A randomised, double blind, placebo-controlled trial of a two-week course of dexamethasone for adult patients with a symptomatic Chronic Subdural Haematoma (Dex-CSDH trial).

Background: Chronic subdural haematoma is a collection of 'old blood' and its breakdown products in the subdural space and predominantly affects older people. Surgical evacuation remains the mainstay in the management of symptomatic cases. Objective: The Dex-CSDH (DEXamethasone in Chronic SubDural Haematoma) randomised trial investigated the clinical effectiveness and cost-effectiveness of dexamethasone in patients with a symptomatic chronic subdural haematoma. Design: This was a parallel, superiority, multicentre, pragmatic, randomised controlled trial. Assigned treatment was administered in a double-blind fashion. Outcome assessors were also blinded to treatment allocation. Setting: Neurosurgical units in the UK. Participants: Eligible participants included adults (aged ≥ 18 years) admitted to a neurosurgical unit with a symptomatic chronic subdural haematoma confirmed on cranial imaging. Interventions: Participants were randomly assigned in a 1 : 1 allocation to a 2-week tapering course of dexamethasone or placebo alongside standard care. Main outcome measures: The primary outcome was the Modified Rankin Scale score at 6 months dichotomised to a favourable (score of 0-3) or an unfavourable (score of 4-6) outcome. Secondary outcomes included the Modified Rankin Scale score at discharge and 3 months; number of chronic subdural haematoma-related surgical interventions undertaken during the index and subsequent admissions; Barthel Index and EuroQol 5-Dimension 5-Level utility index score reported at discharge, 3 months and 6 months; Glasgow Coma Scale score reported at discharge and 6 months; mortality at 30 days and 6 months; length of stay; discharge destination; and adverse events. An economic evaluation was also undertaken, during which the net monetary benefit was estimated at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. Results: A total of 748 patients were included after randomisation: 375 were assigned to dexamethasone and 373 were assigned to placebo. The mean age of the patients was 74 years and 94% underwent evacuation of their chronic subdural haematoma during the trial period. A total of 680 patients (91%) had 6-month primary outcome data available for analysis: 339 in the placebo arm and 341 in the dexamethasone arm. On a modified intention-to-treat analysis of the full study population, there was an absolute reduction in the proportion of favourable outcomes of 6.4% (95% confidence interval 11.4% to 1.4%; p = 0.01) in the dexamethasone arm compared with the control arm at 6 months. At 3 months, the between-group difference was also in favour of placebo (-8.2%, 95% confidence interval -13.3% to -3.1%). Serious adverse events occurred in 60 out of 375 (16.0%) in the dexamethasone arm and 24 out of 373 (6.4%) in the placebo arm. The net monetary benefit of dexamethasone compared with placebo was estimated to be -£97.19. Conclusions: This trial reports a higher rate of unfavourable outcomes at 6 months, and a higher rate of serious adverse events, in the dexamethasone arm than in the placebo arm. Dexamethasone was also not estimated to be cost-effective. Therefore, dexamethasone cannot be recommended for the treatment of chronic subdural haematoma in this population group. Future work and limitations: A total of 94% of individuals underwent surgery, meaning that this trial does not fully define the role of dexamethasone in conservatively managed haematomas, which is a potential area for future study. Trial registration: This trial is registered as ISRCTN80782810. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/15/02) and is published in full in Health Technology Assessment; Vol. 28, No. 12. See the NIHR Funding and Awards website for further award information.

