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Abstract Traumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.

Background Chronic subdural hematoma (CSDH) is a common neurological condition; surgical evacuation is the mainstay of treatment for symptomatic patients. No clear evidence exists regarding the impact of timing of surgery on outcomes. We investigated factors influencing time to surgery and its impact on outcomes of interest.Methods Patients with CSDH who underwent burr-hole craniostomy were included. This is a subset of data from a prospective observational study conducted in the UK. Logistic mixed modelling was performed to examine the factors influencing time to surgery. The impact of time to surgery on discharge modified Rankin Scale (mRS), complications, recurrence, length of stay and survival was investigated with multivariable logistic regression analysis.Results 656 patients were included. Time to surgery ranged from 0 to 44 days (median 1, IQR 1–3). Older age, more favorable mRS on admission, high preoperative Glasgow Coma Scale score, use of antiplatelet medications, comorbidities and bilateral hematomas were associated with increased time to surgery. Time to surgery showed a significant positive association with length of stay; it was not associated with outcome, complication rate, reoperation rate, or survival on multivariable analysis. There was a trend for patients with time to surgery of ≥7 days to have lower odds of favorable outcome at discharge (p=0.061).Conclusions This study provides evidence that time to surgery does not substantially impact on outcomes following CSDH. However, increasing time to surgery is associated with increasing length of stay. These results should not encourage delaying operations for patients when they are clinically indicated.

The impact of Covid-19 on surgical patients worldwide has been substantial. In the United Kingdom (UK) and the Republic of Ireland (RoI), the first wave of the pandemic occurred in March 2020. The aims of this study were to: (1) evaluate the volume of neurosurgical operative activity levels, Covid-19 infection rate and mortality rate in April 2020 with a retrospective cross-sectional cohort study conducted across 16 UK and RoI neurosurgical centres, and (2) compare patient outcomes in a single institution in April-June 2020 with a comparative cohort in 2019. Across the UK and RoI, 818 patients were included. There were 594 emergency and 224 elective operations. The incidence rate of Covid-19 infection was 2.6% (21/818). The overall mortality rate in patients with a Covid-19 infection was 28.6% (6/21). In the single centre cohort analysis, an overall reduction in neurosurgical operative activity by 65% was observed between 2020 ( n  = 304) and 2019 ( n  = 868). The current and future impact on UK neurosurgical operative activity has implications for service delivery and neurosurgical training.

Introduction: Preoperative hair removal is conventional practice within neurosurgery in an attempt to maintain antisepsis. However, there is a lack of evidence to suggest that it makes a difference with regards to infection. This article aims to relate preoperative hair removal to SSIs for paediatric patients., Methods and Materials: A retrospective analysis was conducted from a single paediatric neurosurgical database at the University Hospital of Wales. Patients were grouped according to whether they underwent preoperative hair removal or not. Findings were reviewed in light of the previously published literature., Results: One hundred eighty two paediatric intracranial tumours were operated on between November 2008 and 2019. A total of twenty-six patients (14%) developed an infection post-operatively, of which meningitis was the most common (77%). Eighty-nine operations were undertaken without preoperative hair removal, of which there were a total of fifteen infections (17%). In the hair removal group, there were a total of eleven infections out of ninety-three operations (12%). Overall, the patients without hair removal had a higher infection rate when compared to those with hair removal (17 and 12% respectively), however, this result was not statistically significant ( p -value 0.3989)., Conclusion: We did not find evidence that hair removal in paediatric neurosurgery effects postoperative infection risk.

Objective: Endovascular treatment (EVT) of spinal dural arteriovenous fistulae (SDAVF) has become increasingly popular given its less invasive nature. This study aims to assess radiological obliteration rates after surgery and EVT for SDAVF in a major tertiary referral centre serving a population of 2.2 million., Method: A retrospective review of all patients diagnosed with SDAVF between February 2010 and February 2018 was undertaken, identifying baseline demographics, treatment modality and the final radiological outcome (i.e., persistence of the SDAVF). Patients were identified from the departmental neurovascular database, clinical notes and imaging reports., Results: Twenty patients were identified with an angiographically confirmed SDAVF. Two (10%) were managed conservatively. Nine patients (45%) underwent EVT. Obliteration was achieved in one patient (11%) after a single procedure, while one patient required two sessions. Further surgery was required in five patients (56%) to achieve complete obliteration. Nine patients (45%) underwent surgical disconnection as first treatment. Obliteration was radiologically confirmed in eight patients (89%). No radiological (MRI or angiographic) follow-up data was available for two patients (one from each group) and these were excluded from analysis. In this study, the obliteration rate of SDAVF after surgery was superior compared to EVT (p <0.01)., Conclusion: Complete obliteration and recurrence rates after single treatment with EVT were inferior compared to surgical intervention. EVT may be better suited for specific presentations of SDAVF either in isolation or as an adjunct in multi-modality treatment. A national registry of outcomes may aid ongoing refinement of patient selection for EVT.

Purpose: Objective Structured Clinical Examination (OSCE) is a vital examination that must be passed to graduate as a qualified doctor. The delivery of OSCE teaching was changed to an online format to accommodate COVID-19 restrictions. Therefore, this study evaluates factors that students perceive to affect their virtual learning of clinical skills for OSCE., Methods: In this cross-sectional study, all medical students from across the world who attended "The Respiratory Station" session delivered by OSCEazy (a medical student organization providing free online medical education) in the academic year 2020-2021 received an online questionnaire about their perceptions of this learning opportunity. The survey was created on Google™ forms and consisted of 5-point Likert scales as well as free-text boxes., Results: A total of 556 responses were received (mean age: 24, female: 76.6%). Most students agreed that online OSCE teaching offers more flexibility and convenience (median: 5, IQR: 4-5) but their likeliness to ask questions in either format was similar (median: 4, IQR: 3-5 vs median: 4, IQR: 3-4, p value: 0.94). The use of visual aids (median: 5, IQR: 4-5) and breakout rooms (median: 3, IQR: 2-4) were thought to enhance the quality of virtual OSCE teaching. The biggest concern about online teaching was access to a stable internet connection (69.1%)., Conclusion: The flexibility and convenience of virtual OSCE teaching enables the sharing of knowledge and skills to a wider audience and thus may be a very useful adjunct to face-to-face OSCE teaching in the future., Competing Interests: Movin Peramuna Gamage and Ravanth Baskaran are to be considered as co-first authors. The authors report no conflicts of interest and have no funding sources to declare., (© 2023 Peramuna Gamage et al.)

