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Purpose Penetrating traumatic brain injury (pTBI) is an acute medical emergency with a high rate of mortality. Patients with survivable injuries face a risk of infection stemming from foreign body transgression into the central nervous system (CNS). There is controversy regarding the utility of antimicrobial prophylaxis in managing such patients, and if so, which antimicrobial agent(s) to use. Methods We reviewed patients with pTBI at our institution and performed a PRISMA systematic review to assess the impact of prophylactic antibiotics on reducing risk of CNS infection. Results We identified 21 local patients and 327 cases in the literature. In our local series, 17 local patients received prophylactic antibiotics; four did not. Overall, five of these patients (24%) developed a CNS infection (four and one case of intraparenchymal brain abscess and meningitis, respectively). All four patients who did not receive prophylactic antibiotics developed an infection (three with CNS infections; one superficial wound infection) compared to two of 17 (12%) patients who did receive prophylactic antibiotics. Of the 327 pTBI cases reported in the literature, 216 (66%) received prophylactic antibiotics. Thirty-eight (17%) patients who received antibiotics developed a CNS infection compared to 21 (19%) who did not receive antibiotics (p = 0.76). Conclusions Although our review of the literature did not reveal any benefit, our institutional series suggested that patients with pTBI may benefit from prophylactic antibiotics. We propose a short antibiotic course with a regimen specific to cases with and without the presence of organic debris.

BackgroundDespite the importance of informed consent in healthcare, the readability and specificity of consent forms often impedes patients’ comprehension. Health literacy is linked to patient outcomes, making it essential to address these issues. This study investigates the use of GPT-4 to simplify surgical consent forms and introduces an AI-human expert collaborative approach to validate content appropriateness.MethodsConsent forms from multiple institutions were assessed for readability and simplified using GPT-4, with pre- and post-simplification readability metrics compared using nonparametric tests. Independent reviews by medical authors and a malpractice defense attorney were conducted. Finally, GPT-4’s potential for generatingde novoprocedure-specific consent forms was assessed, with forms evaluated using a validated 8-item rubric and expert subspecialty surgeon review.ResultsAnalysis of 15 academic medical centers’ consent forms revealed significant reductions in average reading time, word rarity, and passive sentence frequency (allPP=0.004), matching the average American’s reading level. Medical and legal sufficiency consistency was confirmed. GPT-4 generated procedure-specific consent forms for five varied surgical procedures at an average 6th-grade reading level. These forms received perfect scores on a standardized consent form rubric and withstood scrutiny upon expert subspeciality surgeon review.ConclusionsThis study demonstrates the first AI-human expert collaboration to enhance surgical consent forms, significantly improving readability without sacrificing clinical detail. Our framework could be extended to other patient communication materials, emphasizing clear communication and mitigating disparities related to health literacy barriers. Ensuring AI technologies are safely incorporated into clinical practice is crucial to reach a wide range of patients, including the most vulnerable.Data Availability StatementThe raw data was not publicly deposited due to incorporating proprietary datasets, such as the Corpus of Contemporary American English. However, data are available on request for replicability.Code Availability StatementThe code used for these analyses are available from the authors on request.

Stereotactic electroencephalography (SEEG) is an increasingly utilized method for invasive monitoring in patients with medically intractable epilepsy. Yet, the lack of standardization for labeling electrodes hinders communication among clinicians. A rational clustering of contacts based on anatomy rather than arbitrary physical leads may help clinical neurophysiologists interpret seizure networks. We identified SEEG electrodes on post-implant CTs and registered them to preoperative MRIs segmented according to an anatomical atlas. Individual contacts were automatically assigned to anatomical areas independent of lead. These contacts were then organized using a hierarchical anatomical schema for display and interpretation. Bipolar-referenced signal cross-correlations were used to compare the similarity of grouped signals within a conventional montage versus this anatomical montage. As a result, we developed a hierarchical organization for SEEG contacts using well-accepted, free software that is based solely on their post-implant anatomical location. When applied to three example SEEG cases for epilepsy, clusters of contacts that were anatomically related collapsed into standardized groups. Qualitatively, seizure events organized using this framework were better visually clustered compared to conventional schemes. Quantitatively, signals grouped by anatomical region were more similar to each other than electrode-based groups as measured by Pearson correlation. Further, we uploaded visualizations of SEEG reconstructions into the electronic medical record, rendering them durably useful given the interpretable electrode labels. In conclusion, we demonstrate a standardized, anatomically grounded approach to the organization of SEEG neuroimaging and electrophysiology data that may enable improved communication among and across surgical epilepsy teams and promote a clearer view of individual seizure networks.

