Efficacy and Safety of Clazosentan After Aneurysmal Subarachnoid Hemorrhage: An Updated Meta-Analysis.

BACKGROUND AND OBJECTIVES: Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH. METHODS: Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment. RESULTS: Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76). CONCLUSION: Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.

External validation of the Glasgow coma scale-pupils in low- to middle-income country patients with traumatic brain injury: Could "motor score-pupil" have higher prognostic value?

Background: The objective of this study is to validate the admission Glasgow coma scale (GCS) associated with pupil response (GCS-P) to predict traumatic brain injury (TBI) patient's outcomes in a low- to middle-income country and to compare its performance with that of a simplified model combining the better motor response of the GCS and the pupilar response (MS-P). Methods: This is a prospective cohort of patients with TBI in a tertiary trauma reference center in Brazil. Predictive values of the GCS, GCS-P, and MS-P were evaluated and compared for 14 day and in-hospital mortality outcomes and length of hospital stay (LHS). Results: The study enrolled 447 patients. MS-P demonstrated better discriminative ability than GCS to predict mortality (AUC 0.736 × 0.658; P < 0.001) and higher AUC than GCS-P (0.736 × 0.704, respectively; P = 0.073). For hospital mortality, MS-P demonstrated better discrimination than GCS (AUC, 0.750 × 0.682; P < 0.001) and higher AUC than GCS-P (0.750 × 0.714; P = 0.027). Both scores were good predictors of LHS (r2 = 0.084 [GCS-P] × 0.079 [GCS] × 0.072 [MS-P]). Conclusion: The predictive value of the GCS, GCS-P, and MS-P scales was demonstrated, thus contributing to its external validation in low- to middle-income country.

Neurotrauma clinicians' perspectives on the contextual challenges associated with traumatic brain injury follow up in low-income and middle-income countries: A reflexive thematic analysis.

BACKGROUND: Traumatic brain injury (TBI) is a major global health issue, but low- and middle-income countries (LMICs) face the greatest burden. Significant differences in neurotrauma outcomes are recognised between LMICs and high-income countries. However, outcome data is not consistently nor reliably recorded in either setting, thus the true burden of TBI cannot be accurately quantified. OBJECTIVE: To explore the specific contextual challenges of, and possible solutions to improve, long-term follow-up following TBI in low-resource settings. METHODS: A cross-sectional, pragmatic qualitative study, that considered knowledge subjective and reality multiple (i.e. situated within the naturalistic paradigm). Data collection utilised semi-structured interviews, by videoconference and asynchronous e-mail. Data were analysed using Braun and Clarke's six-stage Reflexive Thematic Analysis. RESULTS: 18 neurosurgeons from 13 countries participated in this study, and data analysis gave rise to five themes: Clinical Context: What must we understand?; Perspectives and Definitions: What are we talking about?; Ownership and Beneficiaries: Why do we do it?; Lost to Follow-up: Who misses out and why?; Processes and Procedures: What do we do, or what might we do? CONCLUSION: The collection of long-term outcome data plays an imperative role in reducing the global burden of neurotrauma. Therefore, this was an exploratory study that examined the contextual challenges associated with long-term follow-up in LMICs. Where technology can contribute to improved neurotrauma surveillance and remote assessment, these must be implemented in a manner that improves patient outcomes, reduces clinical burden on physicians, and does not surpass the comprehension, capabilities, or financial means of the end user. Future research is recommended to investigate patient and family perspectives, the impact on clinical care teams, and the full economic implications of new technologies for follow-up.

Innate immune cells and myelin profile in multiple sclerosis: a multi-tracer PET/MR study.