Chronic subdural haematoma is one of the most common conditions managed in adult neurosurgery and mainly affects older people. It is an 'old' collection of blood and blood breakdown products found on the surface of the brain. Surgery to drain the liquid collection is effective, with most patients improving. Given that inflammation is involved in the disease process, a commonly used steroid, dexamethasone, has been used alongside surgery or instead of surgery since the 1970s. However, there is no consensus or high-quality studies confirming the effectiveness of dexamethasone for the treatment of chronic subdural haematoma. This study was designed to determine the effectiveness of adding dexamethasone to the normal treatment for patients with a symptomatic chronic subdural haematoma. The benefit of adding dexamethasone was measured using a disability score called the Modified Rankin Scale, which can be divided into favourable and unfavourable outcomes. This was assessed at 6 months after entry into the study. In total, 748 adults with a symptomatic chronic subdural haematoma treated in neurosurgical units in the UK participated. Each participant had an equal chance of receiving either dexamethasone or a placebo because they were assigned randomly. Neither the patients nor the investigators knew who received dexamethasone and who received placebo. Most patients in both groups had an operation to drain the haematoma and experienced significant functional improvement at 6 months compared with their initial admission to hospital. However, patients who received dexamethasone had a lower chance than patients who received placebo of favourable recovery at 6 months. Specifically, 84% of patients who received dexamethasone had recovered well at 6 months, compared with 90% of patients who received placebo. There were more complications in the group that received dexamethasone. This trial demonstrates that adding dexamethasone to standard treatment reduced the chance of a favourable outcome compared with standard treatment alone. Therefore, this study does not support the use of dexamethasone in treating patients with a symptomatic chronic subdural haematoma.

Black blood MRI sequences in the acute management of ruptured and unruptured intracranial aneurysms.

We present an illustrative case series in which high spatial resolution black blood (BB) MRI sequences were used as an adjunct in the acute management of intracranial aneurysms with diagnostic uncertainty regarding rupture status. Several acute management dilemmas are discussed including the surveillance of previously treated ruptured intracranial aneurysms, identifying culprit lesion(s) amongst multiple ruptured intracranial aneurysms, and risk stratifying incidental unruptured intracranial aneurysms. We present our experience which supports the evaluation of this vessel wall imaging technique in larger multi-centre observational studies. MR imaging was performed on a 3.0 Tesla Siemens Somatom Vida system and sequences used included: Susceptibility Weighted Imaging, Diffusion Weighted Imaging & 3D T1 pre- and post-contrast-enhanced BB sequences.

Orbitozygomatic Transsylvian Resection of a Craniopharyngioma: A Step-by-Step Guide.

Adamantinomatous craniopharyngioma (ACP) is a rare sellar region tumor seen in 0.5-2 cases per million persons each year,1 presenting a bimodal distribution that peaks at 5-15 years in children and 45-60 years in adults.2 Arising from embryonic remnants of the Rathke pouch epithelium, ACPs are associated with calcifications in 90% of cases and grow cranially toward the floor of the diencephalon.1 Craniopharyngiomas are benign but locally aggressive tumors, with microsurgery being the best chance of cure.3 The natural history is to compress the optic apparatus and hypothalamic-pituitary axis as they expand, with a propensity to encase the carotids. Endoscopic transbasal approaches have gained wide acceptance in the management of these tumors.4-6 However, open microsurgical approaches via pterional and orbitozygomatic craniotomies afford wider visualization of different corridors that help mitigate the surgical risks.7-9 The orbitozygomatic craniotomy allows lesions that extend above the optic chiasm to be safely approached from an inferior-to-superior corridor.9 The wide exposure of the basal arachnoid cisterns allows protection of the lenticulostriate perforators during resection.8-11 We demonstrate a step-by-step orbitozygomatic approach with dissection of the sylvian, carotid, carotid-oculomotor, chiasmatic, and lamina terminalis cisterns that allowed safe resection of a third ventricular ACP. The patient was a male in his 70s, who presented with progressive headaches and visual impairment. Magnetic resonance imaging showed a multicystic suprasellar lesion extending through the third ventricle. The surgery was performed with no complication (Video 1). Postoperative vision stabilized, and magnetic resonance imaging showed complete resection.

Outcomes of Fluorescence-Guided vs White Light Resection of Glioblastoma in a Single Institution.