BackgroundGeneral large language models (LLMs), such as ChatGPT (GPT-3.5), have demonstrated capability to pass multiple-choice medical board examinations. However, comparative accuracy of different LLMs and LLM performance on assessments of predominantly higher-order management questions is poorly understood.ObjectiveTo assess performance of three LLMs (GPT-3.5, GPT-4, and Google Bard) on a question bank designed specifically for neurosurgery oral boards examination preparation.MethodsThe 149-question Self-Assessment Neurosurgery Exam (SANS) Indications Exam was used to query LLM accuracy. Questions were input in a single best answer, multiple-choice format. Chi-squared, Fisher’s exact, and univariable logistic regression tests assessed differences in performance by question characteristics.ResultsOn a question bank with predominantly higher-order questions (85.2%), ChatGPT (GPT-3.5) and GPT-4 answered 62.4% (95% confidence interval [CI]: 54.1-70.1%) and 82.6% (95% CI: 75.2-88.1%) of questions correctly, respectively. In contrast, Bard scored 44.2% (66/149, 95% CI: 36.2-52.6%). GPT-3.5 and GPT-4 demonstrated significantly higher scores than Bard (bothPP=0.023). Among six subspecialties, GPT-4 had significantly higher accuracy in the Spine category relative to GPT-3.5 and in four categories relative to Bard (allPP=0.042) and Bard (OR=0.76,P=0.014), but not GPT-4 (OR=0.86,P=0.085). GPT-4’s performance on imaging-related questions surpassed GPT-3.5’s (68.6% vs. 47.1%,P=0.044) and was comparable to Bard’s (68.6% vs. 66.7%,P=1.000). However, GPT-4 demonstrated significantly lower rates of “hallucination” on imaging-related questions than both GPT-3.5 (2.3% vs. 57.1%,PP=0.002). Lack of question text description for imaging predicted significantly higher odds of hallucination for GPT-3.5 (OR=1.45,P=0.012) and Bard (OR=2.09,PConclusionOn a question bank of predominantly higher-order management case scenarios intended for neurosurgery oral boards preparation, GPT-4 achieved a score of 82.6%, outperforming ChatGPT and Google’s Bard.

BackgroundInterest surrounding generative large language models (LLMs) has rapidly grown. While ChatGPT (GPT-3.5), a general LLM, has shown near-passing performance on medical student board examinations, the performance of ChatGPT or its successor GPT-4 on specialized exams and the factors affecting accuracy remain unclear.ObjectiveTo assess the performance of ChatGPT and GPT-4 on a 500-question mock neurosurgical written boards examination.MethodsThe Self-Assessment Neurosurgery Exams (SANS) American Board of Neurological Surgery (ABNS) Self-Assessment Exam 1 was used to evaluate ChatGPT and GPT-4. Questions were in single best answer, multiple-choice format. Chi-squared, Fisher’s exact, and univariable logistic regression tests were employed to assess performance differences in relation to question characteristics.ResultsChatGPT (GPT-3.5) and GPT-4 achieved scores of 73.4% (95% confidence interval [CI]: 69.3-77.2%) and 83.4% (95% CI: 79.8-86.5%), respectively, relative to the user average of 73.7% (95% CI: 69.6-77.5%). Question bank users and both LLMs exceeded last year’s passing threshold of 69%. While scores between ChatGPT and question bank users were equivalent (P=0.963), GPT-4 outperformed both (bothPP=0.009) were associated with lower accuracy for ChatGPT, but not for GPT-4 (bothP>0.005). Multimodal input was not available at the time of this study so, on questions with image content, ChatGPT and GPT-4 answered 49.5% and 56.8% of questions correctly based upon contextual context clues alone.ConclusionLLMs achieved passing scores on a mock 500-question neurosurgical written board examination, with GPT-4 significantly outperforming ChatGPT.

Tremor, a common and often primary symptom of Parkinson's disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from 10 patients (9 male, 1 female) performing a naturalistic visual–motor task. From this task, we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.SIGNIFICANCE STATEMENTTremor is a common symptom of Parkinson's disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello–thalamic–cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this article, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson's tremor, while describing the short-timescale dynamics of subcortical–cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.

Background: Age may affect treatment outcome in trials of mild probable Alzheimer’s disease (AD). Objective: We examined age as a moderator of outcome in an exploratory study of deep brain stimulation targeting the fornix (DBS-f) region in participants with AD. Methods: Forty-two participants were implanted with DBS electrodes and randomized to double-blind DBS-f stimulation (“on”) or sham DBS-f (“off”) for 12 months. Results: The intervention was safe and well tolerated. However, the selected clinical measures did not differentiate between the “on” and “off” groups in the intent to treat (ITT) population. There was a significant age by time interaction with the Alzheimer’s Disease Assessment Scale; ADAS-cog-13 (p = 0.028). Six of the 12 enrolled participants

OBJECTIVE Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. METHODS We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. RESULTS The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p

Purpose To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. Materials and methods We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring 24 h after presentation (“later-onset”). Results Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5–7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1–8.2]), and troponin (OR 3.0 [95% CI 1.2–7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. Conclusions Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.