PURPOSE: Neuropathological studies have demonstrated distinct profiles of microglia activation and myelin injury among different multiple sclerosis (MS) phenotypes and disability stages. PET imaging using specific tracers may uncover the in vivo molecular pathology and broaden the understanding of the disease heterogeneity. METHODS: We used the 18-kDa translocator protein (TSPO) tracer (R)-[11C]PK11195 and [11C]PIB PET images acquired in a hybrid PET/MR 3 T system to characterize, respectively, the profile of innate immune cells and myelin content in 47 patients with MS compared to 18 healthy controls (HC). For the volume of interest (VOI)-based analysis of the dynamic data, (R)-[11C]PK11195 distribution volume (VT) was determined for each subject using a metabolite-corrected arterial plasma input function while [11C]PIB distribution volume ratio (DVR) was estimated using a reference region extracted by a supervised clustering algorithm. A voxel-based analysis was also performed using Statistical Parametric Mapping. Functional disability was evaluated by the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite (MSFC), and Symbol Digit Modality Test (SDMT). RESULTS: In the VOI-based analysis, [11C]PIB DVR differed between patients and HC in the corpus callosum (P = 0.019) while no differences in (R)-[11C]PK11195 VT were observed in patients relative to HC. Furthermore, no correlations or associations were observed between both tracers within the VOI analyzed. In the voxel-based analysis, high (R)-[11C]PK11195 uptake was observed diffusively in the white matter (WM) when comparing the progressive phenotype and HC, and lower [11C]PIB uptake was observed in certain WM regions when comparing the relapsing-remitting phenotype and HC. None of the tracers were able to differentiate phenotypes at voxel or VOI level in our cohort. Linear regression models adjusted for age, sex, and phenotype demonstrated that higher EDSS was associated with an increased (R)-[11C]PK11195 VT and lower [11C]PIB DVR in corpus callosum (P = 0.001; P = 0.023), caudate (P = 0.015; P = 0.008), and total T2 lesion (P = 0.007; P = 0.012), while better cognitive scores in SDMT were associated with higher [11C]PIB DVR in the corpus callosum (P = 0.001), and lower (R)-[11C]PK11195 VT (P = 0.013). CONCLUSIONS: Widespread innate immune cells profile and marked loss of myelin in T2 lesions and regions close to the ventricles may occur independently and are associated with disability, in both WM and GM structures.

Remote Follow-Up Technologies in Traumatic Brain Injury: A Scoping Review.

Traumatic brain injury (TBI) remains a leading cause of death and disability worldwide. Motivations for outcome data collection in TBI are threefold: to improve patient outcomes, to facilitate research, and to provide the means and methods for wider injury surveillance. Such data play a pivotal role in population health, and ways to increase the reliability of data collection following TBI should be pursued. As a result, technology-aided follow-up of patients with neurotrauma is on the rise; there is, therefore, a need to describe how such technologies have been used. A scoping review was conducted and reported using the PRISMA extension (PRISMA-ScR). Five electronic databases (Embase, MEDLINE, Global Health, PsycInfo, and Scopus) were searched systematically using keywords derived from the concepts of "telemedicine," "TBI," "outcome assessment," and "patient-generated health data." Forty studies described follow-up technologies (FUTs) utilizing telephones (52.5%, n = 21), short message service (SMS; 10%, n = 4), smartphones (22.5%, n = 9), videoconferencing (10%, n = 4), digital assistants (2.5%, n = 1), and custom devices (2.5%, n = 1) among cohorts of patients with TBI of varying injury severity. Where reported, clinical facilitators, remote follow-up timing and intervals between sessions, synchronicity of follow-up instances, proxy involvement, outcome measures utilized, and technology evaluation efforts are described. FUTs can aid more temporally sensitive assessments and capture fluctuating sequelae, a benefit of particular relevance to TBI cohorts. However, the evidence base surrounding FUTs remains in its infancy, particularly with respect to large samples, low- and middle-income patient cohorts, and the validation of outcome measures for deployment via such remote technology.

Postoperative neutrophil-to-lymphocyte ratio variation is associated with chronic subdural hematoma recurrence.

