Structural and functional connectivity in hydrocephalus: a scoping review.

Optimizing the treatment of hydrocephalus remains a major challenge in adult and pediatric neurosurgery. Currently, clinical treatment relies heavily on anatomic imaging of ventricular size and clinical presentation. The emergence of functional and structural brain connectivity imaging has provided the basis for a new paradigm in the management of hydrocephalus. Here we review the pertinent advances in this field. Following PRISMA-ScR guidelines for scoping reviews, we searched PubMed for relevant literature from 1994 to April 2023 using hydrocephalus and MRI-related terms. Included articles reported original MRI data on human subjects with hydrocephalus, while excluding non-English or pre-1994 publications that didn't match the study framework. The review identified 44 studies that investigated functional and/or structural connectivity using various MRI techniques across different hydrocephalus populations. While there is significant heterogeneity in imaging technology and connectivity analysis, there is broad consensus in the literature that 1) hydrocephalus is associated with disruption of functional and structural connectivity, 2) this disruption in cerebral connectivity can be further associated with neurologic compromise 3) timely treatment of hydrocephalus restores both cerebral connectivity and neurologic compromise. The robustness and consistency of these findings vary as a function of patient age, hydrocephalus etiology, and the connectivity region of interest studied. Functional and structural brain connectivity imaging shows potential as an imaging biomarker that may facilitate optimization of hydrocephalus treatment. Future research should focus on standardizing regions of interest as well as identifying connectivity analysis most pertinent to clinical outcome.

Persistent Racial Disparities in Deep Brain Stimulation for Parkinson's Disease.

We sought to determine whether racial and socioeconomic disparities in the utilization of deep brain stimulation (DBS) for Parkinson's disease (PD) have improved over time. We examined DBS utilization and analyzed factors associated with placement of DBS. The odds of DBS placement increased across the study period, whereas White patients with PD were 5 times more likely than Black patients to undergo DBS. Individuals, regardless of racial background, with 2 or more comorbidities were 14 times less likely to undergo DBS. Privately insured patients were 1.6 times more likely to undergo DBS. Despite increasing DBS utilization, significant disparities persist in access to DBS. ANN NEUROL 2022;92:246-254.

Readmission risk of malignant brain tumor patients undergoing laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB): a covariate balancing weights analysis of the National Readmissions Database (NRD).

PURPOSE: Despite procedural similarities between laser interstitial thermal therapy (LITT) and stereotactic needle biopsy (SNB), LITT induces delayed, pro-inflammatory responses not associated with SNB that may increase the risk of readmission within 30- or 90- days. Here, we explore this hypothesis. METHODS: We queried the National Readmissions Database (NRD, 2010-18) for malignant brain tumor patients who underwent elective LITT or SNB using International Classification of Diseases codes. Readmissions were defined as non-elective inpatient hospitalizations. Survey regression methods and a weighted analysis were utilized to adjust for demographic and clinical differences between LITT and SNB cohorts. RESULTS: During the study period, an estimated 685 malignant brain patients underwent elective LITT and 15,177 underwent elective SNB. Patients undergoing LITT and SNB exhibited comparable median lengths of hospital stay [IQR; LITT = 2 (1, 3); SNB = 1 (1, 2); p = 0.820]. Likelihood of routine discharge was not significantly different between the two procedures (p = 0.263). No significant differences were observed in the odds of 30- or 90-day unplanned readmission between the LITT and SNB cohorts after multivariable adjustment (all p ≥ 0.177). The covariate balancing weighted analysis confirmed comparable 30 or 90-day readmission risk between LITT and SNB treated patients (all p ≥ 0.201). CONCLUSION: The likelihood of 30- and 90-day readmission for malignant brain tumor patients who underwent LITT or SNB are comparable, supporting the safety profile of LITT as therapy for malignant brain cancers.

Using kinematics to re-define the pull test as a quantitative biomarker of the postural response in normal pressure hydrocephalus patients.

