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Digest

The Weekly Signal

Published March 21, 2026

Executive Summary

This week's digest highlights: Consider adjunctive intra-arterial thrombolysis after endovascular thrombectomy for large vessel occlusion to enhance outcomes in select patients with lower eTICI scores and higher NIHSS. Maintain vigilant monitoring for malignant peripheral nerve sheath tumors in schwannomatosis patients, particularly those with NF-related conditions or prior radiation exposure. Surgical...

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

Consider adjunctive intra-arterial thrombolysis with alteplase mg/kg or tenecteplase mg/kg after successful EVT in patients with lower eTICI scores, higher NIHSS, or cardioembolic etiology to potentially improve excellent functional outcomes.

OAdjunctive intra-arterial thrombolysis after successful EVT may enhance functional outcomes in patients with lower eTICI scores, higher NIHSS, or cardioembolic strokes, but further validation is needed before widespread implementation.

High evidencePractice changing

Study snapshot

Design

Systematic review and meta-analysis

Population

Patients with large vessel occlusion undergoing endovascular thrombectomy

Intervention

Adjunctive intra-arterial thrombolysis after successful EVT

Comparator

EVT alone

Primary outcome

Excellent functional outcome (modified Rankin Scale 0-1) at 90 days

Why it matters

Prior to this study, while endovascular thrombectomy (EVT) achieves high recanalization rates for large vessel occlusion, functional outcomes often remain suboptimal. This meta-analysis shows that adjunctive intra-arterial thrombolysis after successful EVT may improve excellent functional outcomes (mRS 0-1) without increasing symptomatic intracerebral hemorrhage risk, with benefits concentrated in specific subgroups (e.g., those with lower eTICI scores, higher NIHSS, cardioembolic etiology, and specific thrombolytic dosages). Clinicians could consider adjunctive IA thrombolysis in these select patient populations, pending further validation.

Practice change

May support considering adjunctive IA thrombolysis in select patients after successful EVT, particularly those with lower recanalization scores, higher NIHSS, or cardioembolic etiology.

More context

Key details

  • Systematic review and meta-analysis of 7 trials (2131 patients)
  • 1081 patients (50.7%) received adjunctive IA thrombolysis
  • Higher odds of excellent functional outcomes (mRS 0-1) with IA thrombolysis (OR 1.44, 95% CI 1.21-1.72)
  • Similar rates of symptomatic intracerebral hemorrhage (OR 1.15, 95% CI 0.75-1.75)
  • Benefits primarily in patients with lower eTICI scores, higher NIHSS, cardioembolic etiology

High-yield

Adjunctive intra-arterial thrombolysis after successful EVT was associated with higher odds of excellent functional outcome (mRS -) at days without increased symptomatic intracerebral hemorrhage.

Clinical context

Despite high recanalization rates with endovascular thrombectomy for large vessel occlusions, functional outcomes remain suboptimal. This study investigates whether adjunctive intra-arterial thrombolysis following successful EVT can improve patient outcomes.

Limitations

Heterogeneity across included studies in patient selection and thrombolytic protocolsSubgroup analyses are observational and require prospective validation

Methodological critique

The meta-analysis followed PRISMA guidelines but included studies with varying protocols and patient populations.

Teaching pearl

When considering adjunctive IA thrombolysis after successful EVT, focus on patients with lower recanalization scores (eTICI <2b), higher NIHSS (>15), and cardioembolic strokes—these subgroups showed the greatest benefit in this analysis.

Funding and COI

Not stated

Tumor / Skull Base

Malignant peripheral nerve sheath tumors in schwannomatosis: systematic review and meta-analysis.

Research • Tumor / Skull Base • Journal of neurosurgery • 2025-11-14

Maintain vigilant monitoring for MPNSTs in schwannomatosis patients, especially those with NF-related disease, prior radiation, or intracranial/intraspinal lesions, and aim for gross-total resection when feasible.

OClinicians should maintain a high index of suspicion for malignant peripheral nerve sheath tumors in schwannomatosis patients, particularly in those with neurofibromatosis-related conditions or prior radiation exposure, as these tumors can present similarly to benign schwannomas but have a significantly elevated mortality rate.

High evidencePractice changing

Study snapshot

Design

Systematic review and meta-analysis

Population

Patients with schwannomatosis (NF2- or SMARCB1-related) and malignant peripheral nerve sheath tumors

Intervention

Various treatments (surgery, radiation, etc.)