INTRODUCTION: Chronic subdural haematoma (CSDH) is one of the most common neurosurgical pathologies. The recurrence of chronic subdural haematomas is an important concern, considering that elderly patients are the most affected and reoperations in these patients may represent a risk of neurological and clinical complications. In accordance with the inflammatory theory regarding CSDH and its recurrence, we aimed to evaluate the role of an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR), as a risk factor and prognostic variable for CSDH recurrence. METHODS: We performed a cohort study of adult patients operated for post-traumatic CSDH traumatic CSDH between January 2015 and December 2019 in our neurotrauma unit, whose data was retrospectively retrieved. We excluded patients with previous inflammatory or infectious diseases as well as use of anticoagulant/antiplatelet medications. Neutrophil and lymphocyte counts were obtained 24 h preoperatively and 48-72 h postoperatively. The primary endpoint was symptomatic recurrence of CSDH up to 1 year after the surgery. An independent sample was used to validate the findings. RESULTS: The testing sample comprised 160 patients (59.4% male, mean age 69.3 ± 14.3 years, recurrence rate 22.5%). Postoperative neutrophil count and NLR were higher in those who recurred, as well as the neutrophils (median 1.15 vs 0.96, p = 0.022) and NLR (median 1.29 vs 0.79, p = 0.001) postoperative-to-preoperative ratios. Preoperative laboratory parameters or other baseline variables were not associated with recurrence. Postoperative NLR ratio (each additional unit, OR 2.53, 95% CI 1.37-4.67, p = 0.003) was independently associated with recurrence. The best cut-off for the postoperative NLR ratio was 0.995 (AUC-ROC 0.67, sensitivity 63.9%, specificity 76.6%). Postoperative NLR ratio ≥ 1 (i.e. a post-operative NLR that does not decrease compared to the preoperative value) was associated with recurrence (OR 4.59, 95% CI 2.00-10.53, p < 0.001). The validation sample analysis (66 patients) yielded similar results (AUC-ROC 0.728, 95% CI 0.594-0.862, p = 0.002) and similar cut-off (≥ 1.05, sensitivity 77.8%, specificity 66.7%). CONCLUSION: NLR ratio can be a useful parameter for the prediction of post-traumatic CSDH recurrence. This hypothesis was validated in an independent sample and the accuracy was moderate.

Ultrasound Findings and Laboratory Predictors of Early Mortality in Patients With Severe Yellow Fever.

OBJECTIVE. Yellow fever is a hemorrhagic disease caused by an arbovirus endemic in South America; outbreaks have occurred in recent years. The purpose of this study was to describe abdominal ultrasound findings in patients with severe yellow fever and correlate them with clinical and laboratory data. MATERIALS AND METHODS. A retrospective cohort study was performed between January and April 2018. The subjects were patients admitted to an ICU with polymerase chain reaction-confirmed yellow fever. Bedside sonography was performed within 48 hours of admission. Images were independently analyzed by two board-certified radiologists. Laboratory test samples were collected within 12 hours of image acquisition. Multivariable logistic regression analysis was performed to identify 30-day mortality predictors; p < .05 was considered statistically significant. RESULTS. Forty-six patients (40 [87%] men, six [13%] women; mean age, 47.5 ± 15.2 years) were evaluated with bedside sonography. Laboratory tests showed high serum levels of aspartate aminotransferase (5319 U/L), total bilirubin (6.2 mg/dL), and creati-nine (4.3 mg/dL). Twenty-six (56.5%) patients died within 30 days of admission (median time to death, 5 days [interquartile range, 2-9 days]). The most frequent ultrasound findings were gallbladder wall thickening (80.4%), increased renal cortex echogenicity (71.7%), increased liver parenchyma echogenicity (65.2%), perirenal fluid (52.2%), and ascites (30.4%). Increased renal echogenicity was associated with 30-day mortality (84.6% versus 55.0%; p = .046) and was an independent predictor of this outcome after multivariate analysis (odds ratio, 10.89; p = .048). CONCLUSION. Reproducible abdominal ultrasound findings in patients with severe yellow fever may be associated with severity of disease and prognosis among patients treated in the ICU.

Preoperative level of neutrophil-lymphocyte ratio: Comparison between cyanotic and acyanotic congenital heart disease.

INTRODUCTION: Elevated neutrophil-lymphocyte ratio (NLR) has been associated with poorer outcomes in children undergoing congenital heart surgery under cardiopulmonary bypass (CPB). OBJECTIVE: To compare preoperative NLR levels between cyanotic and acyanotic children undergoing surgical repair with CPB. METHODS: We performed a retrospective cohort study in 60-paired children (30 with tetralogy of Fallot [TOF] and 30 with ventricular septal defect [VSD]) between January 2018 and December 2019 matched by age, weight, and gender. Preoperative NLR was measured from the last complete blood count test before the surgery. All of them had negative viral screening. RESULTS: The median age in VSD children was 9.5 months (interquartile range [IQR]: 5-12), weight 7 kg (IQR: 5.5-8.7), 19 (63%) was female, and NLR was 0.45 (IQR: 0.3-0.65). The median age in TOF children was 8.5 months (IQR: 5-12), weight 7.6 kg (IQR: 5.8-8.7), 16 (53%) were female, and NLR was 0.67 (IQR: 0.41-1.1). Demographic parameters did not show any statistically significant difference between groups (p > .05). Children with TOF had higher preoperative NLR compared with VSD patients (p = .004). As lower O2 saturation as higher the NLR (p = .005). CONCLUSION: The preoperative level of NLR was higher in cyanotic congenital heart disease patients.

