Precision Effects of Glibenclamide on MRI Endophenotypes in Clinically Relevant Murine Traumatic Brain Injury.

OBJECTIVES: Addressing traumatic brain injury (TBI) heterogeneity is increasingly recognized as essential for therapy translation given the long history of failed clinical trials. We evaluated differential effects of a promising treatment (glibenclamide) based on dose, TBI type (patient selection), and imaging endophenotype (outcome selection). Our goal to inform TBI precision medicine is contextually timely given ongoing phase 2/planned phase 3 trials of glibenclamide in brain contusion. DESIGN: Blinded randomized controlled preclinical trial of glibenclamide on MRI endophenotypes in two established severe TBI models: controlled cortical impact (CCI, isolated brain contusion) and CCI+hemorrhagic shock (HS, clinically common second insult). SETTING: Preclinical laboratory. SUBJECTS: Adult male C57BL/6J mice (n = 54). INTERVENTIONS: Mice were randomized to naïve, CCI±HS with vehicle/low-dose (20 µg/kg)/high-dose glibenclamide (10 µg/mouse). Seven-day subcutaneous infusions (0.4 µg/hr) were continued. MEASUREMENTS AND MAIN RESULTS: Serial MRI (3 hr, 6 hr, 24 hr, and 7 d) measured hematoma and edema volumes, T2 relaxation (vasogenic edema), apparent diffusion coefficient (ADC, cellular/cytotoxic edema), and 7-day T1-post gadolinium values (blood-brain-barrier [BBB] integrity). Linear mixed models assessed temporal changes. Marked heterogeneity was observed between CCI versus CCI+HS in terms of different MRI edema endophenotypes generated (all p < 0.05). Glibenclamide had variable impact. High-dose glibenclamide reduced hematoma volume ~60% after CCI (p = 0.0001) and ~48% after CCI+HS (p = 4.1 × 10-6) versus vehicle. Antiedema benefits were primarily in CCI: high-dose glibenclamide normalized several MRI endophenotypes in ipsilateral cortex (all p < 0.05, hematoma volume, T2, ADC, and T1-post contrast). Acute effects (3 hr) were specific to hematoma (p = 0.001) and cytotoxic edema reduction (p = 0.0045). High-dose glibenclamide reduced hematoma volume after TBI with concomitant HS, but antiedema effects were not robust. Low-dose glibenclamide was not beneficial. CONCLUSIONS: High-dose glibenclamide benefitted hematoma volume, vasogenic edema, cytotoxic edema, and BBB integrity after isolated brain contusion. Hematoma and cytotoxic edema effects were acute; longer treatment windows may be possible for vasogenic edema. Our findings provide new insights to inform interpretation of ongoing trials as well as precision design (dose, sample size estimation, patient selection, outcome selection, and Bayesian analysis) of future TBI trials of glibenclamide.

Cerebrospinal Fluid Biomarkers for Diagnosis and the Prognostication of Acute Ischemic Stroke: A Systematic Review.

Despite the high incidence and burden of stroke, biological biomarkers are not used routinely in clinical practice to diagnose, determine progression, or prognosticate outcomes of acute ischemic stroke (AIS). Because of its direct interface with neural tissue, cerebrospinal fluid (CSF) is a potentially valuable source for biomarker development. This systematic review was conducted using three databases. All trials investigating clinical and preclinical models for CSF biomarkers for AIS diagnosis, prognostication, and severity grading were included, yielding 22 human trials and five animal studies for analysis. In total, 21 biomarkers and other multiomic proteomic markers were identified. S100B, inflammatory markers (including tumor necrosis factor-alpha and interleukin 6), and free fatty acids were the most frequently studied biomarkers. The review showed that CSF is an effective medium for biomarker acquisition for AIS. Although CSF is not routinely clinically obtained, a potential benefit of CSF studies is identifying valuable biomarkers from the pathophysiologic microenvironment that ultimately inform optimization of targeted low-abundance assays from peripheral biofluid samples (e.g., plasma). Several important catabolic and anabolic markers can serve as effective measures of diagnosis, etiology identification, prognostication, and severity grading. Trials with large cohorts studying the efficacy of biomarkers in altering clinical management are still needed.

Electroencephalography for detection of vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective analysis and systematic review.

