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.).

The Sensor Reservoir-does it change management?

BACKGROUND: The Miethke Sensor Reservoir sits within a ventriculoperitoneal shunt system to give a reading of the pressure within the shunt. This information can guide the management of hydrocephalus patients who present frequently with headaches. METHODS: We reviewed a cohort of 12 patients who underwent implantation of a Sensor Reservoir to assess how the management of their symptoms changed over a 4-year period. RESULTS: When comparing the group before the Sensor Reservoir and after the Sensor Reservoir insertion, there was a 75% reduction in number of CT head scans (P<0.05), 100% reduction in episodes of ICP monitoring (P<0.05), 55% reduction in number of X-ray shunt series, and a 50% reduction in acute presentation to hospital with shunt-related symptoms. The number of clinic attendances increased by 44%. In addition, cost analysis showed a saving of £6952 per patients over the 2-year period following Sensor Reservoir insertion as a result of reduced admissions and investigations. Complications were seen in 3 patients-two patients developed shunt-related infections, and 1 patient underwent shunt revision due to a proximal shunt obstruction. Seventy-five percent of patients showed an improvement in their symptoms at the end of the 4-year period. CONCLUSION: Implantation of a Sensor Reservoir in shunt patients with chronic headaches can reduce the number of investigations and hospital admissions and guide management resulting in a clinical improvement.

ETV for successful treatment of holocord syrinx with hydrocephalus: a case report.

AIM: to present evidence for the use of endoscopic third ventriculostomy (ETV) in the treatment of holocord syrinx. METHODS: ETV has been used in the treatment of obstructive hydrocephalus and syringomyelia secondary to Chiari 1 malformation. However, there have been no reports of ETV being utilised in the management of a holocord. We report a case of an 18 year old male with a symptomatic holocord syrinx who was successfully treated via ETV. RESULTS: neurological improvement was noted both immediately and at follow up following ETV. CONCLUSION: ETV may represent a viable treatment option for holocord syrinx in some population groups.

The ventriculo-cholecystic shunt: does CSF volume matter?

INTRODUCTION: The management of hydrocephalus in paediatric patients where the peritoneum has failed can be challenging. One option is to perform a ventriculo-cholecystic shunt. However, little is known about the capacity of the gall bladder to accommodate cerebrospinal fluid (CSF). METHODS: A retrospective case series was performed to include all paediatric patients who received a ventriculo-cholecystic shunt at a single centre, Sheffield Children's Hospital. RESULTS: We identified three patients who had a ventriculo-cholecystic shunt inserted. The shunt survived past 1 year in two patients, who had pre-operative external ventricular drain (EVD) outputs of 8 and 10 ml/h respectively. One patient shunt failed at day four post-op due to distal dysfunction, his pre-operative EVD was over 30 ml/h. CONCLUSIONS: When considering a patient for a ventriculo-cholecystic shunt, caution should be taken if a high CSF output is known, for example, as per an EVD measurement.

Giant vertebrobasilar aneurysm: a rare cause of central sleep apnoea.

We report a case of central sleep apnoea (CSA) due to a giant vertebrobasilar aneurysm with brainstem compression. A flow diverter stent was deployed with coil embolization of the right vertebral artery distal to the posterior inferior cerebellar artery (PICA) to occlude the aneurysm. The patient's symptoms improved following therapy.

Novel Colorimetric and Light Scatter Methods to Identify and Manage Peritoneal Dialysis-Associated Peritonitis at the Point-of-Care.

Introduction: Peritoneal dialysis (PD)-related peritonitis (PDRP) is a common cause of transfer to hemodialysis, patient morbidity, and is a risk factor for mortality. Associated patient anxiety can deter selection of PD for renal replacement therapy. Diagnosis relies on hospital laboratory tests; however, this might be achieved earlier if such information was available at the point-of-care (POC), thereby significantly improving outcomes. The presence of culturable microbes and the concentration of leukocytes in effluent both aid peritonitis diagnosis, as specified in the International Society for Peritoneal Dialysis (ISPD) diagnostic guidelines. Here, we report the development of 2 new methods providing such information in simple POC tests. Methods: One approach uses a tetrazolium-based chemical reporting system, primarily focused on detecting bacterial contamination and associated vancomycin-sensitivity. The second approach uses a novel forward light-scatter device (QuickCheck) to provide an instant quantitative cell count directly from PD patient effluent. Results: The tetrazolium approach detected and correctly distinguished laboratory isolates, taking 10 hours to provide non-quantitative results. We compared the technical performance of the light scatter leukocyte counting approach with spectrophotometry, hemocytometer counting and flow cytometry (Sysmex) using patient effluent samples. QuickCheck had high accuracy (94%) and was the most precise (coefficient of variation <4%), showing minimal bias, overall performing similarly to flow cytometry. Conclusion: These complementary new approaches provide a simple means to obtain information to assist diagnosis at the POC. The first provides antibiotic sensitivity following 10 hours incubation, whereas the second optical approach (QuickCheck), provides instant accurate total leukocyte count.

