Executive Summary
This week's digest highlights: In endovascular treatment for large core ischemic stroke, minimizing thrombectomy attempts and using local sedative anesthesia may reduce the risk of parenchymal hemorrhage. Molecular testing for the PTPRZ-MET fusion gene in recurrent high-grade glioma patients can help identify candidates for targeted therapy trials. In spinal cord injury clinical trials, incorporating...
Owen briefs you on what matters in this week's digest.
Think chief-resident chalk talk: what matters, what changes practice, and where to spend your reading time.
Endovascular / Vascular
Predictors of parenchymal hemorrhage after endovascular treatment in large core ischemic stroke: a post-hoc analysis of the ANGEL-ASPECT trial.
Research • Endovascular / Vascular • Journal of neurointerventional surgery • 2026-03-13
In large core stroke thrombectomy, minimize thrombectomy attempts and consider local sedative anesthesia to potentially reduce parenchymal hemorrhage risk.
OIn large core stroke thrombectomy, limiting the number of attempts and opting for local sedative anesthesia may significantly reduce the risk of parenchymal hemorrhage, though further studies are needed to confirm these findings.
Study snapshot
Design
Post-hoc analysis of multicenter randomized controlled trial
Population
Patients with large infarcts who underwent thrombectomy in the ANGEL-ASPECT trial
Intervention
Mechanical thrombectomy
Comparator
None (single-arm analysis of thrombectomy patients)
Primary outcome
Predictive factors for post-thrombectomy parenchymal hemorrhage
Why it matters
Before this study, we knew that parenchymal hemorrhage (PH) was a feared complication after thrombectomy for large core strokes, but specific modifiable risk factors were not well characterized. This post-hoc analysis of the ANGEL-ASPECT trial identifies alcohol use and increased thrombectomy attempts as independent predictors of PH, while local sedative anesthesia appears protective. For clinicians, this suggests that minimizing thrombectomy passes and considering local sedative anesthesia could potentially reduce PH risk in these high-risk patients.
Practice change
Confirms current practice of minimizing thrombectomy attempts, but may support consideration of local sedative anesthesia in appropriate patients.
More context
Key details
- Post-hoc analysis of the ANGEL-ASPECT randomized trial (NCT04551664)
- 35 patients (16.1%) experienced parenchymal hemorrhage 24-48 hours after thrombectomy
- PH associated with worse functional outcome (mRS score 5 vs 3, acOR 0.31, 95% CI 0.16-0.61, P<0.01)
- Alcohol use independently increased PH risk (acOR 3.22, 95% CI 1.29-8.03, P=0.01)
- Increased thrombectomy attempts independently increased PH risk (acOR 1.43, 95% CI 1.02-2.00, P=0.04)
- Local sedative anesthesia independently reduced PH risk (acOR 0.10, 95% CI 0.01-0.84, P=0.03)
High-yield
In patients with large infarcts undergoing thrombectomy, parenchymal hemorrhage occurred in and was associated with significantly worse functional outcomes (adjusted common OR 0.31, P<0.01).
Clinical context
The efficacy of mechanical thrombectomy for treating large infarcts has been established through multiple recent randomized controlled trials. Nevertheless, hemorrhagic transformation remains one of the significant challenges following thrombectomy in these patients.
Limitations
Post-hoc analysis of a larger trial, not pre-specified for this specific questionRelatively small number of PH events (n=35) limits multivariate model stability
Methodological critique
As a post-hoc analysis, findings should be considered hypothesis-generating rather than definitive.
Teaching pearl
When doing thrombectomy for large core strokes, count your passes carefully—each additional attempt increases parenchymal hemorrhage risk by about 40%, and consider local sedative anesthesia which showed a 90% reduction in hemorrhage risk in this analysis.
Funding and COI
Not stated
Tumor / Skull Base
Vebreltinib for Previously Treated Astrocytoma, IDH-Mutant, Grade 4, and Glioblastoma, IDH Wild-Type with PTPRZ1-MET Fusion Gene: A Multicenter, Phase III Randomized, Open-Label Trial.
Research • Tumor / Skull Base • Cancer communications (London, England) • 2026-03-11
Consider molecular testing for PTPRZ-MET fusion in recurrent high-grade glioma patients to identify candidates for targeted therapy trials.
