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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., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: The role of glucocorticoids without surgical evacuation in the treatment of chronic subdural hematoma is unclear., Methods: In this multicenter, open-label, controlled, noninferiority trial, we randomly assigned symptomatic patients with chronic subdural hematoma in a 1:1 ratio to a 19-day tapering course of dexamethasone or to burr-hole drainage. The primary end point was the functional outcome at 3 months after randomization, as assessed by the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]). Noninferiority was defined by a lower limit of the 95% confidence interval of the odds ratio for a better functional outcome with dexamethasone than with surgery of 0.9 or more. Secondary end points included scores on the Markwalder Grading Scale of symptom severity and on the Extended Glasgow Outcome Scale., Results: From September 2016 through February 2021, we enrolled 252 patients of a planned sample size of 420; 127 were assigned to the dexamethasone group and 125 to the surgery group. The mean age of the patients was 74 years, and 77% were men. The trial was terminated early by the data and safety monitoring board owing to safety and outcome concerns in the dexamethasone group. The adjusted common odds ratio for a lower (better) score on the modified Rankin scale at 3 months with dexamethasone than with surgery was 0.55 (95% confidence interval, 0.34 to 0.90), which failed to show noninferiority of dexamethasone. The scores on the Markwalder Grading Scale and Extended Glasgow Outcome Scale were generally supportive of the results of the primary analysis. Complications occurred in 59% of the patients in the dexamethasone group and 32% of those in the surgery group, and additional surgery was performed in 55% and 6%, respectively., Conclusions: In a trial that involved patients with chronic subdural hematoma and that was stopped early, dexamethasone treatment was not found to be noninferior to burr-hole drainage with respect to functional outcomes and was associated with more complications and a greater likelihood of later surgery. (Funded by the Netherlands Organization for Health Research and Development and others; DECSA EudraCT number, 2015-001563-39.)., (Copyright © 2023 Massachusetts Medical Society.)

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., (© 2023. The Author(s).)

The main treatment strategy for chronic subdural hematoma is surgical intervention. When a conservative pharmacological approach is considered in symptomatic patients, mainly dexamethasone therapy is applied. Recent trials revealed dexamethasone therapy to be an ineffective treatment in symptomatic patients with chronic subdural hematoma. Whether the efficacy of dexamethasone therapy differs in radiological hematoma subtypes is unknown. The aim of this substudy was to identify which hematoma subtype might be favorable for dexamethasone therapy. As part of a randomized controlled trial, symptomatic chronic subdural hematoma patients received 19-days dexamethasone therapy. The primary outcome measure was the change in hematoma size as measured on follow-up computed tomography (CT) after 2 weeks of dexamethasone in six hematoma (architectural and density) subtypes: homogeneous total, laminar, separated and trabecular architecture types, and hematoma without hyperdense components (homogeneous hypodense, isodense) and with hyperdense components (homogeneous hyperdense, mixed density). We analyzed hematoma thickness, midline shift, and volume using multi-variable linear regression adjusting for age, sex and baseline value of the specific radiological parameter. From September 2016 until February 2021, 85 patients were included with a total of 114 chronic subdural hematoma. The mean age was 76 years and 25% were women. Larger decrease in hematoma thickness and midline shift was revealed in hematoma without hyperdense components compared with hematoma with hyperdense components (adjusted [adj.] b -2.2 mm, 95% confidence interval [CI] -4.1 to -0.3 and adj. b -1.3 mm, 95% CI -2.7 to 0.0 respectively). Additional surgery was performed in 57% of patients with the highest observed rate (81%) in separated hematoma. Largest hematoma reduction and better clinical improvement was observed in chronic subdural hematoma without hyperdense components after dexamethasone therapy. Evaluation of these parameters can be part of an individualized treatment strategy.

