Neurosurgery

IntroductionSurgical simulation is an appealing adjunct for educating trainees on a variety of spine surgery techniques, especially non-routine skills like lumbar durotomy repair. However, high costs and significant lead time required to obtain surgical simulators restrict their routine use in most training programs. The goal of the present study was to develop and evaluate a low-cost and open-source 3D printed lumbar durotomy repair simulator for resident education. MethodsThe design of a pre-existing open-source 3D printed spine simulator was modified for a durotomy repair simulation. The simulator was then printed using acrylonitrile butadiene styrene (ABS) filament on a Bambu Lab P1S printer. Current neurosurgical residents from a single institution were recruited to participate in a one hour lab session in which they were tasked with repairing a standardized 1.5 centimeter durotomy. Subjects were surveyed before and after their simulation experience. ResultsSeven simulators were produced taking on average 12.2 hours to print and cost approximately $9.51 each once fully assembled. Of the 14 subjects recruited, only 7 (50%) reported prior experience with lumbar durotomy repair. All subjects were able to successfully complete the simulated task. Exit survey results demonstrated that all subjects (100%) agreed the simulation was useful and expressed interest in participating in future simulation experiences. ConclusionsOur study demonstrated a 3D printed simulator for lumbar durotomy repair could be produced at low cost and was highly valued by neurosurgical trainees. Given our simulators low cost and open-source format, we believe it is highly accessible to most, if not all, residency programs, and has the potential to help expedite mastery of lumbar durotomy repair.

Cervical nerve blocks require high precision due to the proximity of critical structures, such as the spinal cord and the vertebral and carotid arteries. Training opportunities are limited by the risks associated with fluoroscopy-guided procedures, ethical constraints of cadaveric models, and the high cost of commercial simulators. Three-dimensional (3D) printing offers an accessible and customizable alternative for procedural training. A cervical spine simulator was constructed from a multislice CT scan. The cervical spine (C1-C7) was segmented using 3D Slicer and processed in Meshmixer to generate an anatomical 3D model, which was printed in PLA. Soft tissues were reproduced using a ballistic gel formulation composed of glycerin, gelatin, and propylene glycol. Six physicians participated in a five-week training program performing facet, indirect, and direct cervical root blocks under fluoroscopy. Knowledge was assessed pre- and post-training, performance was assessed weekly using OSATS, and validity was evaluated through a Likert-scale survey. This 3D-printed cervical simulator proved to be a valid, low-cost, and reproducible tool for training fluoroscopy-guided cervical nerve blocks.

IntroductionTransarterial embolization is a well-established adjunct in the management of hypervascular head, neck, and spine tumors. Few case-series have described the role of direct percutaneous embolization (DPE). MethodWe report our experience with DPE (with or without transarterial embolization) in patients with head, neck, and spine tumors treated between 2012-2023. Baseline demographics, angiographic imaging, tumoral pathology, and relevant clinical variables were retrospectively reviewed and descriptively analyzed. ResultA total of 55 patients underwent direct percutaneous embolization (19 of whom also received transarterial embolization either before [n=7] or after [n=12] DPE). The most commonly embolized lesions were malignant carcinomas (n=16), followed by juvenile nasopharyngeal angiofibromas (n=11), paragangliomas (n=8), hemangiomas (n=7), and others (hemangioblastoma, schwannoma, neurofibroma, esthesioneuroblastoma, meningioma and hemangiopericytoma). The most common locations were sinonasal/nasopharyngeal (n=21), followed by scalp/subcutaneous (n=18), carotid body (n=6), spinal/paraspinal (n=4), skull base (n=5), and intracranial (n=1). A median of 4 (interquartile range 4-6) twenty-two-gauge spinal needles were used per embolization with a median fluoroscopy time of 50.5 (23.2-77.8) minutes resulting in median radiation exposure of 3055 (840.5-5053.5) mGy. Seven patients received more than one embolic agent, with n-butyl cyanoacrylate (glue, n=44, 81.5%) being the mostly commonly used embolic, followed by ethylene-vinyl alcohol copolymer (Onyx, n=7, 12.9%), 98% dehydrated ethanol (n=7, 12.9%), sodium tetradecyl sulfate (n=2, 3.7%) and poly-vinyl alcohol particles (n=1, 1.8%). The median volume of embolic agent injected was 5.5(4-7.6) mL resulting in total/near-total (90%-99%) angiographic devascularization in 74.5% cases. The median operative blood-loss was 250(75-700) mL. One patient underwent trans-calavarial DPE for a cerebellar hemangioblastoma and suffered diffuse subarachnoid hemorrhage from profuse tumoral bleeding. One patient had an asymptomatic parent-vessel occlusion from retrograde embolic extension. ConclusionOur single-center study reinforces prior experience that DPE of Sino-nasal carcinomas, angiofibromas and paragangliomas with adhesive and non-adhesive liquid embolic agents is safe, feasible and effective. Further, it suggests that these benefits may also be extended to non-traditional head, neck and spine tumors. Caution must be exercised when applying these techniques to intracranial tumors with robust intratumoral arteriovenous shunting.