Background Glioblastoma (GBM) is the most common malignant primary brain tumour and confers a very poor prognosis. Maximal safe resection of tumour is the goal of neurosurgical intervention and may be more easily achieved through the use of surgical adjuncts such as fluorescence-guided surgery (FGS). 5-Aminolevulinic acid (5-ALA) accumulates in GBM tissue and fluoresce red, distinguishing tumour cells from the surrounding tissue and therefore making resection easier. 5-ALA-guided resection in GBM has been shown to increase resection rates and prolong progression-free survival without impacting post-operative morbidity. Radiotherapy and concomitant chemotherapy also improve survival in GBM. Other factors such as patient age and molecular status of the tumour also impact prognosis. Aims The aim of this study was to compare the outcomes of 5-ALA vs white light-guided resection for glioblastoma in the west of Scotland. Methods  This was a retrospective analysis of baseline characteristics (age, sex, tumour molecular markers, radiotherapy, chemotherapy, anatomical location of tumour and treatment group) and outcomes (mortality, survival, degree of resection and performance status) of 239 patients who underwent primary resection of glioblastoma over a four-year period (2017-2020). A variety of statistical methods were used to analyse the relationship between each variable and surgical technique; multivariate Cox regression and the Kaplan-Meier method were used in survival analysis. Results  5-ALA-guided resection substantially improved resection rates (74.0% vs 40.2%). Mortality at 15 months was 5.1% lower in the 5-ALA group (52.0% vs 57.1%, p = 0.53), and patients lived an average of 68 days longer compared to the white light group (444 days vs 376 days, p = 0.21). There were negligible differences between treatment groups in terms of post-operative performance status (PS) and post-operative complications. In our multivariate Cox regression model, six factors were statistically significant at a level of p ≤ 0.05: age, radiotherapy, chemotherapy, O(6)-methylguanine-DNA methyltransferase (MGMT) methylation, anatomical location and >90% resection. Receiving chemotherapy and radiotherapy, MGMT methylation and undergoing >90% resection conferred a survival benefit at 15 months. Older age and multi-focal disease were related to a worsened mortality rate. Undergoing radiotherapy and maximal resection were the two greatest predictors of improved survival, reducing mortality risk by 58% and 51%, respectively. Conclusion 5-ALA-guided resection improved resection rates without impacting post-operative morbidity. 5-ALA-guided resection was associated with improved survival and lower mortality rate, but this was not statistically significant. Receiving chemoradiotherapy, MGMT methylation and undergoing maximal resection conferred a survival benefit, whilst older age and multi-focal disease were associated with a poorer prognosis.

Case report: Delayed outflow obstruction of a DVA: A rare complication of brainstem cavernoma surgery.

Introduction: Developmental venous anomalies (DVAs) are considered variants of normal transmedullary veins. Their association with cavernous malformations is reported to increase the risk of hemorrhage. Expert consensus recommends meticulous planning with MR imaging, use of anatomical "safe zones", intraoperative monitoring of long tracts and cranial nerve nuclei, and preservation of the DVA as key to avoiding complications in brainstem cavernoma microsurgery. Symptomatic outflow restriction of DVA is rare, with the few reported cases in the literature restricted to DVAs in the supratentorial compartment. Case: We present a case report of the resection of a pontine cavernoma complicated by delayed outflow obstruction of the associated DVA. A female patient in her 20's presented with progressive left-sided hemisensory disturbance and mild hemiparesis. MRI revealed two pontine cavernomas associated with interconnected DVA and hematoma. The symptomatic cavernoma was resected via the infrafacial corridor. Despite the preservation of the DVA, the patient developed delayed deterioration secondary to venous hemorrhagic infarction. We discuss the imaging and surgical anatomy pertinent to brainstem cavernoma surgery, as well as the literature exploring the management of symptomatic infratentorial DVA occlusion. Conclusion: Delayed symptomatic pontine venous congestive edema is extremely rare following cavernoma surgery. DVA outflow restriction from a post-operative cavity, intraoperative manipulation, and intrinsic hypercoagulability from COVID-10 infection are potential pathophysiological factors. Improved knowledge of DVAs, brainstem venous anatomy, and "safe entry zones" will further elucidate the etiology of and the efficacious treatment for this complication.

Posterior-Transcallosal Approach to a Choroidal Fissure Arteriovenous Malformation: Video of Adapting a "Bridging Vein Free" Corridor to This Complex Region.