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.

Prognostic factors following resection of intracranial metastases.

Background: The aim of this study was to identify prognostic factors associated with resection of intracranial metastases. Methods: A retrospective case series including patients who underwent resection of cranial metastases from March 2014 to April 2021 at a single center. This identified 112 patients who underwent 124 resections. The median age was 65 years old (24-84) and the most frequent primary cancers were nonsmall cell lung cancer (56%), breast adenocarcinoma (13%), melanoma (6%), and colorectal adenocarcinoma (6%). Postoperative MRI with contrast was performed within 48 hours in 56% of patients and radiation treatment was administered in 41%. GraphPad Prism 9.2.0 was used for the survival analysis. Results: At the time of data collection, 23% were still alive with a median follow-up of 1070 days (68-2484). The 30- and 90-day, and 1- and 5-year overall survival rates were 93%, 83%, 35%, and 17%, respectively. The most common causes of death within 90 days were as follows: unknown (32%), systemic or intracranial disease progression (26%), and pneumonia (21%). Age and extent of neurosurgical resection were associated with overall survival (P < 0.05). Patients aged >70 had a median survival of 5.4 months compared with 9.7, 11.4, and 11.4 for patients <50, 50-59, and 60-69, respectively. Gross-total resection achieved an overall survival of 11.8 months whereas sub-total, debulking, and unclear extent of resection led to a median survival of 5.7, 7.0, and 9.0 months, respectively. Conclusion: Age and extent of resection are potential predictors of long-term survival.

Understanding the Mothers of Children with Spina Bifida and Hydrocephalus in Tanzania.

OBJECTIVE: To identify if there are cultural, medical, educational, economic, nutritional and geographic barriers to the prevention and treatment of spina bifida and hydrocephalus. METHODS: The mothers of infants with spina bifida and hydrocephalus admitted to Muhimbilli Orthopaedic Institute, Dar Es Salaam, Tanzania, between 2013 and 2014 were asked to complete a questionnaire. A total of 299 infants were identified: 65 with myelomeningoceles, 19 with encephaloceles, and 215 with isolated hydrocephalus. The questionnaire was completed by 294 of the mothers. RESULTS: There was a high variation in the geographic origin of the mothers. Approximately 85% traveled from outside of Dar Es Salaam. The mean age was 29 (15-45) years old with a parity of 3 (1-10). The rates of consanguinity, obesity, antiepileptic medication, HIV seropositivity, and family history were 2%, 13%, 0%, 2%, and 2%, respectively. A maize-based diet was found in 84%, and only 3% of woman took folic acid supplementation, despite 61% of mothers stating that they wished to conceive another baby. Unemployment was high (77%), a low level of education was common (76% not attended any school or obtaining a primary level only), and 20% were single mothers. Hospital only was the preferred method of treatment for 94% of the mothers, and 85% of the babies were born in a hospital. CONCLUSIONS: Our study highlights some of the cultural, educational, geographic, nutritional, and economic difficulties in the prevention and management of spina bifida and hydrocephalus in Tanzania.

Holocord syrinx presenting with foot drop.

We present an unusual presentation of holocord syrinx. A 4-year-old boy presenting a 2-week history of right sided foot drop. An MRI revealed a holocord secondary to a chiari one malformation. He successfully underwent a craniocervical decompression. Post operatively the syrinx decreased in size and his foot drop completely resolved.

Neurosurgery and human immunodeficiency virus in the era of combination antiretroviral therapy: a review.

