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Neurosurgery

Ovid Technologies (Wolters Kluwer Health)

Preprints posted in the last 90 days, ranked by how well they match Neurosurgery's content profile, based on 11 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Epidural versus Transcutaneous Spinal Cord Stimulation for Motor Recovery after Spinal Cord Injury: A Comparative Analysis

Bhatia, S.; de Freitas, R. M.; Kanter, J. H.; Buell, T. J.; Okonkwo, D. O.; Pirondini, E.; Prat-Ortega, G.; Capogrosso, M.; Gerszten, P. C.

2026-06-24 rehabilitation medicine and physical therapy 10.64898/2026.06.22.26356277 medRxiv
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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).

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Vertebral Augmentation for Symptomatic Vertebral Hemangiomas: A Systematic Review and Meta-analysis of Pain Relief, Cement Leakage, and Recurrence

Fahim, F.; Javani, M.; Mohammad Moradi, F.; Mojtahedzadeh, A.; Hasheminejad, A.; Khorram, A.; Karimi, M.; Faramin Lashkarian, M.; Hosseini Nejad, A.; Eskandari, F.; Mohammadi, Z.; Rastegar, A.; Simabi, S.; Yazdanpanah, R.; Zali, A.

2026-08-21 neurology 10.64898/2026.08.18.26360715 medRxiv
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Background: Vertebroplasty and balloon kyphoplasty are used for symptomatic vertebral hemangiomas, although comparative evidence is limited. We summarized pain relief, cement leakage, and recurrence after vertebral augmentation and assessed whether direct comparison of the two techniques was feasible. Methods: Five databases were searched from inception to January 2, 2026, with an update on July 5, 2026. Because only one small cohort directly compared vertebroplasty with kyphoplasty, outcomes were pooled as single-arm proportions or, for early pain change, as a mean difference using random-effects models. Prespecified subgroup, sensitivity, small-study effect, and influence analyses were performed. Results: Forty-four studies were included: 33 case series, 10 cohort studies, and one randomized trial. Kyphoplasty-specific evidence comprised one dedicated series and one comparative cohort. Any cement leakage occurred in 10.5% of patients (14 studies; 95% CI 5.7-18.4%), while trim-and-fill gave an exploratory adjusted estimate of 20.4%. Early pain reduction averaged 5.13 points on a 0-10 scale (8 studies; 95% CI 4.48-5.77; I2=89.4%). Complete or near-complete pain relief occurred in 79.4% of patients (10 studies), and recurrence, progression, or retreatment occurred in 3.9% (13 studies). Symptomatic cement leakage was uncommon at 0.4%. Conclusion: The available literature, which is mainly retrospective and vertebroplasty-based, supports substantial pain relief with infrequent symptomatic complications. Kyphoplasty data remain insufficient for a reliable technique comparison. Prospective studies with standardized clinical and imaging outcomes are needed.

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Impact of Operator Technique Preference on Thrombectomy Reperfusion Outcomes

Yelam, T.; Martins, P. N.; Dolia, J.; Batista dos Reis, S.; Grossberg, J. A.; Pabaney, A. H.; G Nogueira, R.; Al-Bayati, A. R.; Haussen, D. C.

2026-07-04 neurology 10.64898/2026.07.01.26357084 medRxiv
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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.

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Temporal and Geographic Variation in Outcomes After Poor-Grade Aneurysmal Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis

de Oliveira Manoel, A. L.; Msheik, A.; Zampieri, F. G.; Peralta, R.; Al Rumaihi, G.; Al-Thani, H.; Suarez, J. I.

2026-07-02 neurology 10.64898/2026.06.29.26356892 medRxiv
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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.

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Machine learning-based neuroimaging for prediction of deep brain stimulation outcomes in movement disorders: Systematic review and meta-analysis

Golzarian, M.-J.; Rajai, S.; Hajiesmailpoor, Z.; Aziza, Z.; Alikhany, A.; Moshayedi, P.

