Neurosurgery

Spinal cord injury (SCI) is a devastating neurological injury that results in the profound loss of voluntary motor function and marked reduction in quality of life. Rehabilitation remains as the standard of care for recovery after SCI; however, it often falls short in recovering meaningful motor function. Spinal cord stimulation (SCS) has emerged as a promising neurostimulation approach to fill this gap and recover lost voluntary motor function. Two main approaches of SCS have been designed and implemented for human use: epidural and transcutaneous SCS. Over the last two decades, several clinical studies have shown convincing evidence that both epidural and transcutaneous SCS can be used in conjunction with rehabilitation to improve motor function of individuals after SCI. Yet fundamental clinical questions remain unanswered: when should clinicians choose epidural or transcutaneous SCS, which technique provides the most durable outcomes, and for whom is each therapy best? Without these answers, widespread and meaningful adoption of either approach into clinical practice will remain limited. To address these questions, in this Review, we define the distinct therapeutic goals, intended use cases, clinical parameters, and responder profiles for both epidural and transcutaneous SCS to guide their eventual adoption into clinical practice. We found that indeed epidural and transcutaneous SCS serve distinct therapeutic roles. Epidural SCS is designed as an assistive therapy that can restore muscle activity and single joint movements immediately within one week of implantation, while transcutaneous SCS is designed as a long-term therapeutic device with cumulative functional gains observed over treatment periods of up to 18 weeks. Lastly, epidural SCS produced benefits for all participants (AIS A-D) despite the extent of their injury, while transcutaneous SCS only consistently benefits individuals with incomplete motor injuries (AIS C-D).

Background: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains associated with high mortality and severe disability, yet contemporary outcomes may differ substantially from historical estimates. We performed a systematic review and meta-analysis to evaluate long-term outcomes after poor-grade aSAH and assess temporal, geographic, and treatment-related factors associated with prognosis. Methods: PubMed/MEDLINE, Embase, Cochrane Central, Scopus, and Google Scholar were searched from inception through March 2026. Studies enrolling consecutive adults with poor-grade aSAH (World Federation of Neurosurgical Societies grades IV-V, Hunt-Hess grades IV-V, or equivalent) reporting mortality and/or functional outcomes at 3 months were included. To minimize survivorship bias, studies excluding untreated patients or patients dying before aneurysm treatment were excluded. Random-effects meta-analyses of proportions were performed using generalized linear mixed models. Prespecified subgroup analyses and exploratory meta-regression analyses evaluated temporal, geographic, and treatment-related factors associated with outcomes. Results: Forty-two studies including 7,726 patients from 16 countries across 4 continents were included. The pooled favorable functional outcome rate was 27.2% (95% CI, 23.9%-30.8%), whereas pooled overall mortality was 53.3% (95% CI, 49.0%-57.5%). Pre- and post-treatment mortality were 25.9% and 33.9%, respectively. Aneurysm treatment rate was 72.0% (95% CI, 65.6%-77.7%). Favorable outcomes improved over time from 13.5% (95% CI, 7.0%-24.3%) in the 1980s to 33.7% in the 1990s but plateaued thereafter. In exploratory meta-regression analyses, higher aneurysm treatment rates were independently associated with improved favorable functional outcome (0.134 log-odds increase per 10% increase in treatment rate; p = 0.01) and lower mortality (-0.224 log-odds per 10% increase in treatment rate; p < .001). Publication year was associated with lower mortality (p = 0.03) but not favorable outcome. Geographic region, country income group, and the proportion of grade V patients were not independently associated with outcomes. Conclusions: Mortality after poor-grade aSAH remains high, but approximately one-third of patients achieved favorable outcome. Higher aneurysm treatment rates were independently associated with improved functional outcomes and lower mortality.

Effective modulation of cortical-subcortical motor circuits is essential for post-stroke recovery, yet progress has been constrained by the absence of non-invasive tools capable of precisely targeting deep brain structures. In this pilot proof of concept study, we explored the feasibility and preliminary neuromodulatory effects of a 12-minute transcranial focused ultrasound (tFUS) protocol targeting the ipsilesional ventral lateral posterior (VLp) thalamus in ischemic stroke patients. Six individuals with upper-limb hemiparesis received individualized, neuronavigation-guided tFUS. Sensorimotor tracking performance improved signiffcantly after a single session. Concurrent EEG revealed reversible beta-power suppression over the ipsilesional motor cortex and enhanced theta-phase synchronization in frontoparietal networks, both of which were associated with behavioral gains. Resting-state fMRI indicated rebalancing of inter-hemispheric motor networks. These preliminary ffndings suggest that thalamic tFUS can modulate both local and networklevel neural activity and is associated with immediate functional improvement, highlighting its potential as a feasible neuromodulation approach for deep motor circuit engagement in post-stroke rehabilitation.

