Strategies to Improve Drug Delivery Across the Blood-Brain Barrier for Glioblastoma.

PURPOSE OF REVIEW: Glioblastoma remains resistant to most conventional treatments. Despite scientific advances in the past three decades, there has been a dearth of effective new treatments. New approaches to drug delivery and clinical trial design are needed. RECENT FINDINGS: We discuss how the blood-brain barrier and tumor microenvironment pose challenges for development of effective therapies for glioblastoma. Next, we discuss treatments in development that aim to overcome these barriers, including novel drug designs such as nanoparticles and antibody-drug conjugates, novel methods of drug delivery, including convection-enhanced and intra-arterial delivery, and novel methods to enhance drug penetration, such as blood-brain barrier disruption by focused ultrasound and laser interstitial thermal therapy. Lastly, we address future opportunities, positing combination therapy as the best strategy for effective treatment, neoadjuvant and window-of-opportunity approaches to simultaneously enhance therapeutic effectiveness with interrogation of on-treatment biologic endpoints, and adaptive platform and basket trials as imperative for future trial design. New approaches to GBM treatment should account for the blood-brain barrier and immunosuppression by improving drug delivery, combining treatments, and integrating novel clinical trial designs.

Racial and Socioeconomic Status among a Patient Population Presenting with Aneurysmal Subarachnoid Hemorrhage versus Unruptured Intracranial Aneurysm: A Single-Center Study.

Racial and socioeconomic health disparities are well documented in the literature. This study examined patient demographics, including socioeconomic status (SES), among individuals presenting with aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (UIA) to identify factors associated with aSAH presentation. A retrospective assessment was conducted of all patients with aSAH and UIA who presented to a large-volume cerebrovascular center and underwent microsurgical treatment from January 2014 through July 2019. Race and ethnicity, insurance type, and SES data were collected for each patient. Comparative analysis of the aSAH and UIA groups was conducted. Logistic regression models were also employed to predict the likelihood of aSAH presentation based on demographic and socioeconomic factors. A total of 640 patients were included (aSAH group, 251; UIA group, 389). Significant associations were observed between race and ethnicity, SES, insurance type, and aneurysm rupture. Non-White race or ethnicity, lower SES, and having public or no insurance were associated with increased odds of aSAH presentation. The aSAH group had poorer functional outcomes and higher mortality rates than the UIA group. Patients who are non-White, have low SES, and have public or no insurance were disproportionately affected by aSAH, which is historically associated with poorer functional outcomes.

Posterior Interhemispheric-Transtentorial Approach for Resection of an Arteriovenous Malformation of the Superior Medullary Velum and Fourth Ventricle: 2-Dimensional Operative Video.

Brain arteriovenous malformations (AVMs) of the fourth ventricle represent a rare subtype associated with an aggressive natural course.1,2 In this case, a woman in her early 50s presented with dizziness. An AVM was diagnosed in the left superior cerebellar peduncle extending into the fourth ventricle. The AVM was supplied by superior cerebellar artery branches and classified as a Spetzler-Martin grade III and a Lawton-Young grade III, with a supplemented grade of 6.3,4 Being a single case report, institutional review board approval was not needed. Patient consent was obtained. The lesion was accessed through a torcular craniotomy and posterior interhemispheric-transtentorial approach, employing gravity to naturally retract the parietooccipital lobe.5-7 Dissection continued into the quadrigeminal and ambient cisterns, where the tentorium was incised parallelling the straight sinus to reach the superior vermis. Partial resection of the lingual and central lobules of the vermis facilitated access to the superior medullary velum. The superior cerebellar artery feeders were divided and followed to the superior cerebellar peduncle and through the superior medullary vellum. A vertical incision in the superior medullary velum facilitated entry into the fourth ventricle, where the AVM nidus was dissected circumferentially and resected en bloc. Intraoperative indocyanine green videoangiography and postoperative digital subtraction angiography confirmed complete obliteration of the AVM. After surgery, the patient experienced mild ataxia, but motor symptoms greatly improved during 3-month follow-up. This video illustrates resection of a complex fourth ventricular AVM through a posterior interhemispheric-transtentorial approach, highlighting pivotal considerations of patient positioning and approach selection to optimize treatment outcome for complex posterior fossa AVM resection.

Arteriovenous shunts of the cervical spine: patient demographics, presentation, patterns of high-risk venous drainage, and updated classification.

BACKGROUND: Intracranial dural arteriovenous (AV) fistula classifications focus on presence/absence of retrograde flow in the cortical veins of the brain as this angiographic finding portends a worse prognosis. However, prior categorization systems of AV shunts in the spine do not incorporate these features. We propose an updated classification for spinal shunting lesions that terms any shunting lesion with retrograde flow in any cortical vein of the brain or spinal cord medullary vein as "high risk". To present this classification, we analyzed our center's most recent experience with cervical spine shunting lesions. METHODS: The electronic medical record at our institution was reviewed to identify shunting lesions of the cervical spine and patient demographics/presentation. Comprehensive craniospinal digital subtraction angiograms were evaluated to classify shunt location, type (arteriovenous malformation (AVM) vs arteriovenous fistula (AVF)), and presence of high-risk venous drainage. RESULTS: Some 52 lesions were identified and categorized as pial/dural/epidural/paravertebral AVFs and intramedullary/extraspinal AVMs. Lesions were classified as high risk or not depending on the presence of retrograde flow into at least one vein that directly drains the spinal cord or brain. All patients who presented with either hemorrhage or infarct had underlying high-risk lesions. Additionally, 50% (17/34) of symptomatic patients with high-risk lesions presented with neurological extremity symptoms (OR=10.0, p=0.037) most of which fit a myelopathic pattern. CONCLUSION: We present an updated classification system for shunting lesions of the spine that focuses on high-risk retrograde flow to the brain or spine in addition to anatomical location in order to better inform patient management.

Dolichoectatic Posterior Inferior Cerebellar Artery Aneurysm Treated With Excision and Posterior Inferior Cerebellar Artery Double Reimplantation Bypass: 2-Dimensional Operative Video.

Posterior inferior cerebellar artery (PICA) aneurysms account for 0.3% of all intracranial aneurysms, and they commonly present with a complex fusiform morphology that necessitates unique bypass strategies.1-5 An adolescent boy with a familial predisposition to aneurysmal subarachnoid hemorrhage was identified as harboring a fusiform aneurysm of the right distal PICA, characterized by 2 outflow branches. Our recommended treatment strategy involved a right far lateral craniotomy, followed by P1 PICA reanastomosis and P2 PICA reimplantation. Informed written consent was obtained. On exposure, the aneurysm was trapped, and the inflow and 2 outflow PICA branches were excised. Revascularization was established through a P1 PICA end-to-end reanastomosis using running continuous suturing techniques, followed by P2 PICA end-to-side reimplantation into a more distal portion of PICA. Subsequent indocyanine green videoangiography confirmed patency of the P2 PICA reimplantation; however, the initial P1 PICA reanastomosis was noted to be thrombosed. After several unsuccessful attempts to dissolve the thrombus, the decision was made to proceed with a P2 PICA side-to-side in situ reimplantation into the V4 segment of the vertebral artery. Indocyanine green videoangiography and postoperative digital subtraction angiography confirmed patency of the PICA double reimplantation bypass. The patient tolerated the procedure well and was discharged home at his neurological baseline. This video showcases the microsurgical treatment of a complex dolichoectatic, distal PICA aneurysm using a double reimplantation technique, in addition to highlighting bypass decision-making processes for managing complex PICA aneurysms.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Endovascular biopsy in neurointerventional surgery: A systematic review.

INTRODUCTION: Endothelial cells (ECs) continuously line the cerebrovasculature. Molecular aberrations in the ECs are hallmarks and contributory factors to the development of cerebrovascular diseases, including intracranial aneurysms and arteriovenous malformations (AVMs). Endovascular biopsy has been introduced as a method to harvest ECs and obtain relevant biologic information. We aimed to summarize the literature on endovascular biopsy in neurointerventional surgery. METHODS: We conducted a comprehensive literature search in multiple databases, identifying eligible studies focusing on neurosurgical applications of endovascular biopsy. The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The relevant information was collected, including study characteristics, biopsy techniques, and key findings. RESULTS: Nine studies met the inclusion criteria and were included. The studies involved the collection of ECs using various endovascular devices including coils, guide wires, different stents, and forceps. Endothelial-enrichment techniques, such fluorescence-activated cell sorting (FACS), collected ECs and facilitated downstream applications of bulk or single-cell RNA sequencing (scRNAseq). The studies provided insights into gene expression profiles and identified potential biomarkers associated with intracranial aneurysms. However, challenges were observed in obtaining an adequate number of ECs and identifying consistent biomarkers. CONCLUSION: Endovascular biopsy of endothelial cells (ECs) in cerebrovascular pathologies shows promise for gene expression profiling. However, many studies have been limited in sample size and underpowered to identify "signature genes" for aneurysm growth or rupture. Advancements in minimally invasive biopsy methods have potential to facilitate applications of precision medicine in the treatment of cerebrovascular disorders.

Microsurgical Resection of Brainstem Cavernous Malformations in Older Adults: A Multicenter, 30-Year Experience.

BACKGROUND AND OBJECTIVES: Microsurgical resection is the only curative intervention for symptomatic brainstem cavernous malformations (BSCMs), but the management of these lesions in older adults (≥65 years) is not well described. This study sought to address this gap by examining the safety and efficacy of BSCM resection in a cohort of older adults. METHODS: Records of patients who underwent BSCM resection over a 30-year period were reviewed retrospectively. Baseline characteristics and outcomes were compared between older (≥65 years) and younger (<65 years) patients. RESULTS: Of 550 patients with BSCM who met inclusion criteria, 41 (7.5%) were older than 65 years. Midbrain (43.9% vs 26.1%) and medullary lesions (19.5% vs 13.6%) were more common in the older cohort than in the younger cohort (P = .01). Components of the Lawton BSCM grading system (ie, lesion size, crossing axial midpoint, developmental venous anomaly, and timing of hemorrhage) were not significantly different between cohorts (P ≥ .11). Mean (SD) Elixhauser comorbidity score was significantly higher in older patients (1.86 [1.06]) than in younger patients (0.66 [0.95]; P < .001). Older patients were significantly more likely than younger patients to have poor outcomes at final follow-up (28.9% vs 13.8%, P = .01; mean follow-up duration, 28.7 [39.1] months). However, regarding relative neurological outcome (preoperative modified Rankin Scale to final modified Rankin Scale), rate of worsening was not significantly different between older and younger patients (23.7% vs 14.9%, P = .15). CONCLUSION: BSCMs can be safely resected in older patients, and when each patient's unique health status and life expectancy are taken into account, these patients can have outcomes similar to younger patients.

Sex differences in patients with and without high-risk factors associated with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Controversy remains regarding the appropriate screening for intracranial aneurysms or for the treatment of aneurysmal subarachnoid hemorrhage (aSAH) for patients without known high-risk factors for rupture. This study aimed to assess how sex affects both aSAH presentation and outcomes for aSAH treatment. METHOD: A retrospective cohort study was conducted of all patients treated at a single institution for an aSAH during a 12-year period (August 1, 2007-July 31, 2019). An analysis of women with and without high-risk factors was performed, including a propensity adjustment for a poor neurologic outcome (modified Rankin Scale [mRS] score > 2) at follow-up. RESULTS: Data from 1014 patients were analyzed (69% [n = 703] women). Women were significantly older than men (mean ± SD, 56.6 ± 14.1 years vs 53.4 ± 14.2 years, p < 0.001). A significantly lower percentage of women than men had a history of tobacco use (36.6% [n = 257] vs 46% [n = 143], p = 0.005). A significantly higher percentage of women than men had no high-risk factors for aSAH (10% [n = 70] vs 5% [n = 16], p = 0.01). The percentage of women with an mRS score > 2 at the last follow-up was significantly lower among those without high-risk factors (34%, 24/70) versus those with high-risk factors (53%, 334/633) (p = 0.004). Subsequent propensity-adjusted analysis (adjusted for age, Hunt and Hess grade, and Fisher grade) found no statistically significant difference in the odds of a poor outcome for women with or without high-risk factors for aSAH (OR = 0.7, 95% CI = 0.4-1.2, p = 0.18). CONCLUSIONS: A higher percentage of women versus men with aSAH had no known high-risk factors for rupture, supporting more aggressive screening and management of women with unruptured aneurysms.

Modafinil Therapy and Mental Status Following Aneurysmal Subarachnoid Hemorrhage: Comprehensive Stroke Center Analysis.

BACKGROUND: Disorders of consciousness impair early recovery after aneurysmal subarachnoid hemorrhage (aSAH). Modafinil, a wakefulness-promoting agent, is efficacious for treating fatigue in stroke survivors, but data pertaining to its use in the acute setting are scarce. This study sought to assess the effects of modafinil use on mental status after aSAH. METHODS: Modafinil timing and dosage, neurological examination, intubation status, and physical and occupational therapy participation were documented. Repeated-measures paired tests were used for a before-after analysis of modafinil recipients. Propensity score matching (1:1 nearest neighbor) for modafinil and no-modafinil cohorts was used to compare outcomes. RESULTS: Modafinil (100-200 mg/day) was administered to 21% (88/422) of aSAH patients for a median (IQR) duration of 10.5 (4-16) days and initiated 14 (7-17) days after aSAH. Improvement in mentation (alertness, orientation, or Glasgow Coma Scale score) was documented in 87.5% (77/88) of modafinil recipients within 72 hours and 86.4% (76/88) at discharge. Of 37 intubated patients, 10 (27%) were extubated within 72 hours after modafinil initiation. Physical and occupational therapy teams noted increased alertness or participation in 47 of 56 modafinil patients (83.9%). After propensity score matching for baseline covariates, the modafinil cohort had a greater mean (SD) change in Glasgow Coma Scale score than the no-modafinil cohort at discharge (2.2 [4.0] vs. -0.2 [6.32], P = 0.003). CONCLUSIONS: A temporal relationship with improvement in mental status was noted for most patients administered modafinil after aSAH. These findings, a favorable adverse-effect profile, and implications for goals-of-care decisions favor a low threshold for modafinil initiation in aSAH patients in the acute-care setting.

Hematologic and Inflammatory Predictors of Outcome in Patients with Brain Arteriovenous Malformations.

OBJECTIVE: This study investigated the prognostic value of admission blood counts for arteriovenous malformation (AVM) outcomes and compared admission blood counts for patients with ruptured and unruptured AVMs. METHODS: A retrospective analysis of patients who underwent surgical treatment for a ruptured cerebral AVM between February 1, 2014, and March 31, 2020, was conducted. The primary outcome was poor neurologic outcome, defined as a modified Rankin Scale score ≥2 in patients with unruptured AVMs or >2 in patients with ruptured AVMs. RESULTS: Of 235 included patients, 80 (34%) had ruptured AVMs. At admission, patients with ruptured AVMs had a significantly lower mean (SD) hemoglobin level (12.78 [2.07] g/dL vs. 13.71 [1.60] g/dL, P < 0.001), hematocrit (38.1% [5.9%] vs. 40.7% [4.6%], P < 0.001), lymphocyte count (16% [11%] vs. 26% [10%], P < 0.001), and absolute lymphocyte count (1.41 [0.72] × 103/µL vs. 1.79 [0.68] × 103/µL, P < 0.001), and they had a significantly higher mean (SD) white blood cell count (10.4 [3.8] × 103/µL vs. 7.6 [2.3] × 103/µL, P < 0.001), absolute neutrophil count (7.8 [3.8] × 103/µL vs. 5.0 [2.5] × 103/µL, P < 0.001), and neutrophil count (74% [14%] vs. 64% [13%], P < 0.001). Among patients with unruptured AVMs, white blood cell count ≥6.4 × 103/µL and absolute neutrophil count ≥3.4 × 103/µL were associated with a favorable neurologic outcome, whereas hemoglobin level ≥13.4 g/dL was associated with an unfavorable outcome. Among patients with ruptured AVMs, hypertension was associated with a 3-fold increase in odds of a poor neurologic outcome. CONCLUSIONS: Patients with ruptured and unruptured AVMs present with characteristic profiles of hematologic and inflammatory parameters evident in their admission blood work.

Flow diversion for basilar quadrifurcation aneurysms.

BACKGROUND: Flow-diverting devices (FDDs), such as the Pipeline Embolization Device, have been gaining traction for treating challenging posterior circulation aneurysms. Few previous studies have focused on using FDDs to treat aneurysms of the basilar quadrifurcation. METHODS: We retrospectively reviewed the use of FDDs to treat patients with basilar quadrifurcation aneurysms. Patients were assessed for aneurysm type, previous aneurysm treatment, technical success, periprocedural complications, and long-term aneurysm occlusion. RESULTS: 34 patients were assessed; aneurysms of the basilar apex (n=23) or superior cerebellar artery (SCA) (n=7), or both (n=1), and posterior cerebral artery (PCA) (n=3). The mean (SD) largest aneurysm dimension was 8.7 (6.1) mm (range 1.9-30.8 mm). 14 aneurysms were previously surgically clipped or endovascularly coiled. All aneurysms had a saccular morphology. Complete or near-complete occlusion was achieved in 30 of 34 patients (88%) at final angiographic follow-up, a mean (SD) of 6.6 (5.4) months (range 0-19 months) postoperatively. No patient experienced postoperative symptomatic occlusions of the SCA or PCA; 4 patients developed asymptomatic posterior communicating artery occlusions; 28 patients (82%) experienced no complications; whereas 3 (9%) experienced major complications and 3 (9%) experienced minor complications; and 1 patient died as a result of subarachnoid hemorrhage. CONCLUSION: Flow diversion may be a safe and effective option to treat basilar quadrifurcation aneurysms. Previously treated basilar quadrifurcation aneurysms with recurrence or residual lesion may benefit from additional treatment with an FDD. Further prospective studies should be directed toward validating these findings.

The VEBAS score: a practical scoring system for intracranial dural arteriovenous fistula obliteration.

BACKGROUND: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes. METHODS: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC. RESULTS: A total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (<75 vs ≥75 years), Borden classification (I vs II-III), arterial feeders (single vs multiple), and past cranial surgery (presence vs absence) were independent predictors of obliteration and used to derive the VEBAS score. A significant increase in the likelihood of complete obliteration (OR=1.37 (1.27-1.48)) with each additional point in the overall patient score (range 0-12) was demonstrated. Within the validation dataset, the predicted probability of complete dAVF obliteration increased from 0% with a 0-3 score to 72-89% for patients scoring ≥8. CONCLUSION: The VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.

A Review of Preoperative Embolization Effectiveness in Patients With Arteriovenous Malformations.

BACKGROUND AND OBJECTIVES: Preoperative embolization of arteriovenous malformations (AVMs) remains controversial. This study sought to analyze the cost-effectiveness of preoperative embolization of AVMs. METHODS: Patients who underwent AVM resection at a single institute (January 1, 2015-December 31, 2020) were analyzed. Patients with preoperative embolization (embolization cohort) were compared with those without preoperative embolization (nonembolization cohort). Cost-effectiveness score (CE) was the primary outcome of interest and was determined by dividing the total 1-year cost by effectiveness, which was derived from a validated preoperative to last follow-up change in the modified Rankin Scale utility score. A lower CE signifies a more cost-effective treatment strategy. RESULTS: Of 188 patients, 88 (47%) underwent preoperative embolization. The mean (SD) total cost was higher in the embolization group than in the nonembolization group ($117 594 [$102 295] vs $84 348 [$82 326]; P < .001). The mean (SD) CE was higher in the embolization cohort ($336 476 [$1 303 842]) than in the nonembolization cohort ($100 237 [$246 255]; P < .001). Among patients with Spetzler-Martin (SM) grade I and II AVMs, the mean (SD) CE was higher in the embolization (n = 40) than in the nonembolization (n = 72) cohort ($164 950 [$348 286] vs $69 021 [$114 938]; P = .004). Among patients with SM grade III AVMs, the mean (SD) CE was lower in the embolization (n = 33) than in the nonembolization (n = 25) cohort ($151 577 [$219 130] vs $189 195 [$446 335]; P = .006). The mean (SD) CE was not significantly different between cohorts among patients with higher-grade AVMs (embolization cohort [n = 3] vs nonembolization cohort [n = 15]: $503 639 [$776 492] vs $2 048 419 [$4 794 758]; P = .49). The mean CE for embolized SM grade III aneurysms was nonsignificant in the ruptured group; however, for the unruptured group, CE was significantly higher in the embolization cohort (n = 26; $160 871 [$240 535]) relative to the nonembolization cohort (n = 15; $108 152 [$166 446]) ( P = .006). CONCLUSION: Preoperative embolization was cost-effective for patients with SM grade III AVMs but not for patients with lower-grade AVMs.

Early Treatment of Ruptured Cerebral Arteriovenous Malformations: Analysis of Neurological Outcomes and Health Care Costs.

BACKGROUND: The timing of surgical resection is controversial when managing ruptured arteriovenous malformations (AVMs) and varies considerably among centers. OBJECTIVE: To retrospectively analyze clinical outcomes and hospital costs associated with delayed treatment in a ruptured cerebral AVM patient cohort. METHODS: Patients undergoing surgical treatment for a ruptured cerebral AVM (January 1, 2015-December 31, 2020) were retrospectively analyzed. Patients who underwent emergent treatment of a ruptured AVM because of acute herniation were excluded, as were those treated >180 days after rupture. Patients were stratified by the timing of surgical intervention relative to AVM rupture into early (postbleed days 1-20) and delayed (postbleed days 21-180) treatment cohorts. RESULTS: Eighty-seven patients were identified. The early treatment cohort comprised 75 (86%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 5 (5) days in the early cohort and 73 (60) days in the delayed cohort ( P < .001). The cohorts did not differ with respect to patient demographics, AVM size, Spetzler-Martin grade, frequency of preoperative embolization, or severity of clinical presentation ( P ≥ .15). Follow-up neurological status was equivalent between the cohorts ( P = .65). The associated mean health care costs were higher in the delayed treatment cohort ($241 597 [$99 363]) than in the early treatment cohort ($133 989 [$110 947]) ( P = .02). After adjustment for length of stay, each day of delayed treatment increased cost by a mean of $2465 (95% CI = $967-$3964, P = .002). CONCLUSION: Early treatment of ruptured AVMs was associated with significantly lower health care costs than delayed treatment, but surgical and neurological outcomes were equivalent.

Transcallosal-Transchoroidal Fissure Approach for Midbrain and Thalamic Cavernous Malformations: 2-Dimensional Operative Video.

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: Cavernous malformations of the third ventricle arise from the medial thalamus and/or periaqueductal midbrain. Microsurgical resection is indicated when the lifetime risk of hemorrhage outweighs the surgical risks. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: superior sagittal sinus, callosomarginal and pericallosal arteries, corpus callosum, foramen of Monro, choroidal fissure, fornix, thalamostriate veins, internal cerebral veins (ICVs), velum interpositum, and thalamus. ESSENTIAL STEPS OF THE PROCEDURE: The patient consents to the procedure. With the patient supine, the head is turned 90° and laterally flexed 45°. A bifrontal craniotomy positioned two-thirds anterior and one-third posterior to the coronal suture is performed. The interhemispheric fissure is opened, and a 2-cm corpus callosotomy is performed. Choroid plexus cauterization exposes the choroidal fissure. Sharp division of the taenia fornicea opens the velum interpositum, where the thalamostriate vein can be followed around the venous angle to the ICV. The anterior septal vein may be divided to communicate between the foramen of Monro and choroidal fissure. Dissection between the ICVs opens the velum interpositum into the third ventricle. PITFALLS/AVOIDANCE OF COMPLICATIONS: Frontal or deep vein occlusion causes venous infarction, and dissection on the nondominant hemisphere is preferred. Other complications include arterial infarction, fornix injury from choroidal fissure dissection or forniceal retraction, and thalamic or midbrain injury during lesion resection. VARIANTS AND INDICATIONS FOR THEIR USE: The contralateral choroidal fissure is used for low-lying medial thalamic and midbrain lesions. The ipsilateral choroidal fissure is used for high-lying or large lesions extending laterally. Transchoroidal approaches are not needed for superior (transcallosal only) or anterior (contralateral transcallosal-contralateral transforaminal) thalamic lesions. Used with permission from Barrow Neurological Institute, Phoenix, Arizona.

Infragalenic triangle as a gateway to dorsal midbrain and posteromedial thalamic lesions: descriptive and quantitative analysis of microsurgical anatomy.

OBJECTIVE: Anatomical triangles provide neurosurgeons with the specificity required to access deep targets, supplementing more general instructions, such as craniotomy and approach. The infragalenic triangle (IGT), bordered by the basal vein of Rosenthal (BVR), precentral cerebellar vein (PCV), and the quadrangular lobule of the cerebellum, is one of a system of anatomical triangles recently introduced to guide dissection to brainstem cavernous malformations and has not been described in detail. This study aimed to quantitatively analyze the anatomical parameters of the IGT and present key nuances for its microsurgical use. METHODS: A midline supracerebellar infratentorial (SCIT) approach through a torcular craniotomy was performed on 5 cadaveric heads, and the IGT was identified in each specimen bilaterally. Anatomical measurements were obtained with point coordinates collected using neuronavigation. Three cadaveric brains were used to illustrate relevant brainstem anatomy, and 3D virtual modeling was used to simulate various perspectives of the IGT through different approach angles. In addition, 2 illustrative surgical cases are presented. RESULTS: The longest edge of the IGT was the lateral edge formed by the BVR (mean ± SD length 19.1 ± 2.3 mm), and the shortest edge was the medial edge formed by the PCV (13.9 ± 3.6 mm). The mean surface area of the IGT was 110 ± 34.2 mm2 in the standard exposure. Full expansion of all 3 edges (arachnoid dissection, mobilization, and retraction) resulted in a mean area of 226.0 ± 48.8 mm2 and a 2.5-times increase in surface area exposure of deep structures (e.g., brainstem and thalamus). Thus, almost the entire tectal plate and its relevant safe entry zones can be exposed through an expanded unilateral IGT except for the contralateral inferior colliculus, access to which is usually hindered by PCV tributaries. Exposure of bilateral IGTs may be required to resect larger midline lesions to increase surgical maneuverability or to access the contralateral pulvinar. CONCLUSIONS: The IGT provides a safe access route to the dorsal midbrain and reliable intraoperative guidance in the deep and complex anatomy of the posterior tentorial incisura. Its potential for expansion makes it a versatile anatomical corridor not only for intrinsic brainstem lesions but also for tumors and vascular malformations of the pineal region, dorsal midbrain, and posteromedial thalamus.