Choroidal fissure arteriovenous malformations (ChFis-AVMs) are uncommon and challenging to treat due to their deep location and pattern of supply.1 The choroidal fissure lies between the thalamus and fornix, from the foramen of Monroe to the inferior choroidal point.2 AVMs in this location receive their supply from the anterior, lateral posterior choroidal artery and medial posterior choroidal arteries and drain to the deep venous system.3 The anterior-transcallosal corridor to the ChFis is favored due to the ease in opening the taenia fornicis from the foramen Monroe, and it increases in length for lesions located more posteriorly.4-7 We present a case of a posterior ChFis-AVM. The patient, a previously healthy woman in her 20s, presented with a sudden severe headache. She was diagnosed with intraventricular hemorrhage. This was managed conservatively with subsequent magnetic resonance imaging and digital subtraction angiography revealing a ChFis-AVM at the body of the left lateral ventricle, between the fornix and superior layer of the tela choroidae. It received its supply from the left lateral posterior choroidal artery and medial posterior choroidal artery and drained directly into the internal cerebral vein, classified as Spetzler-Martin grade II.8 A posterior-transcallosal approach to the ChFis was chosen to reduce the working distance and afford a wider corridor by avoiding cortical bridging veins (Video 1). Complete resection of the AVM was achieved with no additional morbidity. Microsurgery in experienced hands offers the best chance of cure for AVMs.9 In this case we demonstrate how to adapt the transcallosal corridor to the choroidal fissures for safe AVM surgery in this complex location.

Importance of Arachnoid Dissection in Arteriovenous Malformation Microsurgery: A Technical Note.

Intracranial arteriovenous malformations (AVMs) are congenital anomalies where arteries and veins connect without a capillary bed. AVMs are the leading cause of nontraumatic intracerebral hemorrhages in people younger than 35 years old.1 The leptomeninges (arachnoid and pia) form from the meninx primitiva.2,3 Endothelial channels produce a vascular plexus in the meninx connected by primitive arachnoid. Remodeling of the plexus in response to changing metabolic demands results in a recognizable pattern of arteries and veins.2,3 Defects at the level of capillaries during arteriovenous specification are most likely responsible for arteriovenous fistula formation.4-6 Interplay between the congenital dysfunction and flow-related maturation in adulthood, when vasculogenesis has stopped, produces the AVM.6,7 The relationship between the primitive arachnoid and aberrant AVM vessels is preserved and forms the basis of microsurgical disconnection discussed in Video 1. Several authors have described dissecting these natural planes to delineate the abnormal AVM vessels, relax the brain, and avoid morbidity during AVM surgery.8-10 We recommend sharp arachnoid dissection with a scalpel or microscissors, occasionally helped by blunt dissection with patties or bipolar forceps. We present a 2-dimensional video of the microsurgical resection of a right parietal AVM. The patient, a healthy 30-year-old female, presented with intermittent headaches and mild impairment of arithmetic and visuospatial ability. Magnetic resonance imaging and digital subtraction angiography showed a compact 3.5-cm supramarginal gyrus AVM supplied by the middle cerebral artery, with superficial drainage. Complete microsurgical resection was performed without morbidity. We demonstrate the principles of arachnoid dissection requisite to disentanglement of the nidus and safe resection of the AVM.

Two cases of SMA syndrome after neurosurgical injury to the frontal aslant tract.

Supplementary motor area (SMA) syndrome is characterised by transient disturbance in volitional movement and speech production which classically occurs after injury to the medial premotor area. We present two cases of SMA syndrome following isolated surgical injury to the frontal aslant tract (FAT) with the SMA intact. The first case occurred after resection of a left frontal operculum tumour. The second case occurred after a transcortical approach to a ventricular neurocytoma. The clinical picture and fMRI activation patterns during recovery were typical for SMA syndrome and support the theory that the FAT is a critical bundle in the SMA complex function.

Spontaneous obliteration of brain arteriovenous malformations: illustrative cases.

BACKGROUND: Spontaneous angiographic obliteration of a brain arteriovenous malformation (AVM) is considered a rare outcome, with most cases in the literature related to prior hemorrhage in small brain AVMs. The authors present a prospective, single center, consecutive case series. The clinical course and radiographic features of four cases with spontaneous obliteration of brain AVM were analyzed. OBSERVATIONS: The median age of patients in this series was 47.6 years, with an equal gender split. The median maximum brain AVM diameter was 2 cm. The median time to spontaneous obliteration was 26 months, with hemorrhage preceding this in three out of four cases and a prolonged latency in the only case with a nidus size larger than 3 cm and no hemorrhage. LESSONS: The present study provides additional information to allow clinicians to counsel patients about the rare outcomes of conservative management. This work extends our understanding of when this phenomenon can occur by reporting on the differences associated with spontaneous obliteration of larger AVMs.

