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Purpose: The modified Rankin Scale (mRS), a clinician-reported outcome measure of global disability, has never been validated in patients with aneurysmal subarachnoid hemorrhage (aSAH). The aims of this study are to assess: (1) convergent validity of the mRS; (2) responsiveness of the mRS; and (3) the distribution of mRS scores across patient-reported outcome measures (PROMs). Methods: This is a prospective randomized multicenter study. The mRS was scored by a physician for all patients, and subsequently by structured interview for half of the patients and by self-assessment for the other half. All patients completed EuroQoL 5D-5L, RAND-36, Stroke Specific Quality of Life scale (SS-QoL) and Global Perceived Effect (GPE) questionnaires. Convergent validity and responsiveness were assessed by testing hypotheses. Results: In total, 149 patients with aSAH were included for analysis. The correlation of the mRS with EQ-5D-5L was r = − 0.546, while with RAND-36 physical and mental component scores the correlation was r = − 0.439and r = − 0.574 respectively, and with SS-QoL it was r = − 0.671. Three out of four hypotheses for convergent validity were met. The mRS assessed through structured interviews was more highly correlated with the mental component score than with the physical component score of RAND-36. Improvement in terms of GPE was indicated by 83% of patients; the mean change score of these patients on the mRS was − 0.08 (SD 0.915). None of the hypotheses for responsiveness were met. Conclusion: The results show that the mRS generally correlates with other instruments, as expected, but it lacks responsiveness. A structured interview of the mRS is best for detecting disabling neuropsychological complaints. Registration: URL: https://trialsearch.who.int; Unique identifier: NL7859, Date of first administration: 08-07-2019 [ABSTRACT FROM AUTHOR]

Tinnitus is the perception of sound without an external stimulus. Recently, inflammation has been implicated in the pathophysiology of tinnitus. In tinnitus animal models, cytokine levels are increased throughout the whole auditory pathway, and microglia and astrocytes are activated. However, only a few human studies on inflammation in tinnitus were conducted, which generally did not account for confounders such as hearing loss, anxiety and depression. The current study therefore aimed to evaluate the association between inflammation and tinnitus specifically in participants with (near-)normal hearing and without signs of anxiety or depression. In this cross-sectional study, fifty tinnitus participants and fifty healthy controls completed a tinnitus questionnaire and underwent audiometric testing. Complete blood count measures were determined in blood plasma, as well as cytokine concentrations by using the enzyme-linked immunosorbent assay (ELISA) technique. Platelet count and cytokine concentrations of IL-10 and IFN-γ were lower in participants with tinnitus compared to controls, and male sex, lower MCV, lower platelet count, and lower IL-10 and IFN-γ concentrations were significant predictors of tinnitus presence. The current study shows that inflammatory parameters are altered in tinnitus patients after exclusion of important confounders such as hearing loss, anxiety, depression, and inflammatory diseases., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Achieving endocrine remission by gross total resection is challenging in pituitary neuroendocrine tumours (PitNETs) with cavernous sinus invasion. This study aims to assess the safety, feasibility, and optimal dose for intraoperative fluorescence imaging as an added instrument to discriminate PitNET from surrounding tissue using bevacizumab-800CW, targeting vascular endothelial growth factor A (VEGF-A)., Methods: In part I, dose-escalation (0-4∙5-10-25 mg) was performed in 4 groups of 3 patients with PitNETs Knosp grade 3-4. In part II, after interim analysis, the 10 mg and 25 mg groups were expanded to a total of 6 patients. Quantitative fluoroscence molecular endoscopy consisted of wide field fluorescence molecular endoscopy and multi-diameter single fiber reflectance / single fiber fluorescence spectroscopy. Mean fluorescence intensity (MFI) of the fresh surgical specimen was calculated and VEGF-staining was performed., Results: Eighteen patients were included. All doses were well tolerated. Three serious adverse events were registered, but none were tracer-related. Part I showed an adequate in-vivo tumour-to-background ratio for both 10 mg (TBR 2∙00 [1∙86, 2∙19]) and 25 mg (TBR 2∙10, [1∙86, 2∙58]). Part II revealed a substantially higher MFI in the 25 mg group. With both 10 mg and 25 mg a statistically significant difference between tumour and surrounding tissue was detected (p < 0∙0001). All surgical specimens had VEGF-A expression., Conclusion: This study demonstrates the safety and feasibility of quantitative fluorescence molecular endoscopy during PitNET surgery. Both 10 mg and 25 mg bevacizumab-800CW result in clear differentiation in-vivo, with improved contrast ex-vivo (MFI) in the 25 mg group., Trial Registration: NCT04212793 / Study Details| Detection of PitNET Tissue During TSS Using Bevacizumab800CW| ClinicalTrials.gov., Competing Interests: Declarations Ethics approval- This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Groningen (Date 2020/07/27 /METc 2019/713). Consent to participate- Informed consent was obtained from all individual participants included in the study. Competing interests The authors have no relevant financial or non-financial interests to disclose. Author S Kruijff is an editor in the European Journal of Nuclear Medicine and Molecular Imaging., (© 2024. The Author(s).)

