Endovascular Brain-Computer Interfaces in Poststroke Paralysis.

Stroke is a leading cause of paralysis, most frequently affecting the upper limbs and vocal folds. Despite recent advances in care, stroke recovery invariably reaches a plateau, after which there are permanent neurological impairments. Implantable brain-computer interface devices offer the potential to bypass permanent neurological lesions. They function by (1) recording neural activity, (2) decoding the neural signal occurring in response to volitional motor intentions, and (3) generating digital control signals that may be used to control external devices. While brain-computer interface technology has the potential to revolutionize neurological care, clinical translation has been limited. Endovascular arrays present a novel form of minimally invasive brain-computer interface devices that have been deployed in human subjects during early feasibility studies. This article provides an overview of endovascular brain-computer interface devices and critically evaluates the patient with stroke as an implant candidate. Future opportunities are mapped, along with the challenges arising when decoding neural activity following infarction. Limitations arise when considering intracerebral hemorrhage and motor cortex lesions; however, future directions are outlined that aim to address these challenges.

Cerebral venous disorders: Diagnosis and endovascular management.

The role of the venous circulation in neurological diseases has been underestimated. In this review, we present an overview of the intracranial venous anatomy, venous disorders of the central nervous system, and options for endovascular management. We discuss the role the venous circulation plays in various neurological diseases including cerebrospinal fluid (CSF) disorders (intracranial hypertension and intracranial hypotension), arteriovenous diseases, and pulsatile tinnitus. We also shed light on emergent cerebral venous interventions including transvenous brain-computer interface implantation, transvenous treatment of communicating hydrocephalus, and the endovascular treatment of CSF-venous disorders.

Mobile Interventional Stroke Teams Improve Outcomes in the Early Time Window for Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Endovascular thrombectomy for large vessel occlusion stroke is a time-sensitive intervention. The use of a Mobile Interventional Stroke Team (MIST) traveling to Thrombectomy Capable Stroke Centers to perform endovascular thrombectomy has been shown to be significantly faster with improved discharge outcomes, as compared with the drip-and-ship (DS) model. The effect of the MIST model stratified by time of presentation has yet to be studied. We hypothesize that patients who present in the early window (last known well of ≤6 hours) will have better clinical outcomes in the MIST model. METHODS: The NYC MIST Trial and a prospectively collected stroke database were assessed for patients undergoing endovascular thrombectomy from January 2017 to February 2020. Patients presenting in early and late time windows were analyzed separately. The primary end point was the proportion with a good outcome (modified Rankin Scale score of 0-2) at 90 days. Secondary end points included discharge National Institutes of Health Stroke Scale and modified Rankin Scale. RESULTS: Among 561 cases, 226 patients fit inclusion criteria and were categorized into MIST and DS cohorts. Exclusion criteria included a baseline modified Rankin Scale score of >2, inpatient status, or fluctuating exams. In the early window, 54% (40/74) had a good 90-day outcome in the MIST model, as compared with 28% (24/86) in the DS model (P<0.01). In the late window, outcomes were similar (35% versus 41%; P=0.77). The median National Institutes of Health Stroke Scale at discharge was 5.0 and 12.0 in the early window (P<0.01) and 5.0 and 11.0 in the late window (P=0.11) in the MIST and DS models, respectively. The early window discharge modified Rankin Scale was significantly better in the MIST model (P<0.01) and similar in the late window (P=0.41). CONCLUSIONS: The MIST model in the early time window results in better 90-day outcomes compared with the DS model. This may be due to the MIST capturing high-risk fast progressors at an earlier time point. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03048292.

Emergent Large Vessel Occlusion Stroke During New York City's COVID-19 Outbreak: Clinical Characteristics and Paraclinical Findings.

BACKGROUND AND PURPOSE: The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic. Early data suggest higher rate of ischemic stroke in severe COVID-19 infection. We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak. METHODS: This is a retrospective, observational case series. Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19. Patients' demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record. Comparison was made between COVID-19 positive and negative cohorts. The incidence of ELVO stroke was compared with the pre-COVID period. RESULTS: Forty-five consecutive ELVO patients presented during the observation period. Fifty-three percent of patients tested positive for COVID-19. Total patients' mean (±SD) age was 66 (±17). Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81-0.98]; P=0.004). Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12-14.17]; P=0.032). Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04-0.81); P=0.027]). In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47-1.08], P≤0.0001). CONCLUSIONS: More than half of the ELVO stroke patients during the peak time of the New York City's COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White. Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.