2026-07-23 neurology 10.64898/2026.07.22.26358674 medRxiv
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Abstract Background: Deep Brain Stimulation (DBS) surgery is a treatment of choice for movement disorders, and utilizes an implanted electrical pulse generator that administers electrical stimulation to designated brain regions responsible for motor control. The preoperative identification of effective predictive factors is of utmost importance for appropriate patient selection. In this study, we evaluate the potential of machine learning-based neuroimaging for predicting DBS outcomes. (PROSPERO Registration: CRD420261279318) Method: Following the PRISMA statement, eligible studies were selected through searching three databases (PubMed, Scopus, Web of Science) on November 6, 2025. Methodological quality was assessed using the PROBAST+AI tool. Random-effects models pooled discrimination performance (AUC). Heterogeneity was investigated using meta-regressions for age and gender alongside subgroup analysis by type of algorithm. Publication bias was assessed using Egger regression test. Results: Twenty studies were included in the analysis. Most investigations focused on PD, STN-DBS, and postoperative motor improvement, while a smaller number assessed neuropsychiatric outcomes. Overall, the pooled discrimination for models predicting motor outcomes showed an AUC of 0.86, and the pooled models for delirium showed an AUC of 0.87. Regarding the risk of bias assessment, seven studies were classified as low risk, while thirteen were identified as high risk. Conclusion: Machine learning-based neuroimaging shows promising potential for preoperative prediction of DBS outcomes. However, the current literature is characterized by a persistent gap between encouraging discrimination and reliable clinical readiness. The main weakness of the field lies in analytical rigor and generalizability. These models should currently only be considered as promising research tools.

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Corticospinal tract risk modifies motor recovery after minimally invasive surgery for intracerebral hemorrhage: a secondary analysis of MISTIE-III

Murray, O. N.; Jenkins, D.; Walborn, N.; Patel, H. C.; Harston, G. W.; Cootes, T. F.; Klijn, C. J. M.; Ziai, W. C.; Hanley, D. F.; Hammerbeck, U.; Parry-Jones, A. R.

2026-06-11 neurology 10.64898/2026.06.10.26354920 medRxiv
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Objective: Outcome after surgical hematoma evacuation for intracerebral hemorrhage (ICH) depends on hematoma location. As corticospinal tract (CST) integrity affects motor recovery after stroke, we hypothesized that CST integrity drives heterogeneity in surgical outcomes and investigated this in a secondary analysis of MISTIE-III participants. Methods: Risk of CST injury was categorized into four levels, based on the interaction between the CST, the hematoma, and perihematomal edema (PHE) on automatically segmented stability CT: no risk, PHE infiltration, hematoma infiltration, and complete interruption of the CST. Associations with outcome were tested using multivariable linear regression for motor National Institutes of Health Stroke Scale (NIHSS) at day 180 and ordinal regression for modified Rankin Scale (mRS) at day 365, introducing an interaction term between CST risk and treatment group. Results: Day 180 motor NIHSS was significantly lower for 'no risk' ({beta}:-3.77, [95% confidence interval [CI]: -5.8 to -1.70], p=0.0003) and 'PHE infiltration' ({beta}:-2.3, [95%CI: -3.5 to -1.1]; p=0.0002) vs. 'complete interruption'. Surgery was associated with lower Day 180 motor NIHSS in participants with hematoma infiltration ({beta}:-2.07, [95%CI: -3.8 to -0.4], p=0.016). Compared to complete interruption, 'no risk' (adjusted odds ratio [aOR]:0.27, [95%CI: 0.10 to 0.74], p=0.01) and 'PHE infiltration' (aOR:0.41, [95%CI: 0.23 to 0.74]; p=0.003) were associated with lower odds of unfavorable day 365 mRS. Surgery was associated with lower mRS in participants with no risk (aOR:0.23, [95%CI: 0.05 to 0.97, p=0.045). Interpretation: Increasing CST risk is associated with worse motor recovery (day 180) and disability (day 365). CST risk modifies the effect of the MISTIE-III procedure on motor recovery and disability.

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Transauricular vagus nerve stimulation for aneurysmal subarachnoid haemorrhage: a pilot randomised controlled trial

Myers, M.; Robson, F.; Baig, S.; Kular, S.; Aziz, M.; Burchi, E.; Battacharyya, D.; Li, S.; Majid, A.; Ali, A. N.

