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.

Successful treatment of vancomycin-resistant enterococcal infection of an external ventricular drain with 2 weeks of intravenous linezolid.

Hydrocephalus is a common condition worldwide, and is frequently managed by diversion of cerebrospinal fluid (CSF), either externally with a drain or internally with a shunt. An external ventricular drain (EVD) can be an essential treatment modality, but is associated with a risk of infection, most commonly caused by Staphylococcal species, which can result in meningitis or ventriculitis and a delay in the definitive management of the hydrocephalus. Here, we report the case of a patient who required an EVD to manage post-operative hydrocephalus following a craniotomy and microvascular decompression for trigeminal neuralgia. He subsequently developed EVD-associated infection with a vancomycin-resistant Enterococcus faecium (VRE), which was treated successfully with a 2-week course of intravenous linezolid monotherapy. The authors believe this to be the only described case of successful treatment within this time frame of a CSF VRE infection associated with indwelling foreign material.

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.

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.

The Prevalence of Cerebrovascular Abnormalities Detected in Various Diagnostic Subgroups of Spontaneous Subarachnoid Hemorrhage in the Modern Era.

OBJECTIVE: To determine prevalence of cerebrovascular abnormalities in diagnostic subgroups of spontaneous subarachnoid hemorrhage (SAH) in a regional neurosurgical center in the modern era. METHODS: Data of 609 consecutive patients with spontaneous SAH in a 3-year period (August 2010 to August 2013) were prospectively collected. Patients were divided into 3 diagnostic subgroups: computed tomography (CT) positive for SAH; CT negative but positive cerebrospinal fluid examination by spectrophotometry for SAH; CT negative for SAH and inconclusive cerebrospinal fluid examination. All patients fit for intervention underwent CT angiography with or without digital subtraction angiography to identify vascular abnormalities for subsequent treatment. RESULTS: Of 609 patients, 554 were fit for further investigation and consideration of further intervention; 514 patients had confirmed SAH. Mean patient age was 54.0 years; 61.5% of patients were women. Of patients, 390 (75.9%) showed vascular abnormalities on angiography. There were 438 patients (85.2%) with confirmed SAH diagnosed on CT scan (group 1). Vascular abnormalities were detected in 81.1% of patients; 18.9% of patients with positive CT scan had no identifiable cause of SAH. Of patients with confirmed SAH, 76 (14.8%) had negative CT scan but positive lumbar puncture (group 2); 46.1% of patients in this group had vascular abnormalities. Three patients with inconclusive cerebrospinal fluid examination had lesions requiring treatment. Median length of hospital stay in group 1 patients was longer than median length of hospital stay in group 2 patients. CONCLUSIONS: Frequency of vascular abnormalities in spontaneous SAH is lower than the traditionally quoted figure, which has diagnostic and prognostic implications for patient management.

Results of surgical clipping in a neurointerventional dominant department.

OBJECTIVES: It has been 10 years since the publication of International Subarachnoid Aneurysm Trial (ISAT) (1-3) and the first-line treatment for cerebral aneurysms in many UK neurosurgical centres is endovascular occlusion. Local audit has shown a significant reduction in surgical clipping cases since 2002, with a fall from over 150 cases per year pre ISAT, to approximately 25 cases per year currently. More so the cases referred for surgical occlusion represent more challenging lesions. With such a reduction in surgical numbers we felt it prudent to review our recent surgical outcomes. DESIGN: Retrospective analysis of prospectively collected data. SUBJECTS: 47 patients (32 females, 15 males), mean age: 53 (range, 29-74) years underwent surgical clipping of cerebral aneurysms from January 2012 to September 2013. METHODS: Case notes, neuroradiology reports and cerebral angiograms were reviewed. Patient outcome was stratified according to Glasgow Outcome Score; 4-5 good outcome and 1-3 poor outcome. RESULTS: Of the aneurysms clipped, 40 patients had suffered a subarachnoid haemorrhage and 7 were treated for unruptured aneurysms. The reasons for referral for surgical clipping were the presence of an aneurysmal clot 9 (19%), 'failed coiling' 16 (34%) and unsuitability for endovascular intervention due to anatomical considerations 22 (47%). A good outcome was recorded in 20/22 (91%) of patients who underwent clipping for anatomical reasons, 11/16 (69%) of patients who failed endovascular treatment and 5/9 (56%) of patients with an aneurysmal clot (p = 0.05). Of 31 aneurysms with post clipping angiographic studies, 28 (90%) had complete or satisfactory aneurysm obliteration. CONCLUSIONS: In the current era of neurointerventional dominance, the case mix undergoing microsurgical clipping is more challenging than the pre-ISAT cohort; however, post-procedural angiography has demonstrated a relatively high obliteration rate. It is reassuring that good neurological outcomes were observed in patients clipped for anatomical reasons.

The effectiveness of percutaneous balloon compression in the treatment of trigeminal neuralgia in patients with multiple sclerosis.

