Long-term outcomes of mesial temporal laser interstitial thermal therapy for drug-resistant epilepsy and subsequent surgery for seizure recurrence: a multi-centre cohort study.

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to surgical resection for drug-resistant mesial temporal lobe epilepsy (mTLE). Reported rates of seizure freedom are variable and long-term durability is largely unproven. Anterior temporal lobectomy (ATL) remains an option for patients with MRgLITT treatment failure. However, the safety and efficacy of this staged strategy is unknown. METHODS: This multicentre, retrospective cohort study included 268 patients consecutively treated with mesial temporal MRgLITT at 11 centres between 2012 and 2018. Seizure outcomes and complications of MRgLITT and any subsequent surgery are reported. Predictive value of preoperative variables for seizure outcome was assessed. RESULTS: Engel I seizure freedom was achieved in 55.8% (149/267) at 1 year, 52.5% (126/240) at 2 years and 49.3% (132/268) at the last follow-up ≥1 year (median 47 months). Engel I or II outcomes were achieved in 74.2% (198/267) at 1 year, 75.0% (180/240) at 2 years and 66.0% (177/268) at the last follow-up. Preoperative focal to bilateral tonic-clonic seizures were independently associated with seizure recurrence. Among patients with seizure recurrence, 14/21 (66.7%) became seizure-free after subsequent ATL and 5/10 (50%) after repeat MRgLITT at last follow-up≥1 year. CONCLUSIONS: MRgLITT is a viable treatment with durable outcomes for patients with drug-resistant mTLE evaluated at a comprehensive epilepsy centre. Although seizure freedom rates were lower than reported with ATL, this series represents the early experience of each centre and a heterogeneous cohort. ATL remains a safe and effective treatment for well-selected patients who fail MRgLITT.

Antiseizure medication treatment pathways for US Medicare beneficiaries with newly treated epilepsy.

OBJECTIVE: This study was undertaken to characterize antiseizure medication (ASM) treatment pathways in Medicare beneficiaries with newly treated epilepsy. METHODS: This was a retrospective cohort study using Medicare claims. Medicare is the United States' federal health insurance program for people aged 65 years and older plus younger people with disabilities or end-stage renal disease. We included beneficiaries with newly treated epilepsy (International Classification of Diseases codes for epilepsy/convulsions 2014-2017, no ASM in the previous 2 years). We displayed the sequence of ASM fills using sunburst plots overall, then stratified by mood disorder, age, and neurologist prescriber. We tabulated drug costs for each pathway. RESULTS: We included 21 458 beneficiaries. Levetiracetam comprised the greatest number of pill days (56%), followed by gabapentin (11%) and valproate (8%). There were 22 288 unique treatment pathways. The most common pathways were levetiracetam monotherapy (43%), gabapentin monotherapy (10%), and valproate monotherapy (5%). Gabapentin was the most common second- and third-line ASM. Whereas only 2% of pathways involved first-line lacosamide, those pathways accounted for 19% of cost. Gabapentin and valproate use was increased and levetiracetam use was decreased in beneficiaries with mood disorders compared to beneficiaries without mood disorders. Levetiracetam use was increased and gabapentin, valproate, lamotrigine, and topiramate use was decreased in beneficiaries aged >65 years compared with those aged 65 years or less. Lamotrigine, levetiracetam, and lacosamide use was increased and gabapentin use was decreased in beneficiaries whose initial prescriber was a neurologist compared to those whose prescriber was not a neurologist. SIGNIFICANCE: Levetiracetam monotherapy was the most common pathway, although substantial heterogeneity existed. Lacosamide accounted for a small percentage of ASMs but a disproportionately large share of cost. Neurologists were more likely to prescribe lamotrigine compared with nonneurologists, and lamotrigine was prescribed far less frequently than may be endorsed by guidelines. Future work may explore patient- and physician-driven factors underlying ASM choices.

Identification of patients with drug-resistant epilepsy in electronic medical record data using the Observational Medical Outcomes Partnership Common Data Model.

