Dayyani M, Filippov A, Zhang I
… +11 more, Georges J, Saeed Z, Turunen J, Sobhanian N, Yuan H, D'Apuzzo M, Hao Y, Berens ME, Zhang L, Portnow J, Badie B
Neurosurgery
· 2026 Mar · PMID 41854274
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BACKGROUND AND OBJECTIVES: Cerebral edema (CE) is a common contributor to neurological decline after brain tumor resection. While corticosteroids are effective in managing CE perioperatively, their use is associated with...BACKGROUND AND OBJECTIVES: Cerebral edema (CE) is a common contributor to neurological decline after brain tumor resection. While corticosteroids are effective in managing CE perioperatively, their use is associated with significant side effects and potential interference with immunotherapeutic efficacy in patients with malignant brain tumors. This study aimed to evaluate the anti-inflammatory effects of 2 inhibitors of the receptor for advanced glycation end products (RAGE)-TTP488 and FPS-ZM1-on CE development after glioma resection in murine models. METHODS: Mice bearing orthotopic CT-2A gliomas were randomized into 4 treatment groups before undergoing fluorescence-guided microsurgical tumor resection. The groups received perioperative administration (from day -4 to day +7) of TTP488, FPS-ZM1, dexamethasone, or vehicle. Postoperative CE was assessed using serial brain MRI over a 7-day period and quantified using manual segmentation. Neurological function, wound healing, and response to anti-PD-1 immunotherapy were also evaluated. Bulk RNA sequencing was performed to analyze differential gene expression associated with RAGE inhibition. RESULTS: Across all groups, CE peaked on postoperative day 2 and subsided by day 7. On postoperative day 1, both TTP488 and FPS-ZM1 significantly reduced CE compared with vehicle (P = .03 for TTP488; P = .03 for FPS-ZM1). Notably, unlike dexamethasone, neither RAGE inhibitor impaired the efficacy of anti-PD-1 immunotherapy. FPS-ZM1 treatment was also associated with improved neurological recovery, enhanced wound healing, and potentiated anti-PD-1 therapy at higher doses. CONCLUSION: RAGE inhibitors effectively reduced postoperative CE to a degree comparable with dexamethasone, without compromising the efficacy of immunotherapy or wound healing. These findings suggest that RAGE inhibition may offer a promising steroid-sparing strategy for perioperative management of CE in patients with brain tumor undergoing immunotherapy.
Neurosurgery
· 2026 Mar · PMID 41854265
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BACKGROUND AND OBJECTIVES: Cranioplasty (CP) is a critical neurosurgical intervention typically performed after decompressive craniectomy (DC). However, the optimal timing remains uncertain due to conflicting evidence an...BACKGROUND AND OBJECTIVES: Cranioplasty (CP) is a critical neurosurgical intervention typically performed after decompressive craniectomy (DC). However, the optimal timing remains uncertain due to conflicting evidence and heterogeneous study designs. This pooled comparative meta-analysis aims to address this gap. METHODS: We conducted a systematic search for studies reporting outcomes of patients who underwent primary DC followed by CP on September 2024. Ultra-early CP was defined as ≤35 days, early CP as ≤86 days, and late CP as >86 days after DC. Outcomes included functional recovery measured by various scales and procedure-related complications. RESULTS: Thirty-eight studies (n = 4703) were included. Early CP was associated with improved functional outcomes: Karnofsky performance scale (mean difference [MD] 15.50, 95% CI [0.80, 31.80], P < .0001), Barthel Index (MD 13.10, 95% CI [0.24, 25.96], P = .01), functional independence measure (MD 11.23, 95% CI [7.61, 14.85], P < .00001), and activities of daily living (MD 13.65, 95% CI [1.44, 25.86], P = .03), compared with late CP. Other scales showed no significant differences. Overall complication rates did not differ between early and late CP (risk ratio 1.08, 95% CI [0.83, 1.41], P = .55), except for hydrocephalus, which was more common in early CP (risk ratio 1.58, 95% CI [1.07, 2.33], P = .02). No statistically significant differences in complication rates were observed for the ultra-early subgroup. CONCLUSION: Our findings suggest that early CP is associated with improved neurological function and greater daily independence, reflected by higher Karnofsky performance scale, Barthel Index, functional independence measure, and activities of daily living scores, without a significant increase in overall complication rates compared with late CP after DC. However, hydrocephalus appears more frequently after early CP. Standardized, multicenter prospective studies using consistent timing definitions are needed to refine individualized CP strategies.