BACKGROUND For patients with difficult-to-lateralize temporal lobe epilepsy, the use of chronic recordings as a diagnostic tool to inform subsequent surgical therapy is an emerging paradigm that has been reported in adults but not in children. OBSERVATIONS The authors reported the case of a 15-year-old girl with pharmacoresistant temporal lobe epilepsy who was found to have bitemporal epilepsy during a stereoelectroencephalography (sEEG) admission. She underwent placement of a responsive neurostimulator system with bilateral hippocampal depth electrodes. However, over many months, her responsive neurostimulation (RNS) recordings revealed that her typical, chronic seizures were right-sided only. This finding led to a subsequent right-sided laser amygdalohippocampotomy, resulting in seizure freedom. LESSONS In this case, RNS chronic recording provided real-world data that enabled more precise seizure localization than inpatient sEEG data, informing surgical decision-making that led to seizure freedom. The use of RNS chronic recordings as a diagnostic adjunct to seizure localization procedures and laser ablation therapies in children is an area with potential for future study.

BACKGROUND: In times of health resource reallocation, capacities must remain able to meet a continued demand for essential, nonambulatory neurosurgical acute care. This study sought to characterize the demand for and provision of neurosurgical acute care during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This single-center cross-sectional observational analysis compared nonambulatory neurosurgical consult encounters during the peri-surge period (March 9 to May 31, 2020) with those during an analogous period in 2019. Outcomes included consult volume, distribution of problem types, disease severity, and rate of acute operative intervention. RESULTS: A total of 1494 neurosurgical consults were analyzed. Amidst the pandemic surge, 583 consults were seen, which was 6.4 standard deviations below the mean among analogous 2016-2019 periods (mean 873; standard deviation 45, P = 0.001). Between 2019 and 2020, the proportion of degenerative spine consults decreased in favor of spinal trauma (25.6% vs. 34% and 51.9% vs. 41.4%, P = 0.088). Among aneurysmal subarachnoid hemorrhage cases, poor-grade (Hunt and Hess grades 4-5) presentations were more common (30% vs. 14.8%, P = 0.086). A greater proportion of pandemic era consults resulted in acute operative management, with an unchanged absolute frequency of acutely operative consults (123/583 [21.1%] vs. 120/911 [13.2%], P < 0.001). CONCLUSIONS: Neurosurgical consult volume during the pandemic surge hit a 5-year institutional low. Amidst vast reallocation of health care resources, demand for high-acuity nonambulatory neurosurgical care continued and proportionally increased for greater-acuity pathologies. In our continued current pandemic as well as any future situations of mass health resource reallocation, neurosurgical acute care capacities must be preserved.

Background:Insertion of an external ventricular drain (EVD) is a common neurosurgical procedure which may lead to serious complications including infection. Some risk factors associated with EVD infection are well established. Others remain less certain, including specific indications for placement, prior neurosurgery, and prior EVD placement.Objective:To identify risk factors for EVD infections.Methods:We reviewed all EVD insertions at our institution from March 2015 through May 2019 following implementation of a standardized infection control protocol for EVD insertion and maintenance. Cox regression was used to identify risk factors for EVD infections.Results:479 EVDs placed in 409 patients met inclusion criteria, and 9 culture-positive infections were observed during the study period. The risk of infection within 30 days of EVD placement was 2.2% (2.3 infections/1,000 EVD days). Coagulase-negative staphylococci were identified in 6 of the 9 EVD infections). EVD infection led to prolonged length of stay post–EVD-placement (23 days vs 16 days; P = .045). Cox regression demonstrated increased infection risk in patients with prior brain surgery associated with cerebrospinal fluid (CSF) diversion (HR, 8.08; 95% CI, 1.7–39.4; P = .010), CSF leak around the catheter (HR, 21.0; 95% CI, 7.0–145.1; P = .0007), and insertion site dehiscence (HR, 7.53; 95% CI, 1.04–37.1; P = .0407). Duration of EVD use >7 days was not associated with infection risk (HR, 0.62; 95% CI, 0.07–5.45; P = .669).Conclusion:Risk factors associated with EVD infection include prior brain surgery, CSF leak, and insertion site dehiscence. We found no significant association between infection risk and duration of EVD placement.