Purpose: Chronic subdural haematoma (CSDH) is a well-recognized consequence of head injury with a rising incidence worldwide. Whilst symptomatic CSDH warrants consideration of surgical intervention, the management of asymptomatic CSDH (AsCSDH) remains unclear. In this retrospective study, we investigate the natural history of AsCSDH, the requirement for radiological monitoring, and the role of neurosurgical input., Methods: Head injury referrals to a tertiary neurosurgical unit over two years were screened to identify patients with AsCSDH. Clinical, radiological, and outcome parameters were collected for included patients., Results: Of 2725 referrals, 106 (3.9%) patients were eligible for inclusion. The cohort consisted of predominantly male patients (70.8%) with an average age of 81.9 years and independent at baseline (79.3%). Radiological follow-up was recommended by neurosurgery in 4 patients (3.8%). Medical teams performed follow-up imaging for 57 patients (53.8%) culminating in a total of 116 follow-up scans, predominantly for falls or monitoring purposes. Antithrombotic agents were used by 61 patients (57.5%). Anticoagulants were held in 26/37 patients (70.3%) and antiplatelets in 12/29 patients (41.4%), ranging from 7 to 16 days when specified. Only one patient required neurosurgical intervention at 3 months from the time of initial presentation after the development of symptoms., Conclusions: Patients with AsCSDH do not require neuroradiological follow-up or neurosurgical intervention in the majority of instances. Medical professionals should explain to patients, families, and caregivers that the isolated finding of CSDH is not necessarily a cause for concern but safety netting advice regarding AsCSDH should be provided.

Background: Near-peer medical education serves as an important method of delivering education to junior students by senior students. Due to the reduced clinical exposure because of the COVID-19 pandemic, we developed a mentorship scheme to help medical students with their Integrated Structured Clinical Examinations (ISCEs) by providing a combination of near-peer mentorship together with lecture-based teaching on a weekly basis for a 12-week period. Students attended a specialty-focused lecture every Tuesday followed by a small group teaching session organised by their tutor., Methods: A longitudinal evaluative interventional study was undertaken by the international student led medical education organisation, OSCEazy. The teaching programme was organised and conducted by third year medical students to a recruited cohort of second year medical students. Students' perceptions of ISCEs (confidence, anxiety, and overall performance) were evaluated using 5-point Likert scales while their knowledge of the specialty was assessed using 10 single best answer questions which were distributed via Google® forms at the start and end of each week. In addition, we assessed tutor perceptions of their teaching and learning experience., Results: Seventy-two tutees were enrolled in the programme (mean age: 24.4, female: 77.8%). 88.9% of the participants had not attended any online ISCE teaching prior to this. They preferred in-person ISCE teaching as compared to virtual sessions [median 4.5 (IQR 4-5) vs 3 (IQR 3-4), p <  0.0001), respectively]. There was a significant overall increase in knowledge when comparing pre-session and post-session performance [mean 53.7% vs 70.7%, p <  0.0001)]. There was a significant increase in student confidence [Confidence: median 3 (IQR:3-4) vs 4 (IQR 3-4), p <  0.0001] while no change was seen in the anxiety and perception of their overall performance in an ISCE. [Anxiety: median 3 (IQR 2-4) vs 3 (IQR 3-4), p = 0.37, Performance: median 3 (IQR 3-4) vs median 3 (IQR 3-4), p <  0.0001]. The tutors reported an increase in their confidence in teaching ISCEs online [median 3 (IQR 2-3.25) vs median 4 (IQR 4-5), p <  0.0001)]., Conclusion: Online near-peer teaching increases the confidence of both tutees and tutors involved while enhancing the tutees' knowledge of the specialty. Thus, medical schools should incorporate near-peer teaching in their curriculum to enhance the student learning experience., (© 2023. The Author(s).)

Objective: To investigate if COVID-19 UK lockdown measures resulted in a delay in the presentation and treatment of patients with cauda equina syndrome (CES)., Methods: This is a multicenter retrospective study of patients with surgically treated CES across 3 time periods: April-May 2020 (first lockdown), August-September 2020 (no-lockdown group), and January-February 2021 (second lockdown). Data regarding duration of symptoms, time from referral to admission, time from admission to surgery, and postoperative outcomes were collected., Results: A total of 56 patients (male: 26, female: 30, mean age: 44.3 years) were included in the study (n = 14, n = 18, and n = 24 in the 3 time periods, respectively). There was no significant difference in duration of symptoms across the time periods (12.6 days vs. 8.2 days vs. 3.8 days) (P = 0.16). Nearly all the patients were admitted within 48 hours of referral (n = 55, 98.2%). The majority of patients were operated on within 48 hours: first lockdown (n = 12, 85.7%), no-lockdown (n = 16, 88.9%), and second lockdown (n = 21, 87.5%). The length of hospital stay was significantly shorter in the second lockdown (3.3 days) versus the other 2 time periods (4.4 days and 6.4 days) (P = 0.02). Thirteen complications were present, with dural tear being the most common (n = 6, 10.7%). Majority reported symptom improvement (n = 53, 94.6%), with a similar number discharged home (n = 54, 96.4%)., Conclusion: Despite the pandemic, patients with CES were promptly admitted and operated on with good outcomes. Shorter duration of hospital stay could be attributed to adaptation of spinal services., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. There are currently no early biomarkers for prognosis in routine clinical use. Interleukin-6 (IL-6) is a potential biomarker in the context of the established role of neuroinflammation in TBI recovery. Therefore, a systematic review of the literature was performed to assess and summarise the evidence for IL-6 secretion representing a useful biomarker for clinical outcomes. A multi-database literature search between January 1946 and July 2021 was performed. Studies were included if they reported adult TBI patients with IL-6 concentration in serum, cerebrospinal fluid (CSF) and/or brain parenchyma analysed with respect to functional outcome and/or mortality. A synthesis without meta-analysis is reported. Fifteen studies were included, reporting 699 patients. Most patients were male (71.7%), and the pooled mean age was 40.8 years; 78.1% sustained severe TBI. Eleven studies reported IL-6 levels in serum, six in CSF and one in the parenchyma. Five studies on serum demonstrated higher IL-6 concentrations were associated with poorer outcomes, and five showed no signification association. In CSF studies, one found higher IL-6 levels were associated with poorer outcomes, one found them to predict better outcomes and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Despite some inconsistency in findings, it appears that exaggerated IL-6 secretion predicts poor outcomes after TBI. Future efforts require standardisation of IL-6 measurement practices as well as assessment of the importance of IL-6 concentration dynamics with respect to clinical outcomes, ideally within large prospective studies. Prospero registration number: CRD42021271200., (© 2022. The Author(s).)

