The value of additional electrodes when stereo-electroencephalography is inconclusive.

OBJECTIVE: Stereo-electroencephalography (SEEG) is the preferred method for intracranial localization of the seizure-onset zone (SOZ) in drug-resistant focal epilepsy. Occasionally SEEG evaluation fails to confirm the pre-implantation hypothesis. This leads to a decision tree regarding whether the addition of SEEG electrodes (two-step SEEG - 2sSEEG) or placement of subdural electrodes (SDEs) after SEEG (SEEG2SDE) would help. There is a dearth of literature encompassing this scenario, and here we aimed to characterize outcomes following unplanned two-step intracranial EEG (iEEG). METHODS: All 225 adult SEEG cases over 8 years at our institution were reviewed to extract patient data and outcomes following a two-step evaluation. Three raters independently quantified benefits of additional intracranial electrodes. The relationship between two-step iEEG benefit and clinical outcome was then analyzed. RESULTS: Fourteen patients underwent 2sSEEG and nine underwent SEEG2SDE. In the former cohort, the second SEEG procedure was performed for these reasons-precise localization of the SOZ (36%); defining margins of eloquent cortex (21%); and broadening coverage in the setting of non-localizable seizure onsets (43% of cases). Sixty-four percent of 2sSEEG cases were consistently deemed beneficial (Light's κ = 0.80). 2sSEEG performed for the first two indications was much more beneficial than when onsets were not localizable (100% vs 17%, p = .02). In the SEEG2SDE cohort, SDEs identified the SOZ and enabled delineation of margins relative to eloquent cortex in all cases. SIGNIFICANCE: The two-step iEEG is useful if the initial evaluation is broadly concordant with the original electroclinical hypothesis, where it can clarify onset zones or delineate safe surgical margins; however, it provides minimal benefit when the implantation hypothesis is erroneous, and we recommend that 2sSEEG not be generally utilized in such cases. SDE implantation after SEEG minimizes the need for SDEs and is helpful in delineating surgical boundaries relative to ictal-onset zones and eloquent cortex.

Forecasting seizure clusters from chronic ambulatory electrocorticography.

Seizure clusters are seizures that occur in rapid succession during periods of heightened seizure risk and are associated with substantial morbidity and sudden unexpected death in epilepsy. The objective of this feasibility study was to evaluate the performance of a novel seizure cluster forecasting algorithm. Chronic ambulatory electrocorticography recorded over an average of 38 months in 10 subjects with drug-resistant epilepsies was analyzed pseudoprospectively by dividing data into training (first 85%) and validation periods. For each subject, the probability of seizure clustering, derived from the Kolmogorov-Smirnov statistic using a novel algorithm, was forecasted in the validation period using individualized autoregressive models that were optimized from training data. The primary outcome of this study was the mean absolute scaled error (MASE) of 1-day horizon forecasts. From 10 subjects, 394 ± 142 (mean ± SD) electrocorticography-based seizure events were extracted for analysis, representing a span of 38 ± 27 months of recording. MASE across all subjects was .74 ± .09, .78 ± .09, and .83 ± .07 at .5-, 1-, and 2-day horizons. The feasibility study demonstrates that seizure clusters are quasiperiodic and can be forecasted to clinically meaningful horizons. Pending validation in larger cohorts, the forecasting approach described herein may herald chronotherapy during imminent heightened seizure vulnerability.

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

OBJECTIVE: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE). METHODS: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation. RESULTS: Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter. CONCLUSIONS: Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.

Dynamics of seizure-induced behavioral and autonomic arousal.

PURPOSE: Arousal is the most primitive, powerful instinct with survival benefit present in all vertebrates. Even though the arousal systems are classically viewed as "ascending" brainstem phenomena, there is a "descending" cortical feedback system that maintains consciousness. In this study, we provide electrophysiological confirmation that seizures localized to the anterior cingulum can behaviorally manifest as paroxysms of arousal from sleep. METHODS: Temporal dynamics of arousal induced by anterior cingulate seizures were analyzed by using multiple modalities including stereoelectroencephalography (phase lag index and phase amplitude coupling), lead-1 ECG (point-process heart rate variability analysis) and diffusion tractography (DTI). RESULTS: The ictal arousal was associated with an increase in synchronization in the alpha band and an increase in local theta or alpha-gamma phase-amplitude coupling. In comparison to seizures that lacked clinical manifestations, ictal arousal was associated with an increase in heart rate but not heart rate variability. Finally, DTI demonstrated degeneration in white fiber tracts passing between the anterior cingulum and anterior thalamus ipsilateral to the epileptogenic cortex. The patient underwent resection of the anterior cingulum, and histopathology confirmed focal cortical dysplasia type II. CONCLUSION: Anterior cingulate seizures inducing behavioral arousal have identifiable autonomic and EEG signatures.