BackgroundThe clinical outcomes of microsurgery for spinal cord arteriovenous shunts (SCAVSs) exhibit fluctuations due to varying patient selection criteria, underscoring the importance of a standardized surgical grading system that can effectively stratify the feasibility of SCAVSs resection. MethodsA cohort of 308 consecutive patients with surgically treated SCAVSs was randomly divided into a modeling group and a validation group. The surgical grading system was developed based on the independent risk factors of incomplete resection identified in the modeling group and subsequently verified in the validation group. The systems specificity and sensitivity were tested through Receiver Operating Characteristic (ROC) analyses. ResultsMultivariate analysis indicated that metameric AVSs (p=0.007), AVSs with maximum length [≥]3 cm (p=0.017), embedded AVSs (p=0.032) and anterior sulcal artery supply (p=0.013) were independent risk factors of incomplete resection. Subsequently, each of the four parameters is assigned one point, and the SCAVSs grade is calculated by aggregating all parameter scores. The area under ROC curve (AUC) of modeling group and validation group was 0.856 (95% confidence interval [95% CI], 0.794-0.919) and 0.819 (95% CI, 0.747-0.892) respectively. Across the entire cohort, patients with scores ranging from 0 to 4 exhibited complete resection rates of 88.7%, 66.7%, 30.6%, 4.5% and 6.3%. The corresponding rates of severe treatment-related deterioration were found to be at levels of 6.0%, 12.0%, 12.9%, 31.8% and 25.0 %, respectively. Conclusion: The proposed grading system effectively stratifies the surgical feasibility of SCAVSs based on both the probability of achieving complete resection and the treatment risk. Its simplicity renders it a valuable tool for clinical decision-making, as well as a reference point for evaluating treatment outcomes across different centers and surgical techniques.

ObjectivesAcademic medical institutions are the gatekeepers of the physician workforce and shape the future of medicine by regulating medical school admissions as well as residency training. Although broadly the field of medicine is seeing more representation from traditionally underrepresented groups, the critical decision-making platform of academic medicine continues to be uncharacteristically homogeneous, represented mainly by white males. This is even more pronounced in surgical subspecialties, such as academic neurosurgery. This study aims to quantify this phenomenon, uncover its driving factors, and define opportunities for improvement. MethodsUsing a mixed research methodology, academic neurosurgical faculty in the U.S were identified, and their demographic data was collected. An internet search using Google Scholar and Scopus was conducted to determine scholarly activity using number of publications and h-index. ResultsWe found a significant increase in female faculty in academic neurosurgery within the last decade. Comparing the faculty rank amongst male and female faculty, we found that the majority of female faculty are at the assistant professor level (n=36/79; 45.6%) while male faculty are more at the full professor rank (n=265/582; 45.5%). A similar trend was seen for under-represented minority neurosurgery faculty. Strong scholarly activity corelated with a departmental chair position for male faculty, however, this trend was not true for female faculty. There was a significant difference in the number of publications and h-index in female vs male faculty, but only when including male faculty outliers at the full professor level. ConclusionSlowly but steadily, academic neurosurgery is making progress towards a more diverse and representative workforce in the U.S that better reflects the patient population. Facilitating timely progression of females and URM neurosurgeons into senior professorship and academic leadership roles will further advance this essential progress.