Mobile Interventional Stroke Team Model Improves Early Outcomes in Large Vessel Occlusion Stroke: The NYC MIST Trial.

BACKGROUND AND PURPOSE: Triage of patients with emergent large vessel occlusion stroke to primary stroke centers followed by transfer to comprehensive stroke centers leads to increased time to endovascular therapy. A Mobile Interventional Stroke Team (MIST) provides an alternative model by transferring a MIST to a Thrombectomy Capable Stroke Center (TSC) to perform endovascular therapy. Our aim is to determine whether the MIST model is more time-efficient and leads to improved clinical outcomes compared with standard drip-and-ship (DS) and mothership models. METHODS: This is a prospective observational cohort study with 3-month follow-up between June 2016 and December 2018 at a multicenter health system, consisting of one comprehensive stroke center, 4 TSCs, and several primary stroke centers. A total of 228 of 373 patients received endovascular therapy via 1 of 4 models: mothership with patient presentation to a comprehensive stroke center, DS with patient transfer from primary stroke center or TSC to comprehensive stroke center, MIST with patient presentation to TSC and MIST transfer, or a combination of DS with patient transfer from primary stroke center to TSC and MIST. The prespecified primary end point was initial door-to-recanalization time and secondary end points measured additional time intervals and clinical outcomes at discharge and 3 months. RESULTS: MIST had a faster mean initial door-to-recanalization time than DS by 83 minutes (P<0.01). MIST and mothership had similar median door-to-recanalization times of 192 minutes and 179 minutes, respectively (P=0.83). A greater proportion had a complete recovery (National Institutes of Health Stroke Scale of 0 or 1) at discharge in MIST compared with DS (37.9% versus 16.7%; P<0.01). MIST had 52.8% of patients with modified Rankin Scale of ≤2 at 3 months compared with 38.9% in DS (P=0.10). CONCLUSIONS: MIST led to significantly faster initial door-to-recanalization times compared with DS, which was comparable to mothership. This decrease in time has translated into improved short-term outcomes and a trend towards improved long-term outcomes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03048292.

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic. METHODS: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center. CONCLUSION: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.

7T-fMRI: Faster temporal resolution yields optimal BOLD sensitivity for functional network imaging specifically at high spatial resolution.

Recent developments in accelerated imaging methods allow faster acquisition of high spatial resolution images. This could improve the applications of functional magnetic resonance imaging at 7 Tesla (7T-fMRI), such as neurosurgical planning and Brain Computer Interfaces (BCIs). However, increasing the spatial and temporal resolution will both lead to signal-to-noise ratio (SNR) losses due to decreased net magnetization per voxel and T1-relaxation effect, respectively. This could potentially offset the SNR efficiency gains made with increasing temporal resolution. We investigated the effects of varying spatial and temporal resolution on fMRI sensitivity measures and their implications on fMRI-based BCI simulations. We compared temporal signal-to-noise ratio (tSNR), observed percent signal change (%∆S), volumes of significant activation, Z-scores and decoding performance of linear classifiers commonly used in BCIs across a range of spatial and temporal resolution images acquired during an ankle-tapping task. Our results revealed an average increase of 22% in %∆S (p=0.006) and 9% in decoding performance (p=0.015) with temporal resolution only at the highest spatial resolution of 1.5×1.5×1.5mm3, despite a 29% decrease in tSNR (p<0.001) and plateaued Z-scores. Further, the volume of significant activation was indifferent (p>0.05) across spatial resolution specifically at the highest temporal resolution of 500ms. These results demonstrate that the overall BOLD sensitivity can be increased significantly with temporal resolution, granted an adequately high spatial resolution with minimal physiological noise level. This shows the feasibility of diffuse motor-network imaging at high spatial and temporal resolution with robust BOLD sensitivity with 7T-fMRI. Importantly, we show that this sensitivity improvement could be extended to an fMRI application such as BCIs.