Purpose DICER1-mutant primary intracranial sarcoma (PIS-DICER1) is a rare, recently defined high-grade intracranial tumor. This systematic review and meta-analysis aimed to comprehensively investigate its imaging characteristics to improve preoperative diagnostic accuracy and facilitate differential diagnosis. Methods A systematic literature search was conducted in PubMed and Web of Science for studies published up to December 31, 2025. Original studies with pathologically and molecularly confirmed PIS-DICER1 and detailed imaging data were included. Imaging features, including tumor location, margin definition, meningeal contact, intratumoral hemorrhage, enhancement pattern, cystic components, peritumoral edema, and advanced imaging findings (SWI, DWI, MRS, PWI), were extracted and analyzed. Pooled proportions with 95% confidence intervals (CIs) were calculated using a random-effects model. Results Twenty-four studies comprising 110 patients with detailed imaging data were included. The pooled mean age was 18.6 years (95% CI: 15.2-22.0), with a slight female predominance (53.3%, 96/180). Tumors were predominantly supratentorial (87%, 95% CI: 80%-93%). Substantial heterogeneity was observed across studies for location (I2 = 78%). Intratumoral hemorrhage was observed in 85% (95% CI: 78%-91%). Contrast-enhanced MRI demonstrated heterogeneous enhancement in all cases (100%, 95% CI: 96%-100%). Due to sparse data, advanced MRI features could not be quantitatively synthesized, underscoring a critical knowledge gap. Conclusion PIS-DICER1 exhibits imaging features including supratentorial location, intratumoral hemorrhage, heterogeneous enhancement, well-defined margins, and meningeal involvement. These features, particularly in children and young adults with hemorrhagic supratentorial masses, should prompt differential diagnosis. Definitive diagnosis requires molecular confirmation, but recognition of these characteristics facilitates diagnosis and preoperative planning.

Background: Deep brain stimulation (DBS) is a widely used therapy for neurologic and psychiatric disorders. Conventional DBS delivers highly regular stimulation patterns that suppress pathological activity but can induce stimulation-related side effects, limiting the therapeutic window. Introducing controlled temporal variability through stochastic pulse timing may represent an alternative programming dimension to improve tolerability while preserving clinical benefit. Methods: An adult in their 60's with bilateral Vim DBS underwent evaluation of tonic, pink-noise, and white-noise stimulation patterns delivered through his chronically implanted Boston Scientific Genus system using the Chronos research platform. We assessed tremor and stimulation-induced side effects using accelerometry, spiral drawing tasks, standardized speech recordings, and patient-reported paresthesias. Results: Pink noise stimulation preserved meaningful tremor suppression while improving tolerability compared with conventional tonic 130 Hz stimulation. Under tonic stimulation, dysarthria and paresthesias were prominent at 2.0 mA, narrowing the usable therapeutic window. In contrast, pink noise maintained tremor control across the same amplitude range with reduced side-effect burden. White noise stimulation demonstrated intermediate effects, providing improved tolerability relative to tonic stimulation but less tremor suppression than pink noise. Findings were consistent across accelerometry and functional drawing tasks. Conclusion: This study provides first-in-human evidence that temporally structured stochastic pulse timing can preserve therapeutic benefit while expanding the tolerable stimulation range relative to tonic DBS. These findings suggest that temporal structure represents a clinically meaningful programming dimension that may broaden the DBS therapeutic window using software based updates to existing hardware. Further evaluation in larger cohorts is warranted