Quantitative biomarkers are needed for the diagnosis, monitoring and therapeutic assessment of postural instability in movement disorder patients. The goal of this study was to create a practical, objective measure of postural instability using kinematic measurements of the pull test. Twenty-one patients with normal pressure hydrocephalus and 20 age-matched control subjects were fitted with inertial measurement units and underwent 10-20 pull tests of varying intensities performed by a trained clinician. Kinematic data were extracted for each pull test and aggregated. Patients participated in 103 sessions for a total of 1555 trials while controls participated in 20 sessions for a total of 299 trials. Patients were separated into groups by MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pull test score. The center of mass velocity profile easily distinguished between patient groups such that score increases correlated with decreases in peak velocity and later peak velocity onset. All patients except those scored as "3" demonstrated an increase in step length and decrease in reaction time with increasing pull intensity. Groups were distinguished by differences in the relationship of step length to pull intensity (slope) and their overall step length or reaction time regardless of pull intensity (y-intercept). NPH patients scored as "normal" on the MDS-UPDRS scale were kinematically indistinguishable from age-matched control subjects during a standardized perturbation, but could be distinguished from controls by their response to a range of pull intensities. An instrumented, purposefully varied pull test produces kinematic metrics useful for distinguishing clinically meaningful differences within hydrocephalus patients as well as distinguishing these patients from healthy, control subjects.

Pattern of technology diffusion in the adoption of stereotactic laser interstitial thermal therapy (LITT) in neuro-oncology.

PURPOSE: Understanding factors that influence technology diffusion is central to clinical translation of novel therapies. We characterized the pattern of adoption for laser interstitial thermal therapy (LITT), also known as stereotactic laser ablation (SLA), in neuro-oncology using the National Inpatient Sample (NIS) database. METHODS: We identified patients age ≥ 18 in the NIS (2012-2018) with a diagnosis of primary or metastatic brain tumor that underwent LITT or craniotomy. We compared characteristics and outcomes for patients that underwent these procedures. RESULTS: LITT utilization increased ~ 400% relative to craniotomy during the study period. Despite this increase, the total number of LITT procedures performed for brain tumor was < 1% of craniotomy. After adjusting for this time trend, LITT patients were less likely to have > 2 comorbidities (OR 0.64, CI95 0.51-0.79) or to be older (OR 0.92, CI95 0.86-0.99) and more likely to be female (OR 1.35, CI95 1.08-1.69), Caucasian compared to Black (OR 1.94, CI95 1.12-3.36), and covered by private insurance compared to Medicare or Medicaid (OR 1.38, CI95 1.09-1.74). LITT hospital stays were 50% shorter than craniotomy (IRR 0.52, CI95 0.45-0.61). However, charges related to the procedures were comparable between LITT and craniotomy ($1397 greater for LITT, CI95 $-5790 to $8584). CONCLUSION: For neuro-oncology indications, LITT utilization increased ~ 400% relative to craniotomy. Relative to craniotomy-treated patients, LITT-treated patients were likelier to be young, female, non-Black race, covered by private insurance, or with < 2 comorbidities. While the total hospital charges were comparable, LITT was associated with a shorter hospitalization relative to craniotomy.

Resective epilepsy surgery: assessment of randomized controlled trials.

Epilepsy is the most common form of chronic neurologic disease. Here, we review the available randomized controlled trials (RCTs) that examined the efficacy of resective epilepsy surgery in select patients suffering from medically intractable epilepsy (defined as persistent epilepsy despite two or more antiepileptic drugs [AEDs]). Three RCTs (two adult RCTs and one pediatric RCT) consistently supported the efficacy of resective surgery as treatment for epilepsy with semiology localized to the mesial temporal lobe. In these studies, 58-100% of the patients who underwent resective surgery achieved seizure freedom, in comparison to 0-13% of medically treated patients. In another RCT, the likelihood of seizure freedom after resective surgery was independent of the surgical approach (transSylvian [64%] versus subtemporal [62%]). Two other RCTs demonstrated that hippocampal resection is essential to optimize seizure control. But, no significant gain in seizure control was achieved beyond removing 2.5 cm of the hippocampus. Across RCTs, minor complications (deficit lasting < 3 months) and major complications (deficit > 3 months) ranged 2-5% and 5-11% respectively. However, nonincapacitating superior subquadrantic visual-field defects (not typically considered a minor or major complication) were noted in up to 55% of the surgical cohort. The available RCTs provide compelling support for resective surgery as a treatment for mesial temporal lobe epilepsy and offer insights toward optimal surgical strategy.