Parkinson’s Disease (PD) is characterized by distinct motor phenomena that are expressed asynchronously. Understanding the neurophysiological correlates of these different motor states could facilitate monitoring of disease progression and allow improved assessments of therapeutic efficacy, as well as enable optimal closed-loop neuromodulation. We examined neural activity in the basal ganglia and cortex of subjects with PD during a quantitative motor task to decode tremor and bradykinesia — two cardinal motor signs of this disease — and relatively asymptomatic periods of behavior. Analysis of subcortical and cortical signals revealed that tremor and bradykinesia had distinct, nearly opposite neural signatures, while effective motor control displayed unique, differentiating features. The neurophysiological signatures of these motor states depended on the type of signal recorded as well as the location; cortical decoding accuracy generally outperformed subcortical decoding, while tremor and bradykinesia were better decoded from different portions of the subthalamic nucleus (STN). These results provide a roadmap to leverage real-time neurophysiology to understand and treat PD.One Sentence SummaryMotor signs of Parkinson’s disease such as tremor and bradykinesia can be independently decoded from subthalamic and cortical recordings.

BACKGROUND Patients with refractory, bilateral, multifocal epilepsy have few treatment options that typically include a combination of antiseizure medications (ASMs) and vagus nerve stimulation (VNS). A man in his 40s presented with epilepsy refractory to a combination of five ASMs plus VNS; he was still experiencing 7–10 seizures per week. His seizure network involved multiple foci in both frontal and temporal lobes. Bilateral depth electrodes were implanted into the centromedian/parafascicular (CM/PF) complex of the thalamus and connected to the responsive neurostimulation (RNS) system for closed-loop stimulation and neurophysiological monitoring. OBSERVATIONS The patient reported clear improvement in his seizures since the procedure, with a markedly reduced number of seizures and decreased seizure intensity. He also reported stretches of seizure freedom not typical of his preoperative baseline, and his remaining seizures were milder, more often with preserved awareness. Generalized seizures with loss of consciousness have decreased to about one per month. RNS data confirmed a right-sided predominance of the bilateral seizure onsets. LESSONS In this patient with multifocal, bilateral frontotemporal epilepsy, RNS of the CM/PF thalamic complex combined with VNS was found to be beneficial. The RNS device was able to detect seizures propagating through the thalamus, and stimulation produced a decrease in seizure burden and intensity.

Tremor, a common and often primary symptom of Parkinson’s disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from ten patients performing a naturalistic visual-motor task. From this task we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state.SIGNIFICANCE STATEMENTTremor is a common symptom of Parkinson’s disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello-thalamic-cortical circuits, it is unknown how these structures functionally interact to produce tremor. In this manuscript, we analyzed intracranial recordings from the subthalamic nucleus and sensorimotor cortex in patients with PD undergoing deep brain stimulation (DBS) surgery. Using an intraoperative task, we examined tremor in two separate dynamic contexts: when tremor first emerged, and when tremor was sustained. We believe that these findings reconcile several models of Parkinson’s tremor, while describing the short-timescale dynamics of subcortical-cortical interactions during tremor for the first time. These findings may describe a framework for developing proactive and responsive neurostimulation models for specifically treating tremor.

OBJECTIVE External ventricular drain (EVD) placement is a common neurosurgical procedure, and EVD-related infection is a significant complication. We examined the effect of infection control protocol changes on EVD-related infection incidence. METHODS Changes in EVD placement protocol and incidence density of infections after implementation of protocol changes in the neurocritical care unit were tracked from 2007 to 2019. EVD infections were defined using a modified U.S. Centers for Disease Control and Prevention National Healthcare Safety Network surveillance definition of meningitis/ventriculitis for patients with EVDs in situ for at least 2 days confirmed by positive culture. Contribution of protocol changes to EVD infection risk was assessed via multivariate regression. RESULTS Fifteen major changes in EVD protocol were associated with a reduction in infections from 6.7 to 2.0 per 1000 EVD days (95% confidence interval [CI], 4.1-5.3; P

INTRODUCTION The COVID-19 pandemic has caused unprecedented social, geopolitical, and health systems factors that may affect types of patients presenting for essential, non-ambulatory care. Social distancing and lockdowns may reduce the incidence of trauma; however, a significant decline in presentations of acute medical conditions such as stroke and ACS have been reported. Furthermore, health system capacities are substantially altered, with elective surgeries postponed to devote resources to COVID-related illness and high acuity non-COVID illness. METHODS We reviewed all emergency department and inpatient consultations to the neurosurgical service at a Level 1 Trauma Center during an 8-week post-lockdown period (3/15-5/4), quantifying overall volume, as well the distribution of problem types and management endpoints. RESULTS Pandemic period consult volumes were significantly lower than those of parallel periods in 2016–2019 (388 vs. a 4-year average of 576, P