OBJECTIVE: Good functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH) are often dependent on early detection and treatment of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI). There is growing evidence that continuous monitoring with cranial electroencephalography (cEEG) can predict CVS and DCI. Therefore, the authors sought to assess the value of continuous cEEG monitoring for the detection of CVS and DCI in aSAH. METHODS: The cerebrovascular database of a quaternary center was reviewed for patients with aSAH and cEEG monitoring between January 1, 2017, and July 31, 2019. Demographic data, cardiovascular risk factors, Glasgow Coma Scale score at admission, aneurysm characteristics, and outcomes were abstracted from the medical record. Patient data were retrospectively analyzed for DCI and angiographically assessed CVS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and odds ratio for cEEG, transcranial Doppler ultrasonography (TCDS), CTA, and DSA in detecting DCI and angiographic CVS were calculated. A systematic literature review was conducted in accordance with PRISMA guidelines querying the PubMed, Cochrane Controlled Trials Register, Web of Science, and Embase databases. RESULTS: A total of 77 patients (mean age 60 years [SD 15 years]; female sex, n = 54) were included in the study. Continuous cEEG monitoring detected DCI and angiographically assessed CVS with specificities of 82.9% (95% CI 66.4%-93.4%) and 94.4% (95% CI 72.7%-99.9%), respectively. The sensitivities were 11.1% (95% CI 3.1%-26.1%) for DCI (n = 71) and 18.8% (95% CI 7.2%-36.4%) for angiographically assessed CVS (n = 50). Furthermore, TCDS detected angiographically determined CVS with a sensitivity of 87.5% (95% CI 71.0%-96.5%) and specificity of 25.0% (95% CI 7.3%-52.4%). In patients with DCI, TCDS detected vasospasm with a sensitivity of 85.7% (95% CI 69.7%-95.2%) and a specificity of 18.8% (95% CI 7.2%-36.4%). DSA detected vasospasm with a sensitivity of 73.9% (95% CI 51.6%-89.8%) and a specificity of 47.8% (95% CI 26.8%-69.4%). CONCLUSIONS: The study results suggest that continuous cEEG monitoring is highly specific in detecting DCI as well as angiographically assessed CVS. More prospective studies with predetermined thresholds and endpoints are needed to assess the predictive role of cEEG in aSAH.

Microsurgical treatment of ruptured aneurysms beyond 72 hours after rupture: implications for advanced management.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to primary stroke centers are often transferred to neurosurgical and endovascular services at tertiary centers. The effect on microsurgical outcomes of the resultant delay in treatment is unknown. We evaluated microsurgical aSAH treatment > 72 h after the ictus. METHODS: All aSAH patients treated at a single tertiary center between August 1, 2007, and July 31, 2019, were retrospectively reviewed. The additional inclusion criterion was the availability of treatment data relative to time of bleed. Patients were grouped based on bleed-to-treatment time as having acute treatment (on or before postbleed day [PBD] 3) or delayed treatment (on or after PBD 4). Propensity adjustments were used to correct for statistically significant confounding covariables. RESULTS: Among 956 aSAH patients, 92 (10%) received delayed surgical treatment (delayed group), and 864 (90%) received acute endovascular or surgical treatment (acute group). Reruptures occurred in 3% (26/864) of the acute group and 1% (1/92) of the delayed group (p = 0.51). After propensity adjustments, the odds of residual aneurysm (OR = 0.09; 95% CI = 0.04-0.17; p < 0.001) or retreatment (OR = 0.14; 95% CI = 0.06-0.29; p < 0.001) was significantly lower among the delayed group. The OR was 0.50 for rerupture, after propensity adjustments, in the delayed setting (p = 0.03). Mean Glasgow Coma Scale scores at admission in the acute and delayed groups were 11.5 and 13.2, respectively (p < 0.001). CONCLUSIONS: Delayed microsurgical management of aSAH, if required for definitive treatment, appeared to be noninferior with respect to retreatment, residual, and rerupture events in our cohort after adjusting for initial disease severity and significant confounding variables.

Eloquent noneloquence: redefinition of cortical eloquence based on outcomes of superficial cerebral cavernous malformation resection.

OBJECTIVE: Cerebral cavernous malformations (CMs) are pathological lesions that cause discrete cortical disruption with hemorrhage, and their transcortical resections can cause additional iatrogenic disruption. The analysis of microsurgically treated CMs might identify areas of "eloquent noneloquence," or cortex that is associated with unexpected deficits when injured or transgressed. METHODS: Patients from a consecutive microsurgical series of superficial cerebral CMs who presented to the authors' center over a 13-year period were retrospectively analyzed. Neurological outcomes were measured using the modified Rankin Scale (mRS), and new, permanent neurological or cognitive symptoms not detected by changes in mRS scores were measured as additional functional decline. Patients with multiple lesions and surgical encounters for different lesions within the study interval were represented within the cohort as multiple patient entries. Virtual object models for CMs and approach trajectories to subcortical lesions were merged into a template brain model for subtyping and Quicktome connectomic analyses. Parcellation outputs from the models were analyzed for regional cerebral clustering. RESULTS: Overall, 362 CMs were resected in 346 patients, and convexity subtypes were the most common (132/362, 36.5%). Relative to the preoperative mRS score, 327 of 362 cases (90.3%) were in patients who improved or remained stable, 35 (9.7%) were in patients whose conditions worsened, and 47 (13.0%) were in patients who had additional functional decline. Machine learning analyses of lesion objects and trajectory cylinder mapping identified 7 hotspots of novel eloquence: supplementary motor area (bilateral), anterior cingulate cortex (bilateral), posterior cingulate cortex (bilateral), anterior insula (left), frontal pole (right), mesial temporal lobe (left), and occipital cortex (right). CONCLUSIONS: Transgyral and transsulcal resections that circumvent areas of traditional eloquence and navigate areas of presumed noneloquence may nonetheless result in unfavorable outcomes, demonstrating that brain long considered by neurosurgeons to be noneloquent may be eloquent. Eloquent hotspots within multiple large-scale networks redefine the neurosurgical concept of eloquence and call for more refined dissection techniques that maximize transsulcal dissection, intracapsular resection, and tissue preservation. Human connectomics, awareness of brain networks, and prioritization of cognitive outcomes require that we update our concept of cortical eloquence and incorporate this information into our surgical strategies.