Background and Objectives: First-line therapy for most intracranial dural arteriovenous fistulas (dAVFs) is endovascular embolization, but some require microsurgical ligation due to limited endovascular accessibility, anticipated lower cure rates, or unacceptable risk profiles. We investigated the most common surgically treated dAVF locations and the approaches and outcomes of each., Methods: The Consortium for Dural Arteriovenous Fistula Outcomes Research database was retrospectively reviewed. Patients who underwent dAVF microsurgical ligation were included. Patient demographics, angiographic information, surgical details, and postoperative outcomes were collected. The 5 most common surgically treated dAVF locations were analyzed about used surgical approaches and postoperative outcomes. Univariate analyses were performed with statistical significance set at a threshold of P < .05., Results: In total, 248 patients in the Consortium for Dural Arteriovenous Fistula Outcomes Research database met inclusion criteria. The 5 most common surgically treated dAVF locations were tentorial, anterior cranial fossa (ACF), transverse-sigmoid sinus (TSS), convexity/superior sagittal sinus (SSS), and torcular. Most tentorial dAVFs were approached using a suboccipital, lateral supracerebellar infratentorial approach (39.3%); extended retrosigmoid approach (ERS) (25%); or posterior subtemporal approach (19.6%). All ACF dAVFs used a subfrontal approach; 5.3% also included an anterior interhemispheric approach. Most TSS dAVFs were ligated via ERS (31.3%) or subtemporal (31.3%) approaches. All convexity/SSS dAVFs used an interhemispheric approach. All torcular dAVFs used the suboccipital, lateral supracerebellar infratentorial approach, with 10.5% undergoing simultaneous ERS craniotomy. Angiographic occlusion rates after microsurgery were 85.5%, 100%, 75.8%, 79.2%, and 73.7% for tentorial, ACF, TSS, convexity/SSS, and torcular dAVFs, respectively (P = .02); the permanent neurological complication rates were 1.8%, 2.6%, 9.1%, 0%, and 0% (P = .31). There were no statistically significant differences in development of complications (P = .08) or Modified Rankin Scale at the last follow-up (P = .11) by fistula location., Conclusion: Although endovascular embolization is the first-line treatment for most intracranial dAVFs, surgical ligation is an important alternative. ACF and tentorial fistulas particularly demonstrate high rates of postoperative obliteration., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Increased 4-12 Hz oscillatory activity in the cortico-basal ganglia-thalamo-cortical (CBGTC) loop is reported in dystonia. Coherence analysis is a measure of linear coupling between two signals, revealing oscillatory activity drives that are common across motor units. By performing coherence analysis, activity of the CBGTC-loop can be measured with modalities like local field potentials (LFPs), electromyography (EMG), and electro-encephalography (EEG). The aim of this study is to perform a systematic review on the use of coherence analysis for clinical assessment and treatment of dystonia., Methods: A systematic review was performed on a search in Embase and PubMed on June 28th, 2023. All studies incorporating coherence analysis and an adult dystonia cohort were included. Three authors evaluated the eligibility of the articles. Quality was assessed using the QUADAS-2 checklist., Results: A total of 41 articles were included, with data of 395 adult dystonia patients. In the selected records, six different types of coherence were investigated: corticocortical, corticopallidal, corticomuscular, pallidopallidal, pallidomuscular, and intermuscular coherence. Various types of 4-12 coherence were found to be increased in all dystonia subtypes., Conclusion: There is increased 4-12 Hz coherence found between the cortex, basal ganglia, and affected muscles in all dystonia subtypes. However, the relationship between 4-12 Hz coherence and the dystonic clinical state has not been established. DBS treatment leads to a reduction of 4-12 Hz coherence. In combination with the results of this review, the 4-12 Hz frequency band can be used as a promising phenomenon for the development of a biomarker., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SAJEA Lagerweij reports a grant from the Stichting Wetenschapsfonds Dystonie and a personal grant from the University of Groningen. The funder was not involved in the study. M Smit, LM Centen, JW Elting and JMC van Dijk report no disclosures. ME van Egmond participated in a training program sponsored by Medtronic and received a grant from the Stichting Wetenschapsfonds Dystonie. MAJ Tijssen reports grants from the Netherlands Organisation for Health Research and Development Domain: NWO-TTW (2022–9), ZonMW Topsubsidie (91218013) and ZonMW Program Translational Research(40–44,600–98-323). She also received two European Fund for Regional Development from the European Union (01492947 & DIMATIO (EFRO-0059) and a European Joint Programme on Rare Diseases (EJP RD) Networking Support Scheme. A grant from the Health Holland and the PPP allowance program (PPP-2023-00).Furthermore, from the the province of Friesland, the Stichting Wetenschapsfonds Dystonie and unrestricted grants from Ipsen, Actelion and Merz. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Posterior cervical foraminotomy (posterior surgery) is a valid alternative to anterior discectomy with fusion (anterior surgery) as a surgical treatment of cervical radiculopathy, but the quality of evidence has been limited. The purpose of this study was to compare the clinical outcome of these treatments after 2 years of follow-up. We hypothesized that posterior surgery would be noninferior to anterior surgery., Methods: This multicenter, randomized, noninferiority trial assessed patients with single-level cervical radiculopathy in 9 Dutch hospitals with a follow-up duration of 2 years. The primary outcomes measured reduction of cervical radicular pain and were the success ratio based on the Odom criteria, and arm pain and decrease in arm pain, evaluated with the visual analog scale, with a 10% noninferiority margin, which represents the maximum acceptable difference between the new treatment (posterior surgery) and the standard treatment (anterior surgery), beyond which the new treatment would be considered clinically unacceptable. The secondary outcomes were neck pain, Neck Disability Index, Work Ability Index, quality of life, complications (including reoperations), and treatment satisfaction. Generalized linear mixed effects modeling was used for analyses. The study was registered at the Overview of Medical Research in the Netherlands (OMON), formerly the Netherlands Trial Register (NTR5536)., Results: From January 2016 to May 2020, 265 patients were randomized (132 to the posterior surgery group and 133 to the anterior surgery group). Among these, 25 did not have the allocated intervention; 11 of these 25 patients had symptom improvement, and the rest of the patients did not have the intervention due to various reasons. At the 2-year follow-up, of 243 patients, primary outcome data were available for 236 patients (97%). Predicted proportions of a successful outcome were 0.81 after posterior surgery and 0.74 after anterior surgery (difference in rate, -0.06 [1-sided 95% confidence interval (CI), -0.02]), indicating the noninferiority of posterior surgery. The between-group difference in arm pain was -2.7 (1-sided 95% CI, 7.4) and the between-group difference in the decrease in arm pain was 1.5 (1-sided 95% CI, 8.2), both confirming the noninferiority of posterior surgery. The secondary outcomes demonstrated small between-group differences. Serious surgery-related adverse events occurred in 9 patients (8%) who underwent posterior surgery, including 9 reoperations, and 11 patients (9%) who underwent anterior surgery, including 7 reoperations (difference in reoperation rate, -0.02 [2-sided 95% CI, -0.09 to 0.05])., Conclusions: This trial demonstrated that, after a 2-year follow-up, posterior surgery was noninferior to anterior surgery with regard to the success rate and arm pain reduction in patients with cervical radiculopathy., Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The FACET (Foraminotomy ACDF Cost-Effectiveness Trial) was funded by the Netherlands Organisation for Health Research and Development (ZonMw, 843002604). The funder had no role in design, data collection, analysis, interpretation, or writing of the report. The Article Processing Charge for open access publication was funded by the University of Groningen. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/I107 )., (Copyright © 2024 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated.)

Objective: To evaluate the diagnostic application of external ear canal sound measurements in pulsatile tinnitus (PT)., Study Design: Retrospective chart review on a prospective series of sound measurements., Setting: Tertiary referral center., Patients: A cohort of 171 PT patients with sound measurements during diagnostic workup for PT (2016-2023)., Main Outcome Measure: The percentages of PT patients per pathology and diagnosis, with PT objectified by sound measurements., Results: In 57% of the patients, an identifiable etiology that could explain the PT was identified using various imaging modalities. The PT could be detected with a sound measurement in the ear canal in 48% of these patients. In absence of an identifiable etiology, an objective PT was found in only 15% of the cases. PT was more often detected for patients with arterial pathologies than venous or nonvascular pathologies (73% vs 50% and 22%, respectively). Particularly, in PT patients with a DAVF, an objective PT was found for all patients (100%). The sound measurements were found to be more sensitive than auscultation in detecting bruits in PT patients., Conclusion: A sound recording can objectify PT in almost half of the cases with a diagnosis as determined by imaging. In patients where the PT cannot be detected, arterial pathologies (particularly DAVFs) are less likely. Combined with a thorough clinical evaluation and proper imaging studies, sound measurements can be of added value in the clinical pathway of PT patients., Competing Interests: Conflict of interest and source funding: none declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Objective: 11 C-Methionine positron emission tomography (MET-PET) is used for stereotactic radiotherapy planning in meningioma patients. The role of MET-PET during subsequent follow-up (FU) is unclear. We analyzed the uptake of 11 C-Methionine before and after stereotactic radiotherapy (SRT) in patients with a complex meningioma and investigated if there was a difference between patients with progressive disease (PD) and stable disease (SD) during FU., Methods: This retrospective study investigates 62 MET-PETs in 29 complex meningioma patients. Standardized uptake value (SUV) max and SUV peak tumor-to-normal ratios (T/N-ratios) were calculated, comparing the tumor region with both the mirroring intracranial area and the right frontal gray matter. The difference in 11 C-Methionine uptake pre- and post-SRT was analyzed, as well as the change in uptake between PD or SD., Results: Median (IQR) FU duration was 67 months (50.5-91.0). The uptake of 11 C-Methionine in meningiomas remained increased after SRT. Neither a statistically significant difference between MET-PETs before and after SRT was encountered, nor a significant difference in one of the four T/N-ratios between patients with SD versus PD with median (IQR) SUV max T/N R front 2.65 (2.13-3.68) vs 2.97 (1.55-3.54) [p = 0.66]; SUV max T/N mirror 2.92 (2.19-3.71) vs 2.95 (1.74-3.60) [p = 0.61]; SUV peak T/N R front 2.35 (1.64-3.40) vs 2.25 (1.44-3.74) [p = 0.80]; SUV peak T/N mirror 2.38 (1.91-3.36) vs 2.35 (1.56-3.72) [p = 0.95]., Conclusions: Our data do not support use of MET-PET during FU of complex intracranial meningiomas after SRT. MET-PET could not differentiate between progressive or stable disease., (© 2024. The Author(s).)