Magnetic resonance-guided, high-intensity focused ultrasound sonolysis: potential applications for stroke.

Stroke is one of the leading causes of death worldwide and a significant source of long-term morbidity. Unfortunately, a substantial number of stroke patients either are ineligible or do not significantly benefit from contemporary medical and interventional therapies. To address this void, investigators recently made technological advances to render transcranial MR-guided, high-intensity focused ultrasound (MRg-HIFU) sonolysis a potential therapeutic option for both acute ischemic stroke (AIS)-as an alternative for patients with emergent large-vessel occlusion (ELVO) who are ineligible for endovascular mechanical thrombectomy (EMT) or as salvage therapy for patients in whom EMT fails-and intracerebral hemorrhage (ICH)-as a neoadjuvant means of clot lysis prior to surgical evacuation. Herein, the authors review the technological principles behind MRg-HIFU sonolysis, its results in in vitro and in vivo stroke models, and its potential clinical applications. As a noninvasive transcranial technique that affords rapid clot lysis, MRg-HIFU thrombolysis may develop into a therapeutic option for patients with AIS or ICH. However, additional studies of transcranial MRg-HIFU are necessary to ascertain the merit of this treatment approach for thrombolysis in both AIS and ICH, as well as its technical limitations and risks.

GABAA receptor membrane insertion rates are specified by their subunit composition.

γ Amino-butyric acid type-A receptors (GABARs) containing γ2 or δ subunits form separate pools of receptors in vivo, with distinct localization and function. We determined the rate of surface membrane insertion of native and recombinant γ2 and δ subunit-containing GABARs (γ2-GABARs and δ-GABARs). Insertion of the α-bungarotoxin binding site (BBS) tagged γ2 subunit (t-γ2)-containing GABARs in the surface membrane of HEK293 cells occurred within minutes and reached a peak by 30 min. In contrast, insertion of the BBS-tagged δ subunit (t-δ)-containing receptors required longer incubation and peaked in 120 min. Insertion of the t-γ2 subunit-containing receptors was not influenced by assembling α1 or α4 subunits. In contrast, insertion of the α4ß3t-δ subunit-containing receptors was faster than those containing α1ß3t-δ subunits. The rate of insertion of native GABARs in the surface membrane of cultured hippocampal neurons, determined by an antibody saturation assay, was similar to that of the recombinant receptors expressed in HEK293 cells. Insertion of the γ2-GABARs was rapid and new γ2-GABARs were detected on the surface membrane of cell soma and dendrites within minutes. In contrast, insertion of the δ-GABARs was slow and newly inserted receptors were initially present only in the surface membrane of cell soma and later also appeared over the dendrites. Thus the rate of insertion of GABARs was dependent on their subunit composition.

Pro-Ictal State in Human Temporal Lobe Epilepsy.

BACKGROUND: Studies of continuous electroencephalography (EEG) suggest that seizures in individuals with focal-onset epilepsies preferentially occur during periods of heightened risk, typified by pathologic brain activities, termed pro-ictal states; however, the presence of (pathologic) pro-ictal states among a plethora of otherwise physiologic (e.g., sleep­wake cycle) states has not been established. METHODS: We studied a prospective, consecutive series of 15 patients with temporal lobe epilepsy who underwent limbic thalamic recordings in addition to routine (cortical) intracranial EEG for seizure localization. For each participant, pro-ictal (45 minutes before seizure onset) and interictal (4 hours removed from all seizures) EEG segments were divided into 10-minute, nonoverlapping windows, which were randomly distributed into training and validation cohorts in a 1:1 ratio. A deep neural classifier was applied to distinguish pro-ictal from interictal brain activities in a patient-specific fashion. RESULTS: We analyzed 1800 patient-hours of continuous thalamocortical EEG. Distinct pro-ictal states were detected in each participant. The median area under the receiver-operating characteristic curve of the classifier was 0.92 (interquartile range, 0.90­0.96). Pro-ictal states were distinguished at least 45 minutes before seizure onset in 13 of 15 participants; in 2 of 15 participants, they were distinguished up to 35 minutes prior. CONCLUSIONS: On the basis of thalamocortical EEG, pro-ictal states ­ pathologic brain activities during periods of heightened seizure risk ­ could be identified in patients with temporal lobe epilepsy and were detected, in our small sample, more than one half hour before seizure onset.