Introduction: Posterior fossa (PF) tumours are associated with vasogenic oedema causing symptoms of raised intracranial pressure. Preoperatively this is managed with dexamethasone. To minimise steroid related complications, the lowest effective dose should be administered. No neurosurgical guidelines exist for pre-operative dosing of dexamethasone in PF tumours., Methods: A retrospective review was performed of surgically managed cases for patients under 16 years of age between 2013 and 2018 to ascertain the initial dose of dexamethasone with symptomatic PF tumours., Results: Thirty-six patients were identified of which 30 notes were available. Sixteen were male. Median age was 6 years (range 10 months - 15 years). Twenty-two (73%) were referrals from DGH and 8 (27%) presented to our neurosurgical centre. All patients presented with symptomatic PF tumours including headache (97%), vomiting (93%), gait disturbance (43%), and nystagmus (17%). Four (13%) had papilloedema. Average initial stat dexamethasone dose was 9.15 mg; 0.31 mg/kg (range 1-16.7 mg; 0.05 - 1.77 mg/kg). Stratified according to weight, average dose (and range) was 8.8 mg; 0.94 mg/kg (1-16.6 mg; 0.13 - 1.77 mg/kg) in those weighing <10 kg; 9.7 mg; 0.66 mg/kg (4-16.7 mg; 0.21 - 1.35 mg/kg) in 10-20 kg; 12.3 mg;0.52 mg/kg (8-16.7 mg; 0.27 - 0.73mg/kg) in 20-30 kg and 7.8 mg; 0.17mg/kg (2-16.7 mg; 0.0 - 0.39 mg/kg) in >30 kg up to a maximum of 16.6 mg in any 24h period. These results suggest that dosage was higher in those children weighing less. PPI was used in 24 (80%) of cases. All doses were reduced after review by the neurosurgical team and a PPI added., Conclusion: Pre-operative dexamethasone dosing does not always reflect the severity of clinical symptoms for PF tumours. Guidelines are required to correlate clinical symptoms with a suggested suitable dose of dexamethasone to prevent overdose and complications associated with corticosteroid use. We recommend a weight-based regimen as provided by the Food and Drug Administration. The current advice is for 0.02-0.3mg/kg/day in 3-4 divided doses.

Competing Interests: None

Purpose of Review: Traumatic brain injury (TBI) is amongst the leading causes of mortality and morbidity worldwide. However, several pharmacological strategies in the clinical setting remain unsuccessful. Mounting evidence implicates High Mobility Group Box protein 1 (HMGB1) as a unique alternative target following brain injury. Herein, we discuss current understanding of HMGB1 in TBI and obstacles to clinical translation., Recent Findings: HMGB1 plays a pivotal role as a 'master-switch' of neuro-inflammation following injury and in the regulation of neurogenesis during normal development. Animal models point towards the involvement of HMGB1 signalling in prolonged activation of glial cells and widespread neuronal death. Early experimental studies demonstrate positive effects of HMGB1 antagonism on both immunohistochemical and neuro-behavioural parameters following injury. Raised serum/CSF HMGB1 in humans is associated with poor outcomes post-TBI. HMGB1 is a promising therapeutic target post-TBI. However, further studies elucidating receptor, cell, isoform, and temporal effects are required prior to clinical translation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Acute subdural haematoma (ASDH) is a devastating pathology commonly found on CT brain scans of patients with traumatic brain injury. The role of surgical intervention in the elderly has been increasingly questioned due to its associated morbidity and mortality. Therefore, a systematic review and meta-analysis of the literature to quantify the mortality and functional outcomes associated with surgical management of ASDH in the elderly was performed., Design/setting: A multidatabase literature search between January 1990 and May 2020, and meta-analysis of proportions was performed to quantify mortality and unfavourable outcome (Glasgow Outcome scale 1-3; death/ severe disability) rates., Participants: Studies reporting patients aged 60 years or older., Interventions: Craniotomy, decompressive craniectomy, conservative management., Outcome Measures: Mortality and functional outcomes (discharge, long-term follow-up (LTFU))., Results: 2572 articles were screened, yielding 21 studies for final inclusion and 15 for meta-analysis. Pooled estimates of mortality were 39.83% (95% CI 32.73% to 47.14%; 10 studies, 308/739 patients, I 2 =73%) at discharge and 49.30% (95% CI 42.01% to 56.61%; 10 studies, 277/555 patients, I 2 =63%) at LTFU. Mean duration of follow-up was 7.1 months (range 2-12 months). Pooled estimate of percentage of poor outcomes was 81.18% (95% CI 75.61% to 86.21%; 6 studies, 363/451 patients, I 2 =45%) at discharge, and 79.25% (95% CI 72.42% to 85.37%; 8 studies, 402/511 patients, I 2 =66%) at LTFU. Mean duration of follow-up was 6.4 months (range 2-12 months). Potential risk factors for poor outcome included age, baseline functional status, preoperative neurological status and imaging parameters., Conclusions: Outcomes following surgical evacuation of ASDH in patients aged 60 years and above are poor. This constitutes the best level of evidence in the current literature that surgical intervention for ASDH in the elderly carries significant risks, which must be weighed against benefits., Prospero Registration Number: CRD42020189508., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic has had widespread consequences on health care systems around the world. It resulted in extensive changes to the referral patterns, management, and rehabilitation of surgical conditions. We aimed to evaluate the effect the COVID-19 pandemic has had on traumatic brain injury (TBI) specifically. We reviewed the literature published on COVID-19 and TBI referrals, management, and rehabilitation. Significant changes were seen in the referral patterns of TBIs worldwide, explained by changes in societal behaviors and changes in the mechanism of injury. Implementation of strict infection control measures and COVID-19 screening was commonplace, with some reporting changes to operating room protocols. TBI was more likely to be conservatively managed. Rehabilitation services were restricted, with a greater shift towards telemedicine to provide rehabilitative therapy remotely., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Adult hippocampal neurogenesis (AHN) is a form of ongoing plasticity in the brain that supports specific aspects of cognition. Disruptions in AHN have been observed in neuropsychiatric conditions presenting with inflammatory components and are associated with impairments in cognition and mood. Recent evidence highlights important roles of the complement system in synaptic plasticity and neurogenesis during neurodevelopment and in acute learning and memory processes. In this work we investigated the impact of the complement C3/C3aR pathway on AHN and its functional implications for AHN-related behaviours. In C3 -/- mice, we found increased numbers and accelerated migration of adult born granule cells, indicating that absence of C3 leads to abnormal survival and distribution of adult born neurons. Loss of either C3 or C3aR affected the morphology of immature neurons, reducing morphological complexity, though these effects were more pronounced in the absence of C3aR. We assessed functional impacts of the cellular phenotypes in an operant spatial discrimination task that assayed AHN sensitive behaviours. Again, we observed differences in the effects of manipulating C3 or C3aR, in that whilst C3aR -/- mice showed evidence of enhanced pattern separation abilities, C3 -/- mice instead demonstrated impaired behavioural flexibility. Our findings show that C3 and C3aR manipulation have distinct effects on AHN that impact at different stages in the development and maturation of newly born neurons, and that the dissociable cellular phenotypes are associated with specific alterations in AHN-related behaviours., (Copyright © 2021. Published by Elsevier Inc.)