A taxonomy for superficial cerebral cavernous malformations: subtypes of cortical and subcortical lesions.

OBJECTIVE: A taxonomy for superficial cerebral cavernous malformations (CMs), those based cortically in gyral gray matter or subcortically in underlying white matter, is proposed to build on the comprehensive, systematic characterization of CMs in the entire brain. METHODS: Patients with superficial cerebral CMs were retrospectively analyzed from a consecutive surgical series between November 2008 and June 2021 at the authors' center. Superficial cerebral CMs were categorized into 4 subtypes based on their cortical location or, if subcortical, proximity to the nearest cerebral surface: convexity, medial, basal, and sylvian. Lobar location was also included for subtyping: frontal, temporal, parietal, and occipital. RESULTS: A total of 362 CMs were resected in 346 patients. CM subtypes were as follows: 132 (36.5%) convexity, 78 (21.5%) medial, 72 (19.9%) basal, and 80 (22.1%) sylvian. Frontal CMs were most common (155 [42.8%]), followed by parietal (89 [24.6%]), temporal (87 [24.0%]), and occipital (31 [8.6%]). Of all CMs, 302 (83.4%) were cortical and 60 (16.6%) were subcortical. The mean subcortical depth of deep lesions was 2.97 cm, and the mean lesion volume was 4.68 cm3. Overall, 228 lesions (63.0%) were resected through a transgyral approach, and 134 (37.0%) were resected through a transsulcal approach. Good outcomes (modified Rankin Scale [mRS] score ≤ 2) were observed in 314 patients (86.7%) and poor outcomes (mRS score > 2) in 25 patients (6.9%), and 23 patients (6.4%) were lost to late follow-up (mean follow-up duration 11.5 months). Relative outcomes were good (unchanged or improved mRS score) in 327 patients (90.3%) and poor (worse or died) in 35 patients (9.7%). CONCLUSIONS: Superficial cerebral CMs were resected through a gyrus or sulcus to open the subarachnoid dissection corridors, traversing the full extent of sulci to deepen the approach and minimize tissue transgression. Transgyral dissection avoids associated arteries but is inherently transgressive, whereas transsulcal dissection preserves cortical tissue and may reduce morbidity. Superficial cerebral CMs occupy the largest territory of the 7 types, and the size and surface complexity of the cerebrum make taxonomic subtyping valuable for clear anatomical description.

Optimal PHASES Scoring for Risk Stratification of Surgically Treated Unruptured Aneurysms.

OBJECTIVE: The PHASES (Population, Hypertension, Age, Size, Earlier subarachnoid hemorrhage, Site) score was developed to facilitate risk stratification for management of unruptured intracranial aneurysms (UIAs). This study aimed to identify the optimal PHASES score cutoff for predicting neurologic outcomes in patients with surgically treated aneurysms. METHODS: All patients who underwent microneurosurgical treatment for UIA at a large quaternary center from January 1, 2014, to December 31, 2020, were retrospectively reviewed. Inclusion criteria included a modified Rankin Scale (mRS) score of ≤2 at admission. The primary outcome was 1-year mRS score, with a "poor" neurologic outcome defined as an mRS score >2. RESULTS: In total, 375 patients were included in the analysis. The mean (SD) PHASES score for the entire study population was 4.47 (2.67). Of 375 patients, 116 (31%) had a PHASES score ≥6, which was found to maximize prediction of poor neurologic outcome. Patients with PHASES scores ≥6 had significantly higher rates of poor neurologic outcome than patients with PHASES scores <6 at discharge (58 [50%] vs. 90 [35%], P = 0.005) and follow-up (20 [17%] vs. 18 [6.9%], P = 0.002). After adjusting for age, Charlson Comorbidity Index score, nonsaccular aneurysm, and aneurysm size, PHASES score ≥6 remained a significant predictor of poor neurologic outcome at follow-up (odds ratio, 2.75; 95% confidence interval, 1.42-5.36, P = 0.003). CONCLUSIONS: In this retrospective analysis, a PHASES score ≥6 was associated with significantly greater proportions of poor outcome, suggesting that awareness of this threshold in PHASES scoring could be useful in risk stratification and UIA management.

