Executive Summary
This week's digest highlights: Consider implementing dexmedetomidine-based opioid-free anesthesia for supratentorial tumor surgeries to enhance hemodynamic stability. Utilize dual-polymer gel during single-level partial discectomy to improve outcomes for patients suffering from severe leg and back pain. Evaluate the potential of posterior-superior insula deep brain stimulation in selected patients with...
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.
Tumor / Skull Base
Opioid-free Anesthesia for Craniotomy in Supratentorial Tumors: An Open-labeled Single-blinded Randomized Controlled Study.
Research • Tumor / Skull Base • Journal of neurosurgical anesthesiology • 2026-01-15
Consider dexmedetomidine-based opioid-free anesthesia for supratentorial tumor surgery when hemodynamic stability is a priority.
ODexmedetomidine-based opioid-free anesthesia may enhance hemodynamic stability during supratentorial tumor surgeries, but be aware of the need for tailored pain management strategies in the immediate postoperative period.
Study snapshot
Design
Open-labeled single-blinded randomized controlled study
Population
Adult patients (>18 years) with supratentorial tumors undergoing elective craniotomy under general anesthesia
Intervention
Dexmedetomidine-based opioid-free anesthesia
Comparator
Fentanyl-based conventional opioid anesthesia
Primary outcome
Emergence and extubation times
Why it matters
Opioid-free anesthesia (OFA) with dexmedetomidine has been proposed as an alternative to conventional opioid-based regimens for craniotomy, potentially reducing complications. This pilot RCT found OFA provided better hemodynamic stability and improved pain control at 12 hours with similar emergence times. Clinicians could consider OFA as a viable option for supratentorial tumor surgery, particularly in patients where hemodynamic stability is a concern.
Practice change
May support considering opioid-free anesthesia with dexmedetomidine as an alternative for supratentorial tumor surgery.
More context
Key details
- Single-blinded RCT of adults undergoing elective supratentorial tumor craniotomy
- 33 patients completed the study
High-yield
See source article for primary outcome data.
Clinical context
Opioid-free anesthesia offers potential benefits of smoother recovery and reduced complications compared with conventional opioid-based approach.
Limitations
Small sample size (44 randomized, 33 completed) limits statistical powerSingle-center design may limit generalizability
Methodological critique
Small sample size limits statistical power for detecting differences.
Teaching pearl
When managing anesthesia for craniotomy, consider that dexmedetomidine-based OFA can provide the hemodynamic stability you want during pinning without prolonging emergence—just be prepared for potentially different pain management needs in the first 12 hours post-op.
Funding and COI
Not stated
Spine
Dual-Polymer Carboxymethyl Cellulose and Poly(Ethylene Oxide) Gel Reduces Leg and Back Pain in Patients With Severe Leg and Back Pain Following Single-Level Partial Discectomy.
Research • Spine • Spine • 2025-12-19
Consider applying dual-polymer gel during single-level partial discectomy to increase the likelihood of patients achieving high responder status for leg pain relief.
OApplying dual-polymer gel during single-level partial discectomy may enhance leg pain relief outcomes, but clinicians should remain cautious as the evidence primarily supports its use for achieving high responder status rather than overall pain reduction.
Study snapshot
Design
Prospective, randomized, multicenter, patient and evaluator-blinded study
Population
Adults (22-70 years) with unilateral herniation of lumbar disc, severe leg pain (≥60mm VAS) and back pain (≥50mm VAS), undergoing first surgical intervention at L4-L5 or L5-S1
Intervention
Single-level partial discectomy with application of dual-polymer carboxymethyl cellulose and poly(ethylene oxide) gel
Comparator
Standard discectomy surgery alone
Primary outcome
Change from baseline in leg pain VAS score at 6 months
Why it matters
Adjuvant therapies following lumbar discectomy aim to improve pain outcomes beyond surgery alone. This RCT found dual-polymer gel applied during discectomy increased the proportion of high responders for leg pain and provided statistically greater reduction in sciatica bothersomeness. Clinicians could consider this gel as an adjunct during single-level partial discectomy for patients with severe leg and back pain.
Practice change
Could consider dual-polymer gel as an adjunct during single-level partial discectomy to potentially improve pain outcomes.
More context
Key details
- Prospective, randomized, multicenter, patient/evaluator-blinded study at 17 US centers
- Adults (22-70 years) with unilateral lumbar disc herniation and severe leg/back pain undergoing first surgical intervention
High-yield
See source article for primary outcome data.
Clinical context
The study assessed safety and effectiveness of dual-polymer gel for reduction of severe ipsilateral leg and back pain following lumbar single-level partial discectomy.
Limitations
Primary efficacy endpoint (VAS leg pain) was not metPer protocol analysis (n=102) rather than full ITT for efficacy outcomes
Methodological critique
Primary efficacy endpoint not met despite secondary outcome significance.