Background: Transcranial Doppler (TCD) is a technique to assess blood flow velocity in the cerebral arteries. TCD is frequently used to monitor aneurysmal subarachnoid hemorrhage (aSAH) patients. This study compares TCD-criteria for vasospasm and its association with Delayed Cerebral Ischemia (DCI). An overall score based on flow velocities of various intracranial arteries was developed and evaluated., Methods: A retrospective diagnostic accuracy study was conducted between 1998 and 2017 with 621 patients included. Mean flow velocity (MFV) of the cerebral artery was measured between 2-5 days and between 6-9 days after ictus. Cutoff values from the literature, new cutoff values, and a new composite score (Combined Severity Score) were used to predict DCI. Sensitivity, specificity, and area under the curve (AUC) were determined, and logistic regression analysis was performed., Results: The Combined Severity Score showed an AUC 0.64 (95%CI 0.56-.71) at days 2-5, with sensitivity 0.53 and specificity 0.74. The Combined Severity Score had an adjusted Odds Ratio of 3.41 (95CI 1.86-6.32) for DCI. MCA-measurements yielded the highest AUC to detect DCI at day 2-5: AUC 0.65 (95%CI 0.58-0.73). Optimal cutoff MFV of 83 cm/s for MCA resulted in sensitivity 0.73 and specificity 0.50 at days 2-5., Conclusion: TCD-monitoring of aSAH patients may be a valuable strategy for DCI risk stratification. Lower cutoff values can be used in the early phase after the ictus (day 2-5) than are commonly used now. The Combined Severity Score incorporating all major cerebral arteries may provide a meaningful contribution to interpreting TCD measurements., (© 2024. The Author(s).)

Purpose: While hearing loss is a well-known condition following microvascular decompression (MVD) for hemifacial spasm (HFS), tinnitus is an underreported one. This study aims to identify prevalence, characteristics, severity, and predictors of tinnitus following MVD for HFS., Methods: A single-center cohort of 55 HFS patients completed a questionnaire approximately 5 years following MVD. Data encompassed tinnitus presence, side, type, onset, and severity measured by a 10-point Visual Analogue Scale (VAS). Descriptive, correlation, and logistic regression analyses were conducted. RESULTS  : At surgery, participants' median age was 58 years (IQR 52-65). The median duration of HFS symptoms before surgery was 5 years (IQR 3-8), slightly predominant on the left (60%). Postoperative tinnitus was reported by 20 patients (36%), versus nine (16%) that reported preoperative tinnitus. Postoperative tinnitus was ipsilateral on the surgical side in 13 patients (65%), bilateral in six (30%), and contralateral in one (5%). Among patients with bilateral postoperative tinnitus, 33% did not have this preoperatively. Tinnitus was continuous in 70% of cases and pulsatile in 30%. Onset of new tinnitus was in 58% immediately or within days, in 25% within three months, and in 17% between three months and one year after surgery. The mean severity of postoperative tinnitus was 5.1 points on the VAS. Preoperative tinnitus and presence of arachnoid adhesions had suggestive associations with postoperative tinnitus in initial analyses (p = 0.005 and p = 0.065). However, preoperative tinnitus was the only significant predictor of postoperative tinnitus (p = 0.011)., Conclusion: Tinnitus is a common condition following MVD for HFS, with a moderate overall severity. Causes behind postoperative tinnitus remain obscure but could be related to those of postoperative hearing loss in this patient population. Clinicians should be aware of tinnitus following MVD and vigilantly monitor its occurrence, to facilitate prevention efforts and optimize outcome for HFS patients undergoing MVD., (© 2024. The Author(s).)

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recognized treatment for medication-refractory dystonia. Problems in executive functions and social cognition can be part of dystonia phenotypes. The impact of pallidal DBS on cognition appears limited, but not all cognitive domains have been investigated yet. In the present study, we compare cognition before and after GPi DBS. Seventeen patients with dystonia of various aetiology completed pre- and post-DBS assessment (mean age 51 years; range 20-70 years). Neuropsychological assessment covered intelligence, verbal memory, attention and processing speed, executive functioning, social cognition, language and a depression questionnaire. Pre-DBS scores were compared with a healthy control group matched for age, gender and education, or with normative data. Patients were of average intelligence but performed significantly poorer than healthy peers on tests for planning and for information processing speed. Otherwise, they were cognitively unimpaired, including social cognition. DBS did not change the baseline neuropsychological scores. We confirmed previous reports of executive dysfunctions in adult dystonia patients with no significant influence of DBS on cognitive functioning in these patients. Pre-DBS neuropsychological assessments appear useful as they support clinicians in counselling their patients. Decisions about post-DBS neuropsychological evaluations should be made on a case-by-case basis., (© 2023 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Objective: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion., Methods: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs., Results: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment., Conclusions: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Tremor, bradykinesia, and rigidity are incapacitating motor symptoms that can be suppressed with stereotactic neurosurgical treatment like deep brain stimulation (DBS) and ablative surgery (e.g., thalamotomy, pallidotomy). Traditionally, clinicians rely on clinical rating scales for intraoperative evaluation of these motor symptoms during awake stereotactic neurosurgery. However, these clinical scales have a relatively high inter-rater variability and rely on experienced raters. Therefore, objective registration (e.g., using movement sensors) is a reasonable extension for intraoperative assessment of tremor, bradykinesia, and rigidity. The main goal of this scoping review is to provide an overview of electronic motor measurements during awake stereotactic neurosurgery. The protocol was based on the PRISMA extension for scoping reviews. After a systematic database search (PubMed, Embase, and Web of Science), articles were screened for relevance. Hundred-and-three articles were subject to detailed screening. Key clinical and technical information was extracted. The inclusion criteria encompassed use of electronic motor measurements during stereotactic neurosurgery performed under local anesthesia. Twenty-three articles were included. These studies had various objectives, including correlating sensor-based outcome measures to clinical scores, identifying optimal DBS electrode positions, and translating clinical assessments to objective assessments. The studies were highly heterogeneous in device choice, sensor location, measurement protocol, design, outcome measures, and data analysis. This review shows that intraoperative quantification of motor symptoms is still limited by variable signal analysis techniques and lacking standardized measurement protocols. However, electronic motor measurements can complement visual evaluations and provide objective confirmation of correct placement of the DBS electrode and/or lesioning. On the long term, this might benefit patient outcomes and provide reliable outcome measures in scientific research., (© 2024. The Author(s).)

Background: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes., Methods: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC., Results: A total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (<75 vs ≥75 years), Borden classification (I vs II-III), arterial feeders (single vs multiple), and past cranial surgery (presence vs absence) were independent predictors of obliteration and used to derive the VEBAS score. A significant increase in the likelihood of complete obliteration (OR=1.37 (1.27-1.48)) with each additional point in the overall patient score (range 0-12) was demonstrated. Within the validation dataset, the predicted probability of complete dAVF obliteration increased from 0% with a 0-3 score to 72-89% for patients scoring ≥8., Conclusion: The VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration., Competing Interests: Competing interests: Dr. Kansagra is a consultant for Medtronic, Microvention, and Penumbra. Dr. Lanzino is a consultant for Superior Medical Editing. Dr. Kim is a MicroVention consultant, cofounder of SPI Surgical, and has NINDS grants. Dr. Levitt is a consultant for Medtronic and Minnetronix; he has NINDS, AHA, Stryker, and Medtronic grants and equity interest in Proprio. Dr. Gross is a MicroVention and Medtronic consultant. Dr. Derdeyn is a consultant for Penumbra, Genae, and Nono, and receives the support of non-study-related clinical or research efforts from Siemens Healthineers. Dr. Alaraj is a consultant for Cerenovus and Siemens, and has an NIH grant. Dr. Starke has consulting teaching agreements with Penumbra, Abbott, Medtronic, InNeruCo, and Cerenovus. Dr. Peterson is a consultant for Stryker, Penumbra, Medtronic, and Cerenovus, and has a stockholder in RIST Neurovascular. Dr. Samaniego is a MicroVention consultant. Dr. Piccirillo is a Bind-On-Demand insurance medical officer. Dr. Charbel is a Transonic consultant. Dr. Yavagal is a Medtronic, Cerenovus, Rapid Medical, and Neural Analytics consultant. The other authors have no personal, financial, or institutional interests to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Since 2013, deep brain stimulation (DBS) has been reimbursed in the Netherlands as a proven effective treatment for treatment-resistant obsessive-compulsive disorder (OCD). Nevertheless, DBS is still rarely applied, and a national Dutch treatment protocol is lacking., Aim: To prepare a nationwide multidisciplinary treatment protocol for the application of DBS in the treatment of treatment-resistant OCD., Method: Formulation of recommendations for the execution and application of DBS in OCD regarding indication, implantation, optimization of stimulation parameters, and consolidation of long-term effects, based on literature research and consensus among experts represented in the multidisciplinary Dutch DBS in Psychiatry working group., Results: Following indication, DBS electrodes are bilaterally implanted in white matter tracts in the anterior limb of the internal capsule. In previously highly treatment-resistant patients with severe OCD, this leads to an average 66% response rate after optimization of stimulation parameters. Placebo-controlled effects are significant (Hedges&rsquo; g = 0.9). The main reported side effects are transient hypomanic symptoms, fatigue, and subjective cognitive complaints. Perioperative complications are rare. Positive effects remain stable during years of follow-up. DBS is cost-effective and leads to increased quality of life and functional recovery. Nevertheless, DBS is applied infrequently relative to the estimated number of patients with treatment-resistant OCD., Conclusion: By adhering to the described recommendations regarding indication, implantation, optimization, and consolidation, DBS is an effective and safe treatment option for treatment-resistant OCD. A nationwide multidisciplinary treatment protocol can contribute to the implementation of DBS with more and earlier referrals, allowing more patients to benefit from this treatment more quickly.