This research demonstrates that the trans-aqueduct approach is a feasible, minimally invasive access pathway to the third ventricle, offering a potential route to the deep brain for therapeutic technologies. Further pre-clinical investigation is required to thoroughly evaluate physiological tolerance, trauma risk, and the long-term implications of intraventricular implantation. The third ventricle is a high-value site for neuromodulation due to its proximity to deep-brain targets, including the subthalamic nucleus (STN) and globus pallidus internus (GPi). This study defined the anatomical pathway; and evaluated the technical feasibility of retrograde access to the third ventricle via the cerebral aqueduct using minimally invasive interventional techniques. Evaluation was conducted in three phases using human MRI datasets (n=16; mean age 48.4 years) and cadaveric specimens (n=6; mean age 88.2 years). Phase 1 involved morphometric MRI analysis of the aqueduct and ventricles. Phase 2 tested trans-aqueduct access on cadaver specimens via fluoroscopically guided guidewires and catheters. Phase 3 utilized direct anatomical dissections on cadaver specimens (n=3) to morphometrically measure the third ventricular cavity and its relationship to deep-brain nuclei. Measurements across the sample groups showed a mean aqueduct diameter of 1.6 mm (SD=0.14). Third ventricle dimensions averaged 27.6 mm (ventral-dorsal), 19.9 mm (caudal-cranial), and 5.7 mm (lateral). Successful access to the third ventricle was achieved in 83% (5/6) of cadaveric specimens. The optimal technical configuration utilized a 0.018'' angled-tip guidewire and 5-6 Fr catheters; the aqueduct accommodated diameters up to 2.0 mm with minimal resistance. The STN and GPi were localized within 5-20 mm of the ventricular volumetric centroid. The trans-aqueduct approach is a technically feasible, minimally invasive pathway for accessing the third ventricle. This route offers a potential alternative for the delivery of therapeutic neurotechnologies. Further research is required to assess physiological tolerance, trauma risk, and the long-term safety of intraventricular implantation.

BackgroundCavernous sinus dural arteriovenous fistulas (CS-DAVFs) present significant treatment challenges when the inferior petrosal sinus (IPS) is not opacified during cerebral angiography. However, the widely accepted transvenous IPS recanalization approach is associated with a high failure rate. The consistently visible superior ophthalmic vein (SOV) offers a promising alternative, though it has yet to be fully evaluated in large-scale studies. MethodsThis retrospective, case-control study was conducted between May 2017 and October 2024. Data collection for this multicenter, population-based study took place across eight tertiary referral centers. Eligible patients were diagnosed with CS- DAVF with occluded IPS. Endovascular treatment via the transvenous SOV approach versus the IPS recanalization approach in patients with occluded IPS. ResultsOf 178 eligible cases, 70 cases (39.3%) were treated using the transvenous SOV approach, while 108 cases (60.7%) underwent the transvenous IPS approach. The initial treatment success rate was significantly higher in the SOV group compared to the IPS group (91.4% vs. 75.9%; odds ratio [OR], 3.38; 95% CI, 1.30-8.35; P = 0.0092). The overall complication rate was 1.4% in the SOV group and 2.8% in the IPS group (OR, 0.51; 95% CI, 0.04-3.47; P > 0.9999). After classifying the SOV approach into simple and complex types, the SOV-simple type further demonstrated significant advantages, including shorter average operation times (126.20 {+/-} 46.99 minutes, P = 0.0197) and a higher initial treatment success rate (95.7%, P = 0.0027) compared to the IPS group. ConclusionThe SOV approach should be considered a first-line treatment for CS- DAVF patients with invisible IPS. These findings establish a new treatment standard, underscoring the importance of precise preoperative classification and individualized surgical planning.

BackgroundChronic subdural hematoma (CSDH) is characterized by the collection of blood beneath the dura mater. Traditional treatments involve surgical drainage of the hematoma, but recurrence rates can be high. A highly vascularized neo-membrane irrigated by the middle meningeal artery (MMA) may be involved in CSDH re-accumulation. ObjectiveWe conducted a systematic review and meta-analysis of studies that compared the efficacy and safety of MMA embolization to conventional treatment alone for CSDH. Material and MethodsA systematic search of PubMed, Embase Ovid, and ClinicalTrials.gov identified observational and randomized clinical studies comparing MMA embolization to conventional treatment for chronic subdural hematoma. The efficacy outcomes were hematoma recurrence and good functional outcome (as defined by a modified Rankin Scale score (mRS) of 0-2). Safety outcomes were the rate of major complication and mortality. Heterogeneity among studies were evaluated using the I2 statistic. Analyses were conducted using Cochrane Review Manager software, with risk ratios (RR) and 95% confidence intervals (95% CI) presented for key outcomes. Absolute risk reduction (ARR, 95% CI) 1000 patients were also calculated using GRADEpro software. ResultsThe analysis included data from 13 studies (4 RCTs and 9 observational studies) with a total number of 2960 patients (35.3% in the MMA group and 64.7% in the conventional treatment group). Compared to conventional treatment, MMA embolization decreased risk of hematoma recurrence by 60% (13 studies, RR=0.40, 95% CI 0.25-0.63; I2=50%), for an absolute effect of 119 fewer events/1000 patients (95% CI 70-149), with similar risk of major complications (9 studies, RR=0.82, 95% CI=0.54-1.25) and mortality risk (13 studies, RR=0.90, 95% CI=0.54-1.51). In subgroup analyses by study type, pooled results from RCTs showed similar direction effects as those from observational studies for both efficacy and safety outcomes. ConclusionMMA embolization in CSDH management is a safe and effective approach for CSDH.