OMolecular testing for the PTPRZ1-MET fusion in recurrent high-grade gliomas is essential, as it may identify patients who could benefit from targeted therapies like vebreltinib, despite the need for further efficacy validation.
Study snapshot
Design
Multicenter, randomized, open-label phase III trial
Population
Patients aged 18-65 years with previously treated astrocytoma, IDH-mutant, grade 4, or glioblastoma, IDH wild-type, with PTPRZ1-MET fusion gene
Intervention
Vebreltinib 300 mg orally twice daily
Comparator
Standard therapy (temozolomide or cisplatin/etoposide combination)
Primary outcome
Overall survival
Why it matters
Previously, patients with recurrent high-grade gliomas harboring the PTPRZ1-MET fusion had limited therapeutic options beyond standard chemotherapy regimens. This phase III trial demonstrates that vebreltinib, a brain-penetrant MET inhibitor, shows promising activity in this molecularly defined subgroup. While definitive efficacy data are pending, clinicians should consider molecular testing for ZM fusion in appropriate glioma patients to identify candidates for targeted therapy trials.
Practice change
Could consider molecular testing for PTPRZ1-MET fusion in appropriate glioma patients to identify candidates for targeted therapy trials.
More context
Key details
- Multicenter, randomized, open-label phase III trial (FUGEN trial)
- Patients with previously treated astrocytoma, IDH-mutant, grade 4, or glioblastoma, IDH wild-type, with PTPRZ1-MET fusion gene
- ZM fusion present in approximately 15% of secondary glioblastomas
High-yield
Vebreltinib, a next-generation MET inhibitor with enhanced brain penetration, demonstrated encouraging preliminary efficacy in a phase I study with partial responses in of patients with secondary glioblastoma harboring the PTPRZ-MET fusion.
Clinical context
Gliomas represent the most common and lethal malignant primary tumors of the central nervous system. The discovery of the PTPRZ1-MET fusion gene in approximately 15% of secondary glioblastomas has provided important insights into glioma progression and therapeutic vulnerabilities.
Limitations
Open-label design introduces potential bias in outcome assessmentSpecific efficacy results and statistical significance not yet reported in available text
Methodological critique
Open-label design may introduce bias in outcome assessment, particularly for subjective endpoints.
Teaching pearl
When seeing recurrent high-grade glioma patients, remember that approximately 15% of secondary glioblastomas harbor the PTPRZ1-MET fusion—molecular testing could open doors to targeted therapies like vebreltinib that show early promise.
Funding and COI
Not stated
Spine
Enhanced clinical trial stratification in spinal cord injury: the value of electrophysiology.
Research • Spine • Brain : a journal of neurology • 2026-03-05
Consider incorporating somatosensory evoked potential testing in spinal cord injury trial design to improve patient stratification and reduce required sample sizes.
OIncorporating somatosensory evoked potential testing in spinal cord injury trials can significantly enhance patient stratification and reduce sample size, though reliance on electrophysiology should be balanced with clinical assessments to ensure comprehensive evaluation.
Study snapshot
Design
Retrospective stratification analysis of a randomized, placebo-controlled phase 2b trial
Population
Patients aged 18-70 years with acute (4-28 days) cervical spinal cord injury
Intervention
NG101 (anti-Nogo-A antibody)
Comparator
Placebo
Primary outcome
Comparison of treatment effect sizes for recovery of upper extremity motor scores and spinal cord independence measure between stratification methods
Why it matters
Previous spinal cord injury trials have relied primarily on clinical measures for patient stratification, which may not optimally identify those most likely to benefit from plasticity-inducing interventions. This analysis demonstrates that electrophysiological stratification using preserved somatosensory evoked potentials identifies treatment responders more effectively than clinical criteria alone. For trial design, incorporating electrophysiology could substantially reduce required sample sizes while increasing effect sizes.
Practice change
May support incorporating electrophysiological measures in future spinal cord injury trial design to improve patient enrichment.
More context
Key details
- Retrospective stratification analysis of the NISCI randomized, placebo-controlled phase 2b trial (NCT03935321)
- 116 participants with acute cervical spinal cord injury (74 NG101, 41 placebo)
High-yield
Electrophysiological stratification using preserved somatosensory evoked potentials reduced required sample size from to 32 patients and increased effect size from Cohen's d=0.46 to compared to clinical stratification in a spinal cord injury trial.