Radiation-induced cavernous malformations in the spine: patient series.

BACKGROUND: Radiation-induced spinal cord cavernous malformations (RISCCMs) are a rare subset of central nervous system lesions and are more clinically aggressive than congenital cavernous malformations (CMs). The authors assessed the characteristics and outcomes of patients with RISCCM at a single institution and systematically reviewed the pertinent literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. OBSERVATIONS: Among the 146 spinal CMs at the authors' institution, 3 RISCCMs were found. Symptom duration ranged from 0.1 to 8.5 months (mean [standard deviation], 3.2 [4.6] months), and latency ranged from 16 to 29 years (22.4 [9.6] years). All 3 RISCCMs were surgically treated with complete resection; 2 patients had stable outcomes, and 1 improved postoperatively. A review of 1240 articles revealed 20 patients with RISCCMs. Six of these patients were treated with resection, 13 were treated conservatively, and in 1 case, the treatment type was not stated. Five of the 6 patients treated surgically reported improvement postoperatively or at follow-up; 1 was stable, and none reported worsened outcomes. LESSONS: RISCCMs are rare sequelae following radiation that inadvertently affect the spinal cord. Altogether, the frequency of stable and improved outcomes on follow-up suggests that resection could prevent further patient decline caused by symptoms of RISCCM. Therefore, surgical management should be considered primary therapy in patients presenting with RISCCMs.

Expanding the reach of the trans-middle cerebellar peduncle approach: pontine cavernous malformations, tissue transgression beyond the safe entry zone, and the invisible triangle.

OBJECTIVE: In the authors' microsurgical experience, the trans-middle cerebellar peduncle (MCP) approach to the lateral and central pons has been the most common approach to brainstem cavernous malformations (BSCMs). This approach through a well-tolerated safe entry zone (SEZ) allows a wide vertical or posterior trajectory, reaching pontine lesions extending into the midbrain, medulla, and pontine tegmentum. Better understanding of the relationships among lesion location, surgical trajectory, and long-term clinical outcomes could determine areas of safe passage. METHODS: A single-surgeon cohort study of all primary trans-MCP BSCM resections was conducted from July 1, 2017, to June 30, 2021. Preoperative and postoperative MR images were independently reviewed by 3 investigators blinded to the intervention, using a standardized rubric to define BSCM regions of interest (ROIs) involved with a lesion or microsurgical tract. Statistical testing, including the chi-square test with the Bonferroni correction, logistic regression, and structural equation modeling, was performed to analyze relationships between ROIs and clinical outcomes. RESULTS: Thirty-one patients underwent primary trans-MCP BSCM resection during the study period. The median age was 50 years (IQR 24-49 years); 19 (61%) patients were female, and 12 (39%) were male. Seven (23%) patients had familial cavernous malformation syndromes. The median follow-up was 9 months (range 6-37 months). At the last follow-up, composite neurological outcomes were favorable: 22 (71%) patients had 0 (n = 12, 39%) or 1 (n = 10, 32%) major persistent deficit, 5 patients (16%) had 2 deficits, 2 (7%) had 3 deficits, and 1 patient each (3%) had 4 or 6 deficits. Unfavorable composite outcomes were significantly associated with lesions (OR 7.14, p = 0.04) or surgical tracts (OR 12.18, p < 0.001) extending from the superior cerebellar peduncle (SCP) into the contralateral medial midbrain. The ipsilateral dorsal pons was the most frequently implicated ROI involving a surgical tract and the development of new postoperative deficits. This region involved the rhomboid pontine territory and transgression of the pontine tegmentum (OR 7.53, p < 0.001). Structural equation modeling supported medial midbrain and pontine tegmentum transgression as the primary drivers of morbidity. CONCLUSIONS: Trans-MCP resection is a safe and effective treatment for BSCMs, including lesions with marked superior or inferior ipsilateral extension. Two trajectories are associated with increased neurological risk: first, a superomedial trajectory to lesions extending into the midbrain that transgresses the SCP, its decussation, or both; and second, a posteromedial trajectory to lesions extending into the pontine tegmentum. The corticospinal tract, SCP, and pontine tegmentum form an invisible triangle within the pontine white matter tolerant of transgression. When the surgeon works within this triangle, most deep pontine BSCMs, including large lesions, those with contralateral or posterior extension, and others extending into the midbrain and medulla, can be resected safely with the trans-MCP approach.

Publication Speed Across Neurosurgery Journals: A Bibliometric Analysis.