Purpose: Chronic subdural hematoma (CSDH) is a common neurological disease often affecting the elderly. Long-term excess mortality for patients after CSDH has been suggested but causes of death are unknown. We hypothesize that excess mortality of CSDH patients is related to frailty. In this article, we describe mortality rates and causes of death of CSDH patients compared with the general population and assess the association of frailty with mortality., Methods: A cohort study in which consecutive CSDH patients were compared to the general population regarding mortality rates. Furthermore, the association of six frailty indicators (cognitive problems, frequent falling, unable to live independently, unable to perform daily self-care, use of benzodiazepines or psychotropic drugs, and number of medications) with mortality was assessed., Results: A total of 1307 CSDH patients were included, with a mean age of 73.7 (SD ± 11.4) years and 958 (73%) were male. Median follow-up was 56 months (range: 0-213). Compared with controls CSDH patients had a hazard ratio for mortality of 1.34 (95% CI: 1.2-1.5). CSDH patients more often died from cardiovascular diseases (37% vs. 30%) and falls (7.2% vs. 3.7%). Among CSDH patients frequent falling (HR 1.3; 95% CI: 1.0-1.7), inability to live independently (HR 1.4, 95% CI: 1.1-1.8), inability to perform daily self-care (HR 1.5; 95% CI: 1.1-1.9), and number of medications used (HR 1.0; 95% CI: 1.0-1.1) were independently associated with mortality., Conclusions: CSDH patients have higher mortality rates than the general population. Frailty in CSDH patients is associated with higher mortality risk. More attention for the frailty of CSDH patients is warranted., (© 2022. The Author(s).)

Background: Several prognostic models for outcomes after chronic subdural hematoma (CSDH) treatment have been published in recent years. However, these models are not sufficiently validated for use in daily clinical practice. We aimed to assess the performance of existing prediction models for outcomes in patients diagnosed with CSDH., Methods: We systematically searched relevant literature databases up to February 2021 to identify prognostic models for outcome prediction in patients diagnosed with CSDH. For the external validation of prognostic models, we used a retrospective database, containing data of 2384 patients from three Dutch regions. Prognostic models were included if they predicted either mortality, hematoma recurrence, functional outcome, or quality of life. Models were excluded when predictors were absent in our database or available for < 150 patients in our database. We assessed calibration, and discrimination (quantified by the concordance index C) of the included prognostic models in our retrospective database., Results: We identified 1680 original publications of which 1656 were excluded based on title or abstract, mostly because they did not concern CSDH or did not define a prognostic model. Out of 18 identified models, three could be externally validated in our retrospective database: a model for 30-day mortality in 1656 patients, a model for 2 months, and another for 3-month hematoma recurrence both in 1733 patients. The models overestimated the proportion of patients with these outcomes by 11% (15% predicted vs. 4% observed), 1% (10% vs. 9%), and 2% (11% vs. 9%), respectively. Their discriminative ability was poor to modest (C of 0.70 [0.63-0.77]; 0.46 [0.35-0.56]; 0.59 [0.51-0.66], respectively)., Conclusions: None of the examined models showed good predictive performance for outcomes after CSDH treatment in our dataset. This study confirms the difficulty in predicting outcomes after CSDH and emphasizes the heterogeneity of CSDH patients. The importance of developing high-quality models by using unified predictors and relevant outcome measures and appropriate modeling strategies is warranted., (© 2022. The Author(s).)