OBJECTIVE: More than one third of appropriately treated patients with epilepsy have continued seizures despite two or more medication trials, meeting criteria for drug-resistant epilepsy (DRE). Accurate and reliable identification of patients with DRE in observational data would enable large-scale, real-world comparative effectiveness research and improve access to specialized epilepsy care. In the present study, we aim to develop and compare the performance of computable phenotypes for DRE using the Observational Medical Outcomes Partnership (OMOP) Common Data Model. METHODS: We randomly sampled 600 patients from our academic medical center's electronic health record (EHR)-derived OMOP database meeting previously validated criteria for epilepsy (January 2015-August 2021). Two reviewers manually classified patients as having DRE, drug-responsive epilepsy, undefined drug responsiveness, or no epilepsy as of the last EHR encounter in the study period based on consensus definitions. Demographic characteristics and codes for diagnoses, antiseizure medications (ASMs), and procedures were tested for association with DRE. Algorithms combining permutations of these factors were applied to calculate sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for DRE. The F1 score was used to compare overall performance. RESULTS: Among 412 patients with source record-confirmed epilepsy, 62 (15.0%) had DRE, 163 (39.6%) had drug-responsive epilepsy, 124 (30.0%) had undefined drug responsiveness, and 63 (15.3%) had insufficient records. The best performing phenotype for DRE in terms of the F1 score was the presence of ≥1 intractable epilepsy code and ≥2 unique non-gabapentinoid ASM exposures each with ≥90-day drug era (sensitivity = .661, specificity = .937, PPV = .594, NPV = .952, F1 score = .626). Several phenotypes achieved higher sensitivity at the expense of specificity and vice versa. SIGNIFICANCE: OMOP algorithms can identify DRE in EHR-derived data with varying tradeoffs between sensitivity and specificity. These computable phenotypes can be applied across the largest international network of standardized clinical databases for further validation, reproducible observational research, and improving access to appropriate care.

Patient characteristics and antiseizure medication pathways in newly diagnosed epilepsy: Feasibility and pilot results using the common data model in a single-center electronic medical record database.

INTRODUCTION: Efforts to characterize variability in epilepsy treatment pathways are limited by the large number of possible antiseizure medication (ASM) regimens and sequences, heterogeneity of patients, and challenges of measuring confounding variables and outcomes across institutions. The Observational Health Data Science and Informatics (OHDSI) collaborative is an international data network representing over 1 billion patient records using common data standards. However, few studies have applied OHDSI's Common Data Model (CDM) to the population with epilepsy and none have validated relevant concepts. The goals of this study were to demonstrate the feasibility of characterizing adult patients with epilepsy and ASM treatment pathways using the CDM in an electronic health record (EHR)-derived database. METHODS: We validated a phenotype algorithm for epilepsy in adults using the CDM in an EHR-derived database (2001-2020) against source records and a prospectively maintained database of patients with confirmed epilepsy. We obtained the frequency of all antecedent conditions and procedures for patients meeting the epilepsy phenotype criteria and characterized ASM exposure sequences over time and by age and sex. RESULTS: The phenotype algorithm identified epilepsy with 73.0-85.0% positive predictive value and 86.3% sensitivity. Many patients had neurologic conditions and diagnoses antecedent to meeting epilepsy criteria. Levetiracetam incrementally replaced phenytoin as the most common first-line agent, but significant heterogeneity remained, particularly in second-line and subsequent agents. Drug sequences included up to 8 unique ingredients and a total of 1,235 unique pathways were observed. CONCLUSIONS: Despite the availability of additional ASMs in the last 2 decades and accumulated guidelines and evidence, ASM use varies significantly in practice, particularly for second-line and subsequent agents. Multi-center OHDSI studies have the potential to better characterize the full extent of variability and support observational comparative effectiveness research, but additional work is needed to validate covariates and outcomes.

Risk of Acquiring Perioperative COVID-19 During the Initial Pandemic Peak: A Retrospective Cohort Study.