2026-08-31 neurology 10.64898/2026.08.25.26361366 medRxiv
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Background: Aneurysmal subarachnoid haemorrhage (aSAH) is frequently complicated by delayed cerebral ischaemia (DCI), for which current therapies incompletely target the underlying multifactorial pathophysiology. Transauricular vagus nerve stimulation (taVNS) modulates inflammatory, vasoactive and autonomic pathways and may attenuate secondary brain injury after aSAH. Methods: We conducted a prospective, single-centre, single-blind, randomised, sham-controlled pilot trial in adults within 5 days of aneurysm securing for non-traumatic aSAH. Participants were allocated 1:1 to active taVNS (left tragus) or sham (left earlobe) using a portable device delivered for 45 minutes twice daily over 5 days. Primary outcomes were safety (taVNS-related serious adverse events), acceptability, and compliance; secondary outcomes included inflammatory biomarkers, DCI, in-hospital complications, and functional outcomes to 1 month. Results: Thirty patients were randomised (16 taVNS, 14 sham), with numerically more severe aSAH at baseline in the taVNS arm. No taVNS-related serious adverse events occurred; side effects were generally mild and transient, and over 80% of planned sessions were completed. TaVNS produced greater reductions in serum tumour necrosis factor- and trends towards reductions in interleukin-1{beta} and interleukin-10, with numerically fewer DCI events (6.6% vs 35.7%) and neurological impairments (16.7% vs 53.8%), although functional outcomes were not statistically different at 1 month. Conclusions: Early taVNS after aSAH is safe, acceptable, and feasible in the neurocritical care setting and shows biologically plausible signals warranting evaluation in larger multi-centre trials.

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The Psychological Footprint of Unruptured Intracranial Aneurysm Discovery

Renedo, D.; Chen, H.; Sheth, K. N.; Gandhi, D.; Malhotra, A.; Matouk, C. C.

2026-08-31 neurology 10.64898/2026.08.25.26361377 medRxiv
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Background: Unruptured intracranial aneurysms (UIAs) are increasingly identified incidentally, and management balances rupture risk against treatment risk. UIA diagnosis has been linked to psychological distress, but psychotropic medication initiation after UIA discovery has not been compared across the full UIA management spectrum. Methods: We conducted a retrospective cohort study using IBM MarketScan claims (CCAE, MDCD, and MDCR; 2009-2023) among adults with a UIA diagnosis, continuous enrollment for 365 days before and after the index date, and no SAH/rupture on or before the index date. We compared the prevalence of 6 mental-health diagnoses before versus after UIA discovery and used adjusted logistic regression to examine psychotropic medication initiation within 365 days by management strategy (untreated observation as the reference). Results: Among 54,945 patients (untreated, 78.5%; endovascular, 11.3%; clipping, 3.0%; other/uncertain, 7.2%), prevalence of every mental-health diagnosis was higher after UIA discovery, most for depression (+4.6 percentage points) and anxiety (+4.5 points). Medication initiation was most common for benzodiazepines (8.7%). Endovascular treatment was associated with higher adjusted odds of benzodiazepine (aOR, 1.21), SSRI (aOR, 1.20), and sedative-hypnotic (aOR, 1.25) initiation.Surgical clipping demonstrated the broadest association, with higher odds across 5 of 6 classes, including benzodiazepines (aOR, 1.71) and sedative-hypnotics (aOR, 1.86). Benzodiazepines had the lowest 1-year persistence (10.5%) despite being the most commonly initiated class. Findings were consistent across sensitivity analyses, with the exception of the increase in panic disorder, which was no longer observed after applying a 30-day post-index lag. Conclusions: Mental-health diagnoses and psychotropic medication initiation increased after UIA discovery, and medication initiation was most pronounced among patients treated with surgical clipping. These findings support psychological assessment as part of aneurysm management regardless of strategy.

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Patterns of Gabapentin Use in Patients With Cervical Spondylotic Myelopathy

Warner, B. C.; Arkam, F.; Yakdan, S.; Hammo, A.; Ray, W. Z.; Wilcox, A.; Foraker, R.; Lu, C.; Greenberg, J. K.

2026-07-28 neurology 10.64898/2026.07.27.26358977 medRxiv
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Cervical spondylotic myelopathy (CSM) is the most common cause of nontraumatic spinal cord dysfunction in adults and is an increasingly important source of disability as populations age. Gabapentin is widely prescribed for neuropathic pain and may therefore be used for symptoms related to known or undiagnosed CSM. However, there is sparse evidence related specifically to gabapentin's use for CSM-related pain. We investigate gabapentin use and trends over time in patients with CSM compared to matched controls. We observed that gabapentin prescriptions were higher in CSM patients compared to controls across two multi-hospital datasets. These results highlight the need for further research into pharmacologic treatment for chronic pain in CSM.