OBJECTIVE: Many factors influence an author's choice for journal submission, including journal impact factor and publication speed. These and other bibliometric data points have not been assessed in journals dedicated to neurosurgery. METHODS: Eight leading neurosurgery journals were analyzed to identify original articles and reviews, collected via randomized, stratified sampling per published issue per year from 2016 to 2020. Bibliometric data on publication speed were gathered for each article. Journal impact factor, article processing fees, and open access availability were determined using Clarivate Journal Citation Reports. Correlation analysis and a linear regression model were used to estimate the effect of impact factor and publication year on publication speed. RESULTS: Across the 8 neurosurgery journals, 1617 published articles were reviewed. The mean (standard deviation) time from submission to acceptance (SA) was 131 (101) days, from acceptance to online publication was 77 (61) days, and from submission to online publication was 207 (123) days. Higher impact factors correlated with longer publication times for all metrics. Later years of publication correlated with longer times from SA and submission to online publication. For each point increase in a journal's impact factor, multivariate regression modeling estimated a 19.2-day increase in time from SA, a 19.7-day increase in time from acceptance to online publication, and a 38.9-day increase in time from submission to online publication (P < 0.001 for all). CONCLUSIONS: Publication speeds vary widely among neurosurgery journals and appear to be associated with the journal impact factor. Time to publication increased over the study period.

You Take the Low Road: Differential Outcomes After Tangential and Transcortical Approaches to Medial Temporal Brain Arteriovenous Malformations.

OBJECTIVE: Microsurgical resection of medial temporal brain arteriovenous malformations (AVMs) is typically conducted through 2 approaches: the orbitozygomatic-tangential and subtemporal-transcortical. Relative indications and outcomes for these techniques have not been formally compared. METHODS: The cerebrovascular database of a quaternary center was reviewed for patients with medial temporal AVMs treated between January 1, 1997, and July 31, 2021. Demographic characteristics, lesion characteristics, surgical approaches, and outcomes were retrospectively analyzed and compared. Postoperative outcome testing was performed using the Montreal Cognitive Assessment and Global Quality of Life Scale. RESULTS: Fifty-nine patients were assessed. Mean (standard deviation) age was 31 (18) years; 30 (51%) patients were male. Of the AVMs, 29 (49%) were left-sided and 30 (51%) were right-sided. The tangential approach was selected in 20 (34%) cases, whereas the transcortical technique was preferred in 39 (66%). Improved modified Rankin Scale status was significantly associated with the tangential resection technique both in the early postoperative period (P = 0.02) and at last follow-up (P = 0.01). Differences between the tangential and transcortical approaches were not significant with respect to new postoperative deficits (5/20 [25%] vs. 12/39 [31%], P = 0.87) or the presence of residual AVM on follow-up angiography (1/20 [6%] vs. 5/39 [14%], P = 0.65). CONCLUSIONS: The orbitozygomatic-tangential strategy was associated with favorable functional and quality-of-life outcomes after medial temporal AVM resection. These benefits are likely to be attributable to minimization of temporal retraction, avoidance of brain transgression, and avoidance of traction on the vein of Labbé, rendering the orbitozygomatic-tangential approach the preferred option for cases that are anatomically amenable to either strategy.

Residual and Recurrent Spinal Cord Cavernous Malformations: Outcomes and Techniques to Optimize Resection and a Systematic Review of the Literature.

BACKGROUND: Intramedullary spinal cord cavernous malformations (SCCMs) account for only 5% of overall cavernous malformations (CMs). The occurrence of recurrent or residual SCCMs has not been well discussed, nor have the technical nuances of resection. OBJECTIVE: To assess the characteristics of residual SCCMs and surgical outcomes and describe the techniques to avoid leaving lesion remnants during primary resection. METHODS: Demographic, radiologic, intraoperative findings and surgical outcomes data for a cohort of surgically managed intramedullary SCCMs were obtained from an institutional database and retrospectively analyzed. A systematic literature review was performed using PRISMA guidelines. RESULTS: Of 146 SCCM resections identified, 17 were for residual lesions (12%). Patients with residuals included 13 men and 4 women, with a mean age of 43 years (range 16-70). All patients with residual SCCMs had symptomatic presentations: sensory deficits, paraparesis, spasticity, and pain. Residuals occurred between 3 and 264 months after initial resection. Approaches for 136 cases included posterior midline myelotomy (28.7%, n = 39), pial surface entry (37.5%, n = 51), dorsal root entry zone (27.9%, n = 38), and lateral entry (5.9%, n = 8). Follow-up outcomes were similar for patients with primary and residual lesions, with the majority having no change in modified Rankin Scale score (63% [59/93] vs 75% [9/12], respectively, P = .98). CONCLUSION: SCCMs may cause significant symptoms. During primary resection, care should be taken to avoid leaving residual lesion remnants, which can lead to future hemorrhagic events and neurological morbidity. However, satisfactory results are achievable even with secondary or tertiary resections.