OBJECTIVE: To determine the risk of acquiring perioperative COVID-19 infection in previously COVID-19 negative patients. SUMMARY OF BACKGROUND DATA: During the initial peak of the COVID-19 pandemic, there was significant concern of hospital acquired COVID-19 infections. Medical centers rapidly implemented systems to minimize perioperative transmission, including routine preoperative testing, patient isolation, and enhanced cleaning. METHODS: In this retrospective cohort study, medical records of all adult patients who underwent surgery at our quaternary, acute care hospital between March 15 and May 15, 2020 were reviewed. The risk of preoperatively negative patients developing symptomatic COVID-19 within 2-14 days postoperatively was determined. Surgical characteristics, outcomes, and complications were compared between those with and without acquired perioperative COVID-19 infection. RESULTS: Among 501 negative patients undergoing index surgeries, 9 (1.8%) developed symptomatic COVID-19 in the postoperative period; all occurred before implementation of routine preoperative testing [9/243, 3.7% vs 0/258, 0%, odds ratio (OR): 0.048, P = 0.036]. No patient who was polymerase-chain-reaction negative on the day of surgery (n = 170) developed postoperative infection. Perioperative infection was associated with preoperative diabetes (OR: 3.70, P = 0.042), cardiovascular disease (OR: 3.69, P = 0.043), angiotensin receptor blocker use (OR: 6.58, P = 0.004), and transplant surgery (OR: 11.00, P = 0.002), and multiple complications, readmission (OR: 5.50, P = 0.029) and death (OR: 12.81, P = 0.001). CONCLUSIONS: During the initial peak of the COVID-19 pandemic, there was minimal risk of acquiring symptomatic perioperative COVID-19 infection, especially after the implementation of routine preoperative testing. However, perioperative COVID-19 infection was associated with poor postoperative outcome.

Cost-effectiveness analysis of responsive neurostimulation for drug-resistant focal onset epilepsy.

OBJECTIVE: We evaluated the incremental cost-effectiveness of responsive neurostimulation (RNS) therapy for management of medically refractory focal onset seizures compared to pharmacotherapy alone. METHODS: We created and analyzed a decision model for treatment with RNS therapy versus pharmacotherapy using a semi-Markov process. We adopted a public payer perspective and used the maximum duration of 9 years in the RNS long-term follow-up study as the time horizon. We used seizure frequency data to model changes in quality of life and estimated the impact of RNS therapy on the annual direct costs of epilepsy care. The model also included expected mortality, adverse events, and costs related to system implantation, programming, and replacement. We interpreted our results against societal willingness-to-pay thresholds of $50 000, $100 000, and $200 000 per quality-adjusted life year (QALY). RESULTS: Based on three different calculated utility value estimates, the incremental cost-effectiveness ratio (ICER) for RNS therapy (with continued pharmacotherapy) compared to pharmacotherapy alone ranged between $28 825 and $46 596. Multiple sensitivity analyses yielded ICERs often below $50 000 per QALY and consistently below $100 000/QALY. SIGNIFICANCE: Modeling based on 9 years of available data demonstrates that RNS therapy for medically refractory epilepsy very likely falls within the range of cost-effectiveness, depending on method of utility estimation, variability in model inputs, and willingness-to-pay threshold. Several factors favor improved cost-effectiveness in the future. Given the increasing focus on delivering cost-effective care, we hope that this analysis will help inform clinical decision-making for this surgical option for refractory epilepsy.

SARS-COV-2 transmission rate is low when following a COVID+ patient in the operating room.

PURPOSE: Acquiring SARS-CoV-2 infection for uninfected patients undergoing surgical procedures following a COVID positive (COVID+) patient is of significant concern, both for patients seeking medical care in hospital settings and for management of surgical services during pandemic times. METHODS: Using data identifying all COVID+ surgical patients during the initial pandemic peak in New York City (March 15 to May 15, 2020), we analyzed the rate of postoperative symptomatic SARS-CoV-2 infection in COVID negative (COVID-) patients undergoing surgery in the same operating room within 48 h, thus determining nosocomial symptomatic infection rate attributable to COVID operating room exposure. RESULTS: Five COVID- patients directly followed a COVID+ patient, while 19 patients were exposed to COVID+ operating rooms within 24 h. By 48 h, 21 additional patients were exposed. No exposed patients acquired symptomatic SARS-CoV-2 infection postoperatively. CONCLUSION: With implementation of infection prevention and control procedures in the operating room under local pandemic conditions, our findings suggest that the risk of acquiring SARS-CoV-2 infection, when following a COVID+ patient in the same operating room, is very low.

Eyebrow supraorbital keyhole craniotomy for olfactory groove meningiomas with endoscope assistance: case series and systematic review of extent of resection, quantification of postoperative frontal lobe injury, anosmia, and recurrence.