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Quantitative Prognostic Modeling in Aneurysmal Subarachnoid Hemorrhage: Multicenter Validation of the eSAH Score

Salman, S.; Graf von Moy, C.; Haidenberger, F.; Ahmed, M.; Foettinger, F.; Sharma, R.; Gutierrez-Aguirre, S.; de Toledo, O.; Patel, V.; Yujia-Wei, D.; Rezai Jahromi, B.; Brandmeir, N.; Lakkaraju, K.; Ombada, M.; Aguilar-Salinas, P.; Miller, D.; Erickson, B.; Hanel, R.; Tawk, R.; Byrne, R.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358390 medRxiv
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Background: aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods: We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results: the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion: the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

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Decompression Alone Versus Decompression With Fusion for Symptomatic Lumbar Synovial Facet Cysts: A Systematic Review and Meta-analysis

Fahim, F.; Mohammad Moradi, F.; Mojtahedzadeh, A.; Shahinzadeh, A.; Khorram, A.; Amini, P.; Farhadian, D.; Sangtarashha, P.; Faramin Lashkarian, M.; Khazaei, F.; Zali, A.

2026-08-21 neurology 10.64898/2026.08.17.26360613 medRxiv
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Background: Pain relief is the principal patient-centered goal of surgery for symptomatic lumbar synovial facet cysts, yet comparative reviews have often emphasized cyst recurrence. Whether adding fusion improves postoperative pain or reduces later surgery remains uncertain. Objective: To compare decompression alone with decompression plus fusion, with postoperative back- and leg-pain outcomes as the primary domain. Methods: PubMed, Embase, Scopus, Web of Science, and the Cochrane Library were searched from inception to 2 June 2026. Comparative cohorts and case series with at least five patients were eligible. Twenty-two studies were re-extracted for VAS/NRS scores, change scores, and persistent or recurrent pain. Random-effects restricted maximum likelihood models with Hartung-Knapp inference were used; clinically distinct pain outcomes were analyzed separately. Results: Twenty-two studies (16 cohorts, 6 case series; 51,899 participants) were included. Two studies provided compatible final VAS data. Fusion did not improve postoperative back pain (MD -0.04, 95% CI -0.17 to 0.10; I2=0%) or leg pain (MD -0.03, 95% CI -0.28 to 0.21; I2=0%). Postoperative back pain (RR 0.58, 95% CI 0.14-2.30) and leg/radicular symptoms (RR 0.75, 95% CI 0.42-1.32) were also not significantly reduced. Fusion decreased confirmed cyst recurrence (RR 0.29, 95% CI 0.15-0.57) but not reoperation or subsequent lumbar surgery (RR 0.80, 95% CI 0.42-1.50). Conclusion: Current comparative evidence does not demonstrate superior postoperative pain control with routine fusion. Fusion reduces cyst recurrence without clearly reducing reoperation, supporting selective use when instability is present or anticipated.

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Long-Term Functional and Histological Outcomes Following Sutureless Peripheral Nerve Repair Using Nerve Tape in Pigs

Tatarchuk, M. M.; Clizbe, D. R.; Browne, K. D.; Howard, S.; Ghenbot, Y.; Zager, E. L.; Cullen, D. K.; Burrell, J. C.

2026-08-04 neuroscience 10.64898/2026.07.29.741584 medRxiv
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Severe peripheral nerve injuries result in incomplete recovery despite neurorrhaphy. Microsurgical suturing is technically demanding, time-intensive, and may produce variable fascicular alignment. Nerve Tape is an FDA-approved sutureless device enabling rapid, reproducible nerve coaptation. This study compared Nerve Tape with epineurial microsuturing following common peroneal nerve transection in Yucatan minipigs. Over 12 months, both groups demonstrated reinnervation of the tibialis anterior and extensor digitorum brevis, representing proximal and distal muscle targets, respectively. Tibialis anterior recovery was comparable between groups. In contrast, Nerve Tape produced greater distal motor recovery in the extensor digitorum brevis, with approximately 1.8-fold higher compound muscle action potential amplitude and 74.3% versus 46.0% recovery compared with microsutures. Compound nerve action potential amplitudes recorded from the motor branch of the deep peroneal nerve were also greater with Nerve Tape, whereas conduction velocities were comparable. Histological analysis demonstrated preserved fascicular architecture distal to the repair in both groups, with no significant differences in axon count, mean myelinated axon diameter, or g-ratio in the terminal common peroneal nerve or its distal motor branch. Clinical use was demonstrated in a representative case with progressive recovery. Nerve Tape supported durable structural and functional recovery and improved distal motor reinnervation compared with microsuturing.