Singh M, Shlimak AK, Rampichini M
… +11 more, Hasbrouck A, Clancy JB, Chernysh AA, Duffy M, Srinivasan A, Kanekar S, Bajaj A, Scarfo KA, Gokaslan ZL, Leary OP, Guglielmo MA
BACKGROUND AND OBJECTIVES: While prior studies have examined the role of opioids, alcohol, and marijuana use on early postoperative outcomes after elective spine surgery, longitudinal studies evaluating the impact of obj...BACKGROUND AND OBJECTIVES: While prior studies have examined the role of opioids, alcohol, and marijuana use on early postoperative outcomes after elective spine surgery, longitudinal studies evaluating the impact of objectively identified preoperative substance use on 12-month outcomes are lacking. METHODS: This prospective cohort study included adults who underwent preoperative urine toxicology (UTox) screening followed by elective spine surgery between September 2020 and February 2024. Chart review and phone outreach were completed to collect demographic, UTox, surgical, and patient-reported outcomes measures (PROMs) data up to 1-year postoperatively. PROMs, overall and stratified by UTox-identified alcohol, marijuana, and opioid use, were evaluated using repeated-measures analysis of variance (ANOVA) and mixed-effects regression analyses, adjusting for age, sex, BMI, comorbidities, and neurosurgical history. RESULTS: Among 185 participants (mean age 59.5, 57% female), preoperative UTox revealed 16% alcohol use, 23% marijuana use, 21% opioid use, and 39% nonsubstance use. Higher UTox-identified alcohol (16% vs 46%, P < .001) and drug use (45% vs 15%, P < .001) was observed relative to patient reports. Postoperatively, Oswestry Disability Index (ODI) (Preop = 58.9, 3-month = 41.8, 12-month = 54.0, P < .001) and Visual Analog Scale (VAS) (Preop = 7.1, 3-month = 4.7, 12-month = 5.9, P < .001) showed improvements till 3 months and subsequent decline till 12 months. These trends were consistent across cohorts, except opioid users who showed no differences in ODI (P = .762) or VAS (P = .059) across time points. Within-subject mixed-effects regressions revealed that ODI and VAS decreased by 5.7 and 0.8 points per month till 3 months, and increased by 1.1 and 0.1 points per month till 12 months, respectively (P < .05). This was also consistent across cohorts except opioid users, who showed no significant postoperative changes in ODI (P = .451) or VAS (P = .096). CONCLUSION: Objectively measured preoperative alcohol and marijuana use were not associated with altered postoperative outcomes whereas opioid use contributed to lack of early postoperative improvement and worse PROMs at 12 months. UTox screening may aid perioperative decision making, optimize rehabilitation strategies, and improve postoperative recovery. LEVEL OF EVIDENCE: Level II, Prognostic Study.
Musmar B, Patel P, Abdalrazeq H
… +7 more, Lan M, Baldassari M, Momin A, Kumar C, Schaefer J, Self DM, Farrell CJ
Neurosurgery
· 2026 Mar · PMID 41823425
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BACKGROUND AND OBJECTIVES: The optimal timing of cranioplasty (CP) after craniectomy remains uncertain. We aimed to evaluate and compare functional outcomes and complication rates associated with early and late CP after...BACKGROUND AND OBJECTIVES: The optimal timing of cranioplasty (CP) after craniectomy remains uncertain. We aimed to evaluate and compare functional outcomes and complication rates associated with early and late CP after craniectomy. METHODS: We systematically searched PubMed, Scopus, and Web of Science through June 2025. Fifty-five studies (n = 8602 patients) met inclusion criteria, comparing at least 2 distinct CP timing categories. Functional outcomes included Barthel Index (BI), functional independence measure, and modified motor assessment and enhancement scale. Patients were categorized as having undergone ultra-early CP (30-45 days), intermediate CP (45-70 days), early CP (80-100 days), or delayed CP (120-180 days). RESULTS: Early CP significantly improved functional outcomes in BI absolute scores, BI gain scores, absolute functional independence measure scores, and absolute modified motor assessment and enhancement scale scores compared with delayed CP. Ultra-early CP demonstrated the greatest benefit in absolute BI scores and significantly reduced bone flap resorption risk. No significant differences were found in rates of complications. Implant material (autologous vs prosthetic) and traumatic etiology did not significantly affect these outcomes. CONCLUSION: Earlier CP after craniectomy-particularly within 100 days-was associated with improved functional recovery without a significant increase in complications. Although bone flap resorption appeared lower with ultra-early timing, other adverse events such as infection, hydrocephalus, and hematoma did not vary meaningfully across timing windows. These findings suggest that, in carefully selected patients, earlier reconstruction may offer neurological benefits. Because timing was not randomized and may reflect clinical stability and treatment selection, these findings reflect associations and do not establish causality. Further studies are needed.