BACKGROUND: Olfactory groove meningiomas (OGMs) are commonly treated with open craniotomy. Endonasal approaches have also been described. OBJECTIVE: To present clinical and radiographic outcomes for the minimally invasive eyebrow incision supraorbital keyhole approach with endoscopic assistance for OGMs. METHODS: We performed a retrospective single-center cohort study and a systematic literature review. RESULTS: Fifteen patients were identified, all with Grade I meningiomas. Radiographic gross total resection of enhancing tumor was achieved in all patients. Mean frontal lobe fluid-attenuated inversion recovery volume decreased from 11.1 ± 18.3 cm3 preoperatively to 9.9 ± 11.4 cm3 immediately postoperatively, and there was minimal new restricted diffusion (3.2 ± 2.2 cm3; max 7.5 cm3). Median length of stay was 3 days (range 2-8). Vision was improved in 4 (80%) and stable in 1 (20%) of 5 patients with a preoperative deficit. New postoperative anosmia occurred in 3 (23%) of 13 patients with any preoperative olfaction. All patients were satisfied with their cosmetic result at 3 months. After a median follow-up of 32.2 months, there were 2 (13.3%) asymptomatic radiographic recurrences, 1 treated with radiosurgery and the other with endoscopic endonasal approach (EEA). No patients required further craniotomy. Systematic review revealed the present series to be the largest to date reporting disaggregated outcomes for the eyebrow approach to OGM. CONCLUSION: The eyebrow incision supraorbital keyhole craniotomy with endoscopic assistance is a safe and effective approach to OGM with tumor control rates similar to more invasive open approaches and better than the endonasal approach. Rates of frontal lobe injury, CSF leak and anosmia are comparatively low.

Patterns of seizure prophylaxis after oncologic neurosurgery.

BACKGROUND: Evidence supporting routine postoperative antiepileptic drug (AED) prophylaxis following oncologic neurosurgery is limited, and actual practice patterns are largely unknown beyond survey data. OBJECTIVE: To describe patterns and predictors of postoperative AED prophylaxis following intracranial tumor surgery. METHODS: The MarketScan Database was used to analyze pharmacy claims data and clinical characteristics in a national sample over a 5-year period. RESULTS: Among 5895 patients in the cohort, levetiracetam was the most widely used AED for prophylaxis (78.5%) followed by phenytoin (20.5%). Prophylaxis was common but highly variable for patients who underwent open resection of supratentorial intraparenchymal tumors (62.5%, reference) or meningiomas (61.9%). In multivariate analysis, biopsies were less likely to receive prophylaxis (44.8%, OR 0.47, 95% CI 0.33-0.67), and there was near consensus against prophylaxis for infratentorial (9.7%, OR 0.07, CI 0.05-0.09) and transsphenoidal procedures (0.4%, OR 0.003, CI 0.001-0.010). Primary malignancies (52.1%, reference) and secondary metastases (42.2%) were more likely to receive prophylaxis than benign tumors (23.0%, OR 0.63, CI 0.48-0.83), as were patients discharged with home services and patients in the Northeast. There was a large spike in duration of AED use at approximately 30 days. CONCLUSIONS: Use of seizure prophylaxis following intracranial biopsies and supratentorial resections is highly variable, consistent with a lack of guidelines or consensus. Current practice patterns do not support a clear standard of care and may be driven in part by geographic variation, availability of post-discharge services, and electronic prescribing defaults rather than evidence. Given uncertainty regarding effectiveness, indications, and appropriate duration of AED prophylaxis, well-powered trials are needed.

Acellular dermal matrix as an alternative to autologous fascia lata for skull base repair following extended endoscopic endonasal approaches.