Endovascular therapy for ischemic stroke with perfusion-imaging selection.

BACKGROUND: Trials of endovascular therapy for ischemic stroke have produced variable results. We conducted this study to test whether more advanced imaging selection, recently developed devices, and earlier intervention improve outcomes. METHODS: We randomly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR (Flow Restoration) stent retriever or to continue receiving alteplase alone. All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic (CT) perfusion imaging. The coprimary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3). Secondary outcomes included the functional score on the modified Rankin scale at 90 days. RESULTS: The trial was stopped early because of efficacy after 70 patients had undergone randomization (35 patients in each group). The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group (median, 100% vs. 37%; P<0.001). Endovascular therapy, initiated at a median of 210 minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, P=0.002) and improved the functional outcome at 90 days, with more patients achieving functional independence (score of 0 to 2 on the modified Rankin scale, 71% vs. 40%; P=0.01). There were no significant differences in rates of death or symptomatic intracerebral hemorrhage. CONCLUSIONS: In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA ClinicalTrials.gov number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.).

Spatially dynamic recurrent information flow across long-range dorsal motor network encodes selective motor goals.

Performing voluntary movements involves many regions of the brain, but it is unknown how they work together to plan and execute specific movements. We recorded high-resolution ultra-high-field blood-oxygen-level-dependent signal during a cued ankle-dorsiflexion task. The spatiotemporal dynamics and the patterns of task-relevant information flow across the dorsal motor network were investigated. We show that task-relevant information appears and decays earlier in the higher order areas of the dorsal motor network then in the primary motor cortex. Furthermore, the results show that task-relevant information is encoded in general initially, and then selective goals are subsequently encoded in specifics subregions across the network. Importantly, the patterns of recurrent information flow across the network vary across different subregions depending on the goal. Recurrent information flow was observed across all higher order areas of the dorsal motor network in the subregions encoding for the current goal. In contrast, only the top-down information flow from the supplementary motor cortex to the frontoparietal regions, with weakened recurrent information flow between the frontoparietal regions and bottom-up information flow from the frontoparietal regions to the supplementary cortex were observed in the subregions encoding for the opposing goal. We conclude that selective motor goal encoding and execution rely on goal-dependent differences in subregional recurrent information flow patterns across the long-range dorsal motor network areas that exhibit graded functional specialization.

Optimized partial-coverage functional analysis pipeline (OPFAP): a semi-automated pipeline for skull stripping and co-registration of partial-coverage, ultra-high-field functional images.

OBJECTIVE: Ultra-high-field functional MRI (UHF-fMRI) allows for higher spatiotemporal resolution imaging. However, higher-resolution imaging entails coverage limitations. Processing partial-coverage images using standard pipelines leads to sub-optimal results. We aimed to develop a simple, semi-automated pipeline for processing partial-coverage UHF-fMRI data using widely used image processing algorithms. MATERIALS AND METHODS: We developed automated pipelines for optimized skull stripping and co-registration of partial-coverage UHF functional images, using built-in functions of the Centre for Functional Magnetic Resonance Imaging of the Brain's (FMRIB's) Software library (FSL) and advanced normalization tools. We incorporated the pipelines into the FSL's functional analysis pipeline and provide a semi-automated optimized partial-coverage functional analysis pipeline (OPFAP). RESULTS: Compared to the standard pipeline, the OPFAP yielded images with 15 and 30% greater volume of non-zero voxels after skull stripping the functional and anatomical images, respectively (all p = 0.0004), which reflected the conservation of cortical voxels lost when the standard pipeline was used. The OPFAP yielded the greatest Dice and Jaccard coefficients (87 and 80%, respectively; all p < 0.0001) between the co-registered participant gyri maps and the template gyri maps, demonstrating the goodness of the co-registration results. Furthermore, the greatest volume of group-level activation in the most number of functionally relevant regions was observed when the OPFAP was used. Importantly, group-level activations were not observed when using the standard pipeline. CONCLUSION: These results suggest that the OPFAP should be used for processing partial-coverage UHF-fMRI data for detecting high-resolution macroscopic blood oxygenation level-dependent activations.