Back to basal: contemporary cerebrovascular cohort study of the supratentorial-infraoccipital approach.

OBJECTIVE: The objective of this paper was to assess applications of the supratentorial-infraoccipital (STIO) approach for cerebrovascular neurosurgery. METHODS: The authors conducted a cohort study of all consecutive cases in which the STIO approach was used during the study period, December 1995 to January 2021, as well as a systematic review of the literature. RESULTS: Twenty-five cerebrovascular cases were identified in which the STIO approach was used. Diagnoses included arteriovenous malformation (n = 15), cerebral cavernous malformation (n = 5), arteriovenous fistula (n = 4), and aneurysm (n = 1). The arteriovenous malformations consisted of Spetzler-Martin grade II (n = 3), grade III (n = 8), and grade IV (n = 4) lesions. Lesion locations included the occipital lobe (n = 15), followed by the tentorial dural (n = 4), temporal-occipital (n = 3), temporal (n = 1), thalamic (n = 1), and quadrigeminal cistern (n = 1) regions. Many patients (75%) experienced transient visual deficits attributable to retraction of the occipital lobe, all of which resolved. As of last follow-up (n = 12), modified Rankin Scale scores had improved for 6 patients and were unchanged for 6 patients compared with the preoperative baseline. CONCLUSIONS: The STIO approach is a safe and effective skull base approach that provides a specialized access corridor for appropriately selected cerebrovascular lesions.

Cost-Effectiveness of Forgoing Postoperative Catheter Angiography After Microsurgical Occlusion of Spinal Dorsal Intradural Arteriovenous Fistulas.

OBJECTIVE: Spinal dorsal intradural arteriovenous fistulas (DI-AVFs) represent 70% of all spinal vascular lesions. Diagnostic tools include pre- and postoperative digital subtraction angiography (DSA) and intraoperative indocyanine green videoangiography (ICG-VA). ICG-VA has a high predictive value in DI-AVF occlusion, but postoperative DSA remains a core component of postoperative protocols. The aim of this study was to evaluate the potential cost reduction of forgoing postoperative DSA after microsurgical occlusion of DI-AVFs. METHODS: Cohort-based cost effectiveness study of all DI-AVFs within a prospective, single-center cerebrovascular registry from January 1, 2017, to December 31, 2021. RESULTS: Complete data including intraoperative ICG-VA and costs were available for 11 patients. Mean (SD) age was 61.5 (14.8) years. All DI-AVFs were treated with microsurgical clip ligation of the draining vein. ICG-VA showed complete obliteration in all patients. Postoperative DSA was performed for 6 patients and confirmed complete obliteration. Mean (SD) cost contributions for DSA and ICG-VA were $11,418 ($4,861) and $12 ($2), respectively. Mean (SD) total costs were $63,543 ($15,742) and $53,369 ($27,609) for patients who did and did not undergo postoperative DSA, respectively. Comorbidity status was identified as the main driver of total cost (P = 0.01 after adjusting for postoperative DSA status). CONCLUSIONS: ICG-VA is a powerful diagnostic tool in demonstrating microsurgical cure of DI-AVFs, with a negative predictive value of 100%. Eliminating postoperative DSA in patients with confirmed DI-AVF obliteration on ICG-VA may yield substantial cost savings, in addition to sparing patients the risk and inconvenience of a potentially unnecessary invasive procedure.

Endovascular Embolization of Basilar Artery Fenestration Aneurysms: A 21-Year Institutional Case Series.

BACKGROUND AND OBJECTIVES: Basilar artery fenestration is a rare phenomenon sometimes associated with basilar artery fenestration aneurysms (BAFAs). This review investigates the natural history and management outcomes of BAFAs and describes the outcomes of BAFAs treated with embolization. METHODS: A single-center database was queried for all cases of endovascular BAFA treatment. Data on complications, clinical and angiographic outcomes, and retreatment rates were collected. RESULTS: Seventeen aneurysms across 17 patients were treated. The mean (SD) age was 56 (13) years, and 15 (88%) patients were women. Among 15 aneurysms with data available, 2 arose from the fenestration limbs and 13 from both limbs and the vertebral artery. Of 16 aneurysmal projections available, 7 projected anteriorly, 7 posteriorly, and 2 superiorly. Among 17 patients, balloon-assisted coiling was the most common treatment (n = 10), followed by primary coiling (n = 3), stent-assisted coiling (n = 2), coiling with flow diversion (n = 1), and balloon-assisted coiling and flow diversion (n = 1). Complications noted in 5 patients included hemorrhage, thromboembolism, paresthesias, vasospasm, and transient hemiparesis. Among 16 patients with postoperative results available, 12 showed favorable clinical outcomes, 3 were disabled, and 1 died. The rates of postoperative complete (Raymond-Roy Occlusion Classification 1) and incomplete (Raymond-Roy Occlusion Classification 2 and 3) occlusion among 15 patients with available data were 6 and 9, respectively. CONCLUSION: Endovascular management of these rare aneurysms is feasible and safe, with high rates of favorable radiographic and clinical outcomes. This series reflects a general preference toward coiling and stent-assisted coiling, although flow diversion may be considered in select cases.