As the current understanding of COVID-19 continues to evolve, a synthesis of the literature on the neurological impact of this novel virus may help inform clinical management and highlight potentially important avenues of investigation. Additionally, understanding the potential mechanisms of neurologic injury may guide efforts to better detect and ameliorate these complications. In this review, we synthesize a range of clinical observations and initial case series describing potential neurologic manifestations of COVID-19 and place these observations in the context of coronavirus neuro-pathophysiology as it may relate to SARS-CoV-2 infection. Reported nervous system manifestations range from anosmia and ageusia, to cerebral hemorrhage and infarction. While the volume of COVID-19-related case studies continues to grow, previous work examining related viruses suggests potential mechanisms through which the novel coronavirus may impact the CNS and result in neurological complications. Namely, animal studies examining the SARS-CoV have implicated the angiotensin-converting-enzyme-2 receptor as a mediator of coronavirus-related neuronal damage and have shown that SARS-CoV can infect cerebrovascular endothelium and brain parenchyma, the latter predominantly in the medial temporal lobe, resulting in apoptosis and necrosis. Human postmortem brain studies indicate that human coronavirus variants and SARS-CoV can infect neurons and glia, implying SARS-CoV-2 may have similar neurovirulence. Additionally, studies have demonstrated an increase in cytokine serum levels as a result of SARS-CoV infection, consistent with the notion that cytokine overproduction and toxicity may be a relevant potential mechanism of neurologic injury, paralleling a known pathway of pulmonary injury. We also discuss evidence that suggests that SARS-CoV-2 may be a vasculotropic and neurotropic virus. Early reports suggest COVID-19 may be associated with severe neurologic complications, and several plausible mechanisms exist to account for these observations. A heightened awareness of the potential for neurologic involvement and further investigation into the relevant pathophysiology will be necessary to understand and ultimately mitigate SARS-CoV-2-associated neurologic injury.

Background Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration. Objective To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo. Methods A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies. Results A total of 7 of the 9 patients were considered full responders (77.8%; Yale-Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery. Conclusion LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.

Healthcare providers rely on complex biomedical devices to assess, treat, and monitor patients. Ongoing research efforts are attempting to generate and implement better algorithms and mechanisms to ensure the early, accurate, automated, and clinically meaningful recognition of patterns and changes in patient health and pathology. Effecting such evolutionary advances in patient monitoring will likely require large collections of high-resolution physiologic parameter datasets from a broad spectrum of patients. As part of a research program to scientifically improve patient monitoring (with a focus on alarm fatigue mitigation), investigators developed the Medical Technology Interface-Open/Research toolkit with modular conduit components that provide the following capabilities: 1) access to select bedside monitor physiologic signals in real-world clinical settings for near-real-time acquisition, storage, and export of high-resolution patient datastreams in a portable format (.json); 2) establishment of a safe, parallel test environment at the bedside for experimental datastream analyses in a research framework. Deployment and interfacing of toolkit elements with off-the-shelf software solutions in a live emergency department setting enabled the construction of a bedside clinical informatics (BCI) research pipeline infrastructure that featured 1) indexing, search/query, and retrieval of datastreams for sophisticated analyses, experimental processing, and algorithm development; and 2) dataset visualization for expert adjudication of datastream interpretability, alarm clinical significance and severity, and experimental algorithm performance. In order to help institute a collaborative biomedical engineering research resource, this article shares details of the active ED BCI data pipeline and presents preliminary examples of ongoing multimodal data fusion applications.

Objective. Identifying neural activity biomarkers of brain disease is essential to provide objective estimates of disease burden, obtain reliable feedback regarding therapeutic efficacy, and potentially to serve as a source of control for closed-loop neuromodulation. In Parkinson’s disease (PD), microelectrode recordings (MER) are routinely performed in the basal ganglia to guide electrode implantation for deep brain stimulation (DBS). While pathologically-excessive oscillatory activity has been observed and linked to PD motor dysfunction broadly, the extent to which these signals provide quantitative information about disease expression and fluctuations, particularly at short timescales, is unknown. Furthermore, the degree to which informative signal features are similar or different across patients has not been rigorously investigated. We sought to determine the extent to which motor error in PD across patients can be decoded on a rapid timescale using spectral features of neural activity. Approach. Here, we recorded neural activity from the subthalamic nucleus (STN) of subjects with PD undergoing awake DBS surgery while they performed an objective, continuous behavioral assessment that synthesized heterogenous PD motor manifestations to generate a scalar measure of motor dysfunction at short timescales. We then leveraged natural motor performance variations as a ‘ground truth’ to identify corresponding neurophysiological biomarkers. Main results. Support vector machines using multi-spectral decoding of neural signals from the STN succeeded in tracking the degree of motor impairment at short timescales (as short as one second). Spectral power across a wide range of frequencies, beyond the classic ‘β’ oscillations, contributed to this decoding, and multi-spectral models consistently outperformed those generated using more isolated frequency bands. While generalized decoding models derived across subjects were able to estimate motor impairment, patient-specific models typically performed better. Significance. These results demonstrate that quantitative information about short-timescale PD motor dysfunction is available in STN neural activity, distributed across various patient-specific spectral components, such that an individualized approach will be critical to fully harness this information for optimal disease tracking and closed-loop neuromodulation.