Human immunodeficiency virus (HIV) is a global health problem. It renders the central nervous system susceptible to infectious and noninfectious diseases. HIV-positive individuals may present to neurosurgical services with brain lesions of unknown etiology. The differential diagnosis in these cases is broad, including opportunistic infections and malignancies, and investigation should be tailored accordingly. Opportunistic infections of the central nervous system can be complicated by hydrocephalus, and the management is pathogen dependent. Patients may also present to a neurosurgical service with conditions unrelated to their HIV status. This review outlines important conditions that cause brain lesions and hydrocephalus. It addresses the issues of diagnosis and intervention in HIV-positive patients in the era of combination antiretroviral therapy, while not ignoring the potential for opportunistic central nervous system infection in undiagnosed patients. The care of HIV-positive patients presenting to neurosurgical services requires a multidisciplinary approach, which is reflected in the authorship of this review, as well as in the guidance given.

ADP and AMP induce interleukin-1beta release from microglial cells through activation of ATP-primed P2X7 receptor channels.

P2X(7) is a subtype of ATP-gated channels that is highly expressed in astrocytes, microglia, and other immune cells. Activation of P2X(7) purinoceptors by ATP or 3'-O-(4-benzoyl)-benzoyl ATP (BzATP) induces the formation of cytolytic pores and provokes release of interleukin-1beta from immune cells. We investigated the actions of other endogenous nucleotides on recombinant and microglial P2X(7) receptors using electrophysiology, fluorescence imaging, and interleukin-1beta release measurement. We found that initial application of ADP or AMP to Xenopus oocytes expressing P2X(7) receptors was ineffective. However, when ADP and AMP, but not UTP or adenosine, were applied after a brief exposure to ATP or BzATP, they activated P2X(7) receptors in a dose-dependent manner. Moreover, responses to ADP and AMP were also elicited after exposure to low concentrations of ATP and were recorded several minutes after removal of ATP from the extracellular medium. Whole-cell recordings from mouse microglial cells showed that significant responses to ADP and AMP were elicited only after ATP application. YO-PRO-1 dye uptake imaging revealed that, unlike ATP, prolonged application of ADP or AMP did not cause an opening of large cytolytic pores in mouse microglial cells. Finally, ADP and AMP stimulated the release of interleukin-1beta from ATP-primed mouse and human microglial cells. We conclude that selective sensitization of P2X(7) receptors to ADP and AMP requires priming with ATP. This novel property of P2X(7) leads to activation by ATP metabolites and proinflammatory cytokine release from microglia without cytotoxicity.

A truncated form of CKbeta8-1 is a potent agonist for human formyl peptide-receptor-like 1 receptor.

1. Human formyl peptide-receptor-like-1 (FPRL-1) is a promiscuous G protein-coupled receptor (GPCR), and belongs to a chemoattractant receptor family protein. This receptor has been reported to interact with various host-derived peptides and lipids involved in inflammatory responses. We described here, a novel role for FPRL-1 as a high-affinity beta-chemokine receptor for an N-terminally truncated form of the CKbeta8 (CCL23/MPIF-1) splice variant CKbeta8-1 (22-137 aa). 2. RT-PCR analysis of mRNA derived from human tissues and cells revealed a predominant expression of FPRL-1 in inflammatory cells, particularly in neutrophils. 3. Intracellular calcium mobilisation assay, used as screening tool, in recombinant Chinese hamster ovary (CHO-K1) and human embryonic kidney (HEK293s) cells coexpressing FPRL-1 and Galpha(16), demonstrated FPRL-1 is a functional high-affinity receptor for CKbeta8-1 (46-137 aa, sCKbeta8-1), with pEC(50) values of 9.13 and 8.85, respectively. 4. The FPRL-1 activation in CHO-K1 cells is mediated by Galpha(i)/Galpha(o) proteins, as assessed by pertussis toxin sensitivity and inhibition of forskolin-induced cyclic AMP accumulation. 5. Binding experiments were performed with a radio-iodinated synthetic peptide, [(125-)I]-WKYMVm, a known potent FPRL-1 agonist. CHO-K1 cell membranes expressing FPRL-1 bound [(125-)I]-WKYMVm with a K(d) value of 9.34. Many known FPRL-1 agonists were tested and sCKbeta8-1 was the most effective nonsynthetic ligand in displacing the radiolabelled agonist, with a pIC(50) of 7.97. 6. The functional significance of sCKbeta8-1 interaction with FPRL-1 was further demonstrated by the activation of polymorphonuclear leukocytes (PMNs) calcium mobilisation and chemotaxis. These interactions were shown to be via FPRL-1 by specific blockade of PMNs activation in the presence of an FPRL-1 antibody.