Clinical context
There are no approved interventional therapies, aside from neurorehabilitation, that enhance neurological recovery after acute traumatic spinal cord injury. A key challenge is the lack of biomarkers surpassing clinical standards for optimal stratification.
Limitations
Retrospective analysis of a single trial limits generalizabilitySmall sample size for the electrophysiological stratification group (n=32)
Methodological critique
Retrospective nature limits causal inferences about the superiority of electrophysiological stratification.
Teaching pearl
In spinal cord injury trial design, don't overlook electrophysiology—preserved SSEPs can identify treatment responders so effectively that you might need only a quarter of the patients compared to clinical stratification alone.
Funding and COI
Not stated
Functional
Ventriculomegaly and Brain Atrophy in Deep Brain Stimulation: A Literature Review of Technical Challenges, Prognostic Implications, and Surgical Risks.
Research • Functional • Stereotactic and functional neurosurgery • 2026-02-27
In DBS candidates with ventriculomegaly or brain atrophy, employ meticulous image-guided trajectory planning to avoid ventricular wall transgression while recognizing these patients may still benefit from intervention.
OIn patients with ventriculomegaly or brain atrophy undergoing deep brain stimulation, careful image-guided trajectory planning is essential to prevent ventricular wall transgression and mitigate the risk of postoperative confusion, despite the potential for meaningful clinical benefits.
Study snapshot
Design
Narrative literature review
Population
Patients with medication-refractory movement disorders undergoing DBS
Intervention
Deep brain stimulation
Comparator
None
Primary outcome
Impact of ventriculomegaly and brain atrophy on motor outcomes, safety, and surgical complications
Why it matters
Before this review, ventriculomegaly and brain atrophy were recognized as common findings in DBS candidates, but their precise impact on outcomes and risks was debated. This review synthesizes evidence showing these morphometric changes correlate with poorer motor improvement and identifies ventricular wall transgression as a specific risk factor for postoperative confusion. Clinicians should not consider ventriculomegaly and atrophy as absolute contraindications but should employ meticulous image-guided planning to mitigate risks while recognizing patients may still derive quality-of-life benefits.
Practice change
Confirms current practice of meticulous surgical planning in patients with ventriculomegaly or brain atrophy while providing evidence-based risk quantification.
More context
Key details
- Review of literature on ventriculomegaly and brain atrophy in DBS for movement disorders
- Ventriculomegaly and atrophy serve as markers of underlying neurodegenerative burden
- Factors contributing to adverse outcomes include patient comorbidities, surgical technique, and postoperative electrode displacement
- Excellent outcomes are achievable in patients with marked ventriculomegaly and atrophy with meticulous surgical planning
- Modern image-guided software and careful trajectory planning can mitigate risks
- Patients may derive significant quality of life benefits even with modest motor improvements
- Provides evidence-based framework to guide clinical judgment and surgical strategy
High-yield
Transgressing the ventricular wall during STN DBS surgery increases the risk of postoperative confusion by a relative risk of , highlighting the critical importance of trajectory planning in patients with ventriculomegaly.
Clinical context
Deep brain stimulation is a cornerstone treatment for medication-refractory movement disorders. Ventriculomegaly and brain atrophy, common findings in DBS candidates, present technical challenges and potential safety concerns.
Limitations
Narrative review design limits quantitative synthesis and may be subject to selection bias in article inclusionRelies on existing cohort studies with potential heterogeneity in patient populations and outcome measures
Methodological critique
As a narrative review, this study lacks systematic methodology for article selection and quantitative synthesis of evidence.
Teaching pearl
When planning DBS trajectories in patients with ventriculomegaly, use modern image-guided software to meticulously avoid ventricular wall transgression—this single technical detail can dramatically reduce the risk of postoperative confusion.
Funding and COI
Not stated
General Neurosurgery
Topical vancomycin for surgical site infection prophylaxis in craniotomies and noninstrumented spinal procedures: a randomized controlled trial.
Research • General Neurosurgery • Journal of neurosurgery • 2025-11-14
Do not add topical vancomycin to standard systemic antibiotic prophylaxis for SSI prevention in craniotomies and noninstrumented spinal procedures, as it provides no significant benefit.