Recovery of hand and arm function is critical for improving quality of life in individuals with tetraplegia due to spinal cord injury (SCI). Nerve transfer procedures can restore meaningful hand and arm function in chronic SCI, yet postoperative outcomes vary widely. We conducted a prospective, single-arm, open-label trial to assess the impact of intensive, robot-assisted rehabilitation training on functional recovery and cortical reorganization following nerve transfer. The primary endpoint was assessment of hand and arm function measured by the Box and Blocks Test. We report the results from three participants, AIS A at enrollment, who completed six weeks of intensive robotic training at least 1 year after nerve transfer surgery (NCT04041063). All participants demonstrated minimally important difference improvements in at least one secondary clinical outcome. These improvements were accompanied by cortical reorganization measured by transcranial magnetic stimulation motor mapping, indicating integration of the newly established peripheral motor pathways. No serious adverse events related to surgery or rehabilitation occurred. Although recruitment was limited by the COVID-19 pandemic and precludes definitive conclusions regarding efficacy, these findings suggest that standardized, intensive robotic rehabilitation may enhance functional outcomes after nerve transfer surgery for chronic tetraplegia.

Objective: Neuroendoscopy has emerged as a crucial minimally invasive strategy for the treatment of intracranial hemorrhage (ICH). This bibliometric analysis aims to systematically delineate the global research architecture and evolution of neuroendoscopic ICH research over the past two decades. Methods: Relevant publications were retrieved from the Web of Science Core Collection using a reproducible search strategy. Bibliometric tools were applied to analyze contributions from countries, institutions, authors, publications, keywords and journals, enabling the construction of a comprehensive knowledge map and evolutionary framework of this field. Results: A total of 403 articles were identified, involving 2128 authors from 555 institutions across 43 countries. The publication trajectory exhibited fluctuating growth, reflecting the dynamic interplay between clinical demand and technological maturation. China contributed the highest publications and citation impact, followed by the US, jointly anchoring the global influence of the field. The research keywords have evolved from ?intracerebral hemorrhage? and ?initial conservative treatment? to ?augmented reality.? Thematic evolution analysis revealed a clear progression from early emphasis on operative feasibility, safety, and perioperative outcomes toward more rigorous evidence appraisal and the refinement of context-specific clinical indications, accompanied by continuous technological innovation. Conclusion: These findings collectively position neuroendoscopy as a cornerstone of modern ICH management, reshaping clinical strategies toward precision, minimal invasiveness, and multimodal intervention. Future progress will depend on strengthened international collaboration to generate high-quality evidence that supports patient stratification. The integration of emerging technologies, including advanced endoscopic robotics, is expected to further accelerate the translational and clinical landscape of neuroendoscopic ICH therapy.

Directional brain stimulation provides greater control of radial current spread than conventional ring-shaped electrodes. Whether this added flexibility can improve motor function is unclear. Here we examine whether directional and circular stimulation differentially change motor performance in patients with Parkinsons disease. We measured motor behaviors in 31 patients who underwent unilateral subthalamic nucleus brain stimulation surgery (SUNDIAL, NCT03353688) from each of 8 configurations (6 directional contacts and their corresponding rings) during device activation. Objective measures of dexterity, gait, balance, and overall mobility were queried in a double-blind fashion in the practically defined "off" medication state versus preoperative baseline with stimulus amplitude at the center of the therapeutic window. The best versus the worst directional contact on a given row yields significant changes in performance across 5 motor tasks (p<0.001 each task). Specific stimulation directions can worsen function versus baseline, whereas the best direction yields greater improvement than ring stimulation (p=0.005, p=0.001, p=0.007, p<0.001, respectively, across tasks). Although directional DBS improves side effect thresholds versus ring stimulation (p<0.001), the side effect threshold and therapeutic window correlate only modestly with motor improvements. Resting beta power did not predict motor improvements by directional DBS across any of the motor tasks. Optimized directional subthalamic nucleus DBS yields better group-level motor performance than ring stimulation, in addition to known advantages related to tolerability. Prospective studies should evaluate whether these improvements persist over longer time intervals.