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Computer Vision for Real-Time Anatomical Navigation in Neurosurgery: First-in-Human Clinical Evaluation and Iterative Development (IDEAL Stage 1)

Khan, D. Z.; Mao, Z.; Wijekoon, A.; Das, A.; Williams, S. C.; Blandford, A.; Jain, A.; Harris, L.; Borg, A.; Dorward, N. L.; Clarkson, M.; Bano, S.; McCulloch, P.; Stoyanov, D.; Marcus, H.

2026-06-11 surgery 10.64898/2026.06.11.26355205 medRxiv
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Introduction: Precise anatomical navigation is fundamental to safe endoscopic pituitary surgery, a high-stakes procedure characterised by a challenging learning curve. While traditional navigation systems often rely on workflow-disrupting probes or static preoperative imaging, advancements in computer vision AI (CVAI) now enable dynamic, real-time anatomical segmentation directly from live surgical video1-3. Our group has previously conducted a series of preclinical human-computer interaction studies to refine the system's design, alongside digital and high-fidelity physical simulations demonstrating the benefit of AI assistance in improving overall performance, training, and safety4-8. Building on this foundation, the current study represents a first-in-human application of real-time CVAI assistance in the neurosurgical operating room, serving to assess feasibility and safety, and to iteratively improve the system. Method: Guided by DECIDE-AI and IDEAL frameworks, this single-centre evaluation comprises an initial proof-of-concept phase (n=6) for endoscopic transsphenoidal pituitary surgeries. The AI model utilised a DINOv3-derived vision transformer architecture, deployed via a high-performance edge computing unit to achieve low-latency, real-time inference without reliance on cloud infrastructure2. Given the high-risk nature of the procedure and the early stage of clinical AI integration, the system was initially deployed as an educational adjunct on a secondary monitor, ensuring the primary surgical feed remains uncompromised. Functionality and safety were assessed via structured questionnaire, prospective observation, and blinded retrospective review of the recordings of the endoscopic surgical video feed and wider operating room environment. Continuous multi-stakeholder feedback through validated human factors surveys drove iterative technical refinements between cases. Results: Six patients with pituitary adenomas were enrolled. The CVAI system was successfully deployed in four cases, demonstrating acceptable real-time sella segmentation accuracy. Deployment failed pre-operatively in two cases owing to a single recurring system reboot bug. Iterative refinement between cases were driven by our experience and surgical team feedback. This resulted in the integration of additional anatomical structure segmentations (e.g., carotid arteries), enhanced model accuracy via training dataset expansion, and hardware firmware upgrades. Multi-stakeholder surveys demonstrated satisfactory system feasibility, usability, and acceptability among the surgical team. Both prospective observation and retrospective video review confirmed the absence of adverse events, including no significant distraction to the primary surgeon, and there were no AI-related clinical complications. Conclusion: This first-in-human early clinical evaluation demonstrates the feasibility, safety and iterative development of real-time, CVAI-based anatomical navigation during high-stakes neurosurgery. Future work will include a larger single-centre case series (IDEAL Stage 2a) with more surgical teams to further iterate the system and explore its impact on training and workflow. As the underpinning technology improves, deployment will transition to direct intra-operative decision support and integration with other intra-operative navigational technologies.

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From CHESS to CHECKMATE: A Practical Score for Predicting Shunt Dependency Following Subarachnoid Hemorrhage