Risk analysis of hemorrhage in stereo-electroencephalography procedures.

OBJECTIVE: To examine the true incidence of hemorrhage related to stereo-electroencephalography (SEEG) procedures. To analyze risk factors associated with the presence of different types of hemorrhage in SEEG procedures. METHODS: This was a retrospective, single-center observational study examining every SEEG implantation performed at our center from 2009 to 2017. This consisted of 549 consecutive SEEG implantations using a variety of stereotactic and imaging techniques. A hemorrhage grading system was applied by a blinded neuroradiologist to every postimplant and postexplant computed tomography (CT) scan. Hemorrhages were classified as asymptomatic or symptomatic based on neurologic deficit seen on examination. Statistical analysis included multivariate regression using relevant preoperative variables to predict the presence of hemorrhage. RESULTS: One hundred five implantations (19.1%) had any type of hemorrhage seen on postimplant CT. Of these, 93 (16.9%) were asymptomatic and 12 (2.2%) were symptomatic, with 3 implantations (0.6%) resulting in either a permanent deficit (2, 0.4%) or death (1, 0.2%). Male sex, increased number of electrodes, and increasing age were associated with increased risk of postimplant hemorrhage on multivariate analysis. Increasing score in the grading system was related to a statistically significant increase in the likelihood of a symptomatic hemorrhage. SIGNIFICANCE: Detailed examination of every postimplant CT reveals that the total hemorrhage rate appears higher than previously reported. Most of these hemorrhages are small and asymptomatic. Our grading system may be useful to risk stratify these hemorrhages and awaits prospective validation.

Hemispherectomy in adults and adolescents: Seizure and functional outcomes in 47 patients.

OBJECTIVE: To examine longitudinal seizure and functional outcomes after hemispherectomy in adults and adolescents. METHODS: We reviewed 47 consecutive patients older than 16 years who underwent hemispherectomy between 1996 and 2016 at our center. Clinical, electroencephalographic (EEG), imaging, neuropsychological, surgical, and functional status data were analyzed. RESULTS: Thirty-six patients were 18 years or older at surgery; 11 were aged between 16 and 18 years. Brain injury leading to hemispheric epilepsy occurred before 10 years of age in 41 (87%) patients. At a mean follow-up of 5.3 postoperative years (median = 2.9 years), 36 (77%) had Engel class I outcome. Longitudinal outcome analysis showed 84% seizure freedom (Engel IA) at 6 months, 76% at 2 years, and 76% at 5 years and beyond, with stable longitudinal outcomes up to 12 years from surgery. Multivariate analysis demonstrated that acute postoperative seizures and contralateral interictal spikes at 6-month follow-up EEG were associated with seizure recurrence. Patients who could walk unaided preoperatively and had no cerebral peduncle atrophy on brain magnetic resonance imaging were more likely to experience worsening of motor function postoperatively. Otherwise, postoperative ambulatory status and hand function were unchanged. Of the 19 patients who completed neuropsychological testing, 17 demonstrated stable or improved postoperative outcomes. SIGNIFICANCE: Hemispherectomy in adults is a safe and effective procedure, with seizure freedom rates and functional outcome similar to those observed in children.

Techniques for placement of stereotactic electroencephalographic depth electrodes: Comparison of implantation and tracking accuracies in a cadaveric human study.