BACKGROUND: Skull base reconstruction after extended endoscopic endonasal approaches (EEAs) can be challenging. In addition to the nasoseptal flap, which has been adopted by most centers, autologous fascia lata is also often utilized. Harvesting of fascia lata requires a separate thigh incision, may prolong recovery, and results in a visible scar. In principal, the use of non-autologous materials would be preferable to avoid a second incision and maintain the minimally invasive nature of the approach, assuming the CSF leak rate is not compromised. OBJECTIVE: To assess the efficacy of acellular dermal matrix (ADM) as a non-autologous alternative to autologous fascia lata graft for watertight closure of the cranial base following EEAs. METHODS: A retrospective chart review of extended EEAs performed before and after the transition from fascia lata to ADM was performed. Cases were frequency matched for approach, pathology, BMI, use of lumbar drainage, and tumor volume. Power analysis was performed to estimate the sample size needed to demonstrate non-inferiority. RESULTS: ADM was used for watertight closure of the cranial base in 19 consecutive extended endoscopic endonasal approaches (16 gasket-seals and 3 buttons) with 1 postoperative CSF leak at the last follow-up (median 5.3, range 1.0-12.6 months). All patients had high-flow intraoperative leaks. The cohort included 8 meningiomas, 8 craniopharyngiomas, 2 chordomas, and 1 pituicytoma ranging in size from 0.2 to 37.2cm3 (median 5.5, IQR 2.8-13.3 cm3). In 19 historical controls who received fascia lata, there were 2 postoperative CSF leaks. CONCLUSIONS: Preliminary results suggest that ADM provides a non-inferior non-autologous alternative to fascia lata for watertight gasket-seal and button closures following extended EEAs, potentially reducing or eliminating the need to harvest autologous tissue.

Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.

OBJECTIVE: Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes. We aim to validate an automated trajectory planning platform against manually planned trajectories to objectively standardize the process. METHODS: Using the EpiNav platform, we compare automated trajectory planning parameters derived from expert opinion and machine learning to undertake a multicenter validation against manually planned and implemented trajectories in 95 patients with MTLE. We estimate ablation volumes of regions of interest and quantify the size of the avascular corridor through the use of a risk score as a marker of safety. We also undertake blinded external expert feasibility and preference ratings. RESULTS: Automated trajectory planning employs complex algorithms to maximize ablation of the mesial hippocampal head and amygdala, while sparing the parahippocampal gyrus. Automated trajectories resulted in significantly lower calculated risk scores and greater amygdala ablation percentage, whereas overall hippocampal ablation percentage did not differ significantly. In addition, estimated damage to collateral structures was reduced. Blinded external expert raters were significantly more likely to prefer automated to manually planned trajectories. SIGNIFICANCE: Retrospective studies of automated trajectory planning show much promise in improving safety parameters and ablation volumes during LITT for MTLE. Multicenter validation provides evidence that the algorithm is robust, and blinded external expert ratings indicate that the trajectories are clinically feasible. Prospective validation studies are now required to determine if automated trajectories translate into improved seizure freedom rates and reduced neuropsychological deficits.

Laser ablation is effective for temporal lobe epilepsy with and without mesial temporal sclerosis if hippocampal seizure onsets are localized by stereoelectroencephalography.

OBJECTIVE: Selective laser amygdalohippocampotomy (SLAH) using magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is emerging as a treatment option for drug-resistant mesial temporal lobe epilepsy (MTLE). SLAH is less invasive than open resection, but there are limited series reporting its safety and efficacy, particularly in patients without clear evidence of mesial temporal sclerosis (MTS). METHODS: We report seizure outcomes and complications in our first 30 patients who underwent SLAH for drug-resistant MTLE between January 2013 and December 2016. We compare patients who required stereoelectroencephalography (SEEG) to confirm mesial temporal onset with those treated based on imaging evidence of MTS. RESULTS: Twelve patients with SEEG-confirmed, non-MTS MTLE and 18 patients with MRI-confirmed MTS underwent SLAH. MTS patients were older (median age 50 vs 30 years) and had longer standing epilepsy (median 40.5 vs 5.5 years) than non-MTS patients. Engel class I seizure freedom was achieved in 7 of 12 non-MTS patients (58%, 95% confidence interval [CI] 30%-86%) and 10 of 18 MTS patients (56%, 95% CI 33%-79%), with no significant difference between groups (odds ratio [OR] 1.12, 95% CI 0.26-4.91, P = .88). Length of stay was 1 day for most patients (range 0-3 days). Procedural complications were rare and without long-term sequelae. SIGNIFICANCE: We report similar rates of seizure freedom following SLAH in patients with MTS and SEEG-confirmed, non-MTS MTLE. Consistent with early literature, these rates are slightly lower than typically observed with surgical resection (60%-80%). However, SLAH is less invasive than open surgery, with shorter hospital stays and recovery, and severe procedural complications are rare. SLAH may be a reasonable first-line surgical option for patients with both MTS and SEEG confirmed, non-MTS MTLE.

The modified frailty index and 30-day adverse events in oncologic neurosurgery.