Background: We aimed to quantify the need for additional surgery in patients with chronic subdural hematoma (CSDH) primarily treated with dexamethasone and to identify patient characteristics associated with additional surgery., Methods: Data were retrospectively collected from 283 patients with CSDH, primarily treated with dexamethasone, in 3 hospitals from 2008 to 2018. Primary outcome was the need for additional surgery. The association between baseline characteristics and additional surgery was analyzed with univariable and multivariable logistic regression analysis and presented as adjusted odds ratios (aOR)., Results: In total, 283 patients with CSDH were included: 146 patients (51.6%) received 1 dexamethasone course (DXM group), 30 patients (10.6%) received 2 dexamethasone courses (DXM-DXM group), and 107 patients (37.8%) received additional surgery (DXM-SURG group). Patients who underwent surgery more often had a Markwalder Grading Scale of 2 (as compared with 1, aOR 2.05; 95% confidence interval [CI] 0.90-4.65), used statins (aOR 2.09; 95% CI 1.01-4.33), had a larger midline shift (aOR 1.10 per mm; 95% CI 1.01-1.21) and had larger hematoma thickness (aOR 1.16 per mm; 95% CI 1.09-1.23), had a bilateral hematoma (aOR 1.85; 95% CI 0.90-3.79), and had a separated hematoma (as compared with homogeneous, aOR 1.77; 95% CI 0.72-4.38). Antithrombotics (aOR 0.45; 95% CI 0.21-0.95) and trabecular hematoma (as compared with homogeneous, aOR 0.31; 95% CI 0.12-0.77) were associated with a lower likelihood of surgery., Conclusions: More than one-third of patients with CSDH primarily treated with dexamethasone received additional surgery. These patients were more severely affected amongst others with larger hematomas., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: Symptoms of chronic subdural hematoma (CSDH) vary widely, including transient neurological deficit(s) (TND). The precise prevalence and the clinical aspects of TND are yet to be determined. Most TNDs are regarded and treated as symptomatic seizures, but the rationale for this decision is not always clear., Methods: Patients with temporary symptoms were selected from a retrospective cohort of CSDH patients. We analyzed the association of TND characteristics with patients being classified as having a symptomatic seizure and with functional outcome using logistic regression analysis., Results: Of the included 1307 CSDH patients, 113 (8.6%) had at least one episode of TND. Most common TNDs were aphasia/dysphasia, impaired awareness or clonic movements. Of these 113 patients, 50 (44%) were diagnosed with symptomatic seizure(s) by their treating physician. Impaired awareness, clonic movements and the presence of 'positive symptoms' showed the strongest association with the diagnosis symptomatic seizure (OR 36, 95% CI 7.8-163; OR 24, 95% CI 6.4-85; and OR 3.1, 95% CI 1.3-7.2). Aphasia/dysphasia lowered the chance of TND being classified as symptomatic seizure together with a longer TND duration (OR 0.2, 95% CI 0.1-0.6; and OR 0.91, 95% CI 0.84-0.99). Treatment with anti-epileptic drugs was related to unfavorable functional outcome (aOR 5.4, 95% CI 1.4-20.7)., Conclusion: TND was not a rare phenomenon in our cohort of CSDH patients. A TND episode of 5 min, aphasia/dysphasia and/or absence of 'positive' symptoms are suggestive of a different TND pathophysiology than symptomatic seizures. Our results further suggest that treatment of TND in CSDH deserves careful consideration as management choices might influence patient outcome., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Patients with chronic subdural hematoma (CSDH) can have transient neurological deficits deficit (TND) mimicking transient ischemic attacks. The prevalence of TNDs in CSDH varies between 1%-24%, depending on TND definition. Despite this high prevalence the pathophysiology of TND in CSDH is not clear in many cases. In this systematic review, we aim to unravel the responsible mechanism. Pubmed and Embase were searched for all articles concerning the pathophysiology of TND as a presenting symptom in patients with CSDH. There were no publication date restrictions for the articles in the search. Two reviewers independently selected studies for inclusion and subsequently extracted the necessary data. Out of 316 identified references, 15 met the inclusion criteria. Several articles mentioned multiple pathophysiological mechanisms. One of the proposed etiologies of TND was epileptic activity, stated by three articles. In contrast, three different studies stated that seizures are unlikely to cause TND. Five papers suggested that obstruction of blood flow, caused by the hematoma or subsequent swelling, might be the cause. Six articles made no definite statement on the responsible pathophysiological mechanism of TND. Different mechanisms have been proposed to be the cause of TNDs in patients with CSDH. Based on this review, the exact pathophysiology of TND remains unclear. We suggest that future studies on this topic should incorporate MRI of the brain (with diffusion-weighted imaging) and EEG, to provide better insight into TND pathophysiology. The knowledge resulting from future studies might contribute to better understanding of TND and optimal treatment in CSDH., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Chronic subdural hematoma (CSDH) is a frequent pathological entity in daily clinical practice. However, evidence-based CSDH-guidelines are lacking and level I evidence from randomized clinical trials (RCTs) is limited. In order to establish and subsequently implement a guideline, insight into current clinical practice and attitudes toward CSDH-treatment is required. The aim is to explore current practice and attitudes toward CSDH-management in the Netherlands., Methods: A national online survey was distributed among Dutch neurologists and neurosurgeons, examining variation in current CSDH-management through questions on treatment options, (peri)operative management, willingness to adopt new treatments and by presenting four CSDH-cases., Results: One hundred nineteen full responses were received (8% of neurologists, N = 66 and 35% of neurosurgeons, N = 53). A majority of the respondents had a positive experience with burr-hole craniostomy (93%) and with a conservative policy (56%). Around a third had a positive experience with the use of dexamethasone as primary (30%) and additional (33.6%) treatment. These numbers were also reflected in the treatment preferences in the presented cases. (Peri)operative management corresponded among responding neurosurgeons. Most respondents would be willing to implement dexamethasone (98%) if equally effective as surgery and tranexamic acid (93%) if effective in CSDH-management., Conclusion: Variation was found regarding preferential CSDH-treatment. However, this is considered not to be insurmountable when implementing evidence-based treatments. This baseline inventory on current clinical practice and current attitudes toward CSDH-treatment is a stepping-stone in the eventual development and implementation of a national guideline., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Patients with chronic subdural hematoma (CSDH) can present with a variety of signs and symptoms. The relationship of these signs and symptoms with functional outcome is unknown. Knowledge of these associations might aid clinicians in the choice to initiate treatment and may allow them to better inform patients on expected outcomes., Objective: To investigate if presenting signs and symptoms influence functional outcome in patients with CSDH., Methods: We conducted a retrospective analysis of consecutive CSDH patients in three hospitals. Glasgow Outcome Scale Extended (GOS-E) scores were obtained from the first follow-up visit after treatment. An ordinal multivariable regression analysis was performed, to assess the relationship between the different signs and symptoms on the one hand and functional outcome on the other adjusted for potential confounders., Results: We included 1,307 patients, of whom 958 (73%) were male and mean age was 74 (SD ± 11) years. Cognitive complaints were associated with lower GOS-E scores at follow-up (aOR 0.7, 95% CI: 0.5 - 0.8) Headache and higher Glasgow Coma Scale (GCS) scores were associated with higher GOS-E scores. (aOR 1.9, 95% CI: 1.5-2.3 and aOR 1.3, 95% CI: 1.2-1.4)., Conclusion: Cognitive complaints are independently associated with worse functional outcome, whereas headache and higher GCS scores are associated with better outcome. The increased probability of unfavorable outcome in patients with CSDH who present with cognitive complaints favors a more prominent place of assessing cognitive status at diagnosis., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A chronic subdural hematoma is a common neurological disorder that occurs mainly in the elderly. The inciting event is often a minor head trauma and subsequent inflammation may play a role in the pathogenesis. The clinical spectrum can present heterogeneously, and symptom onset and progression can vary from days to weeks. To date surgical evacuation of the subdural collection remains the main treatment approach for symptomatic patients. Evidence is still scarce for dexamethasone as an effective primary conservative treatment strategy. Future research is necessary to elucidate the effect of various pharmacological therapies compared to primary surgery on functional outcome.