Salman, S.; Haidenberger, F.; Ahmad, M.; Rezai Jahromi, B.; Albaramony, N.; Patel, V.; Peel, J.; Ombada, M.; Gutierrez-Aguirre, S.; de Toledo, O.; Aguilar-Salinas, P.; Tawk, R.; Byrne, R.; Hanel, R.; Rabinstein, A.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358389 medRxiv
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Objective: Shunt-dependent hydrocephalus is a common and costly complication of aneurysmal subarachnoid hemorrhage (aSAH), affecting up to 28% of survivors. Existing prediction tools, including the Chronic Hydrocephalus Ensuing from SAH Score (CHESS), have limited discriminative accuracy. We developed the CHECKMATE score, a clinically practical tool to improve prediction of ventriculoperitoneal shunt dependency after aSAH. Methods: In this multicenter retrospective cohort of 486 patients with aSAH from Mayo Clinic (January 1, 2006-December 31, 2021), we used multivariable logistic regression and machine learning to identify independent predictors of ventriculoperitoneal shunt placement. The CHECKMATE score was derived from 5 weighted variables: symptomatic hydrocephalus (10 points), intraventricular hemorrhage (5 points), SAH volume greater than 10 mL (3 points), neutrophil-to-lymphocyte ratio greater than 12 (2 points), and 10-year incremental age thresholds starting at older than 60 years (1 point each). Results: Of 486 patients (mean age, 56.3 years; 64.6% female), 137 (28.2%) required ventriculoperitoneal shunt placement. The CHECKMATE score achieved an area under the curve of 0.808 (compared to 0.737 for CHESS), with a sensitivity of 0.85, specificity of 0.67, and negative predictive value of 0.92 at the optimal cutoff of 14 points. Conclusions: The CHECKMATE score outperforms CHESS for predicting ventriculoperitoneal shunt dependency after aSAH and is easily used at the bedside. Its high negative predictive value helps identify low-risk patients who may benefit from earlier external ventricular drain weaning and shorter hospital stays.

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Multimodal Large Language Models vs. Medical Doctors in Degenerative Lumbar Spine Surgery: A Retrospective Decision Concordance Study of 147 Patients

Hamdan, M.; Harati, A.; Al-Bakheet, A.; Fuetterer, I.; Alshaer, I.

2026-08-06 surgery 10.64898/2026.08.04.26359718 medRxiv
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Objective: To evaluate decision concordance between commercially available multimodal large language models (LLMs), resident doctors, and senior-surgeon ground truth for surgical indication and spinal level in degenerative lumbar spine disease. Methods: We retrospectively analyzed 147 consecutive patients. Each case included clinical documentation and MRI presented as two composite PNG images. Two resident doctors and three multimodal LLMs (GPT 5.5, Claude Sonnet 4.6, Gemini 3.1 Pro) independently assessed operative versus conservative management and, if operative, the surgical level. Analyses used Cochran's Q, McNemar tests with Holm correction, and Bayesian methods. Results: LLMs achieved higher therapy-decision accuracy (66.0%-68.0%; 97-100/147) than residents (54.4%; 80/147) but over-recommended surgery. Conditional level accuracy when surgery was correctly indicated was 71.4% (20/28) for residents versus 33.3%-41.1% for LLMs. Conclusion: Off-the-shelf multimodal LLMs approximate human performance for binary surgical indication but remain inferior for precise level localization. These results establish a practice-relevant baseline of spatial reasoning limitations for tools already used by patients and junior doctors.

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Beyond Binary Vasospasm: A Continuum Model Relating Severity and Distribution to Perfusion Deficits After Aneurysmal SAH

Thaler, C.; Meyer, L.; Tokareva, B.; Geest, V.; Kniep, H. C.; Heitkamp, C.; Dührsen, L.; Meyer, H. S.; Bester, M.; Fiehler, J.; Schlicht, F.

2026-07-18 neurology 10.64898/2026.07.16.26358285 medRxiv
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Background: Cerebral vasospasm is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with delayed cerebral ischemia (DCI) and unfavorable outcome. While CTA-based vasospasm grading is frequently used, its relationship with actual cerebral perfusion remains incompletely understood. This study investigates the association between vasospasm severity and distribution and territorial perfusion deficits. Methods: In this retrospective single-center study, 513 CT examinations (CTA and CT perfusion) from 194 patients with aSAH were analyzed. Vasospasm was graded per vessel segment using the CTA Vasospasm Score, and perfusion deficits were assigned to corresponding vascular territories (left/right anterior circulation, posterior circulation). Vasospasm distribution was further classified by severity and multifocality. Associations between vasospasm score and perfusion deficits were assessed using a generalized linear mixed model with binomial distribution, adjusting for Hunt & Hess grade, modified Fisher score, and days since hemorrhage. Results: Vasospasm was detected in 79.3% of examinations, and a perfusion deficit in at least one territory was present in 62.6%. The proportion of perfusion deficits increased progressively with both vasospasm severity and multifocality, ranging from 21.7-25.0% in the absence of vasospasm to 81.2-82.2% in severe multifocal vasospasm. The CTA Vasospasm Score was significantly associated with perfusion deficits in all territories (OR 1.36-1.50), with stronger associations in the anterior than posterior circulation. Conclusion: Vasospasm severity and distribution are strongly associated with perfusion deficits, supporting a continuum model of ischemic risk. However, the substantial proportion of perfusion deficits occurring independent of vasospasm suggests additional microcirculatory mechanisms not captured by CTA. CT perfusion should be considered complementary to CTA, particularly in clinically deteriorating or non-assessable patients.