Neurosurgery in octogenarians during the COVID-19 pandemic: Results from a tertiary care trauma centre.

BACKGROUND: In 2020, 6% of Scotland's adult population was ≥80 years. Advancements in care mean improved chances of survival at 6-months for older adults following injury to the brain or spine. The Covid-19 pandemic also resulted in local and national policies aimed at protecting the elderly. We sought to evaluate referral patterns and outcomes for patients ≥80 years referred to our institution during this period. OBJECTIVE: To evaluate referral patterns and outcomes for patients ≥80 years referred to our institution both before and during the coronavirus pandemic. DESIGN: Retrospective observational cohort study. SETTING: Tertiary care in a developing major trauma centre (Queen Elizabeth University Hospital, Glasgow). PARTICIPANTS: All patients ≥80 years referred to the on-call neurosurgical service over two four-month periods before (2016-17; n = 1573) and after the onset of Covid-19 (2020; n = 2014). METHODS: Data on demographics, ASA, diagnosis and referral decision were collected. 30-day and 6-month mortality and functional independence were assessed. RESULTS: 246 (before) and 335 (during Covid-19) referred patients were ≥80 years. No gender bias. A significant increase (17%) in acute trauma was seen during the pandemic months. Fewer older adults were transferred (6% to 2% Covid-19) for specialist care, most commonly for chronic subdural haematoma. Most were alive, home and independent at 6 months (47% pre and 63% during Covid-19). CONCLUSIONS: Octogenarians feature disproportionately in acute adult neurosurgical referrals. In our department, local and national responses to the Covid-19 pandemic did not appear to influence this. Robust evidence of neurosurgical outcomes in the older adult is required to fairly distribute resources for our ageing population, but decisions must not be based on age alone.

Trial of Dexamethasone for Chronic Subdural Hematoma.

BACKGROUND: Chronic subdural hematoma is a common neurologic disorder that is especially prevalent among older people. The effect of dexamethasone on outcomes in patients with chronic subdural hematoma has not been well studied. METHODS: We conducted a multicenter, randomized trial in the United Kingdom that enrolled adult patients with symptomatic chronic subdural hematoma. The patients were assigned in a 1:1 ratio to receive a 2-week tapering course of oral dexamethasone, starting at 8 mg twice daily, or placebo. The decision to surgically evacuate the hematoma was made by the treating clinician. The primary outcome was a score of 0 to 3, representing a favorable outcome, on the modified Rankin scale at 6 months after randomization; scores range from 0 (no symptoms) to 6 (death). RESULTS: From August 2015 through November 2019, a total of 748 patients were included in the trial after randomization - 375 were assigned to the dexamethasone group and 373 to the placebo group. The mean age of the patients was 74 years, and 94% underwent surgery to evacuate their hematomas during the index admission; 60% in both groups had a score of 1 to 3 on the modified Rankin scale at admission. In a modified intention-to-treat analysis that excluded the patients who withdrew consent for participation in the trial or who were lost to follow-up, leaving a total of 680 patients, a favorable outcome was reported in 286 of 341 patients (83.9%) in the dexamethasone group and in 306 of 339 patients (90.3%) in the placebo group (difference, -6.4 percentage points [95% confidence interval, -11.4 to -1.4] in favor of the placebo group; P = 0.01). Among the patients with available data, repeat surgery for recurrence of the hematoma was performed in 6 of 349 patients (1.7%) in the dexamethasone group and in 25 of 350 patients (7.1%) in the placebo group. More adverse events occurred in the dexamethasone group than in the placebo group. CONCLUSIONS: Among adults with symptomatic chronic subdural hematoma, most of whom had undergone surgery to remove their hematomas during the index admission, treatment with dexamethasone resulted in fewer favorable outcomes and more adverse events than placebo at 6 months, but fewer repeat operations were performed in the dexamethasone group. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Dex-CSDH ISRCTN number, ISRCTN80782810.).

Dex-CSDH randomised, placebo-controlled trial of dexamethasone for chronic subdural haematoma: report of the internal pilot phase.