Background: The dentate gyrus exhibits life-long neurogenesis of granule-cell neurons, supporting hippocampal dependent learning and memory. Both temporal lobe epilepsy patients and animal models frequently have hippocampal-dependent learning and memory difficulties and show evidence of reduced neurogenesis. Animal and human temporal lobe epilepsy studies have also shown strong innate immune system activation, which in animal models reduces hippocampal neurogenesis. We sought to determine if and how neuroinflammation signals reduced neurogenesis in the epileptic human hippocampus and its potential reversibility., Methods: We isolated endogenous neural stem cells from surgically resected hippocampal tissue in 15 patients with unilateral hippocampal sclerosis. We examined resultant neurogenesis after growing them either as neurospheres in an ideal environment, in 3D cultures which preserved the inflammatory microenvironment and/or in 2D cultures which mimicked it., Results: 3D human hippocampal cultures largely replicated the cellular composition and inflammatory environment of the epileptic hippocampus. The microenvironment of sclerotic human epileptic hippocampal tissue is strongly anti-neurogenic, with sustained release of the proinflammatory proteins HMGB1 and IL-1β. IL-1β and HMGB1 significantly reduce human hippocampal neurogenesis and blockade of their IL-1R and TLR 2/4 receptors by IL1Ra and Box-A respectively, significantly restores neurogenesis in 2D and 3D culture., Conclusion: Our results demonstrate a HMGB1 and IL-1β-mediated environmental anti-neurogenic effect in human TLE, identifying both the IL-1R and TLR 2/4 receptors as potential drug targets for restoring human hippocampal neurogenesis in temporal lobe epilepsy., (© 2021. The Author(s).)

Objective: Traumatic brain injury (TBI) is a global public health problem, causing long-term burden to patients and caregivers. Patients and their families often resort to seeking online information regarding TBI management while awaiting formal health care consultations. Although this information is accessible and immediately available, little is known about the quality of online resources. We evaluated the accessibility, relevance, and readability of information regarding TBI from major online search engines., Methods: TBI-related search terms were entered into 2 online search engines (Google and Yahoo), and the first 30 websites per search were assessed for eligibility. Quality (DISCERN score, JAMA Benchmark score) and readability (Flesch-Kincaid Grade Level, Flesch Reading Ease Score) were assessed. Associations between search ranking, quality, and readability were evaluated., Results: In total, 202 websites were evaluated with mean DISCERN score 36.5 ± 9.9/80, signifying poor global quality, and mean JAMA Benchmark score 2.8 ± 1.1/4. The majority required 9-12 years of education (113/202; 55.9%) according to Flesch-Kincaid Grade Level and categorized as "Difficult" on Flesch Reading Ease Score (94/202; 46.5%). Website quality was not associated with search ranking or readability., Conclusions: There is a paucity of high-quality online resources for patients with TBI. Herein, we highlight: 1) the importance of guidance from healthcare professionals regarding online-information seeking; and 2) recommendations for the most useful online resources available., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Surgical evacuation of acute subdural haematoma (ASDH) in the elderly remains a point of contention due to the significant associated mortality. Therefore, there is a dire need for alternative treatment options. Endoscope-assisted techniques (EAT) have been increasingly reported over the last decade with variable outcomes. In this scoping review, we identify studies reporting the use of EAT for ASDH evacuation in elderly patients. Outcomes and patient selection criteria are discussed to identify patients that may benefit from EAT., Methods: A multi-database literature search was performed between January 1990 and January 2021. Studies including patients aged 60 years or above who underwent EAT for ASDH evacuation with reported outcomes were included., Results: A total of 13 studies and 122 patients were eligible for inclusion. Patient age ranged from 65 to 101 years, and average age from 78.6 to 87.4 years. High comorbidity burden, advanced age, absence of adverse imaging features, and pre-operative neurological status were the most common eligibility criteria for EAT. 52% of all procedures were performed under local anaesthetic (LA). Mortality rates ranged between 0% and 40%, whilst favourable outcomes ranged between 26.7% and 96.4%. Re-bleed was the most commonly reported complication, ranging between 0% and 13%., Conclusions: EAT pose a viable compromise for elderly patients with ASDH that may be unfit for GA. Heterogeneity of patient selection criteria prevents meaningful comparison between EAT and other approaches, and there is a clear impact of patient selection on outcome among studies reporting EAT. Further studies are required to identify the patient cohort that may benefit from this approach., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Traumatic brain injury (TBI) is amongst the leading causes of morbidity and mortality worldwide. The unprecedented emergence of COVID-19 has mandated neurosurgeons to limit viral spread and spare hospital resources whilst trying to adapt management plans for TBI. We aimed to characterize how this affects decision-making on TBI management and drive strategies to cope with future expected waves., Methods: Retrospective TBI data collection from a single tertiary referral unit was performed between: 01/04/2019 - 30/06/2019 ('Pre-Epidemic') and 01/04/2020 - 30/06/20 ('Epidemic'). Demographics, mechanism of injury, TBI severity, radiological findings, alcohol/anticoagulants/antiplatelets use, and management decisions were extracted., Results: 646 TBI referrals were received in 'Pre-Epidemic' (N = 317) and 'Epidemic' (N = 280) groups. There was reduction in RTA-associated TBI (14.8 vs 9.3%; p = .04) and increase in patients on anticoagulants (14.2 vs 23.6%; p = .003) in the 'Epidemic' group. Despite similarities between other TBI-associated variables, a significantly greater proportion of patients were managed conservatively in local referring units without neurosurgical services (39.1 vs 56.8%; p < .0001), predominantly constituted by mild TBI., Conclusion: Despite COVID-19 public health measures, the burden of TBI remains eminent. Increases in local TBI management warrant vigilance from primary healthcare services to meet post-TBI needs in the community.