Chronic subdural hematoma (CSDH) is a frequently occurring neurological disease associated with older age and use of anticoagulants. Symptoms vary from headaches to coma, but cognitive deficits can also be present. However, exact prevalence and severity of cognitive deficits in CSDH are still unknown. In this systematic review, we aim to assess cognitive status of patients with CSDH, at presentation and after treatment. PubMed, Embase and PsycInfo were searched for articles concerning cognition in CSDH. We divided cognitive changes into subjective cognitive deficit (cognitive complaints [CC]) and objective cognitive deficit (cognitive impairment [CI]). Two reviewers independently selected studies for inclusion and subsequently extracted data. Quality assessment was done by means of the Newcastle-Ottawa Scale. Reported prevalence of CC and CI was pooled with random effects meta-analysis. Out of 799 identified references, 22 met inclusion criteria. Twenty-one articles reported on prevalence of CC/CI and one study reported solely on CSDH patients with cognitive deficit. Estimated pooled prevalence of both CC and CI in CSDH at presentation was 45% (95% confidence interval [CI]: 36-54%). Four studies concerned a prospective evaluation of the effect of surgical treatment on cognition. These proved to be of fair to good quality after quality assessment. The estimated pre-treatment prevalence of objectified cognitive impairment was 61% (95% CI: 51-70%) decreasing to 18% (95% CI: 8-32%) post-surgery. From this review it can be concluded that CC and CI are very common in CSDH, with a tendency to improve after treatment. Therefore, we underline the importance of increased attention to cognitive status of these patients, with proper testing methods and treatment-testing intervals.