Incremental Prognostic Value of Coagulopathy in Addition to the Crash Score in Traumatic Brain Injury Patients.

BACKGROUND/OBJECTIVE: Multivariable prognostic scores play an important role for clinical decision-making, information giving to patients/relatives, benchmarking and guiding clinical trial design. Coagulopathy has been implicated on trauma and critical care outcomes, but few studies have evaluated its role on traumatic brain injury (TBI) outcomes. Our objective was to verify the incremental prognostic value of routine coagulopathy parameters in addition to the CRASH-CT score to predict 14-day mortality in TBI patients. METHODS: This is a prospective cohort of consecutive TBI patients admitted to a tertiary university hospital Trauma intensive care unit (ICU) from March/2012 to January/2015. The prognostic performance of the coagulation parameters platelet count, prothrombin time (international normalized ratio, INR) and activated partial thromboplastin time (aPTT) ratio was assessed through logistic regression adjusted for the original CRASH-CT score. A new model, CRASH-CT-Coag, was created and its calibration (Brier scores and Hosmer-Lemeshow (H-L) test), discrimination [area under the receiver operating characteristic curve (AUC-ROC) and the integrated discrimination improvement (IDI)] and clinical utility (net reclassification index) were compared to the original CRASH-CT score. RESULTS: A total 517 patients were included (median age 39 years, 85.1% male, median admission glasgow coma scale 8, neurosurgery on 44.9%). The 14-day mortality observed and predicted by the original CRASH-CT was 22.8% and 26.2%, respectively. Platelet count < 100,000/mm3, INR > 1.2 and aPTT ratio > 1.2 were present on 11.3%, 65.0% and 27.2%, respectively, (at least one of these was altered on 70.6%). All three variables maintained statistical significance after adjustment for the CRASH-CT score. The CRASH-CT-Coag score outperformed the original score on calibration (brier scores 0.122 ± 0.216 vs 0.132 ± 0.202, mean difference 0.010, 95% CI 0.005-0.019, p = 0.036, respectively) and discrimination (AUC-ROC 0.854 ± 0.020 vs 0.813 ± 0.024, p = 0.014; IDI 5.0%, 95% CI 1.3-11.0%). Both scores showed the satisfactory H-L test results. The net reclassification index favored the new model. Considering the strata of low (< 10%), moderate (10-30%) and high (> 30%) risk of death, the CRASH-CT-Coag model yielded a global net correct reclassification of 22.9% (95% CI 3.8-43.4%). CONCLUSIONS: The addition of early markers of coagulopathy-platelet count, INR and aPTT ratio-to the CRASH-CT score increased its accuracy. Additional studies are required to externally validate this finding and further investigate the coagulopathy role on TBI outcomes.

FDG-PET Patterns Predict Amyloid Deposition and Clinical Profile in Corticobasal Syndrome.