Background and Objectives: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs., Methods: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed., Results: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09)., Conclusion: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Objective: Patients with pulsatile tinnitus (PT) are often referred for digital subtraction angiography (DSA) to exclude cranial dural arteriovenous fistula (DAVF). Because DSA is not without risk, the authors studied the sensitivity and specificity of an automated detection algorithm that analyses external ear canal sound measurements to evaluate the presence of DAVF in PT patients., Methods: Between 2015 and 2021, external ear canal sound measurements of 72 PT patients were collected prospectively at our tertiary tinnitus clinic preceding referral of these patients to the neurosurgical department for counseling about DSA. The measurements were analyzed with an algorithm that objectifies a pulsatile sound as a PT coherence index (PTCI) per frequency band., Results: Ultimately, DSA was performed in 49 PT patients. DAVF was revealed in 15 patients (31%). PTCI cutoff values of 0.7 (at 250 Hz) and 0.6 (at 1000 Hz) resulted in sensitivity of 100% (78%-100%) and specificities of 62% (44%-78%) and 68% (49%-83%), respectively, for detecting DAVF on DSA., Conclusions: Analysis of external ear canal sound measurements in PT patients showed 100% sensitivity for detecting DAVF on DSA. This analysis can potentially be used as a screening tool to help clinicians and PT patients to decide on the necessity of DSA. Retrospectively, the use of sound measurement in our cohort would have narrowed the indication for DSA to 23 of 49 cases (47%) without missing a DAVF.

Connectivity-derived 7-Tesla MRI segmentation and intraoperative microelectrode recording can both assist subthalamic nucleus targeting for deep brain stimulation in Parkinson's disease. It remains unclear whether deep brain stimulation electrodes placed in the 7-Tesla MRI segmented subdivision with predominant projections to cortical motor areas (hyperdirect pathway) achieve superior motor improvement and whether microelectrode recording can accurately distinguish the motor subdivision. In 25 patients with Parkinson's disease, deep brain stimulation electrodes were evaluated for being inside or outside the predominantly motor-connected subthalamic nucleus (motor-connected subthalamic nucleus or non-motor-connected subthalamic nucleus, respectively) based on 7-Tesla MRI connectivity segmentation. Hemi-body motor improvement (Movement Disorder Society Unified Parkinson's Disease Rating Scale, Part III) and microelectrode recording characteristics of multi- and single-unit activities were compared between groups. Deep brain stimulation electrodes placed in the motor-connected subthalamic nucleus resulted in higher hemi-body motor improvement, compared with electrodes placed in the non-motor-connected subthalamic nucleus (80% versus 52%, P < 0.0001). Multi-unit activity was found slightly higher in the motor-connected subthalamic nucleus versus the non-motor-connected subthalamic nucleus ( P < 0.001, receiver operating characteristic 0.63); single-unit activity did not differ between groups. Deep brain stimulation in the connectivity-derived 7-Tesla MRI subthalamic nucleus motor segment produced a superior clinical outcome; however, microelectrode recording did not accurately distinguish this subdivision within the subthalamic nucleus., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: Near-infrared spectroscopy (NIRS) is a noninvasive tool to monitor cerebral regional oxygen saturation. Impairment of microvascular circulation with subsequent cerebral hypoxia during delayed cerebral ischemia (DCI) is associated with poor functional outcome after subarachnoid hemorrhage (SAH). Therefore, NIRS could be useful to predict the risk for DCI and functional outcome. However, only limited data are available on NIRS regional cerebral tissue oxygen saturation (rSO 2 ) distribution in SAH. The aim of this study was to compare the distribution of NIRS rSO 2 values in patients with nontraumatic SAH with the occurrence of DCI and functional outcome at 2 months. In addition, the predictive value of NIRS rSO 2 was compared with the previously validated SAFIRE grade (derived from Size of the aneurysm, Age, FIsher grade, World Federation of Neurosurgical Societies after REsuscitation)., Methods: In this study, the rSO 2 distribution of patients with and without DCI after SAH was compared. The optimal cutoff points to predict DCI and outcome were assessed, and its predictive value was compared with the SAFIRE grade., Results: Of 41 patients, 12 developed DCI, and 9 had unfavorable outcome at 60 days. Prediction of DCI with NIRS had an area under the curve of 0.77 (95% confidence interval 0.62-0.92; P = 0.0028) with an optimal cutoff point of 65% (sensitivity 1.00; specificity 0.45). Prediction of favorable outcome with NIRS had an area under the curve of 0.86 (95% confidence interval 0.74-0.98; P = 0.0003) with an optimal cutoff point of 63% (sensitivity 1.00; specificity 0.63). Regression analysis showed that NIRS rSO 2 score is complementary to the SAFIRE grade., Conclusions: NIRS rSO 2 monitoring in patients with SAH may improve prediction of DCI and clinical outcome after SAH., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Thalamotomy alleviates medication-refractory tremors in patients with movement disorders such as Parkinson's Disease (PD), Essential tremor (ET), and Holmes tremor (HT). However, limited data are available on tremor intensity during different thalamotomy stages. Also, the predictive value of the intraoperative tremor status for treatment outcomes remains unclear. Therefore, we aimed to quantify tremor status during thalamotomy and postoperatively. Data were gathered between January 2020 and June 2023 during consecutive unilateral thalamotomy procedures in patients with PD ( n = 13), ET ( n = 8), and HT ( n = 3). MDS-UPDRS scores and tri-axial accelerometry data were obtained during rest, postural, and intention tremor tests. Measurements were performed intraoperatively (1) before lesioning-probe insertion, (2) directly after lesioning-probe insertion, (3) during coagulation, (4) directly after coagulation, and (5) 4-6 months post-surgery. Accelerometric data were recorded continuously during the coagulation process. Outcome measures included MDS-UPDRS tremor scores and accelerometric parameters (peak frequency, tremor amplitude, and area under the curve of power (AUCP)). Tremor intensity was assessed for the insertion effect (1-2), during coagulation (3), post-coagulation effect (1-4), and postoperative effect (1-5). Following insertion and coagulation, tremor intensity improved significantly compared to baseline ( p < 0.001). The insertion effect clearly correlated with the postoperative effect ( ρ = 0.863, p < 0.001). Both tremor amplitude and AUCP declined gradually during coagulation. Peak frequency did not change significantly intraoperatively. In conclusion, the study data show that both the intraoperative insertion effect and the post-coagulation effect are good predictors for thalamotomy outcomes.