Comparator

None (single-arm analysis)

Primary outcome

Overall survival and progression-free survival

Why it matters

Previously, malignant peripheral nerve sheath tumors (MPNSTs) were primarily associated with neurofibromatosis type 1, with limited understanding of their occurrence and outcomes in schwannomatosis. This systematic review characterizes MPNSTs in NF2- and SMARCB1-related schwannomatosis, identifying a high mortality rate (72.9%) and developing a preliminary risk stratification tool. Clinicians should maintain vigilant monitoring for MPNSTs in schwannomatosis patients and consider using the identified prognostic factors (S100 loss, resection extent, lesion location) to guide management.

Practice change

Confirms current practice of vigilant monitoring and aggressive management for MPNSTs in schwannomatosis, with preliminary risk stratification factors that may guide decision-making.

More context

Key details

  • Systematic review and meta-analysis of 39 cases

High-yield

MPNSTs in schwannomatosis carry a mortality rate of , with a risk stratification tool showing hazard ratios of 28.0 for overall survival and for progression-free survival (both p<0.0001).

Clinical context

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas commonly associated with neurofibromatosis type 1 (NF1), whose occurrence in schwannomatosis remains poorly understood. This study aimed to characterize MPNSTs in NF type 2 (NF2)- and SMARCB1-related schwannomatosis through a systematic review and meta-analysis of survival outcomes.

Limitations

Small sample size (39 cases) limits statistical powerRetrospective nature of included studies introduces potential selection bias

Methodological critique

The analysis is limited by small sample size and retrospective data from heterogeneous sources.

Teaching pearl

When evaluating a schwannomatosis patient with new or worsening symptoms, maintain high suspicion for MPNST—these tumors can mimic benign schwannomas but carry a mortality rate over 70%, particularly in NF2-related cases or those with prior radiation exposure.

Funding and COI

Not stated

Spine

Consider surgical intervention for cervical SCI without fracture and dislocation based on clinical and radiographic indications rather than strict time constraints, as both early (< hours) and delayed (> hours) surgery show comparable rates of neurological improvement.

OIn cervical spinal cord injury without fracture or dislocation, prioritize surgical intervention based on clinical and radiographic criteria rather than strict timing, as both early and delayed surgeries yield similar neurological outcomes.

High evidencePractice changing

Study snapshot

Design

Systematic review and meta-analysis

Population

Patients with cervical spinal cord injury without fracture and dislocation

Intervention

Surgical management

Comparator

None (single-arm analysis)

Primary outcome

Neurological improvement

Why it matters

Before this study, the role of surgery in cervical spinal cord injury without fracture and dislocation was unclear, with limited evidence on optimal timing. This meta-analysis demonstrates that surgical management leads to substantial neurological improvement (62-71% of patients) regardless of timing. Clinicians should consider surgical intervention for these injuries based on patient-specific factors rather than strict time windows, as early (<72 hours) and delayed (>72 hours) surgery showed comparable outcomes.

Practice change

Could consider surgical intervention for cervical SCI without fracture/dislocation based on individual patient factors rather than adhering to a strict 72-hour window.

More context

Key details

  • Systematic review and meta-analysis of 16 studies (398 patients)

High-yield

Surgical management of cervical SCI without fracture and dislocation resulted in neurological improvement in of patients operated within hours and of patients operated after hours, with no significant difference between timing groups (p=.8).

Clinical context

Cervical spinal cord injury (SCI) can occur in the absence of easily identifiable osseoligamentous abnormalities, such as fractures and dislocations. The role of surgery in the management of this condition remains to be elucidated.

Limitations

High heterogeneity in included studies regarding surgical techniques and outcome measuresRetrospective design of most studies limits causal inference

Methodological critique

The meta-analysis included studies with substantial heterogeneity in surgical approaches and outcome assessments.

Teaching pearl

When managing cervical SCI without fracture/dislocation, don't let the clock dictate your decision—this meta-analysis shows similar improvement rates whether you operate within 72 hours or later. Focus instead on identifying surgical candidates based on neurological status and imaging findings.

Funding and COI

Not stated

Functional

For Meige syndrome, both GPi and STN DBS targets provide comparable motor improvement and safety profiles at 1 year, allowing target selection based on surgical expertise and patient factors.

OIn selecting DBS targets for Meige syndrome, both GPi and STN provide similar motor improvements and safety, but clinicians should note that preoperative speech/swallowing impairments may indicate a poorer response, emphasizing the need for individualized patient assessment.

Low evidencePractice changing

Study snapshot

Design

Randomized, controlled, double-blind multicenter trial

Population

Patients with Meige syndrome

Intervention

Globus pallidus internus deep brain stimulation (GPi-DBS)

Comparator

Subthalamic nucleus deep brain stimulation (STN-DBS)

Primary outcome

Improvement in motor function as assessed by Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS)

Why it matters

Before this study, there was limited high-quality evidence comparing GPi-DBS and STN-DBS for Meige syndrome, with most data coming from small case series or retrospective analyses. This randomized, double-blind trial provides a comparison showing comparable efficacy and safety between the two targets, while identifying optimal stimulation sites and a preoperative predictor of outcome. Clinicians can consider either target based on patient-specific factors, knowing both offer similar benefits, but should be aware that greater preoperative speech/swallowing impairment may predict poorer response.