ABSTRACT Background: Randomized trials have shown comparable reperfusion rates among stent-retriever, contact-aspiration, and combined thrombectomy techniques. We aim to evaluate the association between operator device-selection preference and procedural performance metrics. Methods: Retrospective analysis of prospective data from a comprehensive stroke center. Preferred technique was defined as a technique used in >50% of an operator's thrombectomies. Main exposure: proportion of usage of a given technique by operators in a certain period; primary endpoint: rate of first-pass effect(FPE). Results: 1405 patients fit inclusion criteria. The first time period(2019- mid 2022/n=839) included 4 operators(3 experienced/1 starting practice), with CoT being overall used in 58.9%, SR in 24.4%, and CA in 16.7%. The second( mid 2022-2024/n=566) included 4 total operators(2 experienced/2 starting), with CA reaching 48.2%, CoT 39.8% and SR 12.0%. The distribution of techniques varied between intra-/inter-operators and most(75.0%) had a preferred technique. The technique with the highest FPE rate was never the most used technique. The chances of operators achieving FPE were not dependent on the previous cumulative success for a given technique. Increasing case volume was associated with higher FPE on average, but the learning rate differed by technique and only contact aspiration had a significant learning curve. The parenchymal hemorrhage rates were comparable for individual operators regardless of technique. Conclusion: Neurointerventionists tended to rely on a preferred technique, which did not necessarily lead to superior reperfusion outcomes. The cumulative success with a given technique did not increase the likelihood of attaining FPE in subsequent cases. Among new operators, a learning curve for contact aspiration was observed.

Responsive neurostimulation (RNS) is an implanted device that delivers direct brain stimulation for drug-resistant focal epilepsy. Individual responses are highly variable, and no validated framework exists to predict outcome or guide lead placement before implantation. We hypothesized that this variability is partly explained by lead placement in relation to patterns of functional connectivity in brain networks. Fourty-nine patients with drug-resistant focal epilepsy who underwent pre-implantation intracranial EEG (iEEG) and RNS implantation across three independent epilepsy centers were retrospectively studied. We developed a composite functional connectivity score, based on simple Spearman correlation, combining the standard deviation and kurtosis of interictal iEEG connectivity distributions to predict the response outcome in a training cohort (HUP, n=18) and validated in two independent cohorts (NYU, n=17; UCSF, n=14). We accounted for a spatial mismatch between iEEG and RNS electrodes with a distance-based correction. The score was extended to generate patient-specific 3D maps of predicted RNS efficacy across 200 simulated, or virtual RNS, lead configurations. Accuracy of the score in predicting clinical outcome was 72% at the group level, 61% at the individual patient level, and, after distance-based optimization, 100% in patients with RNS electrodes placed close to location of iEEG electrodes. Applied to the validation cohort, the same score reached 68% accuracy (71% balanced accuracy, 55% sensitivity, 88% specificity). The spatial combination of the scores at different SEEG contacts localization gives a spatial score for each patient. Responders showed significantly higher spatial scores than non-responders, supporting that actual RNS lead placement in responders was located in map-identified favorable regions. Interictal iEEG functional connectivity predicts individual RNS response across independent epilepsy centers, and patient-specific 3D maps derived from this biomarker could prospectively guide lead implantation toward favorable network regions, opening a promising avenue toward network-informed RNS surgical planning.

Background The optimal management of acute ischemic stroke caused by medium vessel occlusion (MeVO) remains uncertain. Recent randomized trials have failed to demonstrate a clear benefit of endovascular therapy in this population, whereas intra-arterial thrombolysis (IAT) has emerged as a biologically plausible alternative. However, prospective evidence supporting IAT in MeVO is lacking, and the optimal dosing strategy for stand-alone IAT remains undefined. Aim To preliminarily evaluate the efficacy and safety of intra-arterial tenecteplase (IA-TNK) plus standard medical therapy (SMT) compared with SMT alone in patients with acute MeVO stroke, and to explore a stepwise IA-TNK dosing strategy. Design The MeVO-TNK trial is a multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE), exploratory phase II study. A total of 60 participants with imaging-confirmed MeVO will be randomized 1:1 to receive either IA-TNK plus SMT or SMT alone. Participants presenting beyond 6 hours from symptom onset must demonstrate salvageable penumbral tissue on advanced imaging. Those assigned to the intervention group will receive up to two intra-arterial boluses of tenecteplase (0.0625 mg/kg per bolus), with the second bolus administered based on angiographic assessment of reperfusion and safety. Outcomes The primary efficacy outcome is final infarct volume measured at 72{+/-}24 hours after randomization. Secondary efficacy outcomes include the proportions of patients achieving modified Rankin Scale (mRS) scores of 0-1, 0-2 and 0-3 at 90 days, a shift analysis of the mRS distribution at 90 days, early neurological deterioration, and National Institutes of Health Stroke Scale score at 7 days or discharge. The primary safety outcome is symptomatic intracranial hemorrhage within 24 hours. Conclusions This trial will provide preliminary evidence on the biological efficacy, reperfusion potential and safety of stand-alone IA-TNK for acute MeVO stroke, helping to address an important evidence gap and inform the design of future confirmatory studies.

