Risk factors for the development of seizures after cranioplasty in patients that sustained traumatic brain injury: a systematic review

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

High mobility group box protein 1 and white matter injury following traumatic brain injury: perspectives on mechanisms and therapeutic strategies

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Despite significant medical advances over recent decades, many survivors of TBI develop long term neuro-cognitive deficits. Previously, only moderate and severe injuries were thought to account for the devastating consequences of TBI. However, there is increasing evidence that even milder injuries may result in problematic lifelong cognitive and affective disturbances. TBI is typically characterized by an an acute physical injury followed by a protracted innate neuro-inflammatory response. These reponses, mediated via neuronal, astrocyte and microglial cells, amongst others, and may result in widespread neuronal death and a micro-environment that is not conducive to brain repair (Manivannan et al., 2021). Whilst the primary physical injury often evades intervention from a medical perspective, the subsequent neuro-inflammatory response offers a potential therapeutic target. Nonetheless, effective pharmacological strategies continue to elude clinicians and scientists due to the complex underlying pathogenesis and difficulties of modelling such a heterogeneous disease. