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.

Postoperative Outcomes for Spinal Fusion Procedures in Pediatric Patients with Anemia: A Retrospective and Multivariate Analysis.

BACKGROUND: Preoperative anemia is known to be associated with perioperative complications in many surgical interventions. Here, we examine the effects of preoperative anemia on peri-operative complications and postoperative outcomes in pediatric patients undergoing spinal fusion. METHODS: Retrospective analysis was conducted using the American College of Surgeons Pediatric National Surgery Quality Improvement Program Database between 2012-2020. Current Procedural Terminology codes 22800, 22,802, 22,804, 22,840, 22,842, 22,843, and 22,844 were included to represent all primary spinal fusion procedures performed. Patients without preoperative hematocrit (HCT) levels were excluded. Classification of anemia was determined via age- and sex-adjusted HCT levels. Patient demographics, preoperative comorbidities and risk factors, and 30-day postoperative outcomes were compared between the 2 cohorts using univariate analysis. Multivariate logistic regressions were performed to determine if anemia severity was independently associated with worse postoperative outcomes. RESULTS: A total of 30,243 pediatric patients were included in this study, with 26,621 not having preoperative anemia and 3622 having preoperative anemia. Pediatric patients with anemia have increased length of stay (LOS) (6.7 ± 9.6 vs. 5 ± 6, P < 0.001), 30-day unplanned reoperation rate (4% vs. 2.8%, P < 0.001), and total blood transfused (489.9 ± 497.8 vs. 423.4 ± 452.6, P < 0.001). Multivariate analysis supported anemia and degree of its severity as an independent predictor of increased length of stay (LOS), reoperation rate, and postoperative complications. CONCLUSIONS: Preoperative anemia leads to worse outcomes in pediatric spinal fusion procedures. Utilizing HCT recordings could be factored into the equation for optimal patient selection and prevention of post-operative complications.

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 biportal transorbital approach: quantitative comparison of the anterior subfrontal craniotomy, bilateral transorbital endoscopic, and microscopic approaches.

OBJECTIVE: The aim of this study was to assess the surgical use and applicability of a biportal bitransorbital approach. Single-portal transorbital and combined transorbital transnasal approaches have been used in clinical practice, but no study has assessed the surgical use and applicability of a biportal bitransorbital approach. METHODS: Ten cadaver specimens underwent midline anterior subfrontal (ASub), bilateral transorbital microsurgery (bTMS), and bilateral transorbital neuroendoscopic surgery (bTONES) approaches. Morphometric analyses included the length of the bilateral cranial nerves I and II, the optic tract, and A1; the area of exposure of the anterior cranial fossa floor; craniocaudal and mediolateral angles of attack (AOAs); and volume of surgical freedom (VSF; maximal available working volume for a specific surgical corridor and surgical target structure normalized to a height of 10 mm) of the bilateral paraclinoid internal carotid arteries (ICAs), bilateral terminal ICAs, and anterior communicating artery (ACoA). Analyses were conducted to determine whether the biportal approach was associated with greater instrument freedom. RESULTS: The bTMS and bTONES approaches provided limited access to the bilateral A1 segments and the ACoA, which were inaccessible in 30% (bTMS) and 60% (bTONES) of exposures. The average total frontal lobe area of exposure (AOE) was 1648.4 mm2 (range 1516.6-1958.8 mm2) for ASub, 1658.9 mm2 (1274.6-1988.2 mm2) for bTMS, and 1914.9 mm2 (1834.2-2014.2 mm2) for bTONES exposures, with no statistically significant superiority between any of the 3 approaches (p = 0.28). The bTMS and bTONES approaches were significantly associated with decreases of 8.7 mm3 normalized volume (p = 0.005) and 14.3 mm3 normalized volume (p < 0.001) for VSF of the right paraclinoid ICA compared with the ASub approach. No statistically significant difference in surgical freedom was noted between all 3 approaches when targeting the bilateral terminal ICA. The bTONES approach was significantly associated with a decrease of 105% in the (log) VSF of the ACoA compared with the ASub (p = 0.009). CONCLUSIONS: Although the biportal approach is intended to improve maneuverability within these minimally invasive approaches, these results illustrate the pertinent issue of surgical corridor crowding and the importance of surgical trajectory planning. A biportal transorbital approach provides improved visualization but does not improve surgical freedom. Furthermore, although it affords impressive anterior cranial fossa AOE, it is unsuitable for addressing midline lesions because the preserved orbital rim restricts lateral movement. Further comparative studies will elucidate whether a combined transorbital transnasal route is preferable to minimize skull base destruction and maximize instrument access.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Recurrent Glioblastoma and Radiation Necrosis: A Single-Surgeon Case Series.

OBJECTIVE: To evaluate long-term clinical outcomes among patients treated with laser interstitial thermal therapy (LITT) for predicted recurrent glioblastoma (rGBM). METHODS: Patients with rGBM treated by LITT by a single surgeon (2013-2020) were evaluated for progression-free survival (PFS), overall survival (OS), and OS after LITT. RESULTS: Forty-nine patients (33 men, 16 women; mean [SD] age at diagnosis, 58.7 [12.5] years) were evaluated. Among patients with genetic data, 6 of 34 (18%) had IDH-1 R132 mutations, and 7 of 21 (33%) had MGMT methylation. Patients underwent LITT at a mean (SD) of 23.8 (23.8) months after original diagnosis. Twenty of 49 (40%) had previously undergone stereotactic radiosurgery, 37 (75%) had undergone intensity-modulated radiation therapy, and 49 (100%) had undergone chemotherapy. Patients had undergone a mean of 1.2 (0.7) previous resections before LITT. Mean preoperative enhancing and T2 FLAIR volumes were 13.1 (12.8) cm3 and 35.0 (32.8) cm3, respectively. Intraoperative biopsies confirmed rGBM in 31 patients (63%) and radiation necrosis in 18 patients (37%). Six perioperative complications occurred: 3 (6%) cases of worsening aphasia, 1 (2%) seizure, 1 (2%) epidural hematoma, and 1 (2%) intraparenchymal hemorrhage. For the rGBM group, median PFS was 2.0 (IQR, 4.0) months, median OS was 20.0 (IQR, 29.5) months, and median OS after LITT was 6.0 (IQR, 10.5) months. For the radiation necrosis group, median PFS was 4.0 (IQR, 4.5) months, median OS was 37.0 (IQR, 58.0) months, and median OS after LITT was 8.0 (IQR, 23.5) months. CONCLUSIONS: In a diverse rGBM cohort, LITT was associated with a short duration of posttreatment PFS.

Efficacy of a prolonged stability melphalan formulation for intra-arterial treatment of retinoblastoma.

BACKGROUND: Melphalan, which is poorly soluble at room temperature, is widely used for the treatment of retinoblastoma by selective ophthalmic artery infusion. Evomela, a propylene glycol-free formulation of melphalan with improved solubility and stability, has recently been used as an alternative.To compare the safety and efficacy of Evomela with standard-formulation melphalan (SFM) in the treatment of retinoblastoma by selective ophthalmic artery infusion. METHODS: We performed a retrospective case-control study of patients with retinoblastoma undergoing selective ophthalmic artery infusion with SFM or Evomela at a single institution. Cycle-specific percent tumor regression (CSPTR) was estimated by comparing photos obtained during pretreatment examination under anesthesia (EUA) with those obtained during post-treatment EUA 3-4 weeks later. CSPTR, ocular salvage rates, complication rates, operation times (unadjusted and adjusted for difficulty of ophthalmic artery catheterization), and intraprocedural dose expiration rates were compared between Evomela- and SFM-treated groups. Univariate and multivariate analyses were performed. RESULTS: Ninety-seven operations (melphalan: 45; Evomela: 52) for 23 patients with 27 retinoblastomas were studied. The ocular salvage rate was 79% in the SFM-treated group and 69% in the Evomela-treated group. Multivariate regression controlling for tumor grade, patient age, and treatment history revealed no significant differences in ocular salvage rate, CSPTR, complication rates, or operation times. Although the dose expiration rate was higher for the SFM-treated group, the difference was not statistically significant. Notably, there were no ocular or cerebral ischemic complications. CONCLUSION: Evomela has non-inferior safety and efficacy relative to SFM when used for the treatment of retinoblastoma by selective ophthalmic artery infusion.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Management of Low-Grade Gliomas and Radiation Necrosis: A Single-Institution Case Series.

BACKGROUND: Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for ablation of low-grade glioma (LGG) and radiation necrosis (RN). OBJECTIVE: To evaluate the efficacy, safety, and survival outcomes of patients with radiographically presumed recurrent or newly diagnosed LGG and RN treated with LITT. METHODS: The neuro-oncological database of a quaternary center was reviewed for all patients who underwent LITT for management of LGG between 1 January 2013 and 31 December 2020. Clinical data including demographics, lesion characteristics, and clinical and radiographic outcomes were collected. Kaplan-Meier analyses comprised overall survival (OS) and progression-free survival (PFS). RESULTS: Nine patients (7 men, 2 women; mean [SD] age 50 [16] years) were included. Patients underwent LITT at a mean (SD) of 11.6 (8.5) years after diagnosis. Two (22%) patients had new lesions on radiographic imaging without prior treatment. In the other 7 patients, all (78%) had surgical resection, 6 (67%) had intensity-modulated radiation therapy and chemotherapy, respectively, and 4 (44%) had stereotactic radiosurgery. Two (22%) patients had lesions that were wild-type IDH1 status. Volumetric assessment of preoperative T1-weighted contrast-enhancing and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences yielded mean (SD) lesion volumes of 4.1 (6.5) cm3 and 26.7 (27.9) cm3, respectively. Three (33%) patients had evidence of radiographic progression after LITT. The pooled median (IQR) PFS for the cohort was 52 (56) months, median (IQR) OS after diagnosis was 183 (72) months, and median (IQR) OS after LITT was 52 (60) months. At the time of the study, 2 (22%) patients were deceased. CONCLUSIONS: LITT is a safe and effective treatment option for management of LGG and RN, however, there may be increased risk of permanent complications with treatment of deep-seated subcortical lesions.

Analyzing international medical graduate research productivity for application to US neurosurgery residency and beyond: A survey of applicants, program directors, and institutional experience.

Background: The authors investigated perceived discrepancies between the neurosurgical research productivity of international medical graduates (IMGs) and US medical graduates (USMGs) through the perspective of program directors (PDs) and successfully matched IMGs. Methods: Responses to 2 separate surveys on neurosurgical applicant research productivity in 115 neurosurgical programs and their PDs were analyzed. Neurosurgical research participation was analyzed using an IMG survey of residents who matched into neurosurgical residency within the previous 8 years. Productivity of IMGs conducting dedicated research at the study institution was also analyzed. Results: Thirty-two of 115 (28%) PDs responded to the first research productivity survey and 43 (37%) to the second IMG research survey. PDs expected neurosurgery residency applicants to spend a median of 12-24 months on research (Q1-Q3: 0-12 to 12-24; minimum time: 0-24; maximum time: 0-48) and publish a median of 5 articles (Q1-Q3: 2-5 to 5-10; minimum number: 0-10; maximum number: 4-20). Among 43 PDs, 34 (79%) ranked "research institution or associated personnel" as the most important factor when evaluating IMGs' research. Forty-two of 79 (53%) IMGs responding to the IMG-directed survey reported a median of 30 months (Q1-Q3: 18-48; range: 4-72) of neurosurgical research and 12 published articles (Q1-Q3: 6-24; range: 1-80) before beginning neurosurgical residency. Twenty-two PDs (69%) believed IMGs complete more research than USMGs before residency. Of 20 IMGs conducting dedicated neuroscience/neurosurgery research at the study institution, 16 of 18 who applied matched or entered a US neurosurgical training program; 2 applied and entered a US neurosurgical clinical fellowship. Conclusion: The research work of IMGs compared to USMGs who apply to neurosurgery residency exceeds PDs' expectations regarding scientific output and research time. Many PDs perceive IMG research productivity before residency application as superior to USMGs. Although IMGs comprise a small percentage of trainees, they are responsible for a significant amount of US-published neurosurgical literature. Preresidency IMG research periods may be improved with dedicated mentoring and advising beginning before the research period, during the period, and within a neurosurgery research department, providing a formal structure such as a research fellowship or graduate program for IMGs aspiring to train in the US.

Nationwide Readmission Rates and Hospital Charges for Patients With Surgical Evacuation of Nontraumatic Subdural Hematomas: Part 1-Craniotomy.

BACKGROUND: Despite patients experiencing high recurrence and readmission rates after surgical management of nontraumatic subdural hematomas (SDHs), few studies have examined the causes and predictors of unplanned readmissions in this population on a national scale. OBJECTIVE: To analyze independent factors predicting 30-day hospital readmissions after surgical treatment of nontraumatic SDH in patients who survived their index surgery and evaluate hospital readmission rates and charges. METHODS: Using the Nationwide Readmissions Database, we identified patients who underwent craniotomy for nontraumatic SDH evacuation (2010-2015) using a retrospective cohort observational study design. National estimates and variances within the cohort were calculated after stratifying, hospital clustering, and weighting variables. RESULTS: Among 49 013 patients, 10 643 (21.7%) had at least 1 readmission within 30 days of their index treatment and 38 370 (78.3%) were not readmitted. Annual readmission rates did not change during the study period ( P = .74). The most common primary causes of 30-day readmissions were recurrent SDH (n = 3949, 37.1%), venous thromboembolism (n = 1373, 12.9%), and delayed hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (n = 1363, 12.8%). Comorbidities that independently predicted readmission included congestive heart failure, chronic obstructive pulmonary disease, coagulopathy, diabetes mellitus, liver disease, lymphoma, fluid and electrolyte disorders, metastatic cancer, peripheral vascular disease, psychosis, and renal failure ( P ≤ .03). Household income in the 51st to 75th percentile was associated with a decreased risk of readmission. CONCLUSION: National trends in 30-day readmission rates after nontraumatic SDH treatment by craniotomy provide quality benchmarks that can be used to drive quality improvement efforts on a national level.

No woman alone: Dorothy Russell's legacy to neurosurgery.

Dorothy Russell's contributions to neuropathology are pivotal in the evolution of modern neurosurgery. In an era preferential to men in medicine, she entered the second medical school class to include women at the London Hospital Medical College in 1919. In the laboratory of Hubert Turnbull, she met Hugh Cairns, who would become her professional neurosurgeon-neuropathologist partner. In 1929, arriving at McGill's Royal Victoria Hospital in Montreal, where Wilder Penfield and William Cone had just begun a neurosurgical service, Russell elucidated the origin and activity of microglia. Returning to London, Russell continued to work closely with Cairns for many years. Along with J. O. W. Bland, she became the first to culture gliomas and meningiomas. Her work on the effects of and fatality rates associated with head injuries among soldiers during World War II led to the initiation of helmet requirements for motorcyclists. Her textbook, Pathology of the Tumours of the Nervous System, written with Lucien Rubinstein, is considered a landmark text in neurosurgery, neuropathology, and neurooncology. Honored by Penfield and Cone as their first neurosurgery research fellow, Russell was considered a favorite of the Montreal Neurological Institute. Dorothy Russell's extraordinary career elucidating the mysteries of neurosurgical pathology has made an enduring mark on neurosurgery.

Molecular Imaging of Glucose Metabolism for Intraoperative Fluorescence Guidance During Glioma Surgery.

PURPOSE: This study evaluated the use of molecular imaging of fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) as a discriminatory marker for intraoperative tumor border identification in a murine glioma model. PROCEDURES: 2-NBDG was assessed in GL261 and U251 orthotopic tumor-bearing mice. Intraoperative fluorescence of topical and intravenous 2-NBDG in normal and tumor regions was assessed with an operating microscope, handheld confocal laser scanning endomicroscope (CLE), and benchtop confocal laser scanning microscope (LSM). Additionally, 2-NBDG fluorescence in tumors was compared with 5-aminolevulinic acid-induced protoporphyrin IX fluorescence. RESULTS: Intravenously administered 2-NBDG was detectable in brain tumor and absent in contralateral normal brain parenchyma on wide-field operating microscope imaging. Intraoperative and benchtop CLE showed preferential 2-NBDG accumulation in the cytoplasm of glioma cells (mean [SD] tumor-to-background ratio of 2.76 [0.43]). Topically administered 2-NBDG did not create sufficient tumor-background contrast for wide-field operating microscope imaging or under benchtop LSM (mean [SD] tumor-to-background ratio 1.42 [0.72]). However, topical 2-NBDG did create sufficient contrast to evaluate cellular tissue architecture and differentiate tumor cells from normal brain parenchyma. Protoporphyrin IX imaging resulted in a more specific delineation of gross tumor margins than intravenous or topical 2-NBDG and a significantly higher tumor-to-normal-brain fluorescence intensity ratio. CONCLUSION: After intravenous administration, 2-NBDG selectively accumulated in the experimental brain tumors and provided bright contrast under wide-field fluorescence imaging with a clinical-grade operating microscope. Topical 2-NBDG was able to create a sufficient contrast to differentiate tumor from normal brain cells on the basis of visualization of cellular architecture with CLE. 5-Aminolevulinic acid demonstrated superior specificity in outlining tumor margins and significantly higher tumor background contrast. Given the nontoxicity of 2-NBDG, its use as a topical molecular marker for noninvasive in vivo intraoperative microscopy is encouraging and warrants further clinical evaluation.

The Neuroanatomic Studies of Albert L. Rhoton Jr. in Historical Context: An Analysis of Origin, Evolution, and Application.

The incorporation of perspective into art and science revolutionized the study of the brain. Beginning in about 1504, Leonardo da Vinci began to model the ventricles of the brain in three dimensions. A few years later, Andreus Vesalius illustrated radically novel brain dissections. Thomas Willis' work, Cerebri Anatome (1664), illustrated by Christopher Wren, remarkably showed the brain undersurface. Later, in the early 1800s, Charles Bell's accurate images of neural structures changed surgery. In the 1960s, Albert L. Rhoton Jr. (1932-2016) began to earn his place among the preeminent neuroanatomists by focusing his lens on microanatomy to harness a knowledge of microneurosurgery, master microneurologic anatomy, and use it to improve the care of his patients. Although his biography and works are well known, no analysis has been conducted to identify the progression, impact, and trends in the totality of his publications, and no study has assessed his work in a historical context compared with the contributions of other celebrated anatomists. We analyzed 414 of 508 works authored by Rhoton; these studies were analyzed according to subjects discussed, including anatomic region, surgical approaches, subjects covered, anatomic methods used, forms of multimedia, and subspecialty. Rhoton taught detailed neuroanatomy from a surgical perspective using meticulous techniques that evolved as the technical demands of neurosurgery advanced, inspiring students and contemporaries. His work aligns him with renowned figures in neuroanatomy, arguably establishing him historically as the most influential anatomist of the neurosurgical era.