Jung MK, Heo JW, Kim H
… +6 more, Ha EJ, Roh TH, You N, Huh H, Kim SH, Kim DJ
Neurosurgery
· 2026 Mar · PMID 41823399
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BACKGROUND AND OBJECTIVE: Intravenous mannitol serves as an intermediate strategy for reducing intracranial pressure (ICP). Favorable mannitol responsiveness conditions and its impact on prognosis remain poorly understoo...BACKGROUND AND OBJECTIVE: Intravenous mannitol serves as an intermediate strategy for reducing intracranial pressure (ICP). Favorable mannitol responsiveness conditions and its impact on prognosis remain poorly understood. This study aimed to develop a structural causal model (SCMMannitol) to estimate heterogeneous treatment effects and reveal causal relationships between patient status, mannitol response, and prognosis. METHODS: Arterial blood pressure and ICP data were collected from 53 patients with traumatic brain injury. To maintain adequate ICP, arterial blood pressure, and cerebral perfusion pressure, 20% mannitol was administered. Cerebrovascular pressure reactivity (PRx) and resistance of mannitol (RMannitol) were derived. The data set included sex, age, Glasgow Coma Scale, pupil reactivity, major extracranial injury, and Glasgow Outcome Scale-Extended (GOSE). IMPACT and CRASH prognostic models were retrained to include RMannitol. SCM analyzed causal relationships between PRx, RMannitol, and GOSE. RESULTS: Mannitol significantly reduced ICP at pretreatment PRx <0.2 (P < .001). PRx <0.2 yielded lower RMannitol than PRx ≥0.2 (P = .017). RMannitol and GOSE were negatively correlated (Pearson r = -0.33, P = .016). The RMannitol predictive capacity for mortality was 0.81 (cutoff, 0.68; 95% CI, 0.68-0.94; AUROC, P = .001). In the outcome prediction model, PRx before mannitol and RMannitol inclusion improved outcome prediction (P < .05). SCM identified a causal pathway linking PRx before mannitol, RMannitol, and outcomes. SCMMannitol estimated heterogeneous treatment effects of mannitol in an individual patient. CONCLUSION: PRx before mannitol and RMannitol causality suggests that compensatory cerebral vasoconstriction drives mannitol response. RMannitol and GOSE inverse relationship underscores the importance of ICP monitoring and timely treatment escalation. The PRx before mannitol, RMannitol, and GOSE causal relationship suggests that considering both RMannitol and PRx may improve patient outcomes. SCMMannitol may estimate heterogeneous treatment effects, advancing precision medicine for patients with traumatic brain injury.