Objectives: The aim of this study was to explore the rates and potential risks of surgical site infection (SSI) after posterior fossa surgery for tumour resection in children., Methods: We retrospectively reviewed our local paediatric (age < 16 years) database for all cases of posterior fossa (PF) brain tumour surgery between November 2008 and November 2019. We collected patient demographics, tumour histology/location, and the event of postoperative surgical site infection., Results: Overall, 22.1% (n=15) developed SSI out of sixty-eight children undergoing PF surgery for resection of brain tumours; 73.3% of them had a confirmed diagnosis of medulloblastoma. There was no statistically significant difference in the age (5.1 ± 0.60 vs. 6.2 ± 0.97 years; p=0.47) and duration of operation (262 vs. 253 min; p = 0.7655) between the medulloblastoma group and other tumours. Although the rate of postoperative hydrocephalus was higher in the medulloblastoma group (12.9% vs. 0%), this was not associated with increased SSI. Rates of CSF leak between the 2 groups were not different., Conclusion: Medulloblastoma as a pathological entity seems to carry higher risk of postoperative surgical site infection compared to other types of paediatric posterior fossa tumours. Further larger studies are required to look into this causal relationship and other risk factors that might be involved.

Objective: We aim to evaluate whether intraoperative cerebrospinal fluid (CSF) sampling during ventriculo-peritoneal (VP) shunt insertion can predict future VP shunt infection or guide its management., Methods: 83 paediatric patients undergoing VP shunt insertion between February 2013 and July 2019 were retrospectively identified. Patient demographics, presence of pre-operative extra ventricular drain (EVD), pre-operative CSF results, and intra-operative CSF results were identified from patient case notes and electronic clinical databases. All included patients were followed up for a minimum of 6 months for identification of shunt infection., Results: 90 VP shunt insertions were performed in 83 patients. Age at time of shunt insertion ranged from 5 days to 15.8 years (mean 44.2 months). Tumours were the most common aetiology for hydrocephalus (n = 24). 67 cases (74.4%) had intra-operative CSF samples, of which 2 revealed the presence of bacteria. Only 1 patient with intra-operative CSF sampling positive for growth developed shunt infection during follow up. Two cases developed a shunt infection despite normal intra-operative CSF results. Three cases did not have intra-operative CSF sampling but developed a shunt infection during follow up. Intra-operative CSF culture achieved 33.3% sensitivity and 98.4% specificity for predicting future shunt infection (p = 0.154). The Receiver Operator Characteristic (ROC) curve of intra-operative white cell count (WCC) and shunt infection at 6 months follow up yielded an Area Under the Curve (AUC) of 50.3%., Conclusion: Our results show that intraoperative CSF sampling as a method to predict future risk of shunt infection and to help inform future antibiotic prescribing is unreliable. Given an AUC of 50.3%, it is no better than chance as a diagnostic tool. Further larger studies are needed to substantiate this., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Predictive factors for post-traumatic hydrocephalus (PTH) in adults have been elucidated but remain uncertain for children. We aimed to identify the prevalence of PTH in paediatric patients and identify clinical/radiological factors which may increase the probability of children developing PTH., Methods: This was a retrospective study of all patients < 16 years old admitted to our unit with traumatic brain injury (TBI) between March 2013 and June 2018, 108 patients in total. Patients were classified as mild (13-15), moderate (9-12) or severe (3-8) TBI based on admission GCS. Three independent reviewers collected data from case notes. CT scans were reviewed for hydrocephalus using Evan's index. Two-tailed Fisher's exact tests with a p value < 0.05 were considered statistically significant., Results: Median patient age was 7 years, and 65% were males (n = 70). PTH wasn't identified in any patients with mild/moderate TBI (n = 79). In cases of severe TBI (n = 29), three patients developed PTH requiring ventriculoperitoneal shunting (10%; p = 0.02). Radiological features which were significantly more common in the PTH group were intraventricular haemorrhage (p = 0.05) and subarachnoid haemorrhage (p = 0.03). There was also a trend towards a statistically significant association with subdural haematoma (p = 0.07). The need for other neurosurgical procedures, such as fracture elevation and craniotomy, did not increase the probability of developing with PTH (p = 0.08)., Discussion: The prevalence of PTH in our study is 2.7%. Factors which may be associated with a higher probability of developing PTH may include IVH, SAH, severity of TBI, and subdural haematoma. We propose a national prospective multicentre database of paediatric PTH. The data collected on prevalence, presentation, risk factors, and management could guide contemporary management and improve the outcomes of children with PTH.

Introduction: Traumatic brain injury (TBI) is amongst the leading causes of morbidity and mortality worldwide. Despite evidence of neurogenesis post-TBI, survival and integration of newborn neurons remains impaired. High Mobility Group Box protein 1 (HMGB1) is an 'alarmin' released hyper-acutely following TBI and implicated in hosting the neuro-inflammatory response to injury. It is also instrumental in mediating neurogenesis under physiological conditions. Given its dual role in mediating neuro-inflammation and neurogenesis, it serves as a promising putative target for therapeutic modulation. In this review, we discuss neurogenesis post-TBI, neuro-pharmacological aspects of HMGB1, and its potential as a therapeutic target., Methods: PubMed database was searched with varying combinations of the following search terms: HMGB1, isoforms, neurogenesis, traumatic brain injury, Toll-like receptor (TLR), receptor for advanced glycation end-products (RAGE)., Results: Several in vitro and in vivo studies demonstrate evidence of neurogenesis post-injury. The HMGB1-RAGE axis mediates neurogenesis throughout development, whilst interaction with TLR-4 promotes the innate immune response. Studies in the context of injury demonstrate that these receptor effects are not mutually exclusive. Despite recognition of different HMGB1 isoforms based on redox/acetylation status, effects on neurogenesis post-injury remain unexplored. Recent animal in vivo studies examining HMGB1 antagonism post-TBI demonstrate predominantly positive results, but specific effects on neurogenesis and longer-term outcomes remain unclear., Conclusion: HMGB1 is a promising therapeutic target but its effects on neurogenesis post-TBI remains unclear. Given the failure of several pharmacological strategies to improve outcomes following TBI, accurate delineation of HMGB1 signalling pathways and effects on post-injury neurogenesis are vital., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Management of children with disorders of cerebrospinal fluid (CSF) circulation is a common aspect of paediatric neurosurgical practice. Sport and physical activity play an integral role in the lives of patients in this age group. However, there is little evidence to support the dissemination of appropriate advice to children regarding such activities. The aim of this study was to evaluate the perspectives of clinicians across the UK regarding the participation of children with disorders of CSF circulation in sports., Methods: Questionnaires were distributed to Consultant Paediatric Neurosurgeons practising across the UK via the Society of British Neurological Surgeons (SBNS). Five different patient scenarios were supplied, and participants were asked to choose whether they would advise participation in the following sports: Taekwondo, rugby, skiing, and football., Results: An overall response rate of 66.7% (36 out of 54 paediatric neurosurgeons) was achieved. The following percentages of clinicians advocated football, rugby, Taekwondo, and skiing across all scenarios: 96%, 75%, 77%, and 97%, respectively. The majority of responders (91.2%) relied on personal experience when providing advice, whilst 50% used available literature and 19.4% used available guidelines., Conclusions: There is a paucity of evidence in the literature to support the dissemination of appropriate advice to children with disorders of CSF circulation regarding participation in sports. Our findings demonstrate that the majority of clinicians rely on personal experience to make such decisions, emphasizing the necessity of larger scale studies to inform evidence-based guidelines.