OBJECTIVE: Stereotactic electroencephalography (SEEG) is used for the evaluation and identification of the epileptogenic zone (EZ) in patients suffering from medically refractory seizures and relies upon the accurate implantation of depth electrodes. Accurate implantation is critical for identification of the EZ. Multiple electrodes and implantation systems exist, but these have not previously been systematically evaluated for implantation accuracy. This study compares the accuracy of two SEEG electrode implantation methods. METHODS: Thirteen "technique 1" electrodes (applying guiding bolts and external stylets) and 13 "technique 2" electrodes (without guiding bolts and external stylets) were implanted into four cadaver heads (52 total of each) according to each product's instructions for use using a stereotactic robot. Postimplantation computed tomography scans were compared to preimplantation computed tomography scans and to the previously defined targets. Electrode entry and final depth location were measured by Euclidean coordinates. The mean errors of each technique were compared using linear mixed effects models. RESULTS: Primary analysis revealed that the mean error difference of the technique 1 and 2 electrodes at entry and target favored the technique 1 electrode implantation accuracy (P < 0.001). Secondary analysis demonstrated that orthogonal implantation trajectories were more accurate than oblique trajectories at entry for technique 1 electrodes (P = 0.002). Furthermore, deep implantations were significantly less accurate than shallow implantations for technique 2 electrodes (P = 0.005), but not for technique 1 electrodes (P = 0.50). SIGNIFICANCE: Technique 1 displays greater accuracy following SEEG electrode implantation into human cadaver heads. Increased implantation accuracy may lead to increased success in identifying the EZ and increased seizure freedom rates following surgery.

New Techniques and Progress in Epilepsy Surgery.

While open surgical resection for medically refractory epilepsy remains the gold standard in current neurosurgical practice, modern techniques have targeted areas for improvement over open surgical resection. This review focuses on how a variety of these new techniques are attempting to address these various limitations. Stereotactic electroencephalography offers the possibility of localizing deep epileptic foci, improving upon subdural grid placement which limits localization to neocortical regions. Laser interstitial thermal therapy (LITT) and stereotactic radiosurgery can minimally or non-invasively ablate specific regions of interest, with near real-time feedback for laser interstitial thermal therapy. Finally, neurostimulation offers the possibility of seizure reduction without needing to ablate or resect any tissue. However, because these techniques are still being evaluated in current practice, there are no evidence-based guidelines for their use, and more research is required to fully evaluate their proper role in the current management of medically refractory epilepsy.

Deep brain stimulation for severe autism: from pathophysiology to procedure.

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

Direct, intraoperative observation of ~0.1 Hz hemodynamic oscillations in awake human cortex: implications for fMRI.

An almost sinusoidal, large amplitude ~0.1 Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of 'slow sinusoidal hemodynamic oscillations' (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered. As a result, little investigation into the cause of SSHOs has been undertaken, and their potential to confound fMRI analysis, as well as their possible value as a functional biomarker has been largely overlooked. Here, we report direct observation of large-amplitude, sinusoidal ~0.1 Hz hemodynamic oscillations in the cortex of an awake human undergoing surgical resection of a brain tumor. Intraoperative multispectral optical intrinsic signal imaging (MS-OISI) revealed that SSHOs were spatially localized to distinct regions of the cortex, exhibited wave-like propagation, and involved oscillations in the diameter of specific pial arterioles, indicating that the effect was not the result of systemic blood pressure oscillations. fMRI data collected from the same subject 4 days prior to surgery demonstrates that ~0.1 Hz oscillations in the BOLD signal can be detected around the same region. Intraoperative optical imaging data from a patient undergoing epilepsy surgery, in whom sinusoidal oscillations were not observed, is shown for comparison. This direct observation of the '0.1 Hz wave' in the awake human brain, using both intraoperative imaging and pre-operative fMRI, confirms that SSHOs occur in the human brain, and can be detected by fMRI. We discuss the possible physiological basis of this oscillation and its potential link to brain pathologies, highlighting its relevance to resting-state fMRI and its potential as a novel target for functional diagnosis and delineation of neurological disease.