Advancing the frontiers of thalamic neuromodulation: A review of emerging targets and paradigms.

The thalamus is a key structure that plays a crucial role in initiating and propagating seizures. Recent advancements in neuroimaging and neurophysiology have identified the thalamus as a promising target for neuromodulation in drug-resistant epilepsies. This review article presents the latest innovations in thalamic targets and neuromodulation paradigms being explored in pilot or pivotal clinical trials. Multifocal temporal plus or posterior quadrant epilepsies are evaluated with pulvinar thalamus neuromodulation, while centromedian thalamus is explored in generalized epilepsies and Lennox Gastaut syndrome. Multinodal thalamocortical neuromodulation with novel stimulation paradigms such as long bursting or low-frequency stimulation is being investigated to quench the epileptic network excitability. Beyond seizure control, thalamic neuromodulation to restore consciousness is being studied. This review highlights the promising potential of thalamic neuromodulation in epilepsy treatment, offering hope to patients who have not responded to conventional medical therapies. However, it also emphasizes the need for larger randomized controlled trials and personalized stimulation paradigms to improve patient outcomes further.

Epidural Versus Local Anesthesia for Percutaneous Endoscopic Lumbar Discectomy: A Systematic Review and Meta-Analysis.

STUDY DESIGNS: Systematic Review. OBJECTIVE: To examine the impact of anesthesia type on patient-reported outcomes (PROs) and complications after percutaneous endoscopic lumbar discectomy (PELD). SUMMARY OF BACKGROUND DATA: A significant advantage of PELD involves the option to use alternative sedation to general anesthesia (GA). Two options include local anesthesia (LA) and epidural anesthesia (EA). While EA is more involved, it may yield improved pain control and surgical results compared with LA. However, few studies have directly examined outcomes for PELD after LA versus EA, and it remains unknown which technique results in superior outcomes. MATERIALS AND METHODS: A systematic review and meta-analysis of the PubMed, EMBASE, and SCOPUS databases examining PELD performed with LA or EA from inception to August 16, 2021 were conducted. All studies reported greater than 6 months of follow-up in addition to PRO data. PROs, including visual analog scale (VAS)-leg/back, and Oswestry Disability Index (ODI) scores were collected. Complications, recurrent disk herniation, durotomy, and reoperation rates, as well as surgical data, were recorded. All outcomes were compared between pooled studies examining LA or EA. RESULTS: Fifty-six studies consisting of 4465 patients (366 EA, 4099 LA) were included. Overall complication rate, durotomy rate, length of stay, recurrent disk herniation, and reoperation rates were similar between groups. VAS back/leg and ODI scores were all significantly improved at the first and last follow-up appointments in the LA group. VAS leg and ODI scores were significantly improved at the first and last follow-up appointments in the EA group, but VAS back was not. CONCLUSIONS: EA can be a safe and feasible alternative to LA, potentially minimizing patient discomfort during PELD. Conclusions are limited by a high level of study bias and heterogeneity. Further investigation is necessary to determine if PELD under EA may have greater short-term PRO benefits compared with LA.