Despite medical advances, neurological recovery after severe traumatic brain injury (TBI) remains poor. Elevated levels of high mobility group box protein-1 (HMGB1) are associated with poor outcomes; likely via interaction with receptors for advanced-glycation-end-products (RAGE). We examined the hypothesis that HMGB1 post-TBI is anti-neurogenic and whether this is pharmacologically reversible. Post-natal rat cortical mixed neuro-glial cell cultures were subjected to needle-scratch injury and examined for HMGB1-activation/neuroinflammation. HMGB1-related genes/networks were examined using genome-wide RNA-seq studies in cortical perilesional tissue samples from adult mice. Post-natal rat cortical neural stem/progenitor cell cultures were generated to quantify effects of injury-condition medium (ICM) on neurogenesis with/without RAGE antagonist glycyrrhizin. Needle-injury upregulated TNF-α/NOS-2 mRNA-expressions at 6 h, increased proportions of activated microglia, and caused neuronal loss at 24 h. Transcriptome analysis revealed activation of HMGB1 pathway genes/canonical pathways in vivo at 24 h. A 50% increase in HMGB1 protein expression, and nuclear-to-cytoplasmic translocation of HMGB1 in neurons and microglia at 24 h post-injury was demonstrated in vitro. ICM reduced total numbers/proportions of neuronal cells, but reversed by 0.5 μM glycyrrhizin. HMGB1 is activated following in vivo post mechanical injury, and glycyrrhizin alleviates detrimental effects of ICM on cortical neurogenesis. Our findings highlight glycyrrhizin as a potential therapeutic agent post-TBI., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Traumatic bifrontal contusions (TBC) form a recognised clinical entity among patients with traumatic brain injury (TBI). This study aims to systematically review current literature on demographics, management, and predictors of outcomes of patients with TBC. A multi-database literature search (PubMed, Cochrane, OVID Medline/Embase) was performed using PRISMA as a search strategy. Studies were selected by predefined selection criteria (PROSPERO: CRD42018055390), and risk of bias was assessed using an adapted form of ROBINS-I tool. Of the 275 studies yielded by the literature search, seven articles met the criteria for inclusion, all of which were level III evidence. Total cohort consisted of 468 patients; predominantly male (n = 5; 303/417 patients) with average age 44.3 years (range, 7-81). Falls (44.9%) and road traffic accidents (46.6%) were the commonest mechanisms of injury with an average presentation GCS of 9.2 (n = 3, 119 patients). GCS on admission of ≤ 13.1 and contusion volume at day 2 post-injury of ≥ 62.9cm 3 were associated with increased risk of deterioration needing surgical interventions (n = 1, 7 patients). The majority of patients underwent surgery; the average GOS was 4, at an average follow-up duration of 11.7 months (n = 6, 356 patients). The currently available evidence on the management of TBC is scarce. Larger multicentre well-designed studies are needed to further delineate the factors behind acute deterioration, the effectiveness of management options. Once in place, this can be used to develop and test an algorithmic approach to management of TBC resulting in consistently improved outcomes.

Background: Chronic subdural hemorrhage (CSDH) is a common neurosurgical pathology. While acute deterioration is managed surgically, the optimal management of patients with neurologically stable CSDH remains uncertain. Despite an increasing interest in the use of corticosteroids, it is unclear whether this reduces the rate of subsequent crossover to surgery. In this study we evaluate rate of crossover to surgery in such patients managed in our Neurosurgical unit., Methods: A retrospective database search over a 2-year period was performed. A multi-database literature review was also conducted to identify relevant articles reporting rate of subsequent surgery in CSDH patients managed with corticosteroids., Results: A total of 532 CSDH patients were identified. Subsequently, a total of 364 patients who were managed conservatively were included for further analysis. The majority (315 patients; 59.1%) were managed conservatively. Forty-nine patients (9.2%) received steroids as first-line treatment. There was considerable variation in steroid dosing regimens, with the commonest involving 4 mg dexamethasone three times daily for 5 days. Four patients in the steroid group required subsequent surgery (8.2%), compared with 22 conservatively managed patients (7.0%). Statistical analysis revealed no significant difference in the rate of surgery (chi-square 0.089, difference 1, P = 0.77)., Conclusions: Current evidence implicates a potentially beneficial role of dexamethasone in the management of CSDH. However, it remains unclear whether the rate of crossover to surgery is reduced in patients treated with corticosteroids compared with those managed conservatively. A longer duration of study with detailed analysis of individual cases and appropriately randomized cohorts are necessary to draw more reliable conclusions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Hydrocephalus is a major cause of morbidity in the pediatric population, with potentially severe consequences if left untreated. Two viable strategies for management of non-communicating hydrocephalus are endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting. However, there is uncertainty over the safety and efficacy of ETV in younger infants aged 1 year or below. In this systematic review, we aim to elucidate the success rate and procedural risks of ETV in this age group., Methods: A multi-database (PubMed, Embase, Web of Science) literature search between January 1990 and April 2018 was performed in accordance with PRISMA guidelines. Eligible studies were included if they (i) examined non-communicating hydrocephalus; (ii) quantified the success/failure rates of ETV; and (iii) assessed outcomes in children 1 year of age or younger., Results: A total of 19 articles with 399 patients were eligible for inclusion. Mean age at procedure was 4.2 months (range 34 weeks gestation to 12 months), with 116 females and 143 males. Commonest underlying aetiology was congenital aqueductal stenosis (AS) (60.4%). Remaining causes included post-haemorrhagic, post-infection, Chiari malformations, malignancies and others. Overall and AS mean success rates were 51.6% and 56.5% respectively. Overall complication rate was 10.0%, consisting mainly of CSF leak, infection, and haemorrhage. Younger age was significantly associated with poorer ETV success rate when divided into <6 months and 6-12 months of age (44.4 vs 66.7%; p = 0.0007). Underlying pathology had no significant association with ETV outcome when divided into AS and other pathologies (p = 0.53)., Conclusions: Age is significantly associated with ETV success rates. Pathology-dependent effects were not found in this age group. Despite a lower ETV success rate at younger ages (44.4 vs 66.7%), it offers a comparable safety profile that is independent of age. ETV remains a viable treatment option for non-communicating hydrocephalus for infants aged 1 year or younger., Competing Interests: Declaration of competing interest All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2020 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Introduction: Post cranial surgery readmission, largely caused by surgical site infection (SSI), is a marker of patient-care quality requiring comprehensive discharge planning. Currently, discharge assessment is based on clinical recovery and basic laboratory tests, including C-reactive protein (CRP). Although CRP kinetics have been examined postoperatively in a handful of papers, the validity of CRP as a standalone test to predict SSI is yet to be explored. Methods: A prospective observational study was performed on adult patients undergoing elective cranial surgery over a 3-month period. Laboratory data; CRP, white cell count (WCC), neutrophil cell count (NCC), and clinical data were assessed pre and post-operatively and were evaluated as predictors for safe discharge. Readmission rates within 1 month were recorded. Results: In this study, 68 patients were included. About 8.6% were readmitted due to SSI. A postoperativepeak in CRP was seen on day 2 with a value of 57 in the non-readmitted group, and 115 in the readmitted group. CRP dropped gradually to normal levels by day 5 in the non-readmitted group. A secondary CRP rise at day 5 was noted in the readmitted group with a sensitivity, specificity, and negative predictive value of 71%, 90%, and 96%, respectively. Interestingly, our ROC analysis indicates that a CRP value of less than 65 predicts safe discharge with a sensitivity of 86%, specificity of 89% and negative predictive value of 98% of safe discharge (area under the curve, AUC: 0.782). No significant difference in other inflammatory markers was found between both groups. Conclusions: CRP increases postoperatively for 4-5 d which could be a physiological response to surgery, however, prolonged elevation or a secondary increase in CRP may indicate an ongoing infection. Our data validate the potential use of CRP levels to predict SSI. A multicentre study is warranted to investigate the role of CRP in predicting SSI.