Myofascial pain syndrome (MPS) is a major cause of chronic neck pain, with tissue ischemia implicated as a contributing factor. This prospective, single-arm interventional study evaluated the analgesic effect of ultrasound-guided fascia hydrorelease (US-FHR) performed around arteries supplying the neck in patients with chronic neck MPS. Thirteen adults (median age 53.0 years; 38.5% female) underwent US-FHR targeting the perivascular fascia of either the transverse cervical or dorsal scapular artery using 2 mL of normal saline. Pain intensity was assessed by visual analog scale (VAS) at rest and during movement; disability by the 5-item Pain Disability Index, Japanese version (PDI-5-J); and arterial blood flow volume before and after the procedure. The primary outcome, pain VAS during movement, decreased from 49.0 mm (interquartile range [IQR], 44.5-64.0) at baseline to 22.0 mm (IQR, 14.5-31.5) at 15 min and 22.0 mm (IQR, 14.0-34.0) at 1 week (Hodges&-Lehmann median difference, 30.5 mm [95% CI, 24.5 to 36.5] and 28.5 mm [95% CI, 18.5 to 37.0]; both P < 0.001). Pain VAS at rest improved from 21.0 mm (IQR, 13.0-43.5) to 8.0 mm at 15 min and 1 week (median difference, 14.5 mm [95% CI, 9.0 to 24.0; P = 0.001] and 13.5 mm [95% CI, 6.0 to 21.0; P = 0.007]). PDI-5-J decreased from 17.0 (IQR, 10.5-23.0) to 13.0 (IQR, 4.0-17.5) at 1 week (median difference, 5 [95% CI, 2 to 8; P = 0.004]). Blood flow volume increased from 11.2 mL/min (IQR, 4.5-14.4) to 17.2 mL/min (IQR, 6.1-23.7) immediately after US-FHR (median difference, +4.1 mL/min [95% CI, +2.5 to +8.9; P = 0.001]), although transient. One patient experienced transient bleeding that was promptly controlled. In this single-arm feasibility study, US-FHR around the target artery was simple and safe to perform and was associated with reduced neck pain. Because the study lacked a control group, these preliminary findings should be regarded as hypothesis-generating and require confirmation in controlled trials; they may also inform the future evaluation of MPS in other anatomical regions. Trial registration: UMIN Clinical Trials Registry, UMIN000053612.

Background: The Cilostazol Albumin Treatment in Subarachnoid Hemorrhage (CATS) trial evaluates eight active cilostazol-human albumin regimens plus control in patients with aneurysmal subarachnoid hemorrhage. We summarized the rationale for the primary statistical design, compared alternative Phase II methodologies, and evaluated reduced-arm sensitivity scenarios. Methods: The binary primary endpoint is Common Data Elements-defined delayed cerebral ischemia within 14 days after randomization. The selected design is Bayesian adaptive, with a burn-in phase, response-adaptive randomization among active arms while maintaining fixed control allocation, four interim analyses, early stopping for expected success or futility, and a two-dimensional normal dynamic linear model. Primary operating characteristics were obtained from 1,000 virtual trials per scenario using Fixed and Adaptive Clinical Trial Simulator version 7.0.0. Exploratory simulations evaluated six-, four-, and two-active-arm configurations and simplified alternative designs. Results: Compared with fixed equal allocation, the Bayesian adaptive design preserved an approximately 10% false-success probability under the global null while improving probability of success and efficiency in clinically relevant scenarios. Under the Realistic scenario, probability of success increased from 0.61 to 0.86, expected sample size decreased from 400 to 308, and expected duration decreased from 235 to 187 weeks. Under common thresholds, null probability of success was 0.098 for the full anchor and 0.073 for Reduced-6; Reduced-6 probabilities of success were 0.774 and 0.765 in the Realistic and Realistic2 scenarios. However, Reduced-6 omitted two monotherapy anchors and was less robust in Backwards2. In the comparator simulation, the selected design had probability of success of 0.858 and expected sample size of 308.3 under the Realistic scenario, compared with 0.624 to 0.845 and approximately 352 to 400 for simplified comparators. Conclusions: For identifying the most promising cilostazol-human albumin regimen for Phase III rather than confirming efficacy, the Bayesian response-adaptive design with two-dimensional normal dynamic linear model borrowing is more efficient and better aligned than simplified comparators. The full nine-arm design remains preferable because it preserves the complete therapeutic discovery space and is more robust to misspecified or non-smooth response surfaces.