Mobile Interventional Stroke Teams Lead to Faster Treatment Times for Thrombectomy in Large Vessel Occlusion.

BACKGROUND AND PURPOSE: Endovascular recanalization treatment for acute ischemic stroke is a complex, time-sensitive intervention. Trip-and-treat is an interhospital service delivery model that has not previously been evaluated in the literature and consists of a shared mobile interventional stroke team that travels to primary stroke centers to provide on-site interventional capability. We compared treatment times between the trip-and-treat model and the traditional drip-and-ship model. METHODS: We performed a retrospective analysis on 86 consecutive eligible patients with acute ischemic stroke secondary to large vessel occlusion who received endovascular treatment at 4 hospitals in Manhattan. Patients were divided into 2 cohorts: trip-and-treat (n=39) and drip-and-ship (n=47). The primary outcome was initial door-to-puncture time, defined as the time between arrival at any hospital and arterial puncture. We also recorded and analyzed the times of last known well, IV-tPA (intravenous tissue-type plasminogen activator) administration, transfer, and reperfusion. RESULTS: Mean initial door-to-puncture time was 143 minutes for trip-and-treat and 222 minutes for drip-and-ship (P<0.0001). Although there was a trend in longer puncture-to-recanalization times for trip-and-treat (P=0.0887), initial door-to-recanalization was nonetheless 79 minutes faster for trip-and-treat (P<0.0001). There was a trend in improved admission-to-discharge change in National Institutes of Health Stroke Scale for trip-and-treat compared with drip-and-ship (P=0.0704). CONCLUSIONS: Compared with drip-and-ship, the trip-and-treat model demonstrated shorter treatment times for endovascular therapy in our series. The trip-and-treat model offers a valid alternative to current interhospital stroke transfers in urban environments.

Novel and emerging technologies for endovascular thrombectomy.

Endovascular thrombectomy device improvements in recent years have served a pivotal role in improving the success and safety of the thrombectomy procedure. As the intervention gains widespread use, developers have focused on maximizing the reperfusion rates and reducing procedural complications associated with these devices. This has led to a boom in device development. This review will cover novel and emerging technologies developed for endovascular thrombectomy.

The evolution of endovascular electroencephalography: historical perspective and future applications.

Current standard practice requires an invasive approach to the recording of electroencephalography (EEG) for epilepsy surgery, deep brain stimulation (DBS), and brain-machine interfaces (BMIs). The development of endovascular techniques offers a minimally invasive route to recording EEG from deep brain structures. This historical perspective aims to describe the technical progress in endovascular EEG by reviewing the first endovascular recordings made using a wire electrode, which was followed by the development of nanowire and catheter recordings and, finally, the most recent progress in stent-electrode recordings. The technical progress in device technology over time and the development of the ability to record chronic intravenous EEG from electrode arrays is described. Future applications for the use of endovascular EEG in the preoperative and operative management of epilepsy surgery are then discussed, followed by the possibility of the technique's future application in minimally invasive operative approaches to DBS and BMI.

The Promise of Endovascular Neurotechnology: A Brain-Computer Interface to Restore Autonomy to People With Motor Impairment.

ABSTRACT: This Joel A. DeLisa Lecture on endovascular brain-computer interfaces was presented by Dr Thomas Oxley on February 23, 2023, at the Association of Academic Physiatrists Annual Scientific Meeting. The lecture described how brain-computer interfaces replace lost physiological function to enable direct communication between the brain and external digital devices, such as computers, smartphones, and robotic limbs. Specifically, the potential of a novel endovascular brain-computer interface technology was discussed. The brain-computer interface uses a stent-electrode array delivered via the jugular vein and is permanently implanted in a vein adjacent to the motor cortex. In a first-in-human clinical trial, participants with upper limb paralysis who received the endovascular brain-computer interface could use the system independently and at home to operate laptop computers for various instrumental activities of daily living. A Food and Drug Administration-approved trial of the endovascular brain-computer interface in the United States is in progress. Future development of the system will provide recipients with continuous autonomy through digital access with minimal caregiver assistance. Physiatrists and occupational therapists will have a vital role in helping people with paralysis achieve the potential of implantable brain-computer interfaces.