BACKGROUND: Corticobasal syndrome (CBS) is an atypical parkinsonian syndrome related to multiple underlying pathologies. OBJECTIVE: To investigate if individual brain [18 F]fluorodeoxyglucose-positron emission tomography (FDG-PET) patterns could distinguish CBS due to Alzheimer's disease (AD) from other pathologies based on [11 C]Pittsburgh Compound-B (PIB)-PET. METHODS: Forty-five patients with probable CBS were prospectively evaluated regarding cognitive and movement disorders profile. They underwent FDG-PET and were distributed into groups: likely related to AD (CBS FDG-AD) or likely non-AD (CBS FDG-nonAD) pathology. Thirty patients underwent PIB-PET on a hybrid PET-magnetic resonance imaging equipment to assess their amyloid status. FDG and PIB-PET images were classified individually based on visual and semi-quantitative analysis, blinded to each other. Quantitative group analyses were also performed. RESULTS: CBS FDG-AD group demonstrated worse cognitive performances, mostly concerning attention, memory, visuospatial domains, and displayed more myoclonus and hallucinations. The non-AD metabolic group presented more often limb dystonia, ocular motor dysfunction, motor perseveration, and dysarthria. All patients classified as CBS FDG-AD tested positive at PIB-PET compared to 3 of 20 in the non-AD group. The individual FDG-PET classification demonstrated 76.92% of sensitivity, 100% of specificity and positive predictive value and 88.5% of balanced accuracy to detect positive PIB-PET scans. Individuals with positive and negative PIB-PET showed hypometabolism in posterior temporoparietal areas and in thalamus and brainstem, respectively, mainly contralateral to most affected side, disclosing possible metabolic signatures of CBS variants. CONCLUSION: FDG-PET was useful to predict AD and non-AD CBS variants depicting their specific degeneration patterns, different clinical features, and brain amyloid deposition. © 2020 International Parkinson and Movement Disorder Society.

Real-World Data from Nusinersen Treatment for Patients with Later-Onset Spinal Muscular Atrophy: A Single Center Experience.

BackgroundSpinal muscular atrophy (SMA) is a motor neuron disease associated with progressive muscle weakness and motor disability.ObjectiveThis study aims to report the evaluation of nusinersen, an antisense oligonucleotide, on motor function in patients with SMA types 2 and 3.MethodsThis single-center retrospective observational study assessed nusinersen therapy outcomes, measured by HSMFSE or CHOP-INTEND scales, in patients with SMA types 2 and 3, compared to untreated patients, for at least 24 months.ResultsA total of 41 patients with SMA types 2 and 3 under nusinersen treatment were included. In 30 treated patients (mean age: 10.6 years; 14 with SMA type 2), the mean change in HFMSE scores was +1.47 points (SD = 0.4) and +1.60 points (SD = 0.6) after 12 and 24 months of treatment, respectively. In contrast, the control group (N = 37) (mean age: 10.2 years; 20 with SMA type 2) presented a mean change of -1.71 points (SD = 0.02) and -3.93 points (SD = 0.55) after 12 and 24 months of follow-up, respectively. The most severe patients under nusinersen treatment (N = 11) showed a change of +2.37 (SD = 1.13) on the CHOP-INTEND scale after 12 months of follow-up. Disease duration at the beginning of treatment was the main predictor of functional improvement. Despite functional gain and motor stabilization, treatment with nusinersen did not prevent the progression of scoliosis.ConclusionsOur data provide evidence for the long-term safety and efficacy of nusinersen use in the treatment of later-onset SMA, and patients with shorter disease duration showed better response to treatment.

The World Federation of Neurosurgical Societies Young Neurosurgeons Survey (Part I): Demographics, Resources, and Education.

BACKGROUND: Providing a comprehensive and effective neurosurgical service requires adequate numbers of well-trained, resourced, and motivated neurosurgeons. The survey aims to better understand 1) the demographics of young neurosurgeons worldwide; 2) the challenges in training and resources that they face; 3) perceived barriers; and 4) needs for development. METHODS: This was a cross-sectional study in which a widely disseminated online survey (April 2018-November 2019) was used to procure a nonprobabilistic sample from current neurosurgical trainees and those within 10 years of training. Data were grouped by World Bank income classifications and analyzed using χ2 tests because of its categorical nature. RESULTS: There were 1294 respondents, with 953 completed responses included in the analysis. Of respondents, 45.2% were from high-income countries (HICs), 23.2% from upper-middle-income countries, 26.8% lower-middle-income countries, and 4.1% from low-income countries. Most respondents (79.8%) were male, a figure more pronounced in lower-income groups. Neuro-oncology was the most popular in HICs and spinal surgery in all other groups. Although access to computed tomography scanning was near universal (98.64%), magnetic resonance imaging access decreased to 66.67% in low-income countries, compared with 98.61% in HICs. Similar patterns were noted with access to operating microscopes, image guidance systems, and high-speed drills. Of respondents, 71.4% had dedicated time for neurosurgical education. CONCLUSIONS: These data confirm and quantify disparities in the equipment and training opportunities among young neurosurgeons practicing in different income groups. We hope that this study will act as a guide to further understand these differences and target resources to remedy them.