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Exosome-Based Therapy for Spinal Cord Injury Repair: A Systematic Review of Preclinical Evidence and Exploratory Quantitative Synthesis

Fahim, F.; Mahmoodi, H.; Mojtahedzadeh, A.; Faramin Lashkarian, M.; Majlesi, M.; Esmaeeli, M.; Sattari, H.; Maroufi, M.; Mafakhery, P.; Hashemi, S. y.; Koohi Kamali, S.; Mansoori, M.; Aghazadeh, E.; Safari, S.; Khazaei, F.; Zali, A.

2026-07-29 neurology 10.64898/2026.07.27.26359044 medRxiv
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Background: Exosome- and extracellular vesicle-based therapies have emerged as promising cell-free approaches for spinal cord injury repair, with reported effects on inflammation, apoptosis, myelination, axonal regeneration, angiogenesis, blood-spinal cord barrier integrity, and neurogenesis. However, the preclinical evidence is heterogeneous, and the extent to which the available data permit quantitative synthesis remains unclear. Methods: This systematic review was conducted in accordance with PRISMA 2020 and registered in PROSPERO as a preclinical animal intervention review (CRD420261446664). PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched from inception to 1 June 2026 without language or publication-date restrictions. Eligible studies evaluated an exosome- or extracellular vesicle-based intervention for spinal cord injury and reported functional, histological, molecular, electrophysiological, vascular, regenerative, or safety-related outcomes. Risk of bias was assessed using an adapted version of SYRCLE's tool for animal studies, while the first-in-human phase I study was appraised separately using the JBI Critical Appraisal Checklist for Quasi-Experimental Studies. Study characteristics, intervention strategies, outcome domains, and risk-of-bias patterns were synthesized descriptively. Where complete group-level means, standard deviations, and sample sizes were available, exploratory quantitative synthesis was performed using standardized mean differences calculated as Hedges' g. Results: The search identified 1,329 records. After removal of 481 duplicates, 848 records were screened, 108 full-text reports were assessed for eligibility, and 24 studies were included, comprising 23 animal/preclinical studies and one human phase I study. Exosome sources, injury models, administration routes, dosing strategies, and follow-up durations varied substantially. Reported outcomes included locomotor recovery, lesion and tissue preservation, myelination, axonal and neural regeneration, inflammation, apoptosis, angiogenesis, blood-spinal cord barrier repair, neurogenesis, and safety. Among the 23 animal studies, none was judged to be at overall low risk of bias; 20 were classified as unclear risk and three as high risk. The human phase I study was appraised separately and judged to be at high risk of bias for causal efficacy inference. Two studies contributed complete data to the exploratory meta-analysis of Basso, Beattie, and Bresnahan locomotor recovery. Both study-level estimates favored exosome treatment, while the random-effects pooled estimate was imprecise and crossed the null (Hedges' g 3.74; 95% CI -0.53 to 8.00). Conclusions: Exosome- and extracellular vesicle-based therapies demonstrated promising signals across functional and biological domains of spinal cord injury repair. However, the evidence was limited by methodological heterogeneity, unclear risk of bias, inconsistent reporting of vesicle characterization and dosing, and insufficient complete numerical data for robust quantitative synthesis. Preregistered, adequately powered, and transparently reported studies using standardized intervention and outcome-reporting methods are required to clarify therapeutic efficacy and translational potential.

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Cutting Through the Noise: Stochastic Pulse Timing for Deep Brain Stimulation

Baker, M. R.; Bokil, H.; Niketeghad, S.; Miller, K. J.; Klassen, B. T.