Background and Purpose-Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular event, with delayed cerebral ischemia (DCI) representing its most feared complication. High-altitude environments induce profound cerebrovascular adaptations, yet no study has systematically examined aSAH outcomes in chronically hypoxic populations. We characterized clinical features and identified DCI predictors among aSAH patients on the Tibetan Plateau. Methods-This single-center retrospective cohort included 256 consecutive aSAH patients admitted at a tertiary neurosurgical center in Tibet (altitude 2,330-4,920 m) between 2013 and 2015. The primary outcome was DCI per consensus criteria. Multivariable logistic regression identified independent predictors; receiver operating characteristic analysis evaluated model performance. Altitude and hemoglobin were specifically evaluated as altitude-related risk factors. Results-DCI occurred in 26 patients (10.2%). In-hospital mortality was 1.6%. Most patients presented with good-grade aSAH (Hunt-Hess I-II, 73.0%; Fisher I-II, 73.1%). On multivariable analysis, only Fisher grade independently predicted DCI (odds ratio, 3.63 [95% CI, 1.14-11.52]; P=0.029). Neither altitude (P=0.697) nor hemoglobin concentration (P=0.858) was associated with DCI risk. The predictive model achieved an area under the curve of 0.812. At 1-year follow-up, 77.8% achieved favorable functional outcomes (modified Rankin Scale 0-2). Conclusions-Fisher grade is the sole independent predictor of DCI in high-altitude aSAH patients, while chronic hypoxia and compensatory hemoglobin elevation do not significantly modify DCI risk. Established sea-level prognostic frameworks remain valid in high-altitude settings, supporting their continued use for clinical risk stratification. Keywords: aneurysmal subarachnoid hemorrhage; high altitude; delayed cerebral ischemia; Fisher grade; Tibetan Plateau; prognosis

Background: Stroke often causes Upper Limb (UL) functional impairments. The Primary Somatosensory Cortex (S1) plays an important role in motor learning. Repetitive Transcranial Magnetic Stimulation (rTMS) over S1 could enhance UL recovery. We aimed to explore its preliminary effects on UL motor activity and function post-stroke. Methods: An exploratory parallel-group randomized controlled trial in people with chronic stroke (>3 months) and moderate hemiparesis was conducted. Participants received 20 sessions of active or sham 5Hz rTMS over affected S1, with Robot-Assisted Therapy and Task-Oriented Training, 5 days/week for 4 weeks. The primary endpoint was UL motor activity (Action Research Arm Test, ARAT). Secondary measures were the UL Fugl-Meyer Assessment (UL-FMA) and sensory outcomes. Results: The baseline-adjusted mean difference (MD) in ARAT was 4.05 points [0.78, 7.33], favoring active stimulation. Secondary measures did not favor active stimulation (UL-FMA: MD = 2.62 [-1.51, 6.76]; sensory outcomes showed no between-group differences). Conclusion: High-frequency rTMS over S1 may enhance UL motor activity (ARAT), but no evidence for motor impairment (UL-FMA) or sensory domains was found. Compensation rather than restoration may underlie this improvement. Stimulation targets should match the intended recovery domain, although larger trials are needed to confirm these preliminary findings.

Abstract Importance: Drug-resistant focal epilepsy affects approximately 30% of children with epilepsy and carries excess mortality, impaired neurodevelopment, and substantial costs. Epilepsy surgery is underutilized despite proven superiority over medical management. MRI-guided laser interstitial thermal therapy (MRgLITT) is a minimally invasive alternative to open resection, but comparative evidence to guide procedure selection is limited. Objective: To estimate lifetime outcomes and costs of epilepsy surgery versus medical management for pediatric drug-resistant focal epilepsy, and to provide etiology-informed guidance for choosing between open resection and MRgLITT. Design: Markov decision analytic model with a lifetime horizon, parameterized from published systematic reviews, meta-analyses, and cohort studies. Setting: United States, healthcare payer perspective. Participants: Hypothetical cohort of 10-year-old children with drug-resistant focal epilepsy and a seizure focus <3 cm3. Interventions: Best medical management, open resective surgery, or MRgLITT. Main Outcomes and Measures: Quality-adjusted life years (QALYs), lifetime direct medical costs, incremental cost-effectiveness ratios, and lifetime survival. Seizure outcomes were classified as seizure freedom or disabling seizures. Cost-effectiveness was assessed at $100,000/QALY. Results: Both surgical strategies were associated with a 4.6-year survival advantage, 3.6 additional lifetime QALYs, and lower costs than medical management. MRgLITT yielded 22.64 QALYs at $120,943; open resection yielded 22.62 QALYs at $121,650; medical management yielded 19.00 QALYs at $127,471. The difference between MRgLITT and open resection was 0.015 QALYs, reflecting near-equivalent effectiveness; in probabilistic sensitivity analysis, MRgLITT was optimal in 50.3% of iterations and open resection in 38.3%, with neither showing clear superiority. Etiology-specific analyses favored MRgLITT for focal cortical dysplasia and mesial temporal sclerosis, and open resection for tumor-related and cavernoma-related epilepsy. Conclusions and Relevance: Both open resection and MRgLITT were associated with substantially better lifetime outcomes and lower costs than medical management, supporting early surgical referral. Overall effectiveness between surgical approaches was clinically similar, with neither demonstrating clear superiority; the model suggests epilepsy etiology, rather than expected effectiveness alone, should guide procedure selection between MRgLITT and open resection.