The World Federation of Neurosurgical Societies Young Neurosurgeons Survey (Part II): Barriers to Professional Development and Service Delivery in Neurosurgery.

BACKGROUND: Strengthening health systems requires attention to workforce, training needs, and barriers to service delivery. The World Federation of Neurosurgical Societies Young Neurosurgeons Committee survey sought to identify challenges for residents, fellows, and consultants within 10 years of training. METHODS: An online survey was distributed to various neurosurgical societies, personal contacts, and social media platforms (April-November 2018). Responses were grouped by World Bank income classification into high-income countries (HICs), upper middle-income countries (UMICs), low-middle-income countries (LMICs), and low-income countries (LICs). Descriptive statistical analysis was performed. RESULTS: In total, 953 individuals completed the survey. For service delivery, the limited number of trained neurosurgeons was seen as a barrier for 12.5%, 29.8%, 69.2%, and 23.9% of respondents from HICs, UMICs, LMICs, and LICs, respectively (P < 0.0001). The most reported personal challenge was the lack of opportunities for research (HICs, 34.6%; UMICs, 57.5%; LMICs, 61.6%; and LICs, 61.5%; P = 0.03). Other differences by income class included limited access to advice from experienced/senior colleagues (P < 0.001), neurosurgical journals (P < 0.0001), and textbooks (P = 0.02). Assessing how the World Federation of Neurosurgical Societies could best help young neurosurgeons, the most frequent requests (n = 953; 1673 requests) were research (n = 384), education (n = 296), and subspecialty/fellowship training (n = 232). Skills courses and access to cadaver dissection laboratories were also heavily requested. CONCLUSIONS: Young neurosurgeons perceived that additional neurosurgeons are needed globally, especially in LICs and LMICs, and primarily requested additional resources for research and subspecialty training.

Correction: The extravasation of contrast as a predictor of cerebral hemorrhagic contusion expansion, poor neurological outcome and mortality after traumatic brain injury: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0235561.].

Neurosurgeons' experiences of conducting and disseminating clinical research in low- and middle-income countries: a qualitative study protocol.

INTRODUCTION: Low-income and middle-income countries (LMICs) face the greatest burden of neurotrauma. However, most of the research published in scientific journals originates from high-income countries, suggesting those in LMICs are either not engaging in research or are not publishing it. Evidence originating in high-income countries may not be generalisable to LMICs; therefore, it is important to nurture research capacity in LMICs so that a relevant evidence base can be developed. However, little is published about specific challenges or contextual issues relevant to increasing research activity of neurosurgeons in LMICs. Therefore, the aim of this study was to understand neurosurgeons' experiences of, aspirations for and ability to conduct and disseminate clinical research in LMICs. METHODS AND ANALYSIS: This is a pragmatic qualitative study situated within the naturalistic paradigm using focus groups and interviews with a purposive sample of neurosurgeons from LMICs. First, we will conduct asynchronous online focus groups with 36 neurosurgeons to broadly explore issues relevant to the study aim. Second, we will select 20 participants for follow-up semistructured interviews to explore concepts in more depth and detail than could be achieved in the focus group. Interviews will be audio-recorded and transcribed verbatim. A thematic analysis will be conducted following Braun and Clarke's six stages and will be supported by NVIVO software. ETHICS AND DISSEMINATION: The University of Cambridge Psychology Research Ethics Committee reviewed this study and provided a favourable opinion in January 2020 (REF PRE.2020.006). Participants will provide informed consent, be able to withdraw at any time and will have their contributions kept confidential. The findings of the study will be shared with relevant stakeholders and disseminated in conference presentations and journal publications.

Optimal Timing of External Ventricular Drainage after Severe Traumatic Brain Injury: A Systematic Review.