General vs Local Anesthesia for Percutaneous Endoscopic Lumbar Discectomy (PELD): A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review. OBJECTIVES: It remains unknown whether general anesthesia (GA) or local ± epidural anesthesia (LA) results in superior outcomes with percutaneous endoscopic lumbar discectomy (PELD). The present study sought to examine the impact of anesthesia type on patient-reported outcomes (PROs) and complications with PELD. METHODS: Systematic review and meta-analysis examining PELD performed under GA or LA was conducted. Patient-reported outcomes including Visual Analog Scale (VAS)-leg/back, and Oswestry Disability Index (ODI) scores were collected. Complication, recurrent disc herniation, durotomy, and reoperation rates as well as surgical data were recorded. All outcomes were compared between pooled studies examining GA or LA. RESULTS: Sixty-eight studies consisting of 5269 patients (724 GA, 4465 LA) were included in the meta-analysis. Overall complication rate was significantly higher in the GA group (9% vs 4%, P = .003). Durotomy rates, length of stay, recurrent disc herniation and reoperation rates were similar between groups. At the first follow-up timepoint, the LA group demonstrated significant improvements in VAS back and ODI scores (P < .05) while the GA group did not (P > .05). At the final follow-up (> 6 months), the percent of patients achieving an excellent McNab score was significantly higher in the GA vs LA group (P < .001). CONCLUSIONS: Percutaneous endoscopic lumbar discectomy with LA may be associated with greater short-term improvement in VAS back pain and ODI scores. General anesthesia may be associated with more durable pain relief but a higher complication rate. Further systematic investigation is necessary to determine what short and long term benefits are associated with PELD performed under LA and GA.

Pulvinar neuromodulation for seizure monitoring and network modulation in temporal plus epilepsy.

Deep brain stimulation (DBS) is a promising treatment for drug-refractory epilepsies (DRE) when targeting the anterior nuclei of thalamus (ANT). However, targeting other thalamic nuclei, such as the pulvinar, shows therapeutic promise. Our pioneering case study presents the application of ambulatory seizure monitoring using spectral fingerprinting (12.15-17.15 Hz) recorded through Medtronic Percept DBS implanted bilaterally in the medial pulvinar thalami. This technology offers unprecedented opportunities for real-time monitoring of seizure burden and thalamocortical network modulation for effective seizure reduction in patients with bilateral mesial temporal and temporal plus epilepsies that are not suitable for resection.

Interictal localization of the epileptogenic zone: Utilizing the observed resonance behavior in the spectral band of surrounding inhibition.

Introduction: The gold standard for identification of the epileptogenic zone (EZ) continues to be the visual inspection of electrographic changes around seizures' onset by experienced electroencephalography (EEG) readers. Development of an epileptogenic focus localization tool that can delineate the EZ from analysis of interictal (seizure-free) periods is still an open question of great significance for improved diagnosis (e.g., presurgical evaluation) and treatment of epilepsy (e.g., surgical outcome). Methods: We developed an EZ interictal localization algorithm (EZILA) based on novel analysis of intracranial EEG (iEEG) using a univariate periodogram-type power measure, a straight-forward ranking approach, a robust dimensional reduction method and a clustering technique. Ten patients with temporal and extra temporal lobe epilepsies, and matching the inclusion criteria of having iEEG recordings at the epilepsy monitoring unit (EMU) and being Engel Class I ≥12 months post-surgery, were recruited in this study. Results: In a nested k-fold cross validation statistical framework, EZILA assigned the highest score to iEEG channels within the EZ in all patients (10/10) during the first hour of the iEEG recordings and up to their first typical clinical seizure in the EMU (i.e., early interictal period). To further validate EZILA's performance, data from two new (Engel Class I) patients were analyzed in a double-blinded fashion; the EZILA successfully localized iEEG channels within the EZ from interictal iEEG in both patients. Discussion: Out of the sampled brain regions, iEEG channels in the EZ were most frequently and maximally active in seizure-free (interictal) periods across patients in specific narrow gamma frequency band (∼60-80 Hz), which we have termed focal frequency band (FFB). These findings are consistent with the hypothesis that the EZ may interictally be regulated (controlled) by surrounding inhibitory neurons with resonance characteristics within this narrow gamma band.