Copy number variant (CNV) syndromes are often associated with both neurocognitive deficits (NCDs) and congenital heart defects (CHDs). Children and adults with cardiac developmental defects likely to have NCDs leading to increased risk of hospitalisation and reduced level of independence. To date, the association between these two phenotypes have not been explored in relation to CNV syndromes. In order to address this question, we systematically reviewed the prevalence of CHDs in a range of CNV syndromes associated with NCDs. A meta-analysis showed a relationship with the size of CNV and its association with both NCDs and CHDs, and also inheritance pattern. To our knowledge, this is the first review to establish association between NCD and CHDs in CNV patients, specifically in relation to the severity of NCD. Importantly, we also found specific types of CHDs were associated with severe neurocognitive deficits. Finally, we discuss the implications of these results for patients in the clinical setting which warrants further exploration of this association in order to lead an improvement in the quality of patient's life., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Decompressive craniectomy (DC) is used for the treatment of raised intracranial pressure secondary to traumatic brain injury. Cranioplasty is a reconstructive procedure that restores the structural integrity of the skull following (DC). Seizures are a recognised complication of cranioplasty but its incidence and risk factors in TBI patients are unclear. Accurate prognostication can help direct prophylactic and treatment strategies for seizures. In this systematic review, we aim to evaluate current literature on these factors. A PROSPERO-registered systematic review was performed in accordance with PRISMA guidelines. Data was synthesised qualitatively and quantitatively in meta-analysis where appropriate. A total of 8 relevant studies were identified, reporting 919 cranioplasty patients. Random-effects meta-analysis reveals a pooled incidence of post-cranioplasty seizures (PCS) of 5.1% (95% CI 2.6-8.2%). Identified risk factors from a single study included increasing age (OR 6.1, p = 0.006), contusion at cranioplasty location (OR 4.8, p = 0.015), and use of monopolar diathermy at cranioplasty (OR 3.5, p = 0.04). There is an association between an extended DC-cranioplasty interval and PCS risk although it did not reach statistical significance (p = 0.062). Predictive factors for PCS are poorly investigated in the TBI population to date. Heterogeneity of included studies preclude meta-analysis of risk factors. Further studies are required to define the true incidence of PCS in TBI and its predictors, and trials are needed to inform management of these patients., (Crown Copyright © 2019. Published by Elsevier Ltd. All rights reserved.)

Purpose: Subdural haematoma (SDH) is a recognised complication of forceps-assisted delivery (FAD). There are no guidelines regarding its management. This study aims to provide a better insight into the management and outcomes of neonatal SDH post-FAD., Methods: Retrospective review of our neonatal database and systematic review of the literature for neonatal cases that presented with SDH after FAD. Retrospective neurosurgical database search for cases of neonatal SDH post-FAD managed in our unit between January 2007 and January 2017. Systematic review of the literature was performed using PRISMA guidelines. The inclusion criteria are as follows: (1) neonates; (2) forceps-assisted delivery; (3) evidence of SDH on imaging, with or without other traumatic lesions., Results: A literature search yielded nine studies with 30 patients meeting our inclusion criteria. In addition, four cases were identified from our institutional database. Forty-two percent (n = 14) had their SDH managed surgically, with subsequent full neurological recovery in 57%. In comparison, 95% (n = 18) of the conservatively managed patients made a full recovery. Hydrocephalus was present in 1/19 and 11/14 of the conservatively managed and surgically managed patients respectively., Conclusions: Conservative management can lead to a full neurological recovery in SDH following FAD in neonates. However, a significant minority may still need neurosurgical intervention for the SDH or subsequent hydrocephalus; therefore, we advocate early transfer to a specialist neuroscience centre.

Objective: To evaluate current evidence for the effectiveness of virtual reality (VR) interventions in improving neurocognitive performance in individuals who have sustained a traumatic brain injury (TBI)., Methods: A systematic literature search across multiple databases (PubMed, EMBASE, Web of Science) for articles of relevance. Studies were evaluated according to study design, patient cohort, VR intervention, neurocognitive parameters assessed, and outcome. VR interventions were evaluated qualitatively with respect to methodology and extent of immersion and quantitatively with respect to intervention duration., Outcomes: Our search yielded 324 articles, of which only 13 studies including 132 patients with TBI met inclusion criteria. A wide range of VR interventions and cognitive outcome measures is reported. Cognitive measures included learning and memory, attention, executive function, community skills, problem solving, route learning, and attitudes about driving. Several studies (n = 10) reported statistically significant improvements in outcome, and 2 studies demonstrated successful translation to real-life performance., Conclusions: VR interventions hold significant potential for improving neurocognitive performance in patients with TBI. While there is some evidence for translation of gains to activities of daily living, further studies are required to confirm the validity of cognitive measures and reliable translation to real-life performance.