Background: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs., Methods: The CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990-2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed., Results: 60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs., Conclusion: Most ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation., Competing Interests: Competing interests: LJK is a co-founder of Spi Surgical and reports compensation for consultant services from Microvention. IJA reports stock options in Remedy Robotics and compensation from Remedy Robotics and InNeuroCo for consultant services. MRL reports equity interest in Propio, Cerebrotech and Synchron, and grants from Stryker, Volcano Philips and Medtronic. MRL is part of the editorial board of JNIS. APK reports compensation from Penumbra and Microvention for consultant services. WB reports compensation for consultant services from Johnson & Johnson, Stryker, Medtronic Vascular and Microvention; compensation from MIVI Neurovascular for data and safety monitoring services; stock holdings from Marblehead Medical LLC. AJP reports compensation from DePuy Synthes Spine for consultant services. BG reports compensation from Microvention and Medtronic for consultant services. AA reports compensation from Johnson & Johnson and Cerenovous for consultant services. RMS reports consulting and teaching agreements with Penumbra, Abbott, Medtronic, InNeuroCo and Cerenovous. RD reports compensation from Grand Rounds for consultant services and compensation from NIH for other services. CD reports stock options from Euphrates Vascular; compensation from noNO and Penumbra, Inc for data and safety monitoring services. EAS is a proctor with Microvention and reports compensation from Medtronic and Rapid Medical for consultant services., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

The disease status, progression, and treatment effect of essential tremor (ET) patients are currently assessed with clinical scores, such as the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM). The use of objective and rater-independent monitoring of tremors may improve clinical care for patients with ET. Therefore, the focus of this study is to develop an objective accelerometry-based method to quantify ET, based on FTM criteria. Thirteen patients with ET and thirteen matched healthy participants underwent FTM tests to rate tremor severity, paired with tri-axial accelerometric measurements at the index fingers. Analogue FTM assessments were performed by four independent raters based on video recordings. Quantitative measures were derived from the accelerometric data, e.g., the area under the curve of power in the 4-8 Hz frequency band (AUCP) and maximal tremor amplitude. As such, accelerometric tremor scores were computed, using thresholds based on healthy measurements and FTM criteria. Agreement between accelerometric and clinical FTM scores was analyzed with Cohen's kappa coefficient. It was assessed whether there was a relationship between mean FTM scores and the natural logarithm (ln) of the accelerometric outcome measures using linear regression. The agreement between accelerometric and FTM scores was substantial for resting and intention tremor tests (≥72.7%). However, the agreement between accelerometric postural tremor data and clinical FTM ratings (κ = 0.459) was low, although their logarithmic (ln) relationship was substantial (R 2 ≥ 0.724). Accelerometric test-retest reliability was good to excellent (ICC ≥ 0.753). This pilot study shows that tremors can be quantified with accelerometry, using healthy thresholds and FTM criteria. The test-retest reliability of the accelerometric tremor scoring algorithm indicates that our low-cost accelerometry-based approach is a promising one. The proposed easy-to-use technology could diminish the rater dependency of FTM scores and enable physicians to monitor ET patients more objectively in clinical, intraoperative, and home settings., Competing Interests: The authors declare no conflict of interest.

Background: Short-term neck pain after posterior cervical foraminotomy (posterior surgery) compared with anterior cervical discectomy with fusion (anterior surgery) treating cervical radiculopathy has only been assessed once, retrospectively, to our knowledge. The aim of this study was to prospectively evaluate the course of neck pain for 6 weeks after both treatments., Methods: This is a secondary analysis of the multicenter Foraminotomy ACDF Cost-Effectiveness Trial (FACET), conducted from January 2016 to May 2020. Of 389 patients who had single-level, 1-sided cervical radiculopathy and were screened for eligibility, 265 were randomly assigned to undergo posterior surgery (n = 132) or anterior surgery (n = 133). The primary outcome of the present analysis was neck pain, assessed weekly for 6 weeks using the visual analog scale (VAS), on a scale of 0 to 100. The secondary outcomes were arm pain, neck disability, work ability, quality of life, treatment satisfaction, motor and sensory changes, and hospital length of stay. Data were analyzed with mixed model analysis in intention-to-treat samples using 2-sided 95% confidence intervals (CIs)., Results: In the first postoperative week, the mean VAS for neck pain was 56.2 mm (95% CI, 51.7 to 60.8 mm) after posterior surgery and 46.7 mm (95% CI, 42.2 to 51.2 mm) after anterior surgery. The mean between-group difference was 9.5 mm (95% CI, 3.3 to 15.7 mm), which gradually decreased to 2.3 mm (95% CI, -3.6 to 8.1 mm) at postoperative week 6. As of postoperative week 5, there was no significant difference between groups. Responder analyses confirmed this result. Secondary outcomes showed small differences between groups., Conclusions: Insight into the course of neck pain during the first 6 weeks after posterior compared with anterior surgery is provided. Despite initially more neck pain after posterior surgery, patients swiftly improved and, as of postoperative week 5, results similar to those after anterior surgery were observed. Our findings should enable improved patient counseling and enhanced shared decision-making between physicians and patients with cervical radiculopathy, where more neck pain in the first postoperative weeks should be balanced against the benefits of posterior surgery., Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H457 )., (Copyright © 2023 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Objectives: In this paper we describe an automated detection algorithm that objectively detects pulsatile tinnitus (PT) and investigate its performance., Design: Sound measurements were made with a sensitive microphone placed in the outer ear canal in 36 PT-patients referred to our tertiary clinic, along with a registration of the heart rate. A novel algorithm expressed the coherence between the recorded sound and heart rate as a pulsatility index. This index was determined for 6 octave bands of the recorded sound. We assessed the performance of the detection algorithm by comparing it with the judgement of 3 blinded observers., Results: The algorithm showed good agreement compared with the majority judgement of the blinded observers (ROC AUC 0.83). Interobserver reliability for detecting PT in sound recordings by the three blinded observers was substantial (Fleiss's κ=0.64)., Conclusions: The algorithm may be a reliable alternative to subjective assessments of in-canal sound measurements in PT-patients, thus providing clinicians with an objective measure to differentiate between subjective and objective pulsatile tinnitus., Competing Interests: Authors have no conflicts of interest or financial disclosure to report., (Copyright © 2022 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