Background: Delirium occurs frequently in patients with intracerebral hemorrhage (ICH), though its pathogenesis may be multifactorial. Given the potential role of systemic stressors in delirium, we aimed to explore differences in commonly measured markers of physiologic stress between delirious and non-delirious ICH patients. Methods: We performed a single-center cohort study using data from consecutive non-comatose ICH patients over 12 months. ICH and patient characteristics were prospectively collected, and the presence of delirium at any point during hospitalization was diagnosed based on DSM-5 criteria. We retrospectively abstracted admission laboratory values and selected three common markers of physiologic stress for comparison: neutrophil-lymphocyte ratio (NLR), troponin, and glucose. Using multivariable models adjusted for demographics, relevant comorbidities, and ICH severity, we determined associations between delirium and the following: NLR, using linear regression; elevated troponin (>0.05 ng/mL), using binary logistic regression; and elevated glucose (categorized as 130-180 or >180 mg/dL), using ordered logistic regression. Results: Of 284 ICH patients in our cohort, 55% (n=157) had delirium. Patients with delirium were not significantly older than non-delirious patients (mean age 71.7±16.2 vs. 68.3±15.1, p=0.07), but had larger ICH volumes (mean 23.3±24.6 vs. 7.0±10.6 cc, p Conclusions: Delirium after ICH is independently associated with elevated serum markers of physiologic stress, suggesting that systemic factors may be implicated in delirium pathogenesis.

Background During the deep brain stimulation (DBS) electrode implantation operation with microelectrode recordings (MER) in awake patients, somatotopic testing and test stimulation are performed to improve electrode placement and provide the most beneficial symptom reduction possible, while minimizing side effects. As this procedure is commonly used to alleviate abnormal movements associated with Parkinson's disease (PD) and Essential Tremor (ET), intraoperative assessment of a patient's movements is critical to optimizing surgical benefit. However, despite its importance, movement assessment is typically subjective and qualitative. New method Here, we present a detailed description of a low-cost, open-source system as a solution. Results The described system measures movements intraoperatively and in synchrony with neurophysiological recordings for both online visualization and offline analysis. Comparison with existing method(s) Few movement quantification systems are designed to interface with intraoperative neurophysiological recordings; the widespread application of such systems may be limited by their cost and proprietary, closed-source nature. The system presented provides a low-cost, open-source alternative. Conclusions The system outlined in this work may improve the DBS procedure by adding valuable objectivity in movement quantification.

Background/Objectives: To create an open-source method for reconstructing microelectrode recording (MER) and deep brain stimulation (DBS) electrode coordinates along multiple parallel trajectories with patient-specific DBS implantation platforms to facilitate DBS research. Methods: We combined the surgical geometry (extracted from WayPoint Planner), pre-/intra-/postoperative computed tomography (CT) and/or magnetic resonance (MR) images, and integrated them into the Analysis of Functional NeuroImages (AFNI) neuroimaging analysis environment using functions written in Python. Electrode coordinates were calculated from image-based electrode surfaces and recording trajectory depth values. Coordinates were translated into appropriate trajectories, and were tested for proximity to patient-specific or atlas-based anatomical structures. Final DBS electrode coordinates for 3 patient populations (ventral intermediate nucleus [VIM], subthalamic nucleus [STN], and globus pallidus pars interna [GPi]) were calculated. For STN cases, MER site coordinates were then analyzed to see whether they were inside or outside the STN. Results: Final DBS electrode coordinates were described for VIM, STN, and GPi patient populations. 115/169 (68%) STN MER sites were within 1 mm of the STN in AFNI’s Talairach and Tournoux (TT) atlas. Conclusions: DBStar is a robust tool kit for understanding the anatomical location and context of electrode locations, and can easily be used for imaging, behavioral, or electrophysiological analyses.

Background and importance Cerebrospinal fluid shunt placement is used to treat the various causes of hydrocephalus by redirecting the cerebrospinal fluid to the body, most commonly from the ventricle to the peritoneum. Distal catheter displacement from the peritoneal cavity can occur as a complication, necessitating reoperation. Clinical presentation We report 2 such cases in obese patients involving retropulsion of the distal tubing. To address this complication, we implanted a T-connector to the distal catheter construct. Conclusion This study supports the use of a T-connector catheter construct to decrease and prevent the possibility of distal peritoneal catheter retropulsion in cases of elevated intra-abdominal pressure, both prophylactically and in revisions.

ObjectiveTo determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry.MethodsWe performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score–based models with and without delirium category in predicting WLST.ResultsOf 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1–2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0–6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1–37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863–0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909–0.962], p = 0.004).ConclusionDelirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.