Neurogenesis is sustained throughout life in the mammalian brain, supporting hippocampus-dependent learning and memory. Its permanent alteration by status epilepticus (SE) is associated with learning and cognitive impairments. The mechanisms underlying the initiation of altered neurogenesis after SE are not understood. Glial fibrillary acidic protein-positive radial glia (RG)-like cells proliferate early after SE, but their proliferation dynamics and signaling are largely unclear. We have previously reported a polarized distribution of AMPA receptors (AMPARs) on RG-like cells in vivo and postulated that these may signal their proliferation. Here, we examined the acute effects of kainate on hippocampal precursor cells in vitro and in kainate-induced SE on proliferating and quiescent clones of 5-bromo-2-deoxyuridine prelabeled hippocampal precursors in vivo. In vitro, we found that 5 μM kainate shortened the cell cycle time of RG-like cells via AMPAR activation and accelerated cell cycle re-entry of their progeny. It also shifted their fate choice expanding the population of RG-like cells and reducing the population of downstream amplifying neural progenitors. Kainate enhanced the survival of all precursor cell subtypes. Pharmacologically, kainate's proliferative and survival effects were abolished by AMPAR blockade. Functional AMPAR expression was confirmed on RG-like cells in vitro. In agreement with these observations, kainate/seizures enhanced the proliferation and expansion predominantly of constitutively cycling RG-like cell clones in vivo. Our results identify AMPARs as key potential players in initiating the proliferation of dentate RG-like cells and unravel a possible receptor target for modifying the radial glia-like cell response to SE., (© 2018 Wiley Periodicals, Inc.)

Introduction: Neurocutaneous melanosis (NCM) is a sporadic condition characterised by congenital melanocytic nevi and melanocytic thickening of the leptomeninges. It is believed to result from congenital dysplasia of melanin-producing cells within the skin and leptomeninges. The management of cutaneous manifestations remains controversial; for neurological manifestations, outcome remains poor even with the use of radiotherapy and chemotherapy., Patients and Methods: We describe the case of a 5-month-old boy who presented with giant congenital melanocytic nevus and hydrocephalus. MR imaging and CSF immunohistochemistry confirmed leptomeningeal melanosis. We discuss the diagnosis, treatment and prognosis of this rare disorder in the light of recent published literature., Results: Patient required placement of right-sided ventriculoperitoneal shunt to control hydrocephalus. The patient tolerated the procedure well and was discharged home with normal neurological function. A presumptive diagnosis of NCM was made based on the MR characteristics, CSF cytology and clinical presentation. He received trametinib, a MAPK/Erk kinase inhibitor for 7 months. At 30 months of age, he developed left-sided weakness and status epilepticus requiring paediatric intensive care unit admission and ventilator support. The patient eventually succumbed to malignant transformation of leptomeningeal disease., Conclusion: Cutaneous manifestations of NCM are usually congenital, and neurological manifestations develop early in life. Patients with large or multiple congenital nevi should therefore be investigated early to facilitate treatment. MR imaging is the investigation of choice which can further assist in performing biopsy. Symptomatic NCM is refractory to radiotherapy and chemotherapy and has a poor prognosis. A multidisciplinary approach is necessary in the management of NCM patients.

Ruptured intracranial aneurysms in infants are very rare but if missed can lead to poor outcomes. Spontaneously dissecting false aneurysms have been described only in a handful of cases. We report a case of a three-month old girl with deteriorating neurological function due to a ruptured distal middle cerebral artery pseudoaneurysm.

Traumatic brain injury (TBI) poses a major public health problem on a global scale. Its burden results from high mortality and significant morbidity in survivors. This stems, in part, from an ongoing inadequacy in diagnostic and prognostic indicators despite significant technological advances. Traumatic axonal injury (TAI) is a key driver of the ongoing pathological process following TBI, causing chronic neurological deficits and disability. The science underpinning biomarkers of TAI has been a subject of many reviews in recent literature. However, in this review we provide a comprehensive account of biomarkers from animal models to clinical studies, bridging the gap between experimental science and clinical medicine. We have discussed pathogenesis, temporal kinetics, relationships to neuro-imaging, and, most importantly, clinical applicability in order to provide a holistic perspective of how this could improve TBI diagnosis and predict clinical outcome in a real-life setting. We conclude that early and reliable identification of axonal injury post-TBI with the help of body fluid biomarkers could enhance current care of TBI patients by (i) increasing speed and accuracy of diagnosis, (ii) providing invaluable prognostic information, (iii) allow efficient allocation of rehabilitation services, and (iv) provide potential therapeutic targets. The optimal model for assessing TAI is likely to involve multiple components, including several blood biomarkers and neuro-imaging modalities, at different time points., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: External ventricular drain (EVD) insertion is a common neurosurgical procedure. EVD-related infection (ERI) is a major complication that can lead to morbidity and mortality. In this study, we aimed to establish a national ERI rate in the UK and Ireland and determine key factors influencing the infection risk., Methods: A prospective multicentre cohort study of EVD insertions in 21 neurosurgical units was performed over 6 months. The primary outcome measure was 30-day ERI. A Cox regression model was used for multivariate analysis to calculate HR., Results: A total of 495 EVD catheters were inserted into 452 patients with EVDs remaining in situ for 4700 days (median 8 days; IQR 4-13). Of the catheters inserted, 188 (38%) were antibiotic-impregnated, 161 (32.5%) were plain and 146 (29.5%) were silver-bearing. A total of 46 ERIs occurred giving an infection risk of 9.3%. Cox regression analysis demonstrated that factors independently associated with increased infection risk included duration of EVD placement for ≥8 days (HR=2.47 (1.12-5.45); p=0.03), regular sampling (daily sampling (HR=4.73 (1.28-17.42), p=0.02) and alternate day sampling (HR=5.28 (2.25-12.38); p<0.01). There was no association between catheter type or tunnelling distance and ERI., Conclusions: In the UK and Ireland, the ERI rate was 9.3% during the study period. The study demonstrated that EVDs left in situ for ≥8 days and those sampled more frequently were associated with a higher risk of infection. Importantly, the study showed no significant difference in ERI risk between different catheter types., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)