Purpose: Chronic subdural hematoma (CSDH) is associated with high recurrence rates. Radiographic prognostic factors may identify patients who are prone for recurrence and who might benefit further optimization of therapy. In this meta-analysis, we systematically evaluated pre-operative radiological prognostic factors of recurrence after surgery., Methods: Electronic databases were searched until September 2020 for relevant publications. Studies reporting on CSDH recurrence in symptomatic CSDH patients with only surgical treatment were included. Random or fixed effects meta-analysis was used depending on statistical heterogeneity., Results: Twenty-two studies were identified with a total of 5566 patients (mean age 69 years) with recurrence occurring in 801 patients (14.4%). Hyperdense components (hyperdense homogeneous and mixed density) were the strongest prognostic factor of recurrence (pooled RR 2.83, 95% CI 1.69-4.73). Laminar and separated architecture types also revealed higher recurrence rates (RR 1.37, 95% CI 1.04-1.80 and RR 1.76 95% CI 1.38-2.16, respectively). Hematoma thickness and midline shift above predefined cut-off values (10 mm and 20 mm) were associated with an increased recurrence rate (RR 1.79, 95% CI 1.45-2.21 and RR 1.38, 95% CI 1.11-1.73, respectively). Bilateral CSDH was also associated with an increased recurrence risk (RR 1.34, 95% CI 0.98-1.84)., Limitations: Limitations were no adjustments for confounders and variable data heterogeneity. Clinical factors could also be predictive of recurrence but are beyond the scope of this study., Conclusions: Hyperdense hematoma components were the strongest prognostic factor of recurrence after surgery. Awareness of these findings allows for individual risk assessment and might prompt clinicians to tailor treatment measures.

Worldwide, different strategies are being applied for symptomatic chronic subdural hematoma (CSDH). The aim of this study was to evaluate the efficacy of two treatment strategies for symptomatic CSDH: initial dexamethasone (DXM) therapy versus primary surgery by burr hole craniostomy (BHC). We retrospectively collected data for 120 symptomatic CSDH patients in two neurotrauma centers between 2014 and 2016, each with their own treatment protocol. Sixty patients received primary BHC (center A), and another 60 initial DXM therapy (center B). Primary outcome was evaluated by dichotomized modified Rankin Scale (mRS) score (0-3 and 4-6) and Markwalder Grading Scale (MGS) score at 3 months. Secondary outcomes were additional interventions, CSDH recurrence, mortality, complications, and duration of hospital stay. Baseline characteristics were similar in both groups. At 3 months, a favorable mRS score (0-3) was observed in 70% and 76% of patients in cohort A and B, respectively (odds ratio [OR] 0.77, 95% CI 0.30-1.98; p  = 0.59). A favorable MGS score (0-1) was observed in 96% of patients in both groups (OR 0.98, 95% CI 0.45-2.15; p  = 0.95). CSDH recurrence was 12% in cohort A and 22% in cohort B ( p  = 0.15). Mortality was 10% in both cohorts. In cohort B, additional surgery was performed in 83% at a median of 6 days, and significantly more patients had complications (55% vs. 35%, p  = 0.02), a prolonged hospitalization (10 vs. 5 days; p  = 0.02), and one or more follow-up cranial CT's (85% vs. 48%; p  < 0.001). To achieve a favorable clinical outcome, initial DXM therapy was associated with a high rate of crossover to surgery, significantly longer overall hospital stay, and more complications compared with primary surgery.

Background: There is an ongoing debate on the role of corticosteroids in the treatment of chronic subdural hematoma (CSDH). This study aims to evaluate the effectiveness of corticosteroids for the treatment of CSDH compared to surgery., Method: A systematic search was performed in relevant databases up to January 2019 to identify RCTs or observational studies that compared at least two of three treatment modalities: the use of corticosteroids as a monotherapy (C), corticosteroids as an adjunct to surgery (CS), and surgery alone (S). Outcome measures were good neurological outcome, need for reintervention, mortality, and complications. Effect estimates were pooled and presented as relative risk (RR) with 95% confidence interval (95%CI)., Results: Of 796 initially identified studies, 7 were included in the meta-analysis. Risk of bias was generally high. There were no differences in good neurological outcome between treatment modalities. The need for reintervention varied between 4 and 58% in C, 4-12% in CS, and 7-26% in S. The need for reintervention was lower in CS compared with C (RR 3.34 [95% CI 1.53-7.29]; p < 0.01) and lower in CS compared with S (RR 0.44 [95% CI 0.27-0.72]; p < 0.01). Mortality varied between 0 and 4% in C, 0-13% in CS, and 0-44% in S. Mortality was lower in CS compared with S (RR 0.39 [95% CI 0.25-0.63]; p < 0.01). There were no differences in complications between treatment modalities., Conclusions: This meta-analysis suggests that the addition of corticosteroids to surgery might be effective in the treatment of CSDH. However, the results must be interpreted with caution in light of the serious risk of bias of the included studies. This study stresses the need for large randomized trials to investigate the use of corticosteroids in the management of CSDH.