Creating successful new neuromodulation therapies requires innovative trial design and the balancing of a wide variety of complex factors. The ultimate goal is to advance our ability to restore appropriate brain function through the targeted manipulation of neural circuits and, to this end, clinical trials should be just as informative in failure as they are in success. Some aspects of neuromodulation trials are common to all clinical studies, while other aspects are fairly specific to invasive neurosurgical interventions for complex neurological and psychiatric disease. This chapter examines the major factors to be considered in constructing clinical studies to investigate the various forms and applications of novel neuromodulation strategies.

Functional lesions for the treatment of intractable, debilitating psychiatric disease have been created using a variety of techniques over many decades. Here, we describe the relative advantages and disadvantages of laser thermal lesions and the application of this technique to one particular disease, refractory and severe obsessive-compulsive disorder (OCD). Early experience suggests this approach will enable the creation of reliable and morphologically consistent lesions while avoiding some of the pitfalls and complications of other lesion modalities.

OBJECTIVES Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage. DESIGN Prospective observational cohort study. SETTING Neurocritical Care and Stroke Units at a university hospital. PATIENTS Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64). CONCLUSIONS Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Introduction: Established predictors for outcome after intracerebral hemorrhage (ICH) may be subject to self-fulfilling prophecy, as studies examining their effects on mortality have generally not considered changes in code status leading to withdrawal of life-sustaining treatment (WLST). We aimed to identify factors specifically associated with WLST, and hypothesized that impaired consciousness and delirium would be especially implicated. Methods: We analyzed data from consecutive patients admitted with ICH from February-June 2018. ICH score and other clinical predictors were prospectively adjudicated, and most patients had delirium assessments performed by an expert clinician; for those who did not, we established the presence of probable delirium via chart review. Using logistic regression models that adjusted for ICH severity, we determined the association of impaired consciousness on admission (Glasgow Coma Scale [GCS] Results: Of 106 patients in our cohort (mean age 68.7 [SD 17.8], median ICH score 1.5 [IQR 1-2]), WLST occurred in 29% (22/40 with admission GCS 80; OR 8.4, 95% CI 1.7-40.7 for size >30cc; intraventricular hemorrhage and infratentorial location were not significant). Of 92 patients who survived >24 hours without early WLST, 52% had delirium. We found that delirious patients were significantly more likely than patients without delirium to have subsequent WLST (33% vs. 2%, p Conclusion: Impaired consciousness and delirium likely play a significant role in WLST after ICH. However, whether this phenomenon is due to effects on clinician or surrogate decision-making remains unclear.

Introduction: Post-stroke delirium is associated with worse outcomes, yet is likely underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurological deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in a cohort of patients with intracerebral hemorrhage (ICH). Methods: Consecutive patients admitted with ICH received daily assessments for delirium by an expert clinician, all of which included the Confusion Assessment Method for the ICU (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC), a focused bedside cognitive exam, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using DSM-5 criteria, then compared performance of the CAM-ICU and ICDSC with reference-standard diagnosis. Results: We performed 257 assessments on 60 patients (mean age 68.0 [SD 18.4], 62% male, median ICH score 1.5 [IQR 1-2]), of whom 55% had delirium. Symptom fluctuation (61% of all assessments), impaired arousal (37%), psychomotor changes (46%), and sleep-wake disturbances (46%) had a high prevalence and were never rated “unable to assess” (UTA), while inattention (36%), disorganized thinking (18%), and disorientation (27%) were also common but were often UTA (32%, 44%, and 43% of assessments, respectively), most frequently due to aphasia (present in 32% of patients). As the ICDSC may be positive without the presence of symptoms that require verbal assessment, it was more accurate ( Sensitivity= 77%, Specificity= 97%) than the CAM-ICU ( Sensitivity= 41%, Specificity= 88%) relative to the DSM-5-based reference standard. Allowing non-verbal assessments of attention using visual and auditory stimuli decreased the frequency of UTA assessments to 11%. Conclusion: Delirium is common after ICH, but reliance on verbal interaction with patients may confound its assessment and lead to underdiagnosis. The ICDSC’s inclusion of non-verbal features makes it more accurate than the CAM-ICU, but novel tools specifically designed for patients with neurological deficits may be warranted.