Optimally targeting the centromedian nucleus of the thalamus for generalized epilepsy: A meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) of the centromedian nucleus (CM) is an effective therapeutic option for select patients with generalized epilepsy. However, several studies suggest that success varies with active contact location within the CM and the exact target remains undefined. OBJECTIVE: To quantify the association between active contact location and outcomes across all published series of CM DBS. METHODS: A literature search using PRISMA criteria was performed to identify all studies that reported active contact locations PLUS outcomes following DBS of the CM for epilepsy. Patient, disease, treatment, and outcome data were extracted for statistical analysis. Active contact locations were analyzed on a common reference frame and weighted by percent seizure reduction at last follow-up. RESULTS: From 184 studies that were screened for review, 3 studies comprising 47 patients met criteria for inclusion and were analyzed. At time of surgery, mean duration of epilepsy was 18 years. Pooled rates of atonic, atypical absence, generalized tonic-clonic, myoclonic, and tonic epilepsies were 38%, 74%, 68%, 14%, and 60%, respectively. Indirect targeting was used in all these studies. After a mean follow-up duration of 2.3 years, 87% of patients were deemed to be responders with mean seizure reduction of 73% (95% CI: [64%-81%]). Optimal location of the active contact was found to be at the dorsal border of the CM. CONCLUSIONS: Success following DBS of the CM for epilepsy varies by active contact location, even within the CM. Our findings suggest that stimulation within the dorsal region of the CM improves outcomes. Additional studies are needed to further refine these findings.

Thalamic neuromodulation for epilepsy: A clinical perspective.

Thalamic neuromodulation can be an effective therapeutic option for select patients with medically refractory epilepsy. However, successful outcome depends on several factors, beginning with appropriate patient and thalamic target selection. Among thalamic targets, the anterior (ANT) and centromedian (CeM) nuclei have the greatest clinical evidence for efficacy. However, the place of thalamic neuromodulation in the treatment armamentarium for intractable seizures is at the tail end of a long list of options. It's relative efficacy, if any, in relation to other treatment modalities however, can be inferred. As we will discuss, considerable work remains to be done in optimal targeting of thalamic nuclei, appropriate to the epilepsy syndrome and seizure type of the individual patient, which may change our current understanding of the place of thalamic neuromodulation on a range of treatment modality efficacies. Currently, it appears that ANT DBS is most efficacious for limbic epilepsies whereas CM, for generalized, multifocal (especially frontotemporal) epilepsies. Based on controlled studies, the efficacy of ANT and CeM DBS is roughly in line with other neuromodulatory therapies (i.e. RNS, VNS) when assessed within the cohort of patients for which the therapy is indicated. Much improvement is needed to render thalamic DBS more efficacious, and use of optimal targeting strategies, especially direct targeting, can positively affect outcomes. Thalamic neuromodulation is still in its infancy; however, clinical advances in this therapy are being realized.

Ictal high-frequency activity in limbic thalamic nuclei varies with electrographic seizure-onset patterns in temporal lobe epilepsy.

OBJECTIVE: To characterize ictal high-frequency activity (HFA, 80-500 Hz) within the limbic thalami and correlate HFA with seizure onset patterns in patients with temporal lobe epilepsy (TLE). METHODS: Patients with TLE undergoing stereoelectroencephalography (SEEG) for presurgical workup were prospectively recruited for electrode implantation in one of the anterior (AN), centromedian (CeM), or mediodorsal (MD) thalamic nuclei. HFA was computed by three complementary methods: (1.) power-spectral density (PSD), (2.) power-law based (i.e., 1/f) regression, and (3.) envelope-based (ENV) power analysis. Electrographic onset patterns in the seizure onset zone were classified in three distinct patterns, including low amplitude fast activity (LAFA). RESULTS: From 11 patients, 44 seizures were analyzed. Ictal HFA was observed in all three thalamic nuclei. HFA was greatest during ictal onset in the AN and MD and greatest during termination in the CeM (P < 0.001). LAFA-onset seizures were associated with earlier peak HFA compared to those with other onset patterns (P = 0.006). CONCLUSIONS: Dynamics of ictal HFA seem to vary by thalamic subnuclei. AN and MD may facilitate seizure propagation while CeM may play a role in termination. LAFA-onset seizures rapidly propagate to the thalamus. SIGNIFICANCE: Characterizing nucleus-specific ictal dynamics of neural activities facilitates precise therapy for epilepsy treatment with closed-loop deep brain stimulation.

Optimal targeting of the anterior nucleus of the thalamus for epilepsy: a meta-analysis.