The Movement Disorder Society Unified Parkinson's Disease Rating Scale-part III (MDS-UPDRS-III) is designed to be applied in the sitting position. However, to evaluate the clinical effect during stereotactic neurosurgery or to assess bedridden patients with Parkinson's disease (PD), the MDS-UPDRS-III is often used in a supine position. This explorative study evaluates the agreement of the MDS-UPDRS-III in the sitting and the supine positions. In 23 PD patients, the MDS-UPDRS-III was applied in both positions while accelerometric measurements were performed. Video recordings of the assessments were evaluated by two certified raters. Agreement between the sitting and supine MDS-UPDRS-III was studied using Cohen's kappa coefficient. Relationships between the MDS-UPDRS-III tremor scores and accelerometric amplitudes were calculated for both positions with linear regression. A fair to substantial agreement was found for MDS-UPDRS-III scores of individual items in the sitting and supine positions, while combining all tests resulted in a substantial agreement. The inter-rater reliability was fair to moderate for both positions. A logarithmic relationship between tremor scores and accelerometric amplitude was revealed for both the sitting and supine positions. Nevertheless, these data are insufficient to fully support the supine application of the MDS-UPDRS-III. Several recommendations are made to address the sensitivity of the scale to inter-rater variability. In conclusion, although an overall substantial agreement between sitting and supine MDS-UPDRS-III is confirmed, its application in the supine position is not endorsed for the whole range of its individual items. Caution is warranted in interpreting the supine MDS-UPDRS-III, pending additional research.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective neurosurgical treatment for Parkinson's disease. Surgical accuracy is a critical determinant to achieve an adequate DBS effect on motor performance. A two-millimetre surgical accuracy is commonly accepted, but scientific evidence is lacking. A systematic review and meta-analysis of study-level and individual patient data (IPD) was performed by a comprehensive search in MEDLINE, EMBASE and Cochrane Library. Primary outcome measures were (1) radial error between the implanted electrode and target; (2) DBS motor improvement on the Unified Parkinson's Disease Rating Scale part III (motor examination). On a study level, meta-regression analysis was performed. Also, publication bias was assessed. For IPD meta-analysis, a linear mixed effects model was used. Forty studies (1391 patients) were included, reporting radial errors of 0.45-1.86 mm. Errors within this range did not significantly influence the DBS effect on motor improvement. Additional IPD analysis (206 patients) revealed that a mean radial error of 1.13±0.75 mm did not significantly change the extent of DBS motor improvement. Our meta-analysis showed a huge publication bias on accuracy data in DBS. Therefore, the current literature does not provide an unequivocal upper threshold for acceptable accuracy of STN-DBS surgery. Based on the current literature, DBS-electrodes placed within a 2 mm range of the intended target do not have to be repositioned to enhance motor improvement after STN-DBS for Parkinson's disease. However, an indisputable upper cut-off value for surgical accuracy remains to be established. PROSPERO registration number is CRD42018089539., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: During the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS., Materials and Methods: Thirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout)., Results: Postinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01)., Conclusion: The MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The choice between posterior cervical foraminotomy (posterior surgery) and anterior cervical discectomy with fusion (anterior surgery) for cervical foraminal radiculopathy remains controversial., Objective: To investigate the noninferiority of posterior vs anterior surgery in patients with cervical foraminal radiculopathy with regard to clinical outcomes after 1 year., Design, Setting, and Participants: This multicenter investigator-blinded noninferiority randomized clinical trial was conducted from January 2016 to May 2020 with a total follow-up of 2 years. Patients were included from 9 hospitals in the Netherlands. Of 389 adult patients with 1-sided single-level cervical foraminal radiculopathy screened for eligibility, 124 declined to participate or did not meet eligibility criteria. Patients with pure axial neck pain without radicular pain were not eligible. Of 265 patients randomized (132 to posterior and 133 to anterior), 15 were lost to follow-up and 228 were included in the 1-year analysis (110 in posterior and 118 in anterior)., Interventions: Patients were randomly assigned 1:1 to posterior foraminotomy or anterior cervical discectomy with fusion., Main Outcomes and Measures: Primary outcomes were proportion of success using Odom criteria and decrease in arm pain using a visual analogue scale from 0 to 100 with a noninferiority margin of 10% (assuming advantages with posterior surgery over anterior surgery that would justify a tolerable loss of efficacy of 10%). Secondary outcomes were neck pain, disability, quality of life, work status, treatment satisfaction, reoperations, and complications. Analyses were performed with 2-proportion z tests at 1-sided .05 significance levels with Bonferroni corrections., Results: Among 265 included patients, the mean (SD) age was 51.2 (8.3) years; 133 patients (50%) were female and 132 (50%) were male. Patients were randomly assigned to posterior (132) or anterior (133) surgery. The proportion of success was 0.88 (86 of 98) in the posterior surgery group and 0.76 (81 of 106) in the anterior surgery group (difference, -0.11 percentage points; 1-sided 95% CI, -0.01) and the between-group difference in arm pain was -2.8 (1-sided 95% CI, -9.4) at 1-year follow-up, indicating noninferiority of posterior surgery. Decrease in arm pain had a between-group difference of 3.4 (1-sided 95% CI, 11.8), crossing the noninferiority margin with 1.8 points. All secondary outcomes had 2-sided 95% CIs clustered around 0 with small between-group differences., Conclusions and Relevance: In this randomized clinical trial, posterior surgery was noninferior to anterior surgery for patients with cervical radiculopathy regarding success rate and arm pain at 1 year. Decrease in arm pain and secondary outcomes had small between-group differences. These results may be used to enhance shared decision-making., Trial Registration: Netherlands Trial Register Identifier: NTR5536.

This study aims to validate a numerical model developed for assessing personalized circle of Willis (CoW) hemodynamics under pathological conditions. Based on 66 computed tomography angiography images, investigations were obtained from 43 acute aneurysmal subarachnoid hemorrhage (aSAH) patients from a local neurovascular center. The mean flow velocity of each artery in the CoW measured using transcranial Doppler (TCD) and simulated by the numerical model was obtained for comparison. The intraclass correlation coefficient (ICC) over all cerebral arteries for TCD and the numerical model was 0.88 (N = 561; 95% CI 0.84-0.90). In a subgroup of patients who had developed delayed cerebral ischemia (DCI), the ICC had decreased to 0.72 but remained constant with respect to changes in blood pressure, Fisher grade, and location of ruptured aneurysm. Our numerical model showed good agreement with TCD in assessing the flow velocity in the CoW of patients with aSAH. In conclusion, the proposed model can satisfactorily reproduce the cerebral hemodynamics under aSAH conditions by personalizing the numerical model with TCD measurements. Clinical trial registration : [http://www.trialregister.nl/], identifier [NL8114]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, van der Harst, Wei, Bokkers, van Dijk and Uyttenboogaart.)

Objective: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD., Methods: EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated., Results: Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01)., Conclusions: Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement., Significance: We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Aneurysmal rerupture is one of the most important determents for outcome after aneurysmal subarachnoid hemorrhage and still occurs frequently because individual risk assessment is challenging given the heterogeneity in patient characteristics and aneurysm morphology., Objective: To develop and internally validate a practical prediction model to estimate the risk of aneurysmal rerupture before aneurysm closure., Methods: We designed a multinational cohort study of 2 prospective hospital registries and 3 retrospective observational studies to predict the risk of computed tomography confirmed rebleeding within 24 and 72 hours after ictus. We assessed predictors with Cox proportional hazard regression analysis., Results: Rerupture occurred in 269 of 2075 patients. The cumulative incidence equaled 7% and 11% at 24 and 72 hours, respectively. Our base model included hypertension, World Federation of Neurosurgical Societies scale, Fisher grade, aneurysm size, and cerebrospinal fluid drainage before aneurysm closure and showed good discrimination with an optimism corrected c-statistic of 0.77. When we extend the base model with aneurysm irregularity, the optimism-corrected c-statistic increased to 0.79., Conclusion: Our prediction models reliably estimate the risk of aneurysm rerupture after aneurysmal subarachnoid hemorrhage using predictor variables available upon hospital admission. An online prognostic calculator is accessible at https://www.evidencio.com/models/show/2626 ., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

Background: The risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased in postmenopausal women compared with men of similar age, suggesting a role for sex hormones. We aimed to explore whether sex hormones, and age at menarche/menopause have a causal effect on aSAH risk by conducting a 2-sample MR study (Mendelian randomization)., Methods: We obtained sex-specific genetic instruments for serum estradiol, bioavailable testosterone (BioT), SHBG (sex hormone-binding globulin), and age at menarche/menopause from genome-wide association studies. The associated sex-specific aSAH risk was estimated with inverse-variance weighted MR analyses with various statistical sensitivity analyses. Multivariable and cluster MR analyses were performed for BioT and SHBG to account for a genetic and phenotypic correlation between the 2 exposures. The clusters represented (1) single-nucleotide polymorphisms primarily increasing SHBG, with secondary decreasing effects on BioT, and (2) single-nucleotide polymorphisms affecting BioT without affecting SHBG., Results: Univariable MR analyses showed an 18% increased aSAH risk among women per 1-SD increase in genetically determined SHBG levels (odds ratio, 1.18 [95% CI, 1.05-1.34]; P =0.007). Suggestive evidence was identified for a 27% decreased risk of aSAH among women per 1-SD increase in BioT (odds ratio, 0.73 [95% CI, 0.55-0.95]; P =0.02). The latter association disappeared in cluster analysis when only using SHBG-independent variants. MR analyses with variants from the cluster with primary SHBG effects and secondary (opposite) BioT-effects yielded a statistically significant association (odds ratio, 1.21 [95% CI, 1.05-1.40]; P =0.008). No other causal associations were identified., Conclusions: Genetic predisposition to elevated serum levels of SHBG, with secondary lower serum BioT levels, is associated with an increased aSAH risk among women, suggesting that SHBG and BioT causally elevate aSAH risk. Further studies are required to elucidate the underlying mechanisms and their potential as an interventional target to lower aSAH incidence.