Practice change

May support considering either GPi or STN as equally viable DBS targets for Meige syndrome, with selection based on surgical experience and patient-specific factors.

More context

Key details

  • Randomized, controlled, double-blind multicenter trial comparing GPi-DBS vs STN-DBS for Meige syndrome
  • 62 patients randomized (31 per group), all completed 1-year follow-up

High-yield

GPi-DBS and STN-DBS show comparable efficacy and safety for Meige syndrome, with no significant differences in motor improvement, mood, anxiety, or quality of life at 1 year.

Clinical context

Meige syndrome is a focal dystonia affecting cranial and cervical muscles. Deep brain stimulation has emerged as a treatment option, but the optimal target (GPi vs STN) remained unclear.

Limitations

Small sample size (31 patients per group) limits statistical power for detecting subtle differences between targetsSingle-year follow-up may not capture long-term differences in efficacy or adverse events

Methodological critique

The study's double-blind design strengthens internal validity, but the small sample size may limit generalizability.

Teaching pearl

When counseling patients with Meige syndrome about DBS target selection, emphasize that both GPi and STN offer similar benefits, but STN may require lower stimulation parameters—consider this for battery longevity and side effect profile.

Funding and COI

Not stated

General Neurosurgery

Decompressive craniectomy in traumatic brain injury: insights from a 15-year multicentre cohort in Sweden.

Research • General Neurosurgery • Scandinavian journal of trauma, resuscitation and emergency medicine • 2026-02-26

Real-world decompressive craniectomy practice shows substantial center-level variation in patient selection and timing, which may impact complications and outcomes independent of RCT evidence.

OSubstantial center-level variation in decompressive craniectomy practices for traumatic brain injury suggests that local protocols may significantly influence outcomes, highlighting the need for individualized assessment beyond RCT findings.

Moderate evidencePractice changing

Study snapshot

Design

Multicenter retrospective observational cohort study

Population

299 patients undergoing decompressive craniectomy for traumatic brain injury at four Swedish neurosurgical centers (2008-2022)

Intervention

Decompressive craniectomy (primary or secondary)

Comparator

None (observational)

Primary outcome

Characterization of DC practice patterns, complications, and functional outcomes

Why it matters

Previous RCTs like DECRA and RESCUE-ICP provided conflicting evidence about decompressive craniectomy (DC) timing and outcomes in traumatic brain injury, but their strict criteria limit real-world applicability. This multicenter observational study adds contemporary data on DC practice patterns, complications, and outcomes across Swedish neurosurgical centers. Clinicians should recognize that real-world DC use involves substantial center-level variation in patient selection and timing, which may influence outcomes beyond what RCTs capture.

Practice change

Confirms current practice varies widely; may support greater attention to standardizing DC protocols across centers to reduce outcome variability.

More context

Key details

  • Retrospective analysis of 299 TBI patients undergoing DC at four Swedish neurosurgical centers from 2008-2022.
  • Catchment area covered approximately 72% of the Swedish population.
  • Study aimed to characterize real-world DC use, including temporal trends, patient characteristics, timing, techniques, complications, and outcomes.
  • Hypothesized that DC rates and types would remain stable despite RCT publications, but with considerable variation across centers.
  • Compared adult versus pediatric populations, expecting pediatric cases to be rare but with different profiles.
  • Outcomes assessed using Glasgow Outcome Scale at approximately six months post-DC.
  • Statistical analyses included comparisons between centers and patient populations, with multivariable regression for outcome predictors.

High-yield

A -year multicenter Swedish cohort study of decompressive craniectomy for traumatic brain injury reveals substantial variation in practice patterns across centers, with complication rates and outcomes potentially influenced by these differences.

Clinical context

Decompressive craniectomy (DC) for traumatic brain injury (TBI) is controversial, with RCTs providing conflicting evidence about timing and outcomes. Real-world practice patterns and their relationship to outcomes are poorly characterized.

Limitations

Retrospective observational design limits causal inference about treatment effects.Potential for selection bias and unmeasured confounding variables across centers.

Methodological critique

Retrospective design with potential for selection bias limits causal conclusions about DC effectiveness.

Teaching pearl

When considering DC for refractory intracranial hypertension, remember that real-world practice varies significantly between centers—what works in one ICU's workflow may not translate directly to yours, and outcomes may depend as much on local protocols as on patient factors.