OBJECTIVE: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has been shown to be an effective therapeutic option for select patients with limbic epilepsy. However, the optimal target and electrode position for this indication remains undefined. Therefore, the objective of this systematic review and meta-analysis is to quantify the association between active contact location and outcomes across all published series of ANT DBS. METHODS: A literature search using PRISMA criteria was performed to identify all studies that reported both active contact locations and outcomes of DBS in the ANT for epilepsy. Patient, disease, treatment, and outcome data were extracted for statistical analysis. Contact locations of responders (defined as ≥ 50% seizure reduction at last follow-up) versus nonresponders to DBS were analyzed on a common reference frame. Centers of mass, weighted by clinical response, were computed for the contacts in each cohort. RESULTS: From 555 studies that were screened for review, a total of 7 studies comprising 162 patients met criteria for inclusion and were analyzed. Across the cohort, the mean duration of epilepsy was 23 years and the mean pre-DBS seizure frequency was 56 seizures per month. DBS electrodes were implanted using direct targeting in 5 studies (n = 62, 38% of patient cohort) via a transventricular electrode trajectory in 4 studies (n = 123, 76%). At the mean follow-up duration of 2.3 years, 56% of patients were considered responders. Active contacts of responders were 1.6 mm anterior (95% CI 1.5-1.6 mm, p < 0.001) compared to those of nonresponders and were adjacent to the mammillothalamic tract (MTT). CONCLUSIONS: Accurate targeting of the ANT is crucial to successful DBS outcomes in epilepsy. These findings suggest that stimulation within the ANT subregions adjacent to the MTT improves outcomes.

Predictive Factors for Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery: A Single-Center Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is particularly useful for treatment of deep arteriovenous malformations (AVMs) in eloquent territory with a high associated surgical risk. Prior studies have demonstrated high rates of AVM obliteration with SRS (60%-80%) in a latency period of 2-4 years for complete obliteration. Studies have identified several factors associated with successful obliteration of the AVM nidus; however, these present inconsistent and conflicting data. The aim of this single-center study was to examine factors associated with successful obliteration of AVMs treated with SRS. METHODS: A retrospective review was performed of 210 consecutive patients undergoing SRS for brain AVMs between 2010 and 2019. The χ2 test and logistic regression analysis were used to identify patient and AVM factors associated with successful obliteration. RESULTS: Younger age (P = 0.034) and prior embolization (P = 0.012) were associated with complete obliteration. The presence of coronary artery disease was associated with incomplete obliteration (P = 0.04). No AVM characteristics were statistically associated with complete obliteration, although superficial venous drainage (P = 0.08) and frontal location (P = 0.06) trended toward significance. CONCLUSIONS: Successful obliteration of the AVM nidus was significantly associated with younger age and prior embolization. The presence of coronary artery disease negatively affected obliteration rates. These results add to the mixed results seen in the literature and emphasize the need for continued studies to delineate more specific patient and AVM factors that contribute to successful obliteration.

Microendoscopic lumbar discectomy with general versus local anesthesia: A systematic review and meta-analysis.

Background: While general anesthesia (GA) is the most commonly used anesthetic method during lumbar microendoscopic discectomy (MED), local ± epidural anesthesia (LA) has been gaining popularity as an alternate method. Theoretical advantages of LA include reduced morbidity of anesthesia and improved surgeon-patient communication facilitating less nerve root manipulation and yielding improved surgical outcomes. The objective of this systematic review is to examine the impact of anesthesia type on patient reported outcomes (PROs) and complications with MED. Methods: A systematic review and meta-analysis of the available literature examining MED performed under GA or LA was performed. The PubMed, EMBASE and SCOPUS databases were searched from inception to August 16, 2021, utilizing strict inclusion and exclusion criteria with all studies reporting greater than 6 months of follow-up and PRO data. PROs including Visual Analog Scale (VAS)-leg/back, Oswestry Disability Index (ODI), Japanese Orthopedic Association (JOA) and/or 36-Item Short Form (SF-36) physical component scores were collected. Complication, recurrent disc herniation, durotomy and reoperation rates as well as surgical factors were collected. All outcomes were compared between pooled studies examining GA or LA. Risk of bias was assessed with the Newcastle-Ottawa Scale. Results: A total of 23 studies consisting of 2,868 patients (1,335 GA, 1,533 LA) were included in the meta-analysis. There were no significant differences between GA and LA groups in regard to overall complication rate, durotomy rate, recurrent disc herniation rate, reoperation rate, blood loss, or surgical time (p > 0.05). Both groups demonstrated significant improvements in ODI and JOA (p<0.0004), however leg and back VAS was only improved in GA (p<0.0025) and not in LA (p>0.058), and SF-36 only in LA (p=0.003). Conclusions: Patients undergoing MED under both anesthetic techniques demonstrated significant improvements in ODI and JOA, with no significant differences in complication or reoperation rates. However, patients undergoing GA demonstrated significant improvement in VAS leg and back pain at last follow-up while LA did not. LA may be offered to carefully selected patients and prior studies have demonstrated reduced costs and risks with LA. Conclusions are limited by a high level of study bias and heterogeneity. Further investigation is needed to assess the true effects of GA and LA on outcomes after MED.

