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Objective: Chronic subdural hematoma (CSDH) is a common neurological condition and is typically treated with burr hole craniostomy. Nevertheless, conservative treatment may lead to spontaneous hematoma resolution in some patients. This study aims to describe the characteristics of patients who were treated conservatively without the eventual need for additional treatment. Methods: Data were retrospectively collected from patients who were primarily treated conservatively in three hospitals in the Netherlands from 2008 to 2018. The Primary outcome was the nonnecessity of additional treatment within 3 months after the initial CSDH diagnosis. We used univariable and multivariable logistic regression analyses to identify factors associated with not receiving additional treatment. Results: In this study, 83 patients were included and 61 patients (73%) did not receive additional treatment within 3 months. Upon first presentation, the patients had a Markwalder Grading Scale score (MGS) of 0 (n = 5, 6%), 1 (n = 43, 52%), and 2 (n = 35, 42%). Additional treatment was less often received by patients with smaller hematoma volumes (adjusted odds ratio [aOR] 0.78 per 10 mL; 95% confidence interval [CI] 0.64–0.92). Patients using antithrombotic medication also received less additional treatment, but this association was not significant (aOR 2.02; 95% CI 0.61–6.69). Conclusions: Three quarters of the initially conservatively treated CSDH patients do not receive additional management. Typically, these patients have smaller hematoma volumes. Further, prospective research is needed to distinguish which patients require surgical intervention and in whom primary conservative treatment suffices.

BACKGROUND: Migraine prevalence and levels of calcitonin gene-related peptide (CGRP), a peptide involved in migraine pathophysiology, differ between men and women, and appear to be affected by changes in sex hormones. The present study investigated the sex-specific responses to CGRP in human isolated arteries. METHODS: CGRP-induced relaxation of 62 (28 men and 34 women) human isolated middle meningeal arteries (HMMA) and 139 (69 men and 70 women) human isolated coronary arteries (HCA) was compared between men and women in groups <50 years and ≥50 years of age as a proxy for pre- and postmenopausal status in women, as well as matched-age groups for men.RESULTS: In HCA, no differences were observed between male and female tissue, or between the different age groups. However, in HMMA, the maximum response was significantly smaller and CGRP was less potent in females <50 compared with males <50 years of age. No differences were observed between the older age groups. CONCLUSIONS: Sex differences were observed for CGRP-induced relaxation of HMMA, but not HCA. These differences could arise from differential receptor expression in the vascular beds combined with the effect of sex hormones on CGRP and subsequent receptor desensitization.

Background: Orally administered second-generation gepants are effective for the treatment of migraine. The intranasal administration of the third-generation gepant zavegepant might have additional benefits including a rapid onset of action, but it is not clear yet to which extent this has clinical relevance. Methods: We examined the effect of zavegepant on the relaxations induced by calcitonin gene-related peptide (CGRP) in human isolated middle meningeal arteries. Furthermore, we connected the pharmacodynamics and pharmacokinetics of gepants by combining data from clinical and basic research. Results: We showed that 10 nM zavegepant potently antagonized the functional response to CGRP. We also showed that all gepants are effective at inhibiting functional responses to CGRP at their therapeutic plasma concentrations. Conclusions: The relatively low predicted potency of zavegepant to inhibit CGRP-induced relaxation at therapeutic systemic plasma concentrations may point to the relevance of local delivery to the trigeminovascular system through intranasal administration. This approach may have additional benefits for various groups of patients, including overweight patients.