Weber F, Vychopen M, Kurt GZ
… +5 more, Pfahl A, Köhler H, Melzer A, Güresir E, Wach J
Neurosurgery
· 2026 Mar · PMID 41823394
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BACKGROUND AND OBJECTIVES: Peritumoral brain edema (PBE) is common in intracranial meningiomas (IM) and has been linked to postoperative morbidity, yet its impact on cortical oxygenation remains unclear. We investigated...BACKGROUND AND OBJECTIVES: Peritumoral brain edema (PBE) is common in intracranial meningiomas (IM) and has been linked to postoperative morbidity, yet its impact on cortical oxygenation remains unclear. We investigated the association between PBE and local tissue oxygenation using intraoperative in vivo hyperspectral imaging (HSI). METHODS: Twenty-nine patients undergoing microsurgical IM resection with intraoperative HSI were prospectively analyzed. Peritumoral cortical oxygen saturation (StO2) was quantified and correlated with preoperative MRI parameters, including edema volume and contrast-enhancement intensity. Patients were stratified by PBE presence and histopathological subtype (meningotheliomatous vs nonmeningotheliomatous). Group comparisons used t-tests; correlations used Pearson coefficients. RESULTS: PBE was present in 17 (58.6%) cases. Patients with PBE exhibited significantly lower cortical oxygenation than those without (mean StO2 0.49 ± 0.13 vs 0.59 ± 0.10, P = .048). Within the PBE group, edema volume correlated positively with StO2 (r = 0.58, P = .015), whereas tumor contrast enhancement intensity correlated inversely with StO2 (r = -0.59, P = .013). No significant correlation was observed in patients without PBE (r = -0.26, P = .18). Meningotheliomatous IMs showed a trend toward lower StO2 compared with nonmeningotheliomatous tumors (0.51 ± 0.17 vs 0.55 ± 0.07, P = .05). CONCLUSION: PBE in IMs is associated with impaired cortical oxygenation. Larger PBEs paradoxically showed higher StO2, suggesting compensatory mechanisms, while strong tumor enhancement correlated with local hypoxia. These findings suggest that intraoperative HSI may serve as a promising tool for characterizing tumor-brain interactions and support further investigation into PBE pathophysiology.
Lopez RA, Houpt AW, Ozaydin B
… +7 more, Chen S, Machiorlatti M, Bowen I, Sader N, Balsara K, Jea A, Feldman MJ
Neurosurgery
· 2026 Mar · PMID 41817198
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BACKGROUND AND OBJECTIVES: As perinatal care continues to advance, the timing of cerebrospinal fluid diversion in the increasing number of premature children with hydrocephalus remains unclear. Previous studies and clini...BACKGROUND AND OBJECTIVES: As perinatal care continues to advance, the timing of cerebrospinal fluid diversion in the increasing number of premature children with hydrocephalus remains unclear. Previous studies and clinical practices have used the 2000 g weight cutoff as a standard metric for ventriculoperitoneal shunt (VPS) insertion; however, this value has never been validated. We aimed to evaluate the validity of the 2000 g weight cutoff for VPS through systematic review and meta-analysis. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analysis-compliant systematic review was conducted on MEDLINE, EMBASE, and PubMed from 01/01/1975 to 06/17/2025. Included studies reported the shunt outcomes of premature infants who received a VP shunt within the first 3 months of life and documented weight at the time of VP shunt placement. Outcomes of interest were shunt failure, infection, and death. Sixteen studies (18 cohorts) included 779 patients, of whom 160 were under 2000 g at the time of shunt placement. Meta-analysis was conducted using the random effects model and inverse variance method to assess differences in outcomes between cohorts above and below 2000 g. RESULTS: No statistically significant difference was observed between the pooled proportions between subgroups for each outcome. Further subgroup analysis revealed a statistically significant difference (P = .006) in infection rates by splitting the over 2000 g group into a 2000-2500 g and an over 2500 g group. Heterogeneity was substantial for each analysis (P < .001). Weighted, piecewise, linear regressions for outcomes as a function of shunt weight did not demonstrate a clear inflection point for adverse outcomes at the 2000 g mark. CONCLUSION: These findings do not support the 2000 g threshold as a clinically meaningful determinant of suitability for VPS placement. Further research is necessary to delineate other potential modifiable and identifiable drivers of shunt appropriateness.