Neural signal data collection and analysis of Percept™ PC BrainSense recordings for thalamic stimulation in epilepsy.

Deep brain stimulation (DBS) using Medtronic's Percept™ PC implantable pulse generator is FDA-approved for treating Parkinson's disease (PD), essential tremor, dystonia, obsessive compulsive disorder, and epilepsy. Percept™ PC enables simultaneous recording of neural signals from the same lead used for stimulation. Many Percept™ PC sensing features were built with PD patients in mind, but these features are potentially useful to refine therapies for many different disease processes. When starting our ongoing epilepsy research study, we found it difficult to find detailed descriptions about these features and have compiled information from multiple sources to understand it as a tool, particularly for use in patients other than those with PD. Here we provide a tutorial for scientists and physicians interested in using Percept™ PC's features and provide examples of how neural time series data is often represented and saved. We address characteristics of the recorded signals and discuss Percept™ PC hardware and software capabilities in data pre-processing, signal filtering, and DBS lead performance. We explain the power spectrum of the data and how it is shaped by the filter response of Percept™ PC as well as the aliasing of the stimulation due to digitally sampling the data. We present Percept™ PC's ability to extract biomarkers that may be used to optimize stimulation therapy. We show how differences in lead type affects noise characteristics of the implanted leads from seven epilepsy patients enrolled in our clinical trial. Percept™ PC has sufficient signal-to-noise ratio, sampling capabilities, and stimulus artifact rejection for neural activity recording. Limitations in sampling rate, potential artifacts during stimulation, and shortening of battery life when monitoring neural activity at home were observed. Despite these limitations, Percept™ PC demonstrates potential as a useful tool for recording neural activity in order to optimize stimulation therapies to personalize treatment.

DiMANI: diffusion MRI for anatomical nuclei imaging-Application for the direct visualization of thalamic subnuclei.

The thalamus is a centrally located and heterogeneous brain structure that plays a critical role in various sensory, motor, and cognitive processes. However, visualizing the individual subnuclei of the thalamus using conventional MRI techniques is challenging. This difficulty has posed obstacles in targeting specific subnuclei for clinical interventions such as deep brain stimulation (DBS). In this paper, we present DiMANI, a novel method for directly visualizing the thalamic subnuclei using diffusion MRI (dMRI). The DiMANI contrast is computed by averaging, voxelwise, diffusion-weighted volumes enabling the direct distinction of thalamic subnuclei in individuals. We evaluated the reproducibility of DiMANI through multiple approaches. First, we utilized a unique dataset comprising 8 scans of a single participant collected over a 3-year period. Secondly, we quantitatively assessed manual segmentations of thalamic subnuclei for both intra-rater and inter-rater reliability. Thirdly, we qualitatively correlated DiMANI imaging data from several patients with Essential Tremor with the localization of implanted DBS electrodes and clinical observations. Lastly, we demonstrated that DiMANI can provide similar features at 3T and 7T MRI, using varying numbers of diffusion directions. Our results establish that DiMANI is a reproducible and clinically relevant method to directly visualize thalamic subnuclei. This has significant implications for the development of new DBS targets and the optimization of DBS therapy.

Implantation accuracy of novel polyimide stereotactic electroencephalographic depth electrodes-a human cadaveric study.