Background: Ruptured intracranial aneurysms resulting in subarachnoid haemorrhage can be treated by open surgical or endovascular treatment. Despite multiple previous studies, uncertainties on the optimal treatment practice still exists. The resulting treatment variation may result in a variable, potentially worse, patient outcome. To better inform future treatment strategies, this study aims to identify the effectiveness of different treatment strategies in patients with ruptured intracranial aneurysms by investigating long-term functional outcome, complications and cost-effectiveness. An explorative analysis of the diagnostic and prognostic value of radiological imaging will also be performed. Methods: This multi-centre observational prospective cohort study will have a follow-up of 10 years. A total of 880 adult patients with a subarachnoid haemorrhage caused by a ruptured intracranial aneurysm will be included. Calculation of sample size (N = 880) was performed to show non-inferiority of clip-reconstruction compared to endovascular treatment on 1 year outcome, assessed by using the ordinal modified Rankin Scale. The primary endpoint is the modified Rankin Scale score and mortality at 1 year after the initial subarachnoid haemorrhage. Patients will receive ‘non-experimental’ regular care during their hospital stay. For this study, health questionnaires and functional outcome will be assessed at baseline, before discharge and at follow-up visits. Discussion: Despite the major healthcare and societal burden, the optimal treatment strategy for patients with subarachnoid haemorrhage caused by ruptured intracranial aneurysms is yet to be determined. Findings of this comparative effectiveness study, in which in-between centre variation in practice and patient outcome are investigated, will provide evidence on the effectiveness of treatment strategies, hopefully contributing to future high value treatment standa

Background: Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors. Methods: In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders. Results: Based on predetermined in-and exclusion criteria, 275 patients, on average 5.3 (SDa=a2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue. Conclusions: Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient-and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population.

Importance: Testing new medical devices or procedures in terms of safety, effectiveness, and durability should follow the strictest methodological rigor before implementation. Objectives: To review and analyze studies investigating devices and procedures used in intracranial aneurysm (IA) treatment for methods and completeness of reporting and to compare the results of studies with positive, uncertain, and negative conclusions. Data Sources: Embase, MEDLINE, Web of Science, and The Cochrane Central Register of Clinical Trials were searched for studies on IA treatment published between January 1, 1995, and the October 1, 2022. Grey literature was retrieved from Google Scholar. Study Selection: All studies making any kind of claims of safety, effectiveness, or durability in the field of IA treatment were included. Data Extraction and Synthesis: Using a predefined data dictionary and analysis plan, variables ranging from patient and aneurysm characteristics to the results of treatment were extracted, as were details pertaining to study methods and completeness of reporting. Extraction was performed by 10 independent reviewers. A blinded academic neuro-linguist without involvement in IA research evaluated the conclusion of each study as either positive, uncertain, or negative. The study followed Preferring Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Main Outcomes and Measures: The incidence of domain-specific outcomes between studies with positive, uncertain, or negative conclusions regarding safety, effectiveness, or durability were compared. The number of studies that provided a definition of safety, effectiveness, or durability and the incidence of incomplete reporting of domain-specific outcomes were evaluated.Results: Overall, 12 954 studies were screened, and 1356 studies were included, comprising a

Background: Previous randomised controlled trials could not demonstrate that surgical evacuation of intracerebral haemorrhage (ICH) improves functional outcome. Increasing evidence suggests that minimally invasive surgery may be beneficial, in particular when performed early after symptom onset. The aim of this study was to investigate safety and technical efficacy of early minimally invasive endoscopy-guided surgery in patients with spontaneous supratentorial ICH. Methods: The Dutch Intracerebral Haemorrhage Surgery Trial pilot study was a prospective intervention study with blinded outcome assessment in three neurosurgical centres in the Netherlands. We included adult patients with spontaneous supratentorial ICH ≥10mL and National Institute of Health Stroke Scale (NIHSS) score ≥2 for minimally invasive endoscopy-guided surgery within 8 h after symptom onset in addition to medical management. Primary safety outcome was death or increase in NIHSS ≥4 points at 24 h. Secondary safety outcomes were procedure-related serious adverse events (SAEs) within 7 days and death within 30 days. Primary technical efficacy outcome was ICH volume reduction (%) at 24 h. Results: We included 40 patients (median age 61 years; IQR 51–67; 28 men). Median baseline NIHSS was 19.5 (IQR 13.3–22.0) and median ICH volume 47.7mL (IQR 29.4–72.0). Six patients had a primary safety outcome, of whom two already deteriorated before surgery and one died within 24 h. Sixteen other SAEs were reported within 7 days in 11 patients (of whom two patients that already had a primary safety outcome), none device related. In total, four (10%) patients died within 30 days. Median ICH volume reduction at 24 h was 78% (IQR 50–89) and median postoperative ICH volume 10.5mL (IQR 5.1–23.8). Conclusions: Minimally invasive endoscopy-guided surgery within 8 h after symptom onset for supratentorial ICH appears to be safe and can effectively reduce ICH volume. Randomised controlled trials are needed to determine whe