OTopical vancomycin should not be used as an adjunct to standard systemic antibiotic prophylaxis in craniotomies and noninstrumented spinal procedures, as recent high-quality evidence demonstrates it does not significantly reduce surgical site infection rates.
Study snapshot
Design
Randomized controlled trial
Population
Patients undergoing craniotomy or noninstrumented spinal procedures
Intervention
Topical vancomycin application at surgical site plus standard systemic antibiotic prophylaxis
Comparator
Standard systemic antibiotic prophylaxis alone
Primary outcome
Surgical site infection rate at postoperative day 30
Why it matters
Previous studies had suggested potential benefits of topical vancomycin for SSI prophylaxis in neurosurgery, but evidence was limited. This RCT provides high-quality evidence showing no significant reduction in SSI rates with topical vancomycin compared to standard systemic prophylaxis alone. Clinicians should not adopt topical vancomycin as standard practice for craniotomies and noninstrumented spinal procedures based on current evidence.
Practice change
May support discontinuing routine use of topical vancomycin for SSI prophylaxis in craniotomies and noninstrumented spinal procedures given no demonstrated benefit.
More context
Key details
- Randomized controlled trial of topical vancomycin for SSI prophylaxis
- 1103 patients randomly assigned to topical vancomycin plus standard systemic antibiotics (n=552) or standard antibiotics alone (n=551)
- SSI symptoms assessed via standardized patient surveys at postoperative day 30
- No significant reduction in SSI rates with topical vancomycin in overall analysis or when stratified by procedure type
- Sensitivity analysis using various SSI classification schemes showed no significant reduction
- Topical vancomycin use not associated with significant systemic absorption or adverse events
- Authors conclude topical vancomycin should not be established as standard of care without clear evidence of superiority
High-yield
Topical vancomycin added to standard systemic antibiotic prophylaxis did not reduce surgical site infection rates in craniotomies and noninstrumented spinal procedures (3.94% vs 4.10%, p=0.90).
Clinical context
Surgical site infections remain a significant concern in neurosurgical procedures. The role of topical vancomycin as adjunctive prophylaxis has been debated.
Limitations
SSI assessment relied on patient surveys rather than direct clinical evaluation, potentially introducing recall biasStudy may not have been powered to detect small differences in SSI rates between groups
Methodological critique
Reliance on patient self-reported symptoms for SSI assessment rather than direct clinical evaluation represents a potential limitation in outcome measurement.
Teaching pearl
When considering adjunctive measures for SSI prophylaxis, remember that this RCT shows topical vancomycin provides no additional benefit over standard systemic antibiotics alone for craniotomies and noninstrumented spinal procedures—stick with evidence-based practices.
Funding and COI
Not stated
Basic Science
Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes.
Research • Basic Science • Brain : a journal of neurology • 2026-03-05
While not yet ready for clinical application, this study identifies a novel, potentially reversible mechanism of synaptic damage after brain trauma that may inform future therapeutic development for cognitive protection.
OThis study highlights a potentially reversible mechanism of cognitive dysfunction post-TBI involving glial D-serine and synaptic pruning, warranting attention for future therapeutic strategies despite its current low evidence quality.
Study snapshot
Design
Preclinical basic science study
Population
Wild-type mice, genetically modified mice, and human TBI patients (n=41 for tissue analysis)
Intervention
Evaluation of D-serine influence on synaptic damage mechanisms
Comparator
Genetic modifications and control conditions
Primary outcome
Mechanistic understanding of synaptic damage after brain injury
Why it matters
Previous understanding of cognitive loss after brain trauma focused on focal tissue damage with limited therapeutic options. This preclinical study identifies a novel mechanism where prolonged glial D-serine release reactivates developmental synaptic pruning processes, leading to widespread synaptic damage. While not immediately changing clinical practice, this work suggests potential new therapeutic targets for protecting cognitive function after TBI.
Practice change
Could consider this mechanistic understanding when evaluating future therapeutic trials targeting glial D-serine release or synaptic pruning pathways in TBI patients.
More context
Key details
- Preclinical study examining synaptic damage mechanisms after brain trauma
- Used wild-type mice and mice deficient in microglial serine racemase or neuronal GluN2B
- Measured biochemical alterations in synaptic proteins, dendritic spine numbers/morphology, electrophysiological responses, and learning/memory behavior
- Employed single-cell analysis to examine cell-type specific contributions
- Analyzed perilesional tissues from 41 traumatic brain injury patients for mRNA/protein differences
- Found synaptic pruning pathway is reversible at several stages within acute injury period
- Suggests targeting specific molecules in this pathway may represent new therapeutic strategy for TBI
High-yield
Prolonged glial D-serine release after brain injury reactivates developmental synaptic pruning processes through hyperactivation of perisynaptic NMDA receptors, representing a reversible mechanism underlying cognitive dysfunction.
Clinical context
Cognitive losses from severe brain trauma have long been associated with focal tissue damage, with few available pharmacological therapies for patients.
Limitations
Preclinical study using mouse models, limiting direct translation to human clinical practiceMechanistic findings require validation in larger human studies before clinical application
Methodological critique
As a preclinical study primarily using animal models, direct clinical applicability is limited without further human validation.
Teaching pearl
When considering the pathophysiology of cognitive dysfunction after TBI, recognize that this study suggests a potentially reversible mechanism involving glial D-serine release and synaptic pruning—keeping an eye on future therapeutic developments targeting this pathway.
Funding and COI
Not stated
Trials to Know
Phase 1 Study of Ibrutinib and Immuno-Chemotherapy Using Temozolomide, Etoposide, Doxil, Dexamethasone, Ibrutinib,Rituximab (TEDDI-R) in Primary CNS Lymphoma
Trial • Trials to Know • ClinicalTrials.gov • 2026-03-15
Why it matters
This recruiting trial may offer eligible patients access to novel interventions.
Anti-Lag-3 (Relatlimab) and Anti-PD-1 Blockade (Nivolumab) Versus Standard of Care (Lomustine) for the Treatment of Patients With Recurrent Glioblastoma
Trial • Trials to Know • ClinicalTrials.gov • 2026-03-15
Why it matters
This recruiting trial may offer eligible patients access to novel interventions.
MMA Embolization for Refractory Chronic Migraine
Trial • Trials to Know • ClinicalTrials.gov • 2026-03-15
Why it matters
This recruiting trial may offer eligible patients access to novel interventions.
From the Preprint Wire
Immunohistochemical Detection of Neurodegenerative Proteins in Brain Tissue Archived for Decades
Preprint • From the Preprint Wire • medrxiv • 2026-03-02
Why it matters
This preprint demonstrates that archival human brain tissue stored for up to 78 years can still yield reliable immunohistochemical detection of key neurodegenerative proteins like α-synuclein, tau, and β-amyloid. For neurosurgeons, this suggests that historical brain bank collections may remain valuable for research into diseases like Parkinson's and Alzheimer's, potentially informing surgical decision-making in deep brain stimulation or other interventions. However, as an unreviewed preprint, these findings require validation before clinical application.
More context
Key details
- Original paraffin blocks from 41 autopsy brains (1946-1980) showed consistent good staining for α-synuclein, tau, and β-amyloid.
- Newly prepared blocks from long-term fixated tissue had slightly lower scores for Lewy-related pathology and tau, but amyloid-β plaques showed similar or slightly higher scores.
- The findings indicate preserved pathological hallmarks of Lewy body and Alzheimer's diseases in archival tissue, supporting the utility of historical collections for neurodegenerative research.
Real-Time Kinematic Adaptive DBS Reduces Gait Impairment in Parkinson's Disease
Preprint • From the Preprint Wire • medrxiv • 2026-03-02
Why it matters
This preprint reports on a novel adaptive deep brain stimulation system that uses wearable sensors to dynamically adjust stimulation based on real-time gait metrics, potentially offering a more personalized approach to treating gait impairment and freezing of gait in Parkinson's disease. For neurosurgeons involved in DBS programming and management, this represents an important step toward closed-loop systems that could improve patient outcomes, though it's crucial to note this is an unreviewed preprint requiring validation.
More context
Key details
- KaDBS integrates bilateral shank-mounted IMUs with an investigational neurostimulator to enable real-time modulation based on step-detection and probabilistic freezing classification.
- The system demonstrated safety with no serious adverse events and symptom-free reports of 87.5% for the arrhythmicity model and 71.4% for the P(FOG) model, compared to 50.0% for continuous DBS.
- Two participants with 100% time freezing during OFF stimulation achieved complete resolution with KaDBS, suggesting particular benefit for baseline freezers while non-freezers maintained stable gait.