis, we identified optimal thalamic targets and stimulation parameters that enhanced upper-limb motor evoked potentials and grip forces in anesthetized monkeys. This potentiation persisted after white matter lesions. We replicated these results in humans during intra-operative testing. We then designed a stimulation protocol that immediately improved voluntary grip force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.