The modified frailty index (mFI) is emerging as a leading measure for preoperative risk assessment using routinely available medical record data. Our objective was to determine if mFI predicts morbidity and mortality in the diverse national cohort of patients undergoing neurosurgery for intracranial neoplasms. We identified patients in the National Surgical Quality Improvement Program who underwent oncologic neurosurgery procedures between 2008 and 2012. The mFI, ranging from 0 to 1, was calculated as the proportion of 11 possible risk factors present. We assessed the associations between mFI and 30-day mortality, neurologic and medical complications, prolonged length of stay, and unfavorable discharge in univariate and multivariable analyses and compare the index to established risk stratification techniques. A total of 9149 patients were identified. Mortality, severe medical complications, prolonged length of stay, and unfavorable discharge increased incrementally with increasing levels of frailty. Severe neurologic complications were highest in those with low frailty. In multivariable logistic regression analysis, increased frailty increased the odds of all adverse outcomes, including neurologic complications. The mFI increased the ability to predict all outcomes beyond available indices and was the most reliable predictor of neurologic complications. The mFI can be calculated from routinely collected medical record data and is predictive of 30-day adverse outcomes in a wide variety of neurosurgical oncology patients. The index may be a useful component of preoperative risk assessment with implications for shared decision-making, perioperative planning, and risk adjusted outcomes measurement in national quality registries.

Frontal networks associated with command following after hemorrhagic stroke.

BACKGROUND AND PURPOSE: Level of consciousness is frequently assessed by command-following ability in the clinical setting. However, it is unclear what brain circuits are needed to follow commands. We sought to determine what networks differentiate command following from noncommand following patients after hemorrhagic stroke. METHODS: Structural MRI, resting-state functional MRI, and electroencephalography were performed on 25 awake and unresponsive patients with acute intracerebral and subarachnoid hemorrhage. Structural injury was assessed via volumetric T1-weighted MRI analysis. Functional connectivity differences were analyzed against a template of standard resting-state networks. The default mode network (DMN) and the task-positive network were investigated using seed-based functional connectivity. Networks were interrogated by pairwise coherence of electroencephalograph leads in regions of interest defined by functional MRI. RESULTS: Functional imaging of unresponsive patients identified significant differences in 6 of 16 standard resting-state networks. Significant voxels were found in premotor cortex, dorsal anterior cingulate gyrus, and supplementary motor area. Direct interrogation of the DMN and task-positive network revealed loss of connectivity between the DMN and the orbitofrontal cortex and new connections between the task-positive network and DMN. Coherence between electrodes corresponding to right executive network and visual networks was also decreased in unresponsive patients. CONCLUSIONS: Resting-state functional MRI and electroencephalography coherence data support a model in which multiple, chiefly frontal networks are required for command following. Loss of DMN anticorrelation with task-positive network may reflect a loss of inhibitory control of the DMN by motor-executive regions. Frontal networks should thus be a target for future investigations into the mechanism of responsiveness in the intensive care unit environment.

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.

Use of Recommended Neurodiagnostic Evaluation Among Patients With Drug-Resistant Epilepsy.