BackgroundAwake deep brain stimulation (DBS) surgery with microelectrode recording (MER) and test stimulation offers real-time physiologic feedback to refine lead placement, but its relevance is increasingly debated in an era of advanced imaging and streamlined asleep workflows. ObjectiveTo describe a contemporary framework for awake DBS with MER and to evaluate whether, in our hands, this approach results in a final lead position different from what we would have achieved with asleep DBS. MethodsWe outline a standardized workflow combining high-resolution imaging, confirmatory MER, and intraoperative stimulation mapping for an example context of thalamic targeting for essential tremor. To quantify the impact of the awake approach on surgical decision making, we retrospectively reviewed the first 137 consecutively implanted VIM DBS leads placed (awake) by a single surgeon working with a single intraoperative neurologist. In each case, we recorded whether the final lead was implanted along the planned target, whether it was adjusted in depth along the planned trajectory, or whether it was moved to a parallel track. For the parallel track moves, we compared the final lead position to the initially planned imaging target using co-registered pre- and postoperative imaging. ResultsAmong 137 consecutive leads implanted, 116 were implanted in the planned trajectory, with 49 at the planned depth and 67 at an adjusted depth. Twenty-one of the 137 leads were placed along a parallel trajectory based on intraoperative findings, with seventeen having available imaging for further analysis. Post-operative analysis showed that only 2 of the 17 were moved toward the intended target. The remaining 15 were moved away (13) or equidistant (2) from the intended target. ConclusionFeedback from MER and test stimulation in awake DBS cases frequently informs surgical adjustments that deviate from the planned trajectory, often in response to patient-specific physiology not captured by imaging. In the vast majority of our cases, these adjustments would not have been made using an asleep DBS approach, since moves were not made toward the planned target. This indicates that, in our practice, awake surgery results in adjustment of lead position in response to discovered functional anatomy rather than to correct stereotactic inaccuracy. Our findings underscore the continued utility in our practice of awake DBS with MER in tailoring therapy to individual anatomy and functional organization.

Here, we report the final outcomes of a pilot clinical trial testing preliminary efficacy and safety of cervical epidural spinal cord stimulation (SCS) for chronic post-stroke upper-limb hemiparesis (NCT04512690). We implanted seven participants with profound motor deficits (Fugl-Meyer Assessment [FMA] scores 15-35) using two leads implanted unilaterally in the cervical spinal cord for 4 weeks. Under SCS ON, motor function immediately improved regardless of impairment severity (average +32% strength and +5.6 FMA-points). Notably, 3/7 participants with residual corticospinal connectivity to finger muscles regained hand/finger function with SCS. Despite performing only 8.6hrs of motor activity (5.5hrs with SCS ON), participants improved by average +6.6 FMA-points at the end of the study compared to baseline and spasticity decreased in all participants. While all benefited, our preliminary analysis indicates that spared sensory function may be a determinant of responsiveness to SCS. No serious adverse events occurred.

Patients with brain tumors involving language-critical regions face surgical limitations when balancing resection with preservation of function. Non-invasive neuromodulation-induced prehabilitation (NIP) aims to guide preoperative neuroplastic reorganization, potentially facilitating larger resections while preserving function. We investigated whether NIP selectively modulates the targeted language network compared with control networks, and whether such modulation is behaviorally safe. We enrolled 26 patients (mean age = 55.9 {+/-} 11.8 years) from the Prehabilita project (Clinical Trial: NCT05844605) with operable brain tumors affecting language or motor regions. Eleven received language-targeted NIP, combining transcranial magnetic stimulation and/or transcranial direct current stimulation with intensive language training. Fourteen patients with NIP targeting non-language networks, primarily motor networks, served controls. Assessments included task-based functional magnetic resonance imaging (tb-fMRI) and a neuropsychological battery assessing language and cognitive domains before and after prehabilitation. Results indicated a group-specific NIP effect on the language network. In the language-targeted group, tb-fMRI revealed reduced overlap between a region of interest centered on the stimulation target and fMRI-derived language activation maps, whereas no comparable changes were observed in controls. No significant modulation effects were detected in the motor network in either group. These findings indicate that NIP can selectively reorganize the language network, with modulation patterns differing in sensorimotor networks. Importantly, language network modulation occurred while preserving language and cognitive performance. These results support NIP targeting higher-order functions such as language as a safe preoperative strategy that may reduce functional constraints on surgery and enable larger and safer resections in patients with tumors involving language-critical regions.