BACKGROUND Accurate differential diagnosis of complex neurological disorders remains challenging due to overlapping clinical features and heterogeneous disease presentations. Although large language models (LLMs) show promise in clinical reasoning, prior studies benchmark performance against clinician consensus rather than biological ground truth. A neuropathologically confirmed benchmark dataset for evaluating diagnostic AI in neurology is currently lacking. METHODS We introduce NeuroBench, a curated benchmark of complex neurological cases with neuropathologically confirmed gold-standard diagnoses, and DIAGNO, a confidence-aware LLM-based system for neurological diagnosis. NeuroBench comprises 203 retrospective case summaries from the Massachusetts General Hospital Brain Cutting Conference with corresponding autopsy-confirmed diagnoses. DIAGNO generated top-3 differential diagnoses, employing retrieval-augmented generation (RAG) for lower-confidence cases. Performance was assessed by three independent blinded adjudicators who evaluated both DIAGNO and neurologists against neuropathological ground truth. RESULTS NeuroBench encompassed 79 unique neuropathological diagnoses, spanning conditions including cerebrovascular disease, brain tumors, neurological infections, and various neurodegenerative and inflammatory disorders. DIAGNO matched or outperformed neurologists in top-3 accuracy (0.67 versus 0.63) and taxonomy-level accuracy (0.74 versus 0.66). In cases of disagreement, DIAGNO was more often correct than neurologists (29 versus 19 cases). Diagnostic concordance between DIAGNO and neurologists was high (90% agreement in top-3 predictions), even when both were incorrect, suggesting strong alignment in diagnostic reasoning. On NeuroBench, DIAGNO also outperformed GPT-4o baseline and DeepSeek R1 across all top-k accuracy metrics. In a real-world evaluation on eight complex cases with differentials from Mass General Brigham, neurologists rated DIAGNO's reasoning favorably (mean 4.03/5) across multiple dimensions of clinical utility and safety. CONCLUSIONS NeuroBench establishes neuropathological confirmation as the appropriate standard for evaluating diagnostic AI in neurology, moving beyond clinician-referenced benchmarking to define the ceiling of diagnostic accuracy. Evaluated against this standard, DIAGNO achieved expert-level diagnostic performance and received favorable clinician ratings in real-world applications, supporting its potential as a clinical decision-support tool in neurology.

Background: Stroke remains a leading cause of death and long-term disability worldwide, and a substantial proportion of patients experience incomplete recovery despite modern reperfusion strategies. Minocycline is an inexpensive, widely available agent with anti-inflammatory, anti-apoptotic and matrix metalloproteinase-modulating properties that make it an attractive neuroprotective adjunct in acute ischemic stroke or intracerebral hemorrhage. Despite new evidence for minocycline use, its needed an updated quantitative synthesis focused on clinically meaningful outcomes. Methods: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of minocycline in adults with AIS and ICH. A total of 1,633 records were screened. A total of 11 studies comprising 2428 patients were included in the review dataset. Outcomes were analyzed including 90-day disability, neurological recovery, recurrent stroke, and composite vascular events (cardiovascular event, non-fatal stroke, and non-fatal MI). Results: Minocycline was associated with better 90-day neurological recovery, with a greater reduction in NIHSS score at 90 days (mean difference [MD] -2.17, 95% CI -2.68 to -1.65, moderate certainty) and lower functional disability at 90 days measured by mean modified Rankin Scale (mRS) score (MD -0.25, 95% CI -0.38 to -0.13, moderate certainty). Categoric functional outcomes also favored minocycline, including mRS 0-1 at 90 days (odds ratio [OR] 1.21, 95% CI 1.02 to 1.45, high certainty), while the effect for mRS 0-2 at 90 days was borderline (OR 1.21, 95% CI 1.00 to 1.47, moderate certainty). No significant difference was observed for stroke recurrence at 90 days (OR 1.13, 95% CI 0.78 to 1.64). Composite vascular events at 90 days also favored minocycline (OR 1.21, 95% CI 1.02 to 1.45). Conclusions: Minocycline appears to be a promising, low-cost adjunctive therapy for acute ischemic stroke and intracerebral hemorrhage with evidence of improved 90-day functional and neurological outcomes. These findings support prioritization of minocycline for confirmatory trials and highlight its relevance in stroke care and clinical practice.