The Dex-CSDH trial is a randomised, double-blind, placebo-controlled trial of dexamethasone for patients with a symptomatic chronic subdural haematoma. The trial commenced with an internal pilot, whose primary objective was to assess the feasibility of multi-centre recruitment. Primary outcome data collection and safety were also assessed, whilst maintaining blinding. We aimed to recruit 100 patients from United Kingdom Neurosurgical Units within 12 months. Trial participants were randomised to a 2-week course of dexamethasone or placebo in addition to receiving standard care (which could include surgery). The primary outcome measure of the trial is the modified Rankin Scale at 6 months. This pilot recruited ahead of target; 100 patients were recruited within nine months of commencement. 47% of screened patients consented to recruitment. The primary outcome measure was collected in 98% of patients. No safety concerns were raised by the independent data monitoring and ethics committee and only five patients were withdrawn from drug treatment. Pilot trial data can inform on the design and resource provision for substantive trials. This internal pilot was successful in determining recruitment feasibility. Excellent follow-up rates were achieved and exploratory outcome measures were added to increase the scientific value of the trial.

Correction to: Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

After publication of the original article [1], the authors notified that that one of the BNTRC institutional collaborator names was misspelled.

A low cost dural closure simulation model for tomorrow's spinal neurosurgeons.

Introduction: We present a low cost model that can be used to improve a trainee's skills in spinal dural closure. Development of microsurgical skills in a simulated environment provides a safe environment in which patients are protected. We argue that this is likely to improve the quality of dural closure, especially for surgeons early in their training and may lead to a commensurate reduction in post-operative CSF leak. Method: In our model, two consultant spine surgeons assessed the ability of participants to close the spinal dura. Participants were scored both quantitatively (time taken to complete the task) and qualitatively under the category of "surgical performance"- assessed by video and inspection of the closed dural substitute. Results: The cohort under assessment included senior and newly appointed consultants, clinical fellows and thirteen specialty trainees. 10 trainees were assessed a second time and a significant majority improved on both domains: 8 (80%) were faster on their second attempt; surgical performance scores also improved in the majority of trainees (90%). Conclusion: Our results, albeit with small numbers, show that a large proportion of trainees improve with practice with a reduction in overall task time and an improvement in surgical performance. Our model is cost-effective and easy to reproduce: simulation need not be an expensive exercise. This study further validates the use of simulation in modern neurosurgical training.

Dexamethasone for adult patients with a symptomatic chronic subdural haematoma (Dex-CSDH) trial: study protocol for a randomised controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common neurosurgical condition, typically treated with surgical drainage of the haematoma. However, surgery is associated with mortality and morbidity, including up to 20% recurrence of the CSDH. Steroids, such as dexamethasone, have been identified as a potential therapy for reducing recurrence risk in surgically treated CSDHs. They have also been used as a conservative treatment option, thereby avoiding surgery altogether. The hypothesis of the Dex-CSDH trial is that a two-week course of dexamethasone in symptomatic patients with CSDH will lead to better functional outcome at six months. This is anticipated to occur through reduced number of hospital admissions and surgical interventions. METHODS: Dex-CSDH is a UK multi-centre, double-blind randomised controlled trial of dexamethasone versus placebo for symptomatic adult patients diagnosed with CSDH. A sample size of 750 patients has been determined, including an initial internal pilot phase of 100 patients to confirm recruitment feasibility. Patients must be recruited within 72 h of admission to a neurosurgical unit and exclusions include patients already on steroids or with steroid contraindications, patients who have a cerebrospinal fluid shunt and those with a history of psychosis. The decision regarding surgical intervention will be made by the clinical team and patients can be included in the trial regardless of whether operative treatment is planned or has been performed. The primary outcome measure is the modified Rankin Scale (mRS) at six months. Secondary outcomes include the number of CSDH-related surgical interventions during follow-up, length of hospital stay, mRS at three months, EQ-5D at three and six months, adverse events, mortality and a health-economic analysis. DISCUSSION: This multi-centre trial will provide high-quality evidence as to the effectiveness of dexamethasone in the treatment of CSDH. This has implications for patient morbidity and mortality as well as a potential economic impact on the overall health service burden from this condition. TRIAL REGISTRATION: ISRCTN, ISRCTN80782810 . Registered on 7 November 2014. EudraCT, 2014-004948-35 . Registered on 20 March 2015. Dex-CSDH trial protocol version 3, 27 Apr 2017. This protocol was developed in accordance with the SPIRIT checklist. Available as a separate document on request.