Background: Deep brain stimulation (DBS) is used to modulate the activity of dysfunctional brain circuits. The safety and efficacy of DBS in dementia is unknown. Objective: To assess DBS of memory circuits as a treatment for patients with mild Alzheimer’s disease (AD). Methods: We evaluated active “on” versus sham “off” bilateral DBS directed at the fornix-a major fiber bundle in the brain’s memory circuit-in a randomized, double-blind trial (ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01608061","term_id":"NCT01608061"}}NCT01608061) in 42 patients with mild AD. We measured cognitive function and cerebral glucose metabolism up to 12 months post-implantation. Results: Surgery and electrical stimulation were safe and well tolerated. There were no significant differences in the primary cognitive outcomes (ADAS-Cog 13, CDR-SB) in the “on” versus “off” stimulation group at 12 months for the whole cohort. Patients receiving stimulation showed increased metabolism at 6 months but this was not significant at 12 months. On post-hoc analysis, there was a significant interaction between age and treatment outcome: in contrast to patients

OBJECT This report describes the stereotactic technique, hospitalization, and 90-day perioperative safety of bilateral deep brain stimulation (DBS) of the fornix in patients who underwent DBS for the treatment of mild, probable Alzheimer's disease (AD). METHODS The ADvance Trial is a multicenter, 12-month, double-blind, randomized, controlled feasibility study being conducted to evaluate the safety, efficacy, and tolerability of DBS of the fornix in patients with mild, probable AD. Intraoperative and perioperative data were collected prospectively. All patients underwent postoperative MRI. Stereotactic analyses were performed in a blinded fashion by a single surgeon. Adverse events (AEs) were reported to an independent clinical events committee and adjudicated to determine the relationship between the AE and the study procedure. RESULTS Between June 6, 2012, and April 28, 2014, a total of 42 patients with mild, probable AD were treated with bilateral fornix DBS (mean age 68.2 ± 7.8 years; range 48.0–79.7 years; 23 men and 19 women). The mean planned target coordinates were x = 5.2 ± 1.0 mm (range 3.0–7.9 mm), y = 9.6 ± 0.9 mm (range 8.0–11.6 mm), z = −7.5 ± 1.2 mm (range −5.4 to −10.0 mm), and the mean postoperative stereotactic radial error on MRI was 1.5 ± 1.0 mm (range 0.2–4.0 mm). The mean length of hospitalization was 1.4 ± 0.8 days. Twenty-six (61.9%) patients experienced 64 AEs related to the study procedure, of which 7 were serious AEs experienced by 5 patients (11.9%). Four (9.5%) patients required return to surgery: 2 patients for explantation due to infection, 1 patient for lead repositioning, and 1 patient for chronic subdural hematoma. No patients experienced neurological deficits as a result of the study, and no deaths were reported. CONCLUSIONS Accurate targeting of DBS to the fornix without direct injury to it is feasible across surgeons and treatment centers. At 90 days after surgery, bilateral fornix DBS was well tolerated by patients with mild, probable AD. Clinical trial registration no.: NCT01608061 (clinicaltrials.gov)

OBJECTIVETraumatic intracranial hemorrhage (tICH) is a significant source of morbidity and mortality in trauma patients. While prognostic models for tICH outcomes may assist in alerting clinicians to high-risk patients, previously developed models face limitations, including low accuracy, poor generalizability, and the use of more prognostic variables than is practical. This study aimed to construct a simpler and more accurate method of risk stratification for all tICH patients.METHODSThe authors retrospectively identified a consecutive series of 4110 patients admitted to their institution’s level 1 trauma center between 2003 and 2013. For each admission, they collected the patient’s sex, age, systolic blood pressure, blood alcohol concentration, antiplatelet/anticoagulant use, Glasgow Coma Scale (GCS) score, Injury Severity Score, presence of epidural hemorrhage, presence of subdural hemorrhage, presence of subarachnoid hemorrhage, and presence of intraparenchymal hemorrhage. The final study population comprised 3564 patients following exclusion of records with missing data. The dependent variable under study was patient death. A k-fold cross-validation was carried out with the best models selected via the Akaike Information Criterion. These models risk stratified the study partitions into grade I (< 1% predicted mortality), grade II (1%–10% predicted mortality), grade III (10%–40% predicted mortality), or grade IV (> 40% predicted mortality) tICH. Predicted mortalities were compared with actual mortalities within grades to assess calibration. Concordance was also evaluated. A final model was constructed using the entire data set. Subgroup analysis was conducted for each hemorrhage type.RESULTSCross-validation demonstrated good calibration (p < 0.001 for all grades) with a mean concordance of 0.881 (95% CI 0.865−0.898). In the authors’ final model, older age, lower blood alcohol concentration, antiplatelet/anticoagulant use, lower GCS score, and higher Injury Severity Score were all associated with greater mortality. Subgroup analysis showed successful stratification for subarachnoid, intraparenchymal, grade II–IV subdural, and grade I epidural hemorrhages.CONCLUSIONSThe authors developed a risk stratification model for tICH of any GCS score with concordance comparable to prior models and excellent calibration. These findings are applicable to multiple hemorrhage subtypes and can assist in identifying low-risk patients for more efficient resource allocation, facilitate family conversations regarding goals of care, and stratify patients for research purposes. Future work will include testing of more variables, validation of this model across institutions, as well as creation of a simplified model whose outputs can be calculated mentally.