Introduction: Stereoelectroencephalography (sEEG) is a minimally invasive procedure that uses depth electrodes stereotactically implanted into brain structures to map the origin and propagation of seizures in epileptic patients. Implantation accuracy of sEEG electrodes plays a critical role in the safety and efficacy of the procedure. This study used human cadaver heads, simulating clinical practice, to evaluate (1) neurosurgeon's ability to implant a new thin-film polyimide sEEG electrode according to the instructions for use (IFU), and (2) implantation accuracy. Methods: Four neurosurgeons (users) implanted 24 sEEG electrodes into two cadaver heads with the aid of the ROSA robotic system. Usability was evaluated using a questionnaire that assessed completion of all procedure steps per IFU and user errors. For implantation accuracy evaluation, planned electrode trajectories were compared with post-implantation trajectories after fusion of pre- and postoperative computer tomography (CT) images. Implantation accuracy was quantified using the Euclidean distance for entry point error (EPE) and target point error (TPE). Results: All sEEG electrodes were successfully placed following the IFU without user errors, and post-implant survey of users showed favorable handling characteristics. The EPE was 1.28 ± 0.86 mm and TPE was 1.61 ± 0.89 mm. Long trajectories (>50 mm) had significantly larger EPEs and TPEs than short trajectories (<50 mm), and no differences were found between orthogonal and oblique trajectories. Accuracies were similar or superior to those reported in the literature when using similar experimental conditions, and in the same range as those reported in patients. Discussion: The results demonstrate that newly developed polyimide sEEG electrodes can be implanted as accurately as similar devices in the marker without user errors when following the IFU in a simulated clinical environment. The human cadaver ex-vivo test system provided a realistic test system, owing to the size, anatomy and similarity of tissue composition to that of the live human brain.

Utilizing kinematic analysis of postural instability as an objective measure to aid in distinguishing between normal pressure hydrocephalus and Parkinson's disease.

Objective: Patients with normal pressure hydrocephalus (NPH) and Parkinson's Disease (PD) can clinically appear quite similar at baseline evaluation. We sought to investigate the use of kinematic assessment of postural instability (PI) using inertial measurement units (IMUs) as a mechanism of differentiation between the two disease processes. Methods: 20 patients with NPH, 55 patients with PD, and 56 age-matched, healthy controls underwent quantitative pull test examinations while wearing IMUs at baseline. Center of mass and foot position data were used to compare velocity and acceleration profiles, pull test step length, and reaction times between groups and as a function of Unified Parkinson's disease Rating Scale Pull Test (UPDRSPT) score. Results: Overall, the reactive postural response of NPH patients was characterized by slower reaction times and smaller steps compared to both PD patients and healthy controls. However, when patients were grouped by UPDRSPT scores, no reliable objective difference between groups was detected. Conclusion: At their initial evaluation, very few NPH patients demonstrate "normal" or "mild" PI as they appear to be older upon presentation compared to PD patients. As a result, kinematic assessment utilizing IMUs may not be helpful for differentiating between NPH and PD as a function of UPDRSPT score, but rather as a more fine-tuned method to define disease progression. We emphasize the need for further evaluation of incorporating objective kinematic data collection as a way to evaluate PI and improve patient outcomes.

Alzheimer's disease CSF biomarkers correlate with early pathology and alterations in neuronal and glial gene expression.

INTRODUCTION: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early AD pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify CSF biomarkers for AD-related CNS pathophysiologic changes using tissue and fluids with early pathology, free of post-mortem artifact. METHODS: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes. RESULTS: AD pathology on biopsy correlates with CSF ß-amyloid-40/42, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/ß-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights 7 core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data.. DISCUSSION: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking.

Clinical Benefit of Vagus Nerve Stimulation for Epilepsy: Assessment of Randomized Controlled Trials and Prospective Non-Randomized Studies.

We examined the efficacy of vagal nerve stimulation (VNS) for patients suffering from medically intractable epilepsy. Four randomized controlled trials (RCTs - 3 adult RCTs and 1 pediatric RCT) were identified in our comprehensive literature search. Across the 4 studies, high frequency VNS stimulation (frequency >20 Hz) consistently achieved a greater seizure frequency reduction (23.4-33.1%) relative to low frequency VNS stimulation (1 Hz, .6-15.2%). We identified 2 RCTs examining whether the parameters of stimulation influenced seizure control. These studies reported that VNS achieved seizure control comparable to those reported by the first 4 RCTs (22-43% seizure frequency reduction), irrespective of the parameters utilized for VNS stimulation. In terms of VNS associated morbidity, these morbidities were consistently higher in adults who underwent high frequency VNS stimulation (eg dysphonia 37-66%, dyspnea 6-25.3%). However, no such differences were observed in the pediatric population. Moreover, <2% of patients withdrew from the RCTs/prospective studies due to intolerable symptoms. To provide an assessment of how the risks and benefits of VNS impact the patient experience, 1 study assessed the well-being of enrolled patients (as a secondary end point) and found VNS was associated with an overall improvement in well-being. Consistent with this observation, we identified a prospective, non-randomized study that demonstrated improved quality of life for epilepsy patients managed with VNS and best medical practice relative to best medical practice alone. In aggregate, these RCT studies support the efficacy and benefit of VNS as a neuro-modulatory platform in the management of a subset of medically refractory epilepsy patients.