OBJECT: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population and among the former has an incidence of approximately 2%. The pathophysiology of TN in MS patients is believed to be caused by a demyelinating plaque at the root entry zone, and therefore procedures that cause direct nerve damage are thought to be the most effective surgical modality. The authors aimed to compare the efficacy of percutaneous balloon compression (PBC) in TN patients with and without MS. METHODS: Retrospectively collected clinical data on 80 consecutive patients who underwent 144 procedures and who received PBC for TN treatment between January 2000 and January 2010 were analyzed. The cohort included 17 MS and 63 non-MS patients. RESULTS: The mean age at first operation was significantly younger in the MS group compared with the non-MS group (59 years vs 72 years, respectively, p < 0.0001). After a mean follow-up of 43 months (MS group) and 25 months (non-MS group), the symptom recurrence rate following the first operation was higher in the MS group compared with that in the non-MS group (86% vs 47%, respectively, p < 0.01). During long-term follow-up, more than 70% of MS patients required multiple procedures compared with only 44% of non-MS patients. Excellent or satisfactory outcomes were not significantly different between the MS and non-MS cohorts, respectively, at 1 day postoperatively (82% vs 91%, p = 0.35), 3 months postoperatively (65% vs 81%, p = 0.16), and at last follow-up (65% vs 76%, p = 0.34). A similar incidence of postoperative complications was observed in the 2 groups. CONCLUSIONS: PBC is effective in the treatment of trigeminal neuralgia in patients with MS, but, compared with that in non-MS patients, symptom recurrence is higher and requires multiple procedures.

Intracranial aneurysm in a patient with glucocorticoid-remediable aldosteronism.

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal dominant disorder in which the increase in aldosterone secretion produced by Adrenocorticotropic hormone (ACTH) is no longer transient. Here we present a case of a 32-year-old man with GRA who was found to have an intracranial aneurysm following screening. His blood pressure had been well controlled and closely monitored since diagnosis and the institution of treatment at age 13 years. This is a rarely reported example of this manifestation in GRA, and both the treatment and rationale for therapy are discussed below.

Effective management of lower divisional pain in trigeminal neuralgia using balloon traction.

Percutaneous balloon compression (PBC) of the trigeminal ganglion uses a differential injury of axons to interfere with the nerve's ability to transmit signals. In our experience, patients with lower divisional pain (V3) are often more difficult to control using PBC. We describe a modification to the PBC technique for patients with lower division (V3) pain, and present our experience to date.

Persistent hypoglossal artery--an increased risk for intracranial aneurysms?

A 53-year-old hypertensive female smoker presented with a WFNS grade II subarachnoid haemorrhage. Angiography showed a left persistent hypoglossal artery with multiple intracranial aneurysms. She underwent successful coil embolisation of the ruptured aneurysm. We reviewed the literature on persistent hypoglossal artery and found 26% of them have associated intracranial aneurysms. This controversial topic is discussed.

Enterocutaneous fistulae presenting as a late complication of a non-functioning Ventriculo- Peritoneal shunt catheter.

A patient with spina bifida and hydrocephalus who had undergone multiple shunt revisions, presented with a 9 month history of chronic discharging sinuses related to a retained shunt catheter not visible on x-ray. This case report demonstrates the importance of clinical history and investigation in patients with retained catheters presenting with cutaneous sinuses.

Rare case of primary spinal ependymomatosis occurring in a 26-year-old man: a case report.

INTRODUCTION: The authors report a rare case of primary spinal ependymomatosis in a young adult man. Multiple primary ependymomatous lesions were seen on magnetic resonance imaging and no anaplasia was identified on the surgical-pathological analysis. The aetio-pathological mechanism and surgical significance of this rare occurrence is discussed. CASE PRESENTATION: A 26-year-old man of Polish origin presented with a ten-day history of pain in the left leg and lower back. This was followed by difficulty in urinating and a decrease in sensation in both legs. Examination revealed pyramidal signs and mild weakness in both lower limbs. He had early sphincter involvement requiring catheterization. Magnetic resonance imaging of the brain was normal. However, that of the spinal cord revealed multiple intradural spinal lesions, both intra- and extramedullary, extending from the cervical cord down to the cauda equina roots. T12-L1 laminectomy was performed. Multiple intradural, extra- and intra-medullary tumors were seen. After the operation, the patient deteriorated with a sensory level at T4. Post-operative cranio-spinal radiotherapy was administered but there was no clinical improvement in the lower limbs. CONCLUSION: Primary spinal ependymomatosis is a rare phenomenon involving multiple spinal segments in the absence of a primary intracranial tumor. Radical excision is unrealistic in this condition. Biopsy followed by radiotherapy is the preferred method of treatment.

Have ATLS and national transfer guidelines improved the quality of resuscitation and transfer of head-injured patients? A prospective survey from a Regional Neurosurgical Unit.

High-quality resuscitation and care during transfer of head-injured patients is essential to prevent secondary brain injury. We have prospectively assessed the standard of resuscitation in 50 consecutive head-injured patients transferred to our unit, and compared our findings with previous studies performed before the advanced trauma life support course (ATLS) had become widespread and national guidelines on the transfer of head injuries had been produced by the Association of Anaesthetists of Great Britain and Ireland (AAGBI). Delays in transfer, management of the airway, adequate cervical spine assessment, hypoxia (P(a)O(2) <13 kPa), hypotension (systolic BP <90 mmHg), missed injuries and the experience of the medical escort were compared against the standards laid out in ATLS and AAGBI Guidelines. The mean, unavoidable delay from arrival at the local accident and emergency unit to arrival was 7.4+/-1.9h (mean+/-95%CI) with most of the delay being prior to initial referral. Two patients arrived with an unsecured airway with a GCS=8/15; 26 had inadequate cervical spine imaging; 7 patients arrived hypoxic and 2 patients arrived hypotensive; most of these insults occurred during the transfer. Forty-six percent of medical escorts did not fulfil the minimum standard of experience. ATLS and AAGBI guidelines have provided only modest improvements in patient care at the expense of long delays in transfer. The incidence of hypoxia and hypotension remains unacceptably high.