Background: External ventricular drainage (EVD) is frequently used in neurosurgical procedures for cerebrospinal fluid (CSF) drainage. It is, however, associated with high infection rates, namely secondary meningitis and ventriculitis. Based on a previous high prevalence of these infections among patients with EVDs, we have proposed and implemented a protocol in an effort to decrease the infection rate. The aim of this study was to measure the effect of hospital-wide implementation of the EVD handling protocol on secondary EVD infections. Patients and methods: We included 409 consecutive patients who received a new EVD for other indications than infectious pathologies from January 2000 until June 2012. Patients above 18 years of age were divided into pre- (n = 228) and post-protocol (n = 181) groups. Patient and disease demographics, as well as EVD data together with confounders for secondary meningitis were recorded in a database. Propensity score matching was then performed to create groups matched for sex, age, reason for drainage, type of shunt, time in situ and duration of surgery to place the EVD. Binomial logistic regression for confounder adjustment and regression discontinuity analyses were then performed on the matched cohort. Results: Infections occurred more frequently in the pre-protocol group (23% vs 9%, p < 0.001). The incidence of infection was 33/1000 drain-days pre-protocol and 9/1000 drain-days post-protocol. Regression analysis in a propensity score-matched cohort (n = 103 in the pre- and n = 178 in the post-protocol groups) showed that the pre-protocol period was independently associated with more infections (OR 2.69; 95%-CI 1.22–5.95, p = 0.01). Conclusions: The incidence of secondary EVD infections can be reduced significantly by the implementation of a strict hospital-wide EVD handling protocol.

Objective: Chronic subdural hematoma (CSDH) is a common neurological condition, often affecting the elderly. Cognitive impairment is frequently observed at presentation. However, the course and longer term aspects of the cognitive status of CSDH patients are unknown. In this study, we aim to explore the cognitive status of CSDH patients after treatment. Methods: An exploratory study in which CSDH patients were assessed 3 months after treatment and compared to healthy controls. A total of 56 CSDH patients (age 72.1 SD ± 10.8 years with 43 [77%] males) and 60 healthy controls were included (age 67.5 ± SD 4.8 with 34 [57%] males). Cognitive testing was performed using the Telephonic Interview of Cognitive Status-modified (TICS-m), a 12-item questionnaire in which a total of 50 points can be obtained on several cognitive domains. Results: Median time between treatment and cognitive testing was 93 days (range 76–139). TICS-m scores of CSDH patients were significantly lower than healthy controls, after adjusting for age and sex: mean score 34.6 (95% CI: 33.6–35.9) vs. 39.6 (95% CI: 38.5–40.7), p value < 0.001. More than half (54%) of CSDH patients have cognitive scores at follow-up that correspond with cognitive impairment. Conclusion: A large number of CSDH patients show significantly worse cognitive status 3 months after treatment compared to healthy controls. This finding underlines the importance of increased awareness for impaired cognition after CSDH. Further research on this topic is warranted.

Most historical articles have named Johann Jacob Wepfer as the first author to describe a case of chronic subdural hematoma (CSDH). However, the question arises whether these cases truly describe CSDH. Two other names that appear in literature as the first authors to describe a case of CSDH are Thomas Willis and Giovanni Battista Morgagni. In our attempt to find the first description of a CSDH, we studied the original cases described by Willis, Wepfer, and Morgagni. The cases described by Willis and Wepfer cannot be interpreted as cases of CSDH. Willis’s university scholar is more likely to have experienced venous infarction with an underlying septic thrombosis than a CSDH. Wepfer’s cases seem to represent an intraparenchymal hemorrhage from the rupture of a branch or branches of the internal carotid artery, a subarachnoid hemorrhage complicated with hydrocephalus, and a hydrocephalus in tuberculous meningitis. Morgagni’s case described in Letter III, Article 20 in the Sedibus in 1761 seems to be the first accurate historical description of a CSDH, and we believe it should be cited as such. With these early cases of alleged CSDH, we emphasize the importance of misquotation and blind copying of references, which are important citation errors.

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.