Background: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage., Methods: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference., Results: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2-14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3-5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7-12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4-37.7; P , 0.026)., Conclusions: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Background: The role of regional hemodynamics in the intracranial aneurysmal formation, growth, and rupture has been widely discussed based on numerical models over the past decades. Variation of the circle of Willis (CoW), which results in hemodynamic changes, is associated with the aneurysmal formation and rupture. However, such correlation has not been further clarified yet. The aim of this systematic review is to investigate whether simulated hemodynamic indices of the CoW are relevant to the formation, growth, or rupture of intracranial aneurysm. Methods: We conducted a review of MEDLINE, Web of Science, and EMBASE for studies on the correlation between hemodynamics indices of the CoW derived from numerical models and intracranial aneurysm up to December 2020 in compliance with PRISMA guidelines. Results: Three case reports out of 1046 publications met our inclusion and exclusion criteria, reporting 13 aneurysms in six patients. Eleven aneurysms were unruptured, and the state of the other two aneurysms was unknown. Wall shear stress, oscillatory shear index, von-Mises tension, flow velocity, and flow rate were reported as hemodynamic indices. Due to limited cases and significant heterogeneity between study settings, meta-analysis could not be performed. Conclusion: Numerical models can provide comprehensive information on the cerebral blood flow as well as local flow characteristics in the intracranial aneurysm. Based on only three case reports, no firm conclusion can be drawn regarding the correlation between hemodynamic parameters in the CoW derived from numerical models and aneurysmal formation or rupture. Due to the inherent nature of numerical models, more sensitive analysis and rigorous validations are required to determine its measurement error and thus extend their application into clinical practice for personalized management. Prospero registration number: CRD42021125169.

Differentiation of pituitary neuroendocrine tumor (PitNET) tissue from surrounding normal tissue during surgery is challenging. A number of fluorescent agents is available for visualization of tissue discrepancy, with the potential of improving total tumor resection. This review evaluates the availability, clinical and technical applicability of the various fluorescent agents within the field of pituitary surgery. According to PRISMA guidelines, a systematic review was performed to identify reports describing results of in vivo application of fluorescent agents. In this review, 15 publications were included. Sodium Fluorescein (FNa) was considered in two studies. The first study reported noticeable fluorescence in adenoma tissue, the second demonstrated the strongest fluorescence in non-functioning pituitary adenomas. 5-Aminolevulinic acid (5-ALA) was investigated in three studies. One study compared laser-based optical biopsy system (OBS) with photo-diagnostic filter (PD) and found that the OBS was able to detect all microadenomas, even when MRI was negative. The second study retrospectively analyzed twelve pituitary adenomas and found only one positive for fluorescence. The third investigated fifteen pituitary adenomas of which one displayed vague fluorescence. Indocyanine green (ICG) was researched in four studies with variable results. Second-Window ICG yielded no significant difference between functioning and non-functioning adenomas in one study, while a second study displayed 4 times higher fluorescence in tumor tissue than in normal tissue. In three studies, OTL38 showed potential in non-functioning pituitary adenomas. At present, evidence for fluorescent agents to benefit total resection of PitNETs is lacking. OTL38 can potentially serve as a selective fluorescent agent in non-functioning pituitary adenomas in the near future., (© 2022. The Author(s).)

Background and Objectives: The modified Rankin Scale (mRS) is one of the most frequently used outcome measures in trials in patients with an aneurysmal subarachnoid hemorrhage (aSAH). The assessment method of the mRS is often not clearly described in trials, while the method used might influence the mRS score. The aim of this study is to evaluate the inter-method reliability of different assessment methods of the mRS., Methods: This is a prospective, randomized, multicenter study with follow-up at 6 weeks and 6 months. Patients aged ≥ 18 years with aSAH were randomized to either a structured interview or a self-assessment of the mRS. Patients were seen by a physician who assigned an mRS score, followed by either the structured interview or the self-assessment. Inter-method reliability was assessed with the quadratic weighted kappa score and percentage of agreement. Assessment of feasibility of the self-assessment was done by a feasibility questionnaire., Results: The quadratic weighted kappa was 0.60 between the assessment of the physician and structured interview and 0.56 between assessment of the physician and self-assessment. Percentage agreement was, respectively, 50.8 and 19.6%. The assessment of the mRS through a structured interview and by self-assessment resulted in systematically higher mRS scores than the mRS scored by the physician. Self-assessment of the mRS was proven feasible., Discussion: The mRS scores obtained with different assessment methods differ significantly. The agreement between the scores is low, although the reliability between the assessment methods is good. This should be considered when using the mRS in clinical trials., Trial Registration: www.trialregister.nl ; Unique identifier: NL7859., (© 2021. The Author(s).)

Tinnitus is the perception of sound without an external source. The flocculus (FL) and paraflocculus (PFL), which are small lobules of the cerebellum, have recently been implicated in its pathophysiology. In a previous study, the volume of the (P)FL-complex correlated with tinnitus severity in patients that had undergone cerebellopontine angle (CPA) tumor removal. In this study, the relation between tinnitus and gray matter volume (GMV) of the (P)FL-complex, GMV of the other cerebellar lobules and GMV of the cerebellar nuclei is investigated in otherwise healthy participants. Data was processed using the SUIT toolbox, which is dedicated to analysis of imaging data of the human cerebellum. GMV of all cerebellar lobules and nuclei were similar between tinnitus and non-tinnitus participants. Moreover, no relation was present between tinnitus severity, as measured by the Tinnitus Handicap Inventory, and (P)FL-complex GMV, tonsil GMV, or total cerebellar cortical GMV. These results suggest that in otherwise healthy participants, in contrast to participants after CPA tumor removal, no relation between the GMV of neither the (P)FL-complex nor other cerebellar lobules and tinnitus presence and severity exists. These findings indicate that a relation only exists when the (P)FL-complex is damaged, for instance by a CPA tumor. Alternatively, it is possible that differences in (P)FL-complex GMVs are too small to detect with a voxel-based morphometry study. Therefore, the role of the (P)FL-complex in tinnitus remains to be further studied., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mennink, Koops, Langers, Aalbers, van Dijk and van Dijk.)

The most frequently used method for evaluating tremor in Parkinson’s disease (PD) is currently the internationally standardized Movement Disorder Society—Unified PD Rating Scale (MDS-UPDRS). However, the MDS-UPDRS is associated with limitations, such as its inherent subjectivity and reliance on experienced raters. Objective motor measurements using accelerometry may overcome the shortcomings of visually scored scales. Therefore, the current study focuses on translating the MDS-UPDRS tremor tests into an objective scoring method using 3D accelerometry. An algorithm to measure and classify tremor according to MDS-UPDRS criteria is proposed. For this study, 28 PD patients undergoing neurosurgical treatment and 26 healthy control subjects were included. Both groups underwent MDS-UPDRS tests to rate tremor severity, while accelerometric measurements were performed at the index fingers. All measurements were performed in an off-medication state. Quantitative measures were calculated from the 3D acceleration data, such as tremor amplitude and area-under-the-curve of power in the 4−6 Hz range. Agreement between MDS-UPDRS tremor scores and objective accelerometric scores was investigated. The trends were consistent with the logarithmic relationship between tremor amplitude and MDS-UPDRS score reported in previous studies. The accelerometric scores showed a substantial concordance (>69.6%) with the MDS-UPDRS ratings. However, accelerometric kinetic tremor measures poorly associated with the given MDS-UPDRS scores (R2 < 0.3), mainly due to the noise between 4 and 6 Hz found in the healthy controls. This study shows that MDS-UDPRS tremor tests can be translated to objective accelerometric measurements. However, discrepancies were found between accelerometric kinetic tremor measures and MDS-UDPRS ratings. This technology has the potential to reduce rater dependency of MDS-UPDRS measurements and allow more objective intraoperative monitoring of tremor.