Mortality After Microsurgical Treatment of Unruptured Intracranial Aneurysms in the Modern Era.

BACKGROUND: The incidence of mortality after treatment of unruptured intracranial aneurysms (UIAs) has been described historically. However, many advances in microsurgical treatment have since emerged, and most available data are outdated. We analyzed the incidence of mortality after microsurgical treatment of patients with UIAs treated in the past decade. METHODS: The medical records of all patients with UIAs who underwent elective treatment at our large quaternary center from January 1, 2014, to December 31, 2020, were reviewed retrospectively. We analyzed mortality at discharge and 1-year follow-up as the primary outcome using univariate to multivariable progression with P < 0.20 inclusion. RESULTS: During the 7-year study period, 488 patients (mean [SD] age = 58 [12] years) had UIAs treated microsurgically. Of these patients, 61 (12.5%) had a prior subarachnoid hemorrhage. One patient (0.2%) with a dolichoectatic vertebrobasilar aneurysm died while hospitalized, and 7 other patients (8 total; 1.6%) were determined to have died at 1-year follow-up (1 trauma, 2 myocardial infarction, 2 cerebrovascular accident, 1 pulmonary embolism, and 1 subdural hematoma complicated by abscess). On univariate analysis, significant risk factors for mortality at follow-up included diabetes mellitus, preoperative anticoagulant or antiplatelet use, aneurysm calcification, nonsaccular aneurysm, and higher American Society of Anesthesiologists grades (all P < 0.03). On multivariable logistic regression analysis, only nonsaccular aneurysms and higher American Society of Anesthesiologists grades were predictors of mortality. CONCLUSIONS: A low mortality rate is associated with recent microsurgical treatment of UIAs. However, nonsaccular aneurysms and higher American Society of Anesthesiologists grades appear to be predictors of mortality.

Transvenous Embolization of Dural Arteriovenous Fistulas Through the Galenic (Deep Venous) System: Multicenter Case Series and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulas involving the deep venous system have often been treated with microsurgery or transarterial embolization. Increasing familiarity with transvenous navigation and improved endovascular access systems may facilitate transvenous embolization (TVE) for these rare and challenging lesions. METHODS: We performed a retrospective study of neurointerventional databases of 6 high-volume centers. We identified all cases of arteriovenous fistulas with deep transvenous embolizations for arteriovenous fistula. Details regarding demographics, fistula characteristics, treatment considerations, clinical outcomes, and fistula occlusion were obtained and analyzed. The meta-analysis used the same inclusion criteria. RESULTS: Seventeen cases of TVE were identified. The most common reasons for TVE included prior treatment failure with microsurgery (n = 2) or transarterial embolization (n = 3) or inaccessible arterial pedicles (n = 4). For patients with full clinical outcome data (n = 14), 2 patients had worsened modified Rankin Scale, 8 patients had no change, and 4 were improved at a median clinical follow-up of 3.5 months. Angiographic obliteration was achieved in 15/17 cases (88.2%). In 1 case, catheterization around a sharp turn in the basal vein of Rosenthal could not be performed. In another case, despite successful TVE, there was residual lesion which was treated 1 year later by microsurgical clipping and excision. CONCLUSION: Transvenous approaches for embolization of deep arteriovenous fistulas have become possible with modern endovascular catheter systems and liquid embolics. These lesions can be treated safely and effectively through endovascular approaches, which may spare patients the traversal of deep structures needed for microsurgical approaches to these regions. The outcomes of TVE are comparable with published outcomes of microsurgical interruption.

Microsurgical Obliteration of Craniocervical Junction Dural Arteriovenous Fistulas: Multicenter Experience.