Teaching pearl
When doing a discectomy for severe radiculopathy, consider that applying this dual-polymer gel to the annulus, dura, and nerve root might get more patients to that 'high responder' category—especially for sciatica symptoms—even if the VAS doesn't show it.
Funding and COI
Not stated
Functional
Insula Deep Brain Stimulation for Neuropathic Pain: A Cross-Over, Randomized, Sham-Controlled Trial.
Research • Functional • Neuromodulation : journal of the International Neuromodulation Society • 2025-08-18
For selected patients with pharmaco-resistant neuropathic pain who respond to insula TMS, posterior-superior insula DBS may offer meaningful pain reduction with reasonable safety.
OPosterior-superior insula DBS may provide significant pain relief for selected patients with pharmaco-resistant neuropathic pain who previously responded to insula TMS, but further phase 3 trials are needed to confirm these findings.
Study snapshot
Design
Phase 2 randomized, double-blind, sham-controlled, cross-over trial
Population
Adults with chronic pharmaco-resistant neuropathic pain who previously responded to deep repetitive transcranial magnetic stimulation of posterior-superior insula
Intervention
Posterior-superior insula deep brain stimulation
Comparator
Sham stimulation
Primary outcome
Proportion of participants achieving ≥30% reduction in average pain intensity compared with baseline
Why it matters
Before this study, neuropathic pain often remained refractory despite available treatments, with limited evidence for deep brain stimulation targeting the insula. This randomized trial shows that posterior-superior insula DBS has a high posterior probability of being more effective than sham stimulation for reducing pain intensity and interference. Clinicians could consider this as a potential option for carefully selected patients with pharmaco-resistant neuropathic pain who respond to prior insula stimulation testing, while awaiting confirmatory phase 3 trials.
Practice change
Could consider posterior-superior insula DBS for carefully selected patients with pharmaco-resistant neuropathic pain who respond to prior insula stimulation testing.
More context
Key details
- Phase 2 randomized, double-blind, sham-controlled, cross-over trial
- Targeted posterior-superior insula in patients with chronic pharmaco-resistant neuropathic pain
- Participants had previously responded to deep repetitive transcranial magnetic stimulation of same region
- Study included double-blind (2 × 3 months), single-blind (3 months), and open-label (6 months) phases
- Secondary outcomes included pain interference, quality of life, and neuropsychiatric assessments
- No major adverse events reported; stimulation was well tolerated
High-yield
Posterior-superior insula DBS demonstrated an 82.3% posterior probability of higher responder rates than sham, with credible intervals suggesting substantial benefit, and was well-tolerated without major adverse events.
Clinical context
Neuropathic pain affects a significant portion of the population, with many experiencing refractory conditions. This study evaluated posterior-superior insula DBS for pharmaco-resistant neuropathic pain.
Limitations
Small sample size of 10 participants limits generalizabilityCross-over design may carry carryover effects despite washout periods
Methodological critique
Small sample size (n=10) limits statistical power and generalizability.
Teaching pearl
When considering DBS for refractory neuropathic pain, target patients who have shown prior response to non-invasive insula stimulation—this study's inclusion criteria may help identify those most likely to benefit from surgical intervention.
Funding and COI
Not stated
Basic Science
PTBP1 knockdown reprograms glioma stem cells into neuronal-like cells and suppresses tumorigenesis via the DUSP5-ERK1/2 signaling pathway.
Research • Basic Science • Neuro-oncology • 2026-03-28
Preclinical evidence; no immediate practice change pending clinical validation.
OWhile the preclinical findings suggest that targeting PTBP1 may reprogram glioma stem cells and suppress tumor growth, clinicians should remain cautious as these results require further validation in clinical trials before any therapeutic application.
Study snapshot
Design
Basic science preclinical study with integrated transcriptomic analysis, single-cell RNA-seq, and mouse model validation
Population
65 patients with glioma (specimen analysis) and mouse orthotopic models
Intervention
PTBP1 knockdown via lentiviral vectors and A2-PLGA/venetoclax nanoparticle treatment
Comparator
None (single-arm preclinical validation)
Primary outcome
Tumor suppression and glioma stem cell differentiation into neuronal-like cells
Why it matters
Before this study, we knew that glioblastoma stem cells drive tumor recurrence and resistance, but targeting them effectively remained a major challenge. This work adds a novel molecular pathway (PTBP1/DUSP5/ERK1/2) that regulates glioma stem cell differentiation and identifies a repurposed drug (venetoclax) delivered via nanoparticles as a potential therapeutic strategy. Clinicians should now be aware of PTBP1 as a promising target and consider that nanoparticle-delivered venetoclax could enter future clinical trials for glioblastoma.
Practice change
Does not change current clinical practice but may inform future translational work.