Real world validation of activity recognition algorithm and development of novel behavioral biomarkers of falls in aged control and movement disorder patients.

The use of wearable sensors in movement disorder patients such as Parkinson's disease (PD) and normal pressure hydrocephalus (NPH) is becoming more widespread, but most studies are limited to characterizing general aspects of mobility using smartphones. There is a need to accurately identify specific activities at home in order to properly evaluate gait and balance at home, where most falls occur. We developed an activity recognition algorithm to classify multiple daily living activities including high fall risk activities such as sit to stand transfers, turns and near-falls using data from 5 inertial sensors placed on the chest, upper-legs and lower-legs of the subjects. The algorithm is then verified with ground truth by collecting video footage of our patients wearing the sensors at home. Our activity recognition algorithm showed >95% sensitivity in detection of activities. Extracted features from our home monitoring system showed significantly better correlation (~69%) with prospectively measured fall frequency of our subjects compared to the standard clinical tests (~30%) or other quantitative gait metrics used in past studies when attempting to predict future falls over 1 year of prospective follow-up. Although detecting near-falls at home is difficult, our proposed model suggests that near-fall frequency is the most predictive criterion in fall detection through correlation analysis and fitting regression models.

Rates of operative intervention for infection after synthetic or autologous cranioplasty: a National Readmissions Database analysis.

OBJECTIVE: The aim of this study was to characterize the clinical utilization and associated charges of autologous bone flap (ABF) versus synthetic flap (SF) cranioplasty and to characterize the postoperative infection risk of SF versus ABF using the National Readmissions Database (NRD). METHODS: The authors used the publicly available NRD to identify index hospitalizations from October 2015 to December 2018 involving elective ABF or SF cranioplasty after traumatic brain injury (TBI) or stroke. Subsequent readmissions were further characterized if patients underwent neurosurgical intervention for treatment of infection or suspected infection. Survey Cox proportional hazards models were used to assess risk of readmission. RESULTS: An estimated 2295 SF and 2072 ABF cranioplasties were performed from October 2015 to December 2018 in the United States. While the total number of cranioplasty operations decreased during the study period, the proportion of cranioplasties utilizing SF increased (p < 0.001), particularly in male patients (p = 0.011) and those with TBI (vs stroke, p = 0.012). The median total hospital charge for SF cranioplasty was $31,200 more costly than ABF cranioplasty (p < 0.001). Of all first-time readmissions, 20% involved surgical treatment for infectious reasons. Overall, 122 SF patients (5.3%) underwent surgical treatment of infection compared with 70 ABF patients (3.4%) on readmission. After accounting for confounders using a multivariable Cox model, female patients (vs male, p = 0.003), those discharged nonroutinely (vs discharge to home or self-care, p < 0.001), and patients who underwent SF cranioplasty (vs ABF, p = 0.011) were more likely to be readmitted for reoperation. Patients undergoing cranioplasty during more recent years (e.g., 2018 vs 2015) were less likely to be readmitted for reoperation because of infection (p = 0.024). CONCLUSIONS: SFs are increasingly replacing ABFs as the material of choice for cranioplasty, despite their association with increased hospital charges. Female sex, nonroutine discharge, and SF cranioplasty are associated with increased risk for reoperation after cranioplasty.