External ventricular drainage (EVD) may be used for therapeutic cerebrospinal fluid (CSF) drainage to control intracranial pressure (ICP) after traumatic brain injury (TBI). However, there is currently uncertainty regarding the optimal timing for EVD insertion. This study aims to compare patient outcomes for patients with early and late EVD insertion. Following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, MEDLINE/EMBASE/Scopus/Web of Science/Cochrane Central Register of Controlled Trials were searched for published literature involving at least 10 severe TBI (sTBI) patients from their inception date to December 2019. Outcomes assessed were mortality, functional outcome, ICP control, length of stay, therapy intensity level, and complications. Twenty-one studies comprising 4542 sTBI patients with an EVD were included; 19 of the studies included patients with an early EVD, and two studies had late EVD placements. The limited number of studies, small sample sizes, imbalance in baseline characteristics between the groups and poor methodological quality have limited the scope of our analysis. We present the descriptive statistics highlighting the current conflicting data and the overall lack of reliable research into the optimal timing of EVD. There is a clear need for high quality comparisons of early vs. late EVD insertion on patient outcomes in sTBI.

The extravasation of contrast as a predictor of cerebral hemorrhagic contusion expansion, poor neurological outcome and mortality after traumatic brain injury: A systematic review and meta-analysis.

BACKGROUND: The active extravasation of contrast on CT angiography (CTA) in primary intracerebral hemorrhages (ICH) is recognized as a predictive factor for ICH expansion, unfavorable outcomes and mortality. However, few studies have been conducted on the setting of traumatic brain injury (TBI). PURPOSE: To perform a literature systematic review and meta-analysis of the association of contrast extravasation on cerebral hemorrhagic contusion expansion, neurological outcomes and mortality. DATA SOURCES: The PubMed, Cochrane Library, Medline, Scielo, VHL and IBECS databases up to September 21, 2019, were searched for eligible studies. STUDY SELECTION: A total of 505 individual titles and abstracts were identified and screened. A total of 36 were selected for full text analysis, out of which 4 fulfilled all inclusion and exclusion criteria. DATA ANALYSIS: All 4 studies yielded point estimates suggestive of higher risk for hematoma expansion with contrast extravasation and the summary RR was 5.75 (95%CI 2.74-10.47, p<0.001). Contrast extravasation was also associated with worse neurological outcomes (RR 3.25, 95%CI 2.24-4.73, p<0.001) and higher mortality (RR 2.77, 95%CI 1.03-7.47, p = 0.04). DATA SYNTHESIS: This study is a Systematic Review and Meta-Analysis revealed the extravasation of contrast is a useful imaging sign to predict hematoma expansion, worse neurological outcomes and higher mortality. LIMITATIONS: Only four articles were selected. CONCLUSIONS: The extravasation of contrast in the setting of TBI is a useful imaging sign to predict hematoma expansion, worse neurological outcomes and higher mortality.

Diagnostic accuracy of imaging studies for diagnosing root avulsions in post-traumatic upper brachial plexus traction injuries in adults.

BACKGROUND: There is no consensus about which type of imaging study, computed tomography myelography (CTM) or magnetic resonance imaging (MRI), provides better information concerning root avulsion in adult brachial plexus injuries. METHODS: Patients with upper brachial plexus traumatic injuries underwent both CTM and MRI and surgical exploration. The imaging studies were analyzed by two independent radiologists and the data were compared with the intraoperative findings. The statistical analysis was based on dichotomous classification of the nerve roots (normal or altered). The interobserver agreement was assessed using Cohen's Kappa. The accuracy of CTM and MRI in comparison with the intraoperative findings was evaluated using the same methodology. RESULTS: Fifty-two adult patients were included. CTM tended to yield slightly higher percentages of alterations than MRI The interobserver agreement was better on CTM than on MRI for all nerve roots: C5, 0.9960 (strong) vs. 0.145 (poor); C6, 0.970 (strong) vs. 0.788 (substantial); C7, 0.969 (strong) vs. 0.848 (strong). The accuracy regarding the intraoperative findings was also higher on CTM (moderate, kappa 0.40-0.59) than on MRI (minimal, kappa 0.20-0.39) for all nerve roots. Accordingly, the overall percentage concordance (both normal or both altered) was superior in the CTM evaluation (approx. 70-75% vs. 60-65%). CTM was superior for both sensitivity and specificity at all nerve roots. CONCLUSION: CTM had greater interobserver agreement and higher diagnostic accuracy than MRI in adult patients with root avulsions due to brachial plexus injury.