BACKGROUND: Dural arteriovenous fistulas (dAVFs) located at craniocervical junction are extremely rare (1%-2% of intracranial/spinal dAVFs). Their angio-architectural complexity renders endovascular embolization to be challenging given multiple small feeders with risk of embolysate reflux into vertebral artery and limited transvenous access. The available literature discussing microsurgery for these lesions is limited to few case reports. OBJECTIVE: To report a multicenter experience assessing microsurgery safety/efficacy. METHODS: Prospectively maintained registries at 13 North American centers were queried to identify craniocervical junction dAVFs treated with microsurgery (2006-2021). RESULTS: Thirty-eight patients (median age 59.5 years, 44.7% female patients) were included. The most common presentation was subarachnoid/intracranial hemorrhage (47.4%) and myelopathy (36.8%) (92.1% of lesions Cognard type III-V). Direct meningeal branches from V3/4 vertebral artery segments supplied 84.2% of lesions. All lesions failed (n = 5, 13.2%) or were deemed inaccessible/unsafe to endovascular treatment. Far lateral craniotomy was the most used approach (94.7%). Intraoperative angiogram was performed in 39.5% of the cases, with angiographic cure in 94.7% of cases (median imaging follow-up of 9.2 months) and retreatment rate of 5.3%. Favorable last follow-up modified Rankin Scale of 0 to 2 was recorded in 81.6% of the patients with procedural complications of 2.6%. CONCLUSION: Craniocervical dAVFs represent rare entity of lesions presenting most commonly with hemorrhage or myelopathy because of venous congestion. Microsurgery using a far lateral approach provides robust exposure and visualization for these lesions and allows obliteration of the arterialized draining vein intradurally as close as possible to the fistula point. This approach was associated with a high rate of angiographic cure and favorable clinical outcomes.

Comparison of Intraoperative Indocyanine Green Videoangiography vs Postoperative Catheter Angiography to Confirm Microsurgical Occlusion of Spinal Dorsal Intradural Arteriovenous Fistulas.

BACKGROUND: Dorsal intradural arteriovenous fistulas (DI-AVFs) represent 80% of spinal AVFs. Microsurgical clip occlusion is a durable treatment that uses preoperative and postoperative digital subtraction angiography (DSA) as standard practice. Intraoperative indocyanine green videoangiography (ICG-VA) is a valuable intraoperative adjunct in these cases. Intraoperative ICG-VA findings have not been compared with postoperative DSA findings. OBJECTIVE: To assess the diagnostic value of intraoperative ICG-VA vs postoperative DSA for spinal DI-AVFs. METHODS: A multi-institutional database of vascular malformations was queried for all surgically managed cases of DI-AVF. Patients with both intraoperative ICG-VA and postoperative DSA were included. Demographic and radiologic data, intraoperative findings, and surgical outcomes data were retrospectively analyzed. RESULTS: Forty-five patients with DI-AVF were identified (male sex, 32; mean age, 61.9 [range, 26-85] years). All DI-AVFs were treated with interruption of the fistula with clip occlusion of the draining vein. Intraoperative ICG-VA showed complete obliteration in all patients. Postoperative DSA was performed for 40 patients and confirmed complete obliteration in all patients. The negative predictive value of ICG-VA confirming complete occlusion of the DI-AVFs was 100%. Eighteen patients (47%) experienced clinical improvement, and 16 (42%) experienced no change in condition. CONCLUSION: ICG-VA is useful for intraoperative identification of DI-AVFs and confirmation of complete microsurgical occlusion. Correlation between intraoperative ICG-VA and postoperative DSA findings demonstrates the diagnostic power of ICG-VA. This finding suggests that postoperative DSA is unnecessary when intraoperative ICG-VA confirms complete occlusion of the DI-AVF, which will spare patients the procedural risk and cost of this invasive procedure.

Giant cerebral cavernous malformations: redefinition based on surgical outcomes and systematic review of the literature.

OBJECTIVE: Giant cerebral cavernous malformations (GCCMs) are rare vascular malformations. Unlike for tumors and aneurysms, there is no clear definition of a "giant" cavernous malformation (CM). As a result of variable definitions, working descriptions and outcome data of patients with GCCM are unclear. A new definition of GCCM related to surgical outcomes is needed. METHODS: An institutional database was searched for all patients who underwent resection of CMs > 1 cm in diameter. Patient information, surgical technique, and clinical and radiographic outcomes were assessed. A systematic review was performed to augment an earlier published review. RESULTS: In the authors' institutional cohort of 183 patients with a large CM, 179 with preoperative and postoperative modified Rankin Scale (mRS) scores were analyzed. A maximum CM diameter of ≥ 3 cm was associated with greater risk of severe postoperative decline (≥ 2-point increase in mRS score). After adjustment for age and deep versus superficial location, size ≥ 3 cm was strongly predictive of severe postoperative decline (OR 4.5, 95% CI 1.2-16.9). A model with CM size and deep versus superficial location was developed to predict severe postoperative decline (area under the receiver operating characteristic curve 0.79). Thirteen more patients with GCCMs have been reported in the literature since the most recent systematic review, including some patients who were treated earlier and not discussed in the previous review. CONCLUSIONS: The authors propose that cerebral CMs with a diameter ≥ 3 cm be defined as GCCMs on the basis of the inflection point for functional and neurological outcomes. This definition is in line with the definitions for other giant lesions. It is less exclusive than earlier definitions but captures the rarity of these lesions (approximately 1% incidence) and variation in outcomes. GCCMs remain operable with potentially favorable outcomes. The term "giant" is not meant to deter or contraindicate surgery.