Importance: Interdisciplinary practice parameters recommend that patients with drug-resistant epilepsy (DRE) undergo comprehensive neurodiagnostic evaluation, including presurgical assessment. Reporting from specialized centers suggests long delays to referral and underuse of surgery; however, longitudinal data are limited to characterize neurodiagnostic evaluation among patients with DRE in more diverse US settings and populations. Objective: To examine the rate and factors associated with neurodiagnostic studies and comprehensive evaluation among patients with DRE within 3 US cohorts. Design, Setting, and Participants: A retrospective cross-sectional study was conducted using the Observational Medical Outcomes Partnership Common Data Model including US multistate Medicaid data, commercial claims data, and Columbia University Medical Center (CUMC) electronic health record data. Patients meeting a validated computable phenotype algorithm for DRE between January 1, 2015, and April 1, 2020, were included. No eligible participants were excluded. Exposure: Demographic and clinical variables were queried. Main Outcomes and Measures: The proportion of patients receiving a composite proxy for comprehensive neurodiagnostic evaluation, including (1) magnetic resonance or other advanced brain imaging, (2) video electroencephalography, and (3) neuropsychological evaluation within 2 years of meeting the inclusion criteria. Results: A total of 33 542 patients with DRE were included in the Medicaid cohort, 22 496 in the commercial insurance cohort, and 2741 in the CUMC database. A total of 31 516 patients (53.6%) were women. The proportion of patients meeting the comprehensive evaluation main outcome in the Medicaid cohort was 4.5% (n = 1520); in the commercial insurance cohort, 8.0% (n = 1796); and in the CUMC cohort, 14.3% (n = 393). Video electroencephalography (24.9% Medicaid, 28.4% commercial, 63.2% CUMC) and magnetic resonance imaging of the brain (35.6% Medicaid, 43.4% commercial, 52.6% CUMC) were performed more regularly than neuropsychological evaluation (13.0% Medicaid, 16.6% commercial, 19.2% CUMC) or advanced imaging (3.2% Medicaid, 5.4% commercial, 13.1% CUMC). Factors independently associated with greater odds of evaluation across all 3 data sets included the number of inpatient and outpatient nonemergency epilepsy visits and focal rather than generalized epilepsy. Conclusions and Relevance: The findings of this study suggest there is a gap in the use of diagnostic studies to evaluate patients with DRE. Care setting, insurance type, frequency of nonemergency visits, and epilepsy type are all associated with evaluation. A common data model can be used to measure adherence with best practices across a variety of observational data sources.

Motor deficits correlate with resting state motor network connectivity in patients with brain tumours.

While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery.

The Use of Stereotactic Radiosurgery to Treat Functional Disorders: A Topic Discussion.

Stereotactic radiosurgery (SRS) is a well-known modality for the treatment of malignant brain tumors. SRS, however, can also be used to treat non-malignant functional disorders such as epilepsy, tremor, trigeminal neuralgia (TN), obsessive compulsive disorder (OCD), and intractable pain among others. Given the limited prospective data guiding treatment of these benign disorders, this article serves as a consolidated discussion of the application of SRS for functional ailments, hopefully serving as a reference for those considering application of this technique in clinical practice.

Endonasal transsphenoidal surgery for planum sphenoidale versus tuberculum sellae meningiomas.

OBJECTIVE: The aim of this study was to determine if the distinction between planum sphenoidale (PS) and tuberculum sellae (TS) meningiomas is clinically meaningful and impacts the results of the endoscopic endonasal approach (EEA). METHODS: A consecutive series of patients who were 18 years of age or older and underwent EEA for newly diagnosed grade I PS meningiomas (PSMs) and TS meningiomas (TSMs) between October 2007 and May 2021 were included. The PS and TS were distinguished by drawing a line passing through the center of the TS and perpendicular to the PS on postcontrast T1-weighted MRI. Probabilistic heatmaps were created to display the actual distribution of tumor volumes. Tumor volume, extent of resection (EOR), visual outcome, and complications were assessed. RESULTS: The 47 tumors were distributed in a smooth continuum. Using an arbitrary definition, 24 (51%) were PSMs and 23 (49%) were TSMs. The mean volume of PSMs was 5.6 cm3 compared with 4.5 cm3 for TSMs. Canal invasion was present in 87.5% of PSMs and 52% of TSMs. GTR was achieved in 38 (84%) of 45 cases in which it was the goal, slightly less frequently for PSMs (78%) compared with TSMs (91%), although the difference was not significant. Th mean EOR was 99% ± 2% for PSMs and 98% ± 11% for TSMs. Neither the suprasellar notch angle nor the percentage of tumor above the PS impacted the rate of GTR. After a median follow-up of 28.5 months (range 0.1-131 months), there were 2 (5%) recurrences after GTR (n = 38) both of which occurred in patients with PSMs. Forty-two (89%) patients presented with preoperative impaired vision. Postoperative vision was stable or improved in 96% of patients with PSMs and 91% of patients with TSMs. CSF leakage occurred in 4 (16.6%) patients with a PSM, which resolved with only lumbar drainage, and in 1 (4.3%) patient with a TSM, which required reoperation. CONCLUSIONS: PSM and TSMs arise in a smooth distribution, making the distinction arbitrary. Those classified as PSMs were larger and more likely to invade the optic canals. Surgical outcome for both locations was similar, slightly favoring TSMs. The arbitrary distinction between PSMs and TSMs is less useful at predicting outcome than the lateral extent of the tumor, regardless of the site of origin.