Abstract: Background: Lacunar stroke is a common and disabling cerebrovascular disease. Small-vessel vasculopathy is thought to be the most common underlying cause, but this has only been identified on histopathology. 7T MRI allows small vessels to be seen in vivo. This study aimed to investigate rates of small vessel vasculopathy in lacunar stroke using 7T MRI. Methods: Patients with lacunar stroke at an Australian tertiary stroke centre were prospectively screened and recruited to the study. Patients underwent 7T MRI with T1, T2, time-of-flight (TOF), diffusion-weighted imaging (DWI) and susceptibility-weighted imaging (SWI) sequences. Images were interpreted by two blinded neuroradiologists. Results: The likely symptomatic perforator could be identified in 16/19 (84%) of cases. Amongst cases where the symptomatic perforator was observed, 14/16 (88%) of the symptomatic perforator vessels had focal stenosis consistent with steno-occlusive vasculopathy. There were 3/19 (16%) of cases with associated large artery vasculopathy. There were 7/16 (44%) cases where an occluded perforator was seen. The majority of patients had at least one vascular risk factor (15/19, 79%) and there were no cases where non-atherosclerotic vasculopathy was suspected. Conclusions: Lacunar stroke is commonly associated with small vessel vasculopathy, likely due to atherosclerosis, which can be identified in vivo with 7T MRI time-of-flight imaging.

Importance: The transition from medical school to residency forms a national training network, yet its large-scale structure and implications for trainee outcomes remain poorly characterized. Objective: To evaluate the US residency match as a network and assess how institutional position relates to residency placement, educational debt, and specialty choice. Design: Cross-sectional analysis of publicly reported 2025 residency match outcomes. Setting: 107 US MD-granting medical schools and 301 residency institutions with available match data. Participants: 14,616 US MD students matching into residency in 2025 (convenience sample). Exposure: Institutional position within the residency match network, quantified using PageRank network centrality. The relative strength of each school's graduating class was defined as the median centrality of residency destinations across graduates (placement score). Main Outcomes and Measures: Residency placement outcomes, mean medical school debt at graduation, and specialty choice (primary care vs surgical specialties) in relation to institutional position within the residency match network. Network-derived measures were also compared with NIH funding, residency reputation, and student selectivity. Results: Among 14,616 US MD students matched across 107 medical schools and 301 residency institutions (approximately 73.5% of total US MD cohort), network-derived measures of institutional influence closely aligned with benchmarks of institutional standing such as NIH funding, residency reputation, and student selectivity (Spearman's Rho; = 0.72-0.86; all p < .001). Graduate outcomes varied systematically across institutions. Graduates of highly connected medical schools were more likely to match into highly connected residency programs (87.3% for top-quintile vs 41.0% for bottom-quintile schools). Schools with higher placement scores had graduates with lower educational debt, reduced entry into primary care, and increased entry into surgical or competitive specialties. Compared with bottom-decile schools, top-decile schools (stratified by placement score) had 37% lower mean graduate debt, 24% lower primary care entry, and 75% higher surgical specialty entry. Higher educational debt was not associated with entry into higher-compensated specialties. Conclusions and Relevance: The residency match network reflects a hierarchical structure of institutional standing. Graduates of higher- and lower-positioned medical schools experience systematically different residency placement outcomes. These findings provide a population-level, behavior-based perspective on institutional influence and its relationship to training pathways.