Background and ObjectivesThere is growing interest in thalamic sampling during epilepsy stereoelectroencephalography (sEEG). Data on thalamic sEEG safety, accuracy, and anterior (ANT), centromedian (CM), and pulvinar (PUL) nucleus connectomics is scarce. Here, we report the safety, accuracy and connectivity of thalamic sEEG and compare results to epilepsy DBS. MethodsThis single-center study included all patients with epilepsy implanted with thalamic sEEG or DBS between 2018 and 2024. Stereo-EEG surgery used a frameless stereotactic articulating arm, 3D printed stereotactic guide, or robot (sEEG lead diameter 0.8mm). DBS surgery used a rigid frame and cannula (1.81mm outer diameter). Post-surgical complications were identified by chart and imaging review. For each thalamic lead, accuracy was defined as the distance from the nearest electrode contact to the targeted nucleus Morel atlas volume (ANT, CM, or PUL), using an open-source toolbox. Estimated volumes of tissue activation/sampling were calculated for each most proximate contact for thalamocortical connectivity analysis. Connectivity analyses used a normative structural connectome, and connectivity patterns were compared. Results160 thalamic sEEG leads and 188 DBS leads were implanted across 109 and 83 patients, respectively. One sEEG patient (0.9%) developed a symptomatic intraparenchymal hemorrhage with transient weakness of the contralateral upper extremity. Eight patients with DBS had transient post-surgical symptomatic complications, three with radiographic findings. Targeting accuracy was excellent for sEEG and DBS with median proximity of 0.30mm and 0.23mm, respectively; sEEG was associated with greater variability and more outliers (proximity[&ge;]3mm; 4% vs. 0, p=0.004). Thalamocortical connectivity patterns were highly consistent between sEEG and DBS cohorts with excellent overlap for ANT, CM and PUL subgroups (Spearmans {rho}=0.86-0.98, p<1e-5). The ANT subgroup showed preferential connectivity to prefrontal and mesial temporal cortices; CM with perirolandic cortex, supplementary motor area, and subcortical regions; and PUL with mesial and neocortical temporal, and parieto-occipital regions, with some territories of overlap or under-engagement. DiscussionThalamic sEEG demonstrates a favorable safety profile, excellent targeting accuracy, and representative thalamocortical network engagement relative to DBS. Favorable sEEG safety profile may reflect difference in lead cross-sectional area (5.1-fold smaller than DBS cannula). Distinct ANT, CM, and PUL thalamocortical connectivity profiles support individualized, hypothesis-driven targeting.