A comparison of levobupivacaine 0.5% and racemic bupivacaine 0.5% for extradural anesthesia for caesarean section.

BACKGROUND AND OBJECTIVES: Bupivacaine is available as a racemic mixture of its enantiomers, dextrobupivacaine and levobupivacaine. Both in vitro and in vivo studies show that dextrobupivacaine has a greater inherent central nervous system (CNS) and cardiovascular toxicity than levobupivacaine. Clinical studies show levobupivacaine to have similar local anesthetic potency to the racemate. The aim of this study was to investigate the clinical efficacy and safety of levobupivacaine compared with racemic bupivacaine for extradural anesthesia. METHODS: We studied 62 patients undergoing elective caesarean delivery who received 25 mL of either levobupivacaine 0.5% or bupivacaine 0.5%, extradurally, in a randomized, double-blind study. RESULTS: The 2 groups were similar in terms of time to block suitable for surgery, segmental spread, and duration of sensory block. However, lower-limb motor block was significantly longer in the levobupivacaine group but of significantly less intensity. CONCLUSIONS: Levobupivacaine produces an extradural block that is similar to bupivacaine, and is a suitable local anesthetic agent for caesarean delivery.

Comparison of drug-eluting and bare-metal stents in patients with diabetes undergoing primary percutaneous coronary intervention: what is the evidence?

A best evidence topic was written according to a structured protocol. The question addressed was, should the practising interventional cardiologist use drug-eluting stents (DESs) or bare-metal stents (BMSs) when undertaking primary percutaneous coronary intervention (PCI) in diabetic patients. The relevant outcomes that were used to determine the answer to this question included: in-stent restenosis, target vessel revascularization (TVR), mortality, myocardial infarction and in-stent thrombosis. The OVID Medline database was used to carry out the reported search for abstracts of relevant journal articles. Altogether 102 papers were found, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. From the evidence available, we conclude that in-stent restenosis is less likely to occur over a follow-up of at least 6 months if a DES is used instead of a BMS. Furthermore, TVR is less likely to be required in diabetic patients who receive a DES in comparison with a BMS. Nevertheless, no significant difference in mortality between stents was detected by the studies reviewed. This included no difference in the incidence of cardiac and non-cardiac causes of death. There was evidence showing that DESs are associated with a decrease in the risk of myocardial infarction and, in particular, a decrease in non-Q-wave myocardial infarction. However, there was also conflicting evidence demonstrating no significant difference in the incidence of myocardial infarction between diabetic patients who had received a BMS or a DES. Moreover, the available evidence showed no significant difference in the risk of in-stent thrombosis for all DESs with the exception of Sirolimus eluting stents in which the evidence was not consistent. In summary, the available evidence supports the use of DESs over BMSs in diabetic patients undergoing primary PCI.

Selective knock-down of P2X7 ATP receptor function by dominant-negative subunits.

Among the family of P2X ATP-gated cation channels, the P2X7 receptor is a homomeric subtype highly expressed in immune cells of the monocyte-macrophage lineage. We report here that the WC167-168AA mutation in the ectodomain of P2X7 produced nonfunctional subunits with strong dominant-negative effect on wild-type P2X7 receptors (77% inhibition with cotransfection of wild-type and mutant DNA at a ratio of 3:1). The C168A single mutant was also very effective in suppressing P2X7 receptor function (72% reduction at a DNA ratio of 3:1), indicating the major role played by the C168A mutation in this inhibition. The dominant-negative effect is selective; the mutant subunit did not suppress the function of other receptor-channel subtypes. The reduced current responses in cells coexpressing wild-type and dominant-negative subunits display wild-type characteristics in both agonist affinity and ionic selectivity, strongly suggesting that the heteromeric channels are functionally impaired. The mutant subunits also suppressed the P2X7-dependent pore formation as assessed by uptake of the propidium dye YO-PRO-1 (Molecular Probes, Eugene, OR) in response to 2',3'-O-(4-benzoyl)-benzoyl-ATP (BzATP) in transfected human embryonic kidney 293 cells. Native responses to BzATP as well as ATP-induced ethidium dye uptake were significantly knocked down (31 +/- 9% and 25 +/- 7% of control, respectively) in mouse macrophage cell line RAW264.7 transfected with the mutant subunits. Therefore, these dominant-negative subunits provide selective genetic tools to investigate the functional roles of native P2X7 receptors.