Superior cortical venous anatomy for endovascular device implantation: a systematic review.

Endovascular electrode arrays provide a minimally invasive approach to access intracranial structures for neural recording and stimulation. These arrays are currently used as brain-computer interfaces (BCIs) and are deployed within the superior sagittal sinus (SSS), although cortical vein implantation could improve the quality and quantity of recorded signals. However, the anatomy of the superior cortical veins is heterogenous and poorly characterised. MEDLINE and Embase databases were systematically searched from inception to December 15, 2023 for studies describing the anatomy of the superior cortical veins. A total of 28 studies were included: 19 cross-sectional imaging studies, six cadaveric studies, one intraoperative anatomical study and one review. There was substantial variability in cortical vein diameter, length, confluence angle, and location relative to the underlying cortex. The mean number of SSS branches ranged from 11 to 45. The vein of Trolard was most often reported as the largest superior cortical vein, with a mean diameter ranging from 2.1 mm to 3.3 mm. The mean vein of Trolard was identified posterior to the central sulcus. One study found a significant age-related variability in cortical vein diameter and another identified myoendothelial sphincters at the base of the cortical veins. Cortical vein anatomical data are limited and inconsistent. The vein of Trolard is the largest tributary vein of the SSS; however, its relation to the underlying cortex is variable. Variability in cortical vein anatomy may necessitate individualized pre-procedural planning of training and neural decoding in endovascular BCI. Future focus on the relation to the underlying cortex, sulcal vessels, and vessel wall anatomy is required.

Safety and efficacy of cangrelor in endovascular thrombectomy compared with glycoprotein IIb/IIIa Inhibitors.

BACKGROUND: Cangrelor, an intravenous P2Y12-receptor inhibitor, is a reversible and short-acting antithrombotic medication non-inferior to irreversible glycoprotein IIb/IIIa inhibitors (GPIs) like eptifibatide. There are insufficient data to compare the medications in endovascular thrombectomies (EVTs) requiring emergent platelet inhibition. OBJECTIVE: To review our institution's experience with cangrelor in EVT and compares its safety and efficacy against GPIs. METHODS: A large healthcare system retrospective review identified all patients who had received cangrelor or eptifibatide intraoperatively during EVT between December 2018 and March 2023 for this cohort study. Clinical data were reviewed. Functional status was defined by the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS) at multiple time points. Multivariate regression was performed. RESULTS: Of 1010 EVT patients, 36 cangrelor and 104 eptifibatide patients were selected. There were no differences in baseline function or presentations. Cangrelor was frequently administered for stenting tandem occlusions (n=16, 44.4%), and successful reperfusion occurred in 30 (83.3%) patients. On multivariate analysis, cangrelor was associated with decreased odds of hemorrhagic conversion (adjusted OR (aOR)=0.76, P=0.004) and symptomatic hemorrhage (aOR=0.86, P=0.021). There were no differences in thrombotic re-occlusion. Cangrelor was associated with a lower 24-hour NIHSS score (7.0 vs 12.0, P=0.013) and discharge NIHSS score (3.0 vs 9.0, P=0.004). There were no differences in in-hospital mortality or length of stay. Cangrelor was associated with improved odds of favorable outcome, defined as mRS score 0-2, at discharge (aOR=2.69, P=0.001) and on 90-day follow-up (aOR=2.23, P=0.031). CONCLUSION: Cangrelor was associated with a decreased risk of hemorrhagic conversion and might lead to favorable functional outcomes for patients during hospitalization in comparison with GPIs. Prospective studies are warranted to investigate its use in EVT.

Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients: The Stentrode With Thought-Controlled Digital Switch (SWITCH) Study.