2026-07-09 neurology 10.64898/2026.07.08.26357382 medRxiv
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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

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ICH-CARE: ICH-integrated Care for Accelerated Response to Hemorrhage Using a Phased Approach.

Salman, S.; English, S.; Mooney, L.; Miller, D.; Ng, L.; Kramer, C.; Ombada, M.; Tawk, R.; Freeman, W. D.

2026-07-21 neurology 10.64898/2026.07.18.26358392 medRxiv
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Introduction: Intracerebral hemorrhage (ICH) carries higher morbidity and mortality than ischemic stroke. Recent studies have demonstrated improved patient outcomes by applying ultra-early bundled interventions including blood pressure management, coagulopathy reversal, and osmotic therapy. Effective strategies to deliver these ultra-early treatment options are currently being explored. On December 19th, 2022, the Mayo Clinic Comprehensive Stroke Center (CSC) launched the "ICH Phases'' communication system to accelerate ICH patient care. Objective: To evaluate adherence to the AHA/ASA guidelines in acute ICH care following the implementation of our novel-tiered paging system. Methods: We retrospectively reviewed patients admitted with spontaneous ICH during 2024 and 2025. We excluded traumatic cases. We extracted clinical data such as time to imaging, documentation of ICH score, blood pressure control, reversal of anticoagulation, venous thrombo-embolism (VTE) prophylaxis and discharge disposition. Results: Among 67 patients, 68.7% underwent CT imaging within 25 minutes. We documented the ICH score within 6 hours in 82.9% of patients. Nearly 94.7% of patients with SBP>140 mm Hg received antihypertensive therapy, yet only 18% reached target BP within 60 minutes. We completed the reversal of anticoagulation within 120 minutes in 75% of patients. VTE prophylaxis was initiated within 24 hours in 91% of patients. Discussion: Our novel system demonstrated adherence to the AHA/ASA guidelines, and time sensitive benchmarks in neuroimaging, reversal of anticoagulation, and VTE prophylaxis. Early BP control remains a challenge, that highlights the discrepancy between guidelines and real-ground implementation. Conclusion: A novel tiered paging system is effective for enhancing early ICH care. Such a holistic system remains critical for sustained improvement in quality of care.

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Validation of an Assessment Scale for a Low-Tech Laparoscopic Appendectomy Simulation and Its Relevance for Formative Self-Assessment

Tumameu Kouam, T. H.; Renoult, L.; Poitevin, M.; Jourdin, L.; Herve, C.; Meignan, P.; Podevin, G.; Schmitt, F.

2026-07-21 medical education 10.64898/2026.07.20.26358477 medRxiv
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Introduction: Laparoscopic appendectomy is an ideal procedure for acquiring laparoscopic skills through simulation. Nevertheless, technical training is time consuming for surgical trainers to provide constructive feedback, but this could be improved by the development of validated tools that enable appropriate formative self-assessment. For this reason, we developed a structured assessment scale for a laparoscopic appendectomy exercise using a low-fidelity simulator. The objective of this study was to validate the scale for use in formative self-assessment. Methods: During laparoscopic simulation sessions in 2025-2026, participants with varying levels of experience performed a standardized laparoscopic appendectomy (LAP) exercise on a low-fidelity simulator. Performance was assessed through formative self- and external assessment using a specific scale derived from the OSATS (Objective Structured Assessment of Technical Skills) score. Content and construct validity, internal consistency, reproducibility, and reliability in both hetero- and self-assessment were analyzed. Results: Thirty-two participants were included in the validation study of the LAP scale, including 7 medical students, 17 residents in pediatric, visceral, urological, and gynecological surgery, and 8 practicing surgeons. The content of the scale was deemed relevant by 80% of the users. It demonstrated excellent construct validity, with scores increasing according to level of experience: 9.9 +/- 0.7 among students, 12.7 +/- 3.3 among junior residents, 16.6 +/- 3.3 among experienced residents, and 18.8 +/- 0.9 among practicing surgeons (p < 0.0001). Reproducibility and internal consistency were significant, while inter and intrarater reliability were excellent (correlation coefficients r = 0.90 and 0.91; p < 0.0001), as was the correlation between external and self-assessment (r = 0.81; p < 0.0001). Self-assessment was more reliable among experienced learners than among novices. Conclusion: This standardized LAP scale is validated for both external and self-assessment, the latter requiring prior training to be reliable and formative.