Stereotactic Radiosurgery for A Randomized Trial of Unruptured Brain Arteriovenous Malformations-Eligible Patients: A Meta-Analysis.

BACKGROUND: The outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) were controversial, and they suggested that intervention is inferior to medical management for unruptured brain arteriovenous malformations (AVMs). However, several studies have shown that stereotactic radiosurgery (SRS) is an acceptable therapy for unruptured AVMs. OBJECTIVE: To test the hypothesis that ARUBA intervention arm's SRS results are meaningfully inferior to those from similar populations reported by other studies. METHODS: We performed a literature review to identify SRS studies of patients who met the eligibility criteria for ARUBA. Patient, AVM, treatment, and outcome data were extracted for statistical analysis. Regression analyses were pooled to identify factors associated with post-SRS obliteration and hemorrhage. RESULTS: The study cohort included 8 studies comprising 1620 ARUBA-eligible patients who underwent SRS. At the time of AVM diagnosis, 36% of patients were asymptomatic. The mean follow-up duration was 80 months. Rates of radiologic, symptomatic, and permanent radiation-induced changes were 45%, 11%, and 2%, respectively. The obliteration rate was 68% at last follow-up. The post-SRS hemorrhage and mortality rates were 8%, and 2%, respectively. Lower Spetzler-Martin grade (odds ratios [OR] = 0.84 [0.74-0.95], P = .005), lower radiosurgery-based AVM score (OR = 0.75 [0.64-0.95], P = .011), lower Virginia Radiosurgery AVM Scale (OR = 0.86 [0.78-0.95], P = .003), and higher margin dose (OR = 1.13 [1.02-1.25], P = .025) were associated with obliteration. CONCLUSION: SRS carries a favorable risk to benefit profile for appropriately selected ARUBA-eligible patients, particularly those with smaller volume AVMs. Our findings suggest that the results of ARUBA do not reflect the real-world safety and efficacy of SRS for unruptured AVMs.

Stereotactic radiosurgery for ruptured versus unruptured intracranial arteriovenous malformations.

Background: There are a limited data examining the effects of prior hemorrhage on outcomes after stereotactic radiosurgery (SRS). The goal of this study was to identify risk factors for arteriovenous malformation (AVM) rupture and compare outcomes, including post-SRS hemorrhage, between patients presenting with ruptured and unruptured AVMs. Methods: A retrospective review of consecutive patients undergoing SRS for intracranial AVMs between 2009 and 2019 at our institution was conducted. Chi-square and multivariable logistic regression analyses were utilized to identify patient and AVM factors associated with AVM rupture at presentation and outcomes after SRS including the development of recurrent hemorrhage in both ruptured and unruptured groups. Results: Of 210 consecutive patients with intracranial AVMs treated with SRS, 73 patients (34.8%) presented with AVM rupture. Factors associated with AVM rupture included smaller AVM diameter, deep venous drainage, cerebellar location, and the presence of intranidal aneurysms (P < 0.05). In 188 patients with adequate follow-up time (mean 42.7 months), the overall post-SRS hemorrhage rate was 8.5% and was not significantly different between ruptured and unruptured groups (10.3 vs. 7.5%, P = 0.51). There were no significant differences in obliteration rate, time to obliteration, or adverse effects requiring surgery or steroids between unruptured and ruptured groups. Conclusion: Smaller AVM size, deep venous drainage, and associated intranidal aneurysms were associated with rupture at presentation. AVM rupture at presentation was not associated with an increased risk of recurrent hemorrhage or other complication after SRS when compared to unruptured AVM presentation. Obliteration rates were similar between ruptured and unruptured groups.