Devarajan A, Gal ZT, Rangwala SD
… +14 more, Han JS, Philbrick BD, Le C, Pain M, Bonet J, Oushy S, Smith E, Orbach DB, Shigematsu T, Berenstein A, Fifi JT, Ghatan S, See AP, Morgenstern PF
Neurosurgery
· 2026 Mar · PMID 41817186
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BACKGROUND AND OBJECTIVES: Hydrocephalus is a comorbid condition in patients with vein of Galen malformations (VOGMs), and its management is complicated by venous hypertension, elevating surgical risk. Endoscopic third v...BACKGROUND AND OBJECTIVES: Hydrocephalus is a comorbid condition in patients with vein of Galen malformations (VOGMs), and its management is complicated by venous hypertension, elevating surgical risk. Endoscopic third ventriculostomy (ETV) is commonly used for cerebrospinal fluid (CSF) diversion in children, but there are limited available data on its efficacy and safety for patients with VOGM. We aimed to review our experiences with ETV across 2 high-volume centers for VOGM patients with hydrocephalus. METHODS: A two-center retrospective review identified all patients with VOGM who underwent ETV. Demographics, clinical presentation, procedural history, and outcomes were reviewed. ETV success scores were calculated. RESULTS: Twelve patients with VOGM underwent ETV; 66.7% was male, with a median age of 6 months. Seven (58.3%) were still undergoing VOGM embolization before ETV, and 4 had a history of hydrocephalus with acute-on-chronic exacerbation. Eight patients (66.7%) presented with obstructive hydrocephalus because of aqueductal stenosis (58.3%) and with intraventricular hemorrhage without CSF pathway stenosis (8.3%). Three (25.0%) required external ventricular drain placement or fontanelle taps pre-ETV, and choroid plexus cauterization was performed in 4 patients (33.3%). Technical success of ETV was achieved in all cases. One patient experienced venous bleeding at the ventriculostomy site. Postoperative complications occurred in 2 patients: one with transient truncal ataxia and the other with seizure activity, all of which resolved by discharge. At most recent follow-up, 10 patients (83.3%) have minimal residual arteriovenous shunting of their VOGM. The mean ETV success score was 60.8, and 11 patients (91.7%) experienced clinical improvement with ETV patency at the 6-month follow-up. One patient required conversion to a ventriculoperitoneal shunt because of lack of improvement at 6 months. CONCLUSION: This largest-to-date series on VOGM-associated hydrocephalus treated with ETV demonstrates high safety and efficacy across 2 independent high-volume centers. In patients with VOGM demonstrating clinical deterioration secondary to hydrocephalus, ETV with possible choroid plexus cauterization is a viable CSF diversion strategy to consider.
Peng W, Melvani N, Saraswat E
… +5 more, Eberle AT, Catapano JS, Huguenard AL, Rahmani R, Lawton MT
Neurosurgery
· 2026 Mar · PMID 41805191
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In an era in which digital connectivity transcends geographical borders, multimedia platforms can affect neurosurgical education on a global scale. Multimedia educational programs are reaching neurosurgeons worldwide, ex...In an era in which digital connectivity transcends geographical borders, multimedia platforms can affect neurosurgical education on a global scale. Multimedia educational programs are reaching neurosurgeons worldwide, exposing them to complex cases and novel techniques that they might not otherwise see. After collecting analytical data on engagement with Barrow Neurological Institute's Barrow Live Surgery, Neurosurgery Base Camp, and Seven Series, as well as its educational posts published on the social media platforms YouTube, Instagram, and X, a survey was developed to measure the effect of each program on viewer confidence and knowledge. Data from academic institutions with active neurosurgical multimedia channels (>30 000 impressions) were used as a comparator. Statistical tests were conducted using R (version 4.3.2) with significance defined as P < .05. Between October 23, 2020, and July 18, 2024, Barrow Neurological Institute's educational material had 1 906 197 views and 21 754 hours of total watch time, reaching more than 30 low- and middle-income countries. Barrow Neurological Institute had the most impressions and the highest impression-to-subscriber ratio among comparable institutions. Viewers preferred engaging with videos in a continuous series rather than with segmented episodes. Forty-nine percent of survey respondents resided outside the United States, and 26% were from low- and middle-income countries. Based on a 10-point Likert scale, median confidence in treating complex cases increased from 1 to 4 (P < .001) and confidence in recognizing disease pathophysiology increased from 2.5 to 5.5 (P < .001). Our results suggest that free online media can democratize access to advanced neurosurgical education, especially in areas with limited access to specialized training.