Background: Chronic subdural haematoma (CSDH) is a common neurological disease with a rapidly rising incidence due to increasing age and widespread use of anticoagulants. Surgical intervention by burr-hole craniotomy (BHC) is the current standard practice for symptomatic patients, but associated with complications, a recurrence rate of up to 30% and increased mortality. Dexamethasone (DXM) therapy is, therefore, used as a non-surgical alternative but considered to achieve a lower success rate. Furthermore, the benefit of DXM therapy appears much more deliberate than the immediate relief from BHC. Lack of evidence and clinical equipoise among caregivers prompts the need for a head-to-head randomised controlled trial. The objective of this study is to compare the effect of primary DXM therapy versus primary BHC on functional outcome and cost-effectiveness in symptomatic patients with CSDH., Methods/design: This study is a prospective, multicentre, randomised controlled trial (RCT). Consecutive patients with a CSDH with a Markwalder Grading Scale (MGS) grade 1 to 3 will be randomised to treatment with DXM or BHC. The DXM treatment scheme will be 16 mg DXM per day (8 mg twice daily, days 1 to 4) which is then halved every 3 days until a dosage of 0.5 mg a day on day 19 and stopped on day 20. If the treatment response is insufficient (i.e. persistent or progressive symptomatology due to insufficient haematoma resolution), additional surgery can be performed. The primary outcomes are the functional outcome by means of the modified Rankin Scale (mRS) score at 3 months and cost-effectiveness at 12 months. Secondary outcomes are quality of life at 3 and 12 months using the Short Form Health Survey (SF-36) and Quality of Life after Brain Injury Overall Scale (QOLIBRI), haematoma thickness after 2 weeks on follow-up computed tomography (CT), haematoma recurrence during the first 12 months, complications and drug-related adverse events, failure of therapy within 12 months after randomisation and requiring intervention, mortality during the first 3 and 12 months, duration of hospital stay and overall healthcare and productivity costs. To test non-inferiority of DXM therapy compared to BHC, 210 patients in each treatment arm are required (assumed adjusted common odds ratio DXM compared to BHC 1.15, limit for inferiority < 0.9). The aim is to include a total of 420 patients in 3 years with an enrolment rate of 60%., Discussion: The present study should demonstrate whether treatment with DXM is as effective as BHC on functional outcome, at lower costs., Trial Registration: EUCTR 2015-001563-39 . Date of registration: 29 March 2015.

Background: Chronic subdural hematoma (CSDH) is one of the more frequent pathologic entities in daily neurosurgical practice. Historically, CSDH was considered progressive recurrent bleeding with a traumatic cause. However, recent evidence has suggested a complex intertwined pathway of inflammation, angiogenesis, local coagulopathy, recurrent microbleeds, and exudates. The aim of the present review is to collect existing data on pathophysiology of CSDH to direct further research questions aiming to optimize treatment for the individual patient., Methods: We performed a thorough literature search in PubMed, Ovid, EMBASE, CINAHL, and Google scholar, focusing on any aspect of the pathophysiology and nonsurgical treatment of CSDH., Results: After a (minor) traumatic event, the dural border cell layer tears, which leads to the extravasation of cerebrospinal fluid and blood in the subdural space. A cascade of inflammation, impaired coagulation, fibrinolysis, and angiogenesis is set in motion. The most commonly used treatment is surgical drainage. However, because of the pathophysiologic mechanisms, the mortality and high morbidity associated with surgical drainage, drug therapy (dexamethasone, atorvastatin, tranexamic acid, or angiotensin-converting enzyme inhibitors) might be a beneficial alternative in many patients with CSDH., Conclusions: Based on pathophysiologic mechanisms, animal experiments, and small patient studies, medical treatment may play a role in the treatment of CSDH. There is a lack of level I evidence in the nonsurgical treatment of CSDH. Therefore, randomized controlled trials, currently lacking, are needed to assess which treatment is most effective in each individual patient., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)