Funding and COI

Not stated

Basic Science

The [C]AZ PET radioligand shows promise for selective PARP imaging in brain tumors, but remains a research tool requiring further validation before clinical implementation.

OThe [11C]AZ14193391 PET radioligand shows potential for selective PARP1 imaging in glioblastoma, but its current status as a research tool necessitates further validation before clinical use.

Low evidencePractice changing

Study snapshot

Design

Basic science translational study

Population

Non-human primates, healthy volunteers, and patients with glioblastoma

Intervention

[11C]AZ14193391 PET imaging

Comparator

None

Primary outcome

Demonstration of subtype selective PARP1 binding in brain tissue

Why it matters

Previous PARP1 imaging agents lacked subtype selectivity and had limited application in brain imaging, particularly for neuro-oncology. This study introduces a novel PET radioligand that enables selective imaging of PARP1 binding in the human brain, including glioblastoma tumors. While this doesn't change clinical practice immediately, it provides a crucial tool for future research in diagnosis, treatment monitoring, and drug development for brain tumors.

Practice change

Confirms current practice as this remains a research tool; could consider future applications in clinical trials for PARP inhibitor therapies in neuro-oncology.

More context

Key details

  • Basic science study evaluating a novel PARP1 inhibitor labeled with carbon-11 as a PET radioligand
  • Translational approach spanning in vitro studies, non-human primate PET, healthy volunteer PET, and patient imaging
  • PARP1 is a key enzyme in DNA damage repair and established cancer drug target
  • Previous PARP imaging lacked subtype selectivity, particularly for brain applications
  • Study demonstrates feasibility of imaging PARP1 in human brain for the first time
  • Potential applications in neuro-oncology research, diagnosis, and drug development

High-yield

The novel PET radioligand [C]AZ enables subtype-selective imaging of PARP binding in the human brain, demonstrating robust binding in healthy tissue and elevated contrast in glioblastoma tumors.

Clinical context

PARP1 is a key enzyme in DNA damage repair and an established target for cancer treatment. Non-invasive imaging of PARP in brain has been an unmet need in neuro-oncology.

Limitations

Preclinical/early clinical study with limited patient numbers in the glioblastoma cohortNo direct comparison to existing PARP imaging agents or clinical outcomes data

Methodological critique

The translational approach from animals to humans strengthens the findings, but the early-phase design limits clinical conclusions.

Teaching pearl

When evaluating novel imaging agents, look for translational validation across species—this study's progression from non-human primates to healthy volunteers to patients strengthens its potential clinical relevance.

Funding and COI

Not stated

From the Preprint Wire

Why it matters

This preprint explores how incorporating Parkinson's disease-specific neural mechanisms into the validation of digital mobility outcomes (DMOs) could improve their convergent validity with motor severity scales, which is crucial for regulatory approval and clinical use in monitoring mobility decline. For neurosurgeons involved in deep brain stimulation or other neuromodulatory treatments for PD, better-validated DMOs could enhance pre- and post-operative assessment and long-term management, though this work is preliminary and has not undergone peer review.

More context

Key details

  • Principal component analysis of task-based functional neuroimaging data identified a measure linked to PD motor network dysfunction.
  • Deep learning optimization showed strong DMO-severity convergence (ρ=|0.81-0.82|) across contexts, with reduced Attractor Complexity Index (indicating greater dysfunction) enhancing this convergence (rrb=|0.63-0.29|).
  • The authors propose that integrating mechanistic evidence into DMO validation could improve convergent and construct validity, supporting regulatory approval and clinical adoption.

Phase 2a trial of SARS-CoV-2 monoclonal antibody AER002 shows no efficacy in Long COVID

Preprint • From the Preprint Wire • medrxiv • 2026-03-09

Why it matters

This preprint reports a randomized controlled trial of a monoclonal antibody targeting persistent SARS-CoV-2 in Long COVID, a condition neurosurgeons may encounter in patients with post-viral neurological sequelae. As an unreviewed preprint, it offers early insight into potential therapeutic approaches for a debilitating condition with limited treatment options, but requires cautious interpretation pending peer review.

More context

Key details

  • No significant differences in PROMIS-29 Physical Health Summary Score (primary endpoint) or secondary measures of physical, cognitive, and neurologic function between treatment and placebo arms.
  • Post-hoc analysis indicated participants with lower baseline SARS-CoV-2 antibody levels and higher drug exposure reported greater perceived benefit on the Patient Global Impression of Change scale.
  • Findings may inform future trial design, such as targeting specific patient subgroups or optimizing dosing, for monoclonal antibodies in Long COVID.

Policy & Systems / Advocacy

Advocacy and Health Policy News

News • Policy & Systems / Advocacy • AANS • 2026-03-21

Why it matters

See source for full details on this policy development.