ImportanceIntraventricular hemorrhage (IVH) is associated with high morbidity and mortality. A strong need exists for treatment advances. IRRAflow(R) was recently introduced as a method for minimally invasive, controlled, and accelerated IVH wash-out. However, no current evidence supports this technology. Here, we present the first pivotal safety/efficacy evaluation in a randomized controlled setting. ObjectiveTo evaluate the safety and efficacy of active hematoma irrigation using the IRRAflow(R) device compared with standard external ventricular drainage (EVD) for the IVH treatment. Design, setting, and participantsThis investigator-initiated, prospective multi-center, 1:1 randomized, single-blinded, clinical trial was conducted at the Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022 to November 24, 2022. The trial was set to include 58 IVH patients with prespecified interim analysis at final endpoint collection for the first 20 patients. InterventionsPatients were randomized to receive either IRRAflow(R) or standard EVD treatment. The IRRAflow(R) performs periodic active irrigation and aspiration contrary to standard passive gravity-driven EVD. Main outcomes and measuresOutcomes were chosen to reflect key IRRAflow(R) value propositions. The primary outcome was rate of catheter occlusions. The main outcome of the prespecified interim analysis was risk of severe adverse events (SAEs). Secondary outcomes were hematoma clearance rate, shunt dependency rate, procedure time for primary catheter placement, length of intensive care unit (ICU) stay, treatment duration, functional outcome (modified Rankin Scale (mRS) and extended Glasgow Outcome Scale (eGOS)) 90 days after inclusion, adverse events (AEs) (including catheter-related infections and procedure-related complications), and overall survival. ResultsThe study was terminated early due to a significantly increased risk of SAEs in the IRRAflow(R) group compared with EVD (risk difference = 0.43, 95% confidence interval (CI) (0.059;0.813), p=0.044), incidence rate ratio divided by person time = 6.0, 95%CI 1.38-26.11) p=0.012). The catheter occlusion rate was 37.5% in the IRRAflow(R) group versus 6.6% in the EVD group (p=0.141), which met the prespecified 0.2 alpha level. The median procedure time for primary catheter placement was 53.5 min compared with 12 min in the control group (p=0.0001). No significant difference was observed for other secondary outcomes. The majority of SAEs had a causal relationship with the intervention. Conclusion and relevanceWe found that the current IRRAflow(R) treatment is encumbered by a significantly increased number of SAEs. We recommend caution when using the device. Based on root-cause analysis, our recommendation is that a number of changes be implemented to improve the safety of the device in IVH treatment. We believe that our results are pivotal in ensuring the future safety of patients with IVH. Trial registrationClicalTrials.gov identifier: NCT05204849, registered 15 December 2021, updated 24 December 2022.

BackgroundHypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are connective tissue disorders marked by chronic pain, joint instability, and extensive multisystem involvement. Despite affecting an estimated 1 in 500 individuals, these conditions remain poorly understood, and current diagnostic categories lack clarity and consistency. This study aimed to characterize the clinical presentation, comorbidities, and healthcare burden of individuals with hEDS and HSD through a large-scale international survey. Methods and FindingsA cross-sectional, anonymous online survey was distributed globally between September 2023 and March 2024. Of 9,258 responses, 3,906 participants met inclusion criteria and were included in analysis. The 418-item questionnaire covered symptom domains, diagnoses, healthcare access, and quality of life. Responses were statistically analyzed using chi-square and Mann-Whitney U tests with Bonferroni correction and compared to the All of Us dataset (n=354,400). Participants reported high rates of gastrointestinal disorders (84.3% hEDS, 69.0% HSD), with 21.2% of hEDS participants diagnosed with gastroparesis and 7.1% requiring feeding devices. Dysautonomia was common, affecting 71.4% of those with hEDS and 40.3% with HSD (p<0.0001), with postural orthostatic tachycardia syndrome (POTS) as the most frequently reported subtype. Neurological complications were also prevalent, with hEDS participants reporting significantly higher rates of tethered cord syndrome (4.6%, 0.9%), Chiari malformation (6.3%, 0.9%), and small fiber neuropathy (10.0%, 4.4%) compared to those with HSD. Chronic pain was nearly universal (98.8% hEDS, 92.7% HSD). On average, hEDS participants reported 24 comorbid diagnoses and HSD participants 17, with diagnostic delays averaging over 20 years. Notably, 50% of those reporting HSD met hEDS criteria, while 26% of those reporting hEDS did not meet full criteria, underscoring persistent diagnostic uncertainty. ConclusionsThis global survey underscores the profound multisystemic burden, diagnostic ambiguity, and unmet clinical needs faced by individuals with hEDS and HSD. The high prevalence of immune-mediated, neurological, gastrointestinal, and autonomic dysfunctions, alongside the frequent identification of triggering events such as infections and hormonal transitions, challenges the conventional framework that defines these disorders as purely connective tissue in origin. Instead, our findings support the hypothesis that hEDS and/or HSD may represent complex syndromes in which connective tissue fragility may be a downstream consequence rather than the primary cause. This reframing has critical implications for diagnosis, pathophysiology, and therapeutic development, and highlights the need for mechanistic studies that explore distinct etiologies beyond the connective tissue paradigm.

BackgroundInflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH. MethodsIn this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation. Blood and cerebrospinal fluid (CSF) were collected to quantify inflammatory markers. Cerebral vasospasm severity and functional outcomes (modified Rankin Scale, mRS) were analyzed. ResultsNo adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than sham (p < 0.001). In the taVNS group, TNF- was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); IL-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%), with significant improvement from admission to first follow-up (p = 0.014), unlike the sham group (p = 0.18). The taVNS group had a significantly lower rate of discharge to skilled nursing facility or hospice (p = 0.04). ConclusiontaVNS is a non-invasive method of neuro- and systemic immunomodulation. This trial supports that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04557618

BackgroundDolichoectatic Vertebrobasilar fusiform aneurysm (DVBFAs) presents a clinical challenge due to its complex anatomical features and associated neurological complications. This meta-analysis evaluates the clinical outcomes of endovascular treatment (EVT), open surgery, and conservative management for VBDA. MethodsA systematic review of the PubMed, Scopus, and Web of Science databases was conducted to identify studies reporting on radiologically confirmed DVBFAs. Clinical outcomes were assessed using the modified Rankin Scale (mRS) and mortality rates. Meta-regression was performed to identify potential predictors of treatment outcomes. ResultsTen studies with 219 patients were analyzed. Of the cohort, 58.4% underwent EVT, 24.6% received open surgery, and 16.9% were managed conservatively. The overall proportion of patients achieving a good clinical outcome (mRS <3) was 46.8%, with EVT showing the highest proportion at 59.4%, compared to 32.3% for open surgery and 24.7% for conservative management (p = 0.0145). The overall mortality rate was 25.98%, with EVT having the lowest mortality rate at 10.06%, followed by open surgery at 44.44% and conservative management at 63.30% (p = 0.0004). Subgroup analyses revealed statistically significant differences between treatment approaches in clinical outcomes and mortality. ConclusionEVT appears to provide better clinical outcomes for DVBFAs, though mortality rates remain high across all treatment modalities. The absence of significant differences in subgroup analysis suggests the need for further randomized controlled trials (RCTs) of EVT vs. conservative management to establish definitive treatment guidelines.

BackgroundDeep brain stimulation (DBS) is a neuromodulation technique used to treat various refractory conditions relating to movement disorders. Its application in the stroke population has shown increasing interest in recent years, introducing promising initial results as a potential therapeutic modality for post-stroke rehabilitation. ObjectivesThis systematic review and meta-analysis critically examine the efficacy and safety of DBS for post-stroke pain, cognitive and motor outcomes. MethodsThe study was registered in PROSPERO (Registration number CRD42024586415). Following PRISMA protocol, we systematically searched PubMed, EMBASE, CINAHL and Cochrane Library databases. The primary outcome was the effectiveness of DBS in improving pain and motor functions after stroke. Secondary outcomes were the effectiveness of DBS in improving cognitive function and post-intervention complications. ResultsThe final quantitative synthesis included 10 studies reporting 109 patients. The overall pooled 1-year response rate was 0.82 [95% CI: 0.65 - 0.92] (p = 0.03), long-term response rate was 0.71 [95% CI: 0.32 - 0.92] (p < 0.01) on the random effects model. Reported overall procedural-related adverse events was 7% [95% CI: 0.04 - 0.15] and efficacy on chronic post-stroke pain VAS/BPI reduction was from 8.24 [95% CI: 7.55 - 8.72] at baseline to 4.60 [95% CI: 3.63 - 5.57], respectively (p < 0.01). A single-individual study on motor function recovery showed promising initial phase I trial results, with significant functional motor recovery and low rates of adverse events at 9%. Procedural-associated mortality was either not reported or not observed. ConclusionsDBS is a promising and novel approach for post-stroke deficits rehabilitation. With prospective initial results, further high-quality randomized trials are needed to conclusively establish efficacy across diverse post-stroke conditions, particularly for motor function recovery. Key pointsO_LIThe study demonstrated a high 1-year response rate of 82% and a long-term response rate of 71%, defined as at least a 30% improvement in symptoms. DBS showed significant efficacy in alleviating chronic post-stroke pain (CPSP), improving motor functions, and enhancing cognitive outcomes. C_LIO_LIDeep Brain Stimulation exhibited a low adverse event rate of 7%, with no procedural-related mortality reported during an average follow-up period of 29.2 months. C_LIO_LIDespite promising results, the study emphasized the need for larger, high-quality randomized controlled trials to validate findings, particularly for motor recovery. Current evidence is still very limited, as reported by early-stage trials. Further exploration of clinical feasibility, cost-effectiveness, and quality-of-life impacts should be highly considered. C_LI