Abstract Aims and scope Evidence from randomised controlled trials (RCTs) has transformed stroke care. There are no systematically collected data on the amount of public funding, critical to delivering trials, going into stroke RCTs. To understand the extent of stroke RCT funding by national and EU funding bodies across Europe, the European Stroke Organisation Trials Alliance (ESOTA) conducted a survey of its member nations. Methods This is an observational study of research funding in Europe. The ESOTA steering group sent an electronic survey to the leads of the 16 participating national networks from 14 countries. Structured survey questions included who the funding bodies were in each country, the number of RCT applications put forward for public national or EU funding, the number of successful and failed applications, and the amount of funding granted between 01/01/2022 and 31/12/2023. Results Responses were received from 13 of 14 participating countries. There was significant variation in the number of grant applications submitted by individual countries, ranging from 0-17 during the 24-month survey period. The median number of funded studies per country was 1 (IQR 3, range 0-9) representing a median success rate of 47.1 % (IQR 21.1-59.4%), with no RCTs granted joint European funding. Conclusions Our survey highlights significant inequities in stroke trial funding across Europe. Given the encouraging rate of successful applications overall, it is important for all member networks to submit proposals. This is particularly pertinent for multicentre trials, given the evolution of evidence base in stroke towards large trials, across diverse populations.

Background: Prognostication in large vessel occlusion (LVO) stroke remains challenging. Although several prognostic models exist, their comparison to clinician performance, human-model interaction, and specific sources of human bias remain poorly understood. Methods: Using pre-treatment clinical and CT data from the MR CLEAN trial (n=500), six neurologists predicted three-month modified Rankin Scale (mRS) scores for 40 patients, both unaided and assisted by a validated feature-based model (MR PREDICTS). Human performance was benchmarked against MR PREDICTS and a multimodal, interpretable deep learning (DL) approach using raw imaging data. We explicitly assessed neurologists? ability to estimate model-required imaging features and identified systematic human biases. Models were additionally validated in a larger MR CLEAN trial cohort (n=404). Results: For predicting the full mRS distribution, standalone models achieved good ordinal agreement (MR PREDICTS quadratic weighted kappa (QWK) 0.51 [0.24 to 0.70]; DL model 0.49 [0.25 to 0.67]), significantly outperforming unaided neurologists (QWK 0.27 [0.10, 0.42]). Neurologists showed systematic overoptimism, predicting lower mRS scores than observed. Furthermore, there was poor accuracy in extracting imaging features. Raters? ASPECTS predictions deviated by 3.4 points from the confirmed scores, and collateral score accuracy was 44.6%. However, for predicting binary mRS (0-2 vs. 3-6), accuracy was comparable between unaided neurologists (64.17% [55.42% to 72.92%]) and models (MR PREDICTS 67.50% [52.50% to 82.50%]; DL model 63.16% [47.37% to 78.95%]). Model-assistance modestly improved and harmonized neurologists? predictions (QWK 0.41 [0.22 to 0.55]; binary accuracy 68.75% [58.33% to 78.34%]. Model performance remained robust in the larger cohort. Conclusions: Multimodal prognostic models outperform clinicians in predicting the full range of mRS outcomes, while human error in imaging assessment and systematic optimism bias are primary drivers of prognostic inaccuracy. End-to-end DL models eliminate human-input variability and hold strong potential as an automated second opinion to support prognostication and decision-making in acute LVO stroke.

Introduction: Generative artificial intelligence (AI) can produce realistic clinical scenarios on demand and deliver immediate, individualized feedback, yet its use to teach ethical reasoning, rather than to address the ethics of AI itself, remains underexplored in interprofessional healthcare education. Aim: This pilot study examined how interprofessional healthcare students perceived an AI-enhanced, case-based platform designed to support ethical decision-making across physical therapy, occupational therapy, speech-language pathology, and audiology. Methods: Students enrolled in an interprofessional education course completed an online module of 20 instructor-vetted, AI-generated ethics cases and an optional post-activity survey of Likert-scale and open-ended items. Quantitative data were analyzed descriptively and qualitative responses were analyzed through content analysis. Results: Ten students responded. Within this small sample, perceptions of platform utility and usability were strongly positive, with all respondents agreeing that immediate feedback and scenario variety supported learning. Perceptions were more divided when the platform was compared directly with traditional classroom learning, and respondents identified pacing and auto-scrolling as usability concerns. Conclusions: These preliminary findings suggest AI-enhanced case-based platforms can engage students and support applied ethics learning but are best positioned to complement rather than replace traditional instruction. Findings are exploratory given the small, demographically limited sample.