Importance: Brain-computer interface (BCI) implants have previously required craniotomy to deliver penetrating or surface electrodes to the brain. Whether a minimally invasive endovascular technique to deliver recording electrodes through the jugular vein to superior sagittal sinus is safe and feasible is unknown. Objective: To assess the safety of an endovascular BCI and feasibility of using the system to control a computer by thought. Design, Setting, and Participants: The Stentrode With Thought-Controlled Digital Switch (SWITCH) study, a single-center, prospective, first in-human study, evaluated 5 patients with severe bilateral upper-limb paralysis, with a follow-up of 12 months. From a referred sample, 4 patients with amyotrophic lateral sclerosis and 1 with primary lateral sclerosis met inclusion criteria and were enrolled in the study. Surgical procedures and follow-up visits were performed at the Royal Melbourne Hospital, Parkville, Australia. Training sessions were performed at patients' homes and at a university clinic. The study start date was May 27, 2019, and final follow-up was completed January 9, 2022. Interventions: Recording devices were delivered via catheter and connected to subcutaneous electronic units. Devices communicated wirelessly to an external device for personal computer control. Main Outcomes and Measures: The primary safety end point was device-related serious adverse events resulting in death or permanent increased disability. Secondary end points were blood vessel occlusion and device migration. Exploratory end points were signal fidelity and stability over 12 months, number of distinct commands created by neuronal activity, and use of system for digital device control. Results: Of 4 patients included in analyses, all were male, and the mean (SD) age was 61 (17) years. Patients with preserved motor cortex activity and suitable venous anatomy were implanted. Each completed 12-month follow-up with no serious adverse events and no vessel occlusion or device migration. Mean (SD) signal bandwidth was 233 (16) Hz and was stable throughout study in all 4 patients (SD range across all sessions, 7-32 Hz). At least 5 attempted movement types were decoded offline, and each patient successfully controlled a computer with the BCI. Conclusions and Relevance: Endovascular access to the sensorimotor cortex is an alternative to placing BCI electrodes in or on the dura by open-brain surgery. These final safety and feasibility data from the first in-human SWITCH study indicate that it is possible to record neural signals from a blood vessel. The favorable safety profile could promote wider and more rapid translation of BCI to people with paralysis. Trial Registration: ClinicalTrials.gov Identifier: NCT03834857.

Vascular remodeling in sheep implanted with endovascular neural interface.

Objective.The aim of this work was to assess vascular remodeling after the placement of an endovascular neural interface (ENI) in the superior sagittal sinus (SSS) of sheep. We also assessed the efficacy of neural recording using an ENI.Approach.The study used histological analysis to assess the composition of the foreign body response. Micro-CT images were analyzed to assess the profiles of the foreign body response and create a model of a blood vessel. Computational fluid dynamic modeling was performed on a reconstructed blood vessel to evaluate the blood flow within the vessel. Recording of brain activity in sheep was used to evaluate efficacy of neural recordings.Main results.Histological analysis showed accumulated extracellular matrix material in and around the implanted ENI. The extracellular matrix contained numerous macrophages, foreign body giant cells, and new vascular channels lined by endothelium. Image analysis of CT slices demonstrated an uneven narrowing of the SSS lumen proportional to the stent material within the blood vessel. However, the foreign body response did not occlude blood flow. The ENI was able to record epileptiform spiking activity with distinct spike morphologies.Significance. This is the first study to show high-resolution tissue profiles, the histological response to an implanted ENI and blood flow dynamic modeling based on blood vessels implanted with an ENI. The results from this study can be used to guide surgical planning and future ENI designs; stent oversizing parameters to blood vessel diameter should be considered to minimize detrimental vascular remodeling.

Stimulating the Facial Nerve to Treat Ischemic Stroke: A Systematic Review.

Acute ischemic stroke (AIS) is a common devastating disease that has increased yearly in absolute number of cases since 1990. While mechanical thrombectomy and tissue plasminogen activator (tPA) have proven to be effective treatments, their window-of-efficacy time is very short, leaving many patients with no viable treatment option. Over recent years there has been a growing interest in stimulating the facial nerves or ganglions to treat AIS. Pre-clinical studies have consistently demonstrated an increase in collateral blood flow (CBF) following ganglion stimulation, with positive indications in infarct size and neurological scores. Extensive human trials have focused on trans-oral electrical stimulation of the sphenopalatine ganglion, but have suffered from operational limitations and non-significant clinical findings. Regardless, the potential of ganglion stimulation to treat AIS or elongate the window-of-efficacy for current stroke treatments remains extremely promising. This review aims to summarize results from recent trial publications, highlight current innovations, and discuss future directions for the field. Importantly, this review comes after the release of four important clinical trials that were published in mid 2019.