Cerebral hemodynamics play an important role in the development of cerebrovascular diseases. In this work, we propose a numerical framework for modeling patient-specific cerebral blood flow, using commonly available clinical datasets. Our hemodynamic model was developed using Simscape Fluids library in Simulink, based on a block diagram language. Medical imaging data obtained from computerized tomography angiography (CTA) in 59 patients with aneurysmal subarachnoid hemorrhage was used to extract arterial geometry parameters. Flow information obtained from transcranial Doppler (TCD) measurement was employed to calibrate input parameters of the hemodynamic model. The results show that the proposed numerical model can reproduce blood flow in the circle of Willis (CoW) per patient per measurement set. The resistance at the distal end of each terminal branch was the predominant parameter for the flow distribution in the CoW. The proposed model may be a promising tool for assessing cerebral hemodynamics in patients with cerebrovascular disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shen, Wei , Bokkers , Uyttenboogaart  and Van Dijk.)

The prognosis of aneurysmal subarachnoid hemorrhage (aSAH) is highly variable. This study aims to investigate whether skeletal muscle atrophy and myosteatosis are associated with poor outcome after aSAH. In this study, a cohort of 293 consecutive aSAH-patients admitted during a 4-year period was retrospectively analyzed. Cross-sectional muscle measurements were obtained at the level of the third cervical vertebra. Muscle atrophy was defined by a sex-specific cutoff value. Myosteatosis was defined by a BMI-specific cutoff value. Poor neurological outcome was defined as modified Rankin Scale 4-6 at 2 and 6-month follow-up. Patient survival state was checked until January 2021. Generalized estimating equation was performed to assess the effect of muscle atrophy / myosteatosis on poor neurological outcome after aSAH. Cox regression was performed to analyze the impact of muscle atrophy and myosteatosis on overall survival. The study found that myosteatosis was associated with poor neurological condition (WFNS 4-5) at admission after adjusting for covariates (odds ratio [OR] 2.01; 95%CI 1.05,3.83; P = .03). It was not associated with overall survival (P = .89) or with poor neurological outcomes (P = .18) when adjusted for other prognostic markers. Muscle atrophy was not associated with overall survival (P = .58) or neurological outcome (P = .32) after aSAH. In conclusion, myosteatosis was found to be associated with poor physical condition directly after onset of aSAH. Skeletal muscle atrophy and myosteatosis were however irrelevant to outcome in the Western-European aSAH patient. Future studies are needed to validate these finding., Competing Interests: The authors have declared that no competing interests exist.

Subjective tinnitus is the perception of sound without the presence of an external source. Increasing evidence suggests that tinnitus is associated with inflammation. In this systematic review, the role of inflammation in subjective tinnitus was studied. Nine animal and twenty human studies reporting inflammatory markers in both humans and animals with tinnitus were included. It was established that TNF-α and IL-1β are increased in tinnitus, and that microglia and astrocytes are activated as well. Moreover, platelet activation may also play a role in tinnitus. In addition, we elaborate on mechanisms of inflammation in tinnitus, and discuss potential treatment options targeting inflammatory pathways.

Background and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture., Methods: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage., Results: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (≥7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90)., Conclusions: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.

Background and Purpose: Delayed cerebral ischaemia (DCI) is a severe complication of aneurysmal subarachnoid hemorrhage that can significantly impact clinical outcome. Cerebral vasospasm is part of the pathophysiology of DCI and therefore a computed tomography angiography (CTA) Vasospasm Score was developed and an exploration was carried out of whether this score predicts DCI and subsequent poor outcome after aneurysmal subarachnoid hemorrhage., Methods: The CTA Vasospasm Score sums the degree of angiographic cerebral vasospasm of 17 intradural arterial segments. The score ranges from 0 to 34 with a higher score reflecting more severe vasospasm. Outcome measures were cerebral infarction due to DCI (CI-DCI), radiological and clinical DCI, and unfavorable functional outcome defined as a modified Rankin Scale >2 at 6 months. Receiver operating characteristic analyses were used to assess predictive value and to determine optimal cut-off scores. Inter-rater reliability was evaluated by Cohen's kappa coefficient., Results: This study included 59 patients. CI-DCI occurred in eight patients (14%), DCI in 14 patients (24%) and unfavorable outcome in 12 patients (20%). Median CTA Vasospasm Scores were higher in patients with (CI-)DCI and poor outcome. Receiver operating characteristic analysis revealed the highest area under the curve on day 5: CI-DCI 0.89 (95% confidence interval [CI] 0.79-0.99), DCI 0.68 (95% CI 0.50-0.87) and functional outcome 0.74 (95% CI 0.57-0.91). Cohen's kappa between the two raters was moderate to substantial (0.57-0.63)., Conclusions: This study demonstrates that the CTA Vasospasm Score on day 5 can reliably identify patients with a high risk of developing (CI-)DCI and unfavorable outcome., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

There is a growing interest in deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) as a potential therapeutic modality for Parkinson's disease dementia (PDD). Low-frequency stimulation has yielded encouraging results in individual patients; however, these are not yet sustained in larger studies. With the aim to expand the understanding of NBM-DBS, we share our experience with serendipitous NBM-DBS in patients treated with DBS of the internal Globus pallidus (GPi) for Parkinson's disease. Since NBM is anatomically located ventral to GPi, several GPi-treated patients appeared to have the distal contact of DBS-electrode(s) positioned in the NBM. We hypothesized that unintentional high-frequency NBM-DBS over a period of one year would result in the opposite effect of low-frequency NBM-stimulation and cause cognitive decline. We studied a cohort of 33 patients with bilateral high-frequency DBS in the GPi for Parkinson's disease, of which twelve were unintentionally co-stimulated in NBM. The subgroups of unintentional unilateral ( N = 7) and bilateral NBM-DBS ( N = 5) were compared to the control group of bilateral GPi-DBS ( N = 11). Here, we show that unintentional high-frequency NBM-DBS did not cause a significantly faster decline in cognitive function. Further research is warranted for characterizing the therapeutic role of NBM-DBS.

Background: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance., Objective: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs., Methods: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models., Results: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes., Conclusions: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications., Competing Interests: Competing interests: RMS research is supported by the Neurosurgery Research and Education Foundation, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, and by the National Institute of Health (R01NS111119-01A1) and (UL1TR002736, KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. The paper's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. RMS has an unrestricted research grant from Medtronic and has consulting and teaching agreements with Penumbra, Abbott, Medtronic, InNeuroCo, and Cerenovus. LJK reports funding support from the NINDS, consultant fees from Microvention, and stock ownership in Spi Surgical. MRL reports funding support from the National Institute of Neurological Disorders and Stroke, American Heart Association, Stryker, and Medtronic; consultant fees from Medtronic and Minnetronix; and equity interest from Proprio. AA reports funding support from the NIH, and consultant fees from Cerenovus. JFP reports consultant fees from Transonic. APK reports consultant fees from Medtronic and Penumbra. FTC reports serving as medical advisor for Bind-On Demand Health Insurance. DRY reports consultant fees from Medtronic, Cerenovus, and Rapid Medical and Neural Analytics. ECP reports consultant fees from Stryker Neurovascular, Penumbra, Medtronic, and Cerenovus, and stock ownership in RIST Neurovascular. BAG reports consultant fees from Microvention., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIAs) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA., Methods: For this IPD meta-analysis, we performed an Embase and PubMed search for studies published up to December 1, 2020. We included studies that (1) had a prospective study design; (2) included 50 or more patients with UIA; (3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and (4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial vs sporadic UIA using a Cox proportional hazard regression model adjusted for PHASES score and smoking. We performed 2 analyses: (1) only studies defining first-degree relatives as parents, children, and siblings and (2) all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings., Results: We pooled IPD from 8 cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings, and children in 6 cohorts (29% Dutch, 55% Finnish, 15% Japanese), totaling 2,297 patients (17% familial, 399 patients) with 3,089 UIAs and 7,301 person-years follow-up. Rupture occurred in 10 familial cases (rupture rate: 0.89%/person-year; 95% confidence interval [CI] 0.45-1.59) and 41 sporadic cases (0.66%/person-year; 95% CI 0.48-0.89); adjusted hazard ratio (HR) for familial cases 2.56 (95% CI 1.18-5.56). After adding the 2 cohorts excluding siblings as first-degree relatives, resulting in 9,511 patients, the adjusted HR was 1.44 (95% CI 0.86-2.40)., Discussion: The risk of rupture of UIA is 2.5 times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account., (© 2021 American Academy of Neurology.)