More context
Key details
- Analyzed H&E-stained specimens from 65 glioma patients using deep learning-based morphological classification
- Used mouse models with tissue clearing and 3D imaging for validation
- PTBP1 regulates DUSP5 expression post-transcriptionally and modulates ERK1/2 phosphorylation dynamics
- Lentiviral knockdown of PTBP1 validated function in vitro and in orthotopic models
- Structure-based drug screening identified venetoclax as a PTBP1-targeting agent
- Nanotherapeutic strategy repurposes venetoclax (clinical leukemia drug) for glioma treatment
- Establishes PTBP1/DUSP5/ERK1/2 axis as governing glioma stem cell proliferation and differentiation
High-yield
See source article for primary outcome data.
Clinical context
Glioblastoma has a median survival of months with limited efficacy from current therapies like resection, radiotherapy, and temozolomide. Resistance and recurrence remain major challenges due to glioma stem cells.
Limitations
Preclinical study using mouse models may not fully translate to human glioblastoma patientsLack of clinical trial data limits immediate applicability to patient care
Methodological critique
Preclinical mouse models limit direct clinical applicability without human trial validation.
Teaching pearl
When evaluating glioma stem cell targets, look beyond proliferation markers to differentiation pathways like PTBP1/DUSP5/ERK1/2—reprogramming stem cells into neuronal-like cells may be more effective than simply killing them.
Funding and COI
Not stated
Trials to Know
Tenecteplase vs. Alteplase Bridging for Large Vessel Occlusion Stroke
Trial • Trials to Know • ClinicalTrials.gov • 2026-04-12
Why it matters
This phase 3 trial directly compares tenecteplase to alteplase as bridging therapy before mechanical thrombectomy for acute large vessel occlusion stroke. It addresses a critical evidence gap in neurointerventional practice by determining whether tenecteplase offers superior efficacy or safety over the current standard alteplase, potentially changing pre-thrombectomy pharmacological management for this high-acuity neurosurgical population.
More context
Key details
- Phase 3, Recruiting
Focused Ultrasound with Bevacizumab for Recurrent Glioblastoma
Trial • Trials to Know • ClinicalTrials.gov • 2026-04-12
Why it matters
This trial addresses the critical need for more effective treatments in recurrent glioblastoma, where options are limited and prognosis remains poor. It evaluates whether combining microbubble-mediated focused ultrasound (FUS-MB) with bevacizumab enhances drug delivery and efficacy compared to bevacizumab alone, potentially offering a novel approach to improve outcomes in this challenging patient population.
More context
Key details
- Phase 3, Recruiting
Hypofractionated Re-irradiation for Recurrent Glioblastoma
Trial • Trials to Know • ClinicalTrials.gov • 2026-04-12
Why it matters
This Phase 1 trial addresses the challenging clinical scenario of recurrent glioblastoma in patients with good prognosis, testing hypofractionated radiation therapy as a re-irradiation strategy. It matters to neurosurgeons because it explores a potentially more efficient and tolerable radiation approach for this aggressive tumor recurrence, which could inform post-surgical adjuvant treatment decisions and improve local control outcomes.
More context
Key details
- Phase 1, Recruiting
From the Preprint Wire
Global Research Architecture and Evolution of Neuroendoscopy for Intracranial Hemorrhage: A Bibliometric Analysis
Preprint • From the Preprint Wire • medrxiv • 2026-03-30
Why it matters
This preprint provides a comprehensive bibliometric analysis of neuroendoscopy research for intracranial hemorrhage (ICH) over two decades, offering neurosurgeons insights into global trends, key contributors, and evolving themes in this minimally invasive field. As an unreviewed preprint, it highlights the growing emphasis on precision and technological integration in ICH management, but readers should interpret findings cautiously pending peer review.
More context
Key details
- Analyzed 403 articles from 43 countries, showing fluctuating growth tied to clinical demand and technology maturation.
- China led in publications and citation impact, with the US as a key collaborator, shaping global research influence.
- Research themes evolved from initial conservative treatment and safety to augmented reality and patient stratification, indicating a shift toward precision and innovation.
Missed Appointments and Clinical Outcomes in Veterans with PTSD/TBI
Preprint • From the Preprint Wire • medrxiv • 2026-03-30
Why it matters
This preprint analyzes over 2 billion outpatient appointments in the Veterans Health Administration (VHA) and finds that higher no-show rates are associated with increased hospitalization and mortality risks in veterans with PTSD or traumatic brain injury (TBI). For neurosurgeons managing TBI patients, this suggests appointment adherence could serve as a simple marker for identifying high-risk individuals needing targeted follow-up. However, as an unreviewed preprint, these findings require validation before clinical application.
More context
Key details
- Analyzed 2.16 billion VHA outpatient appointments (2000-2024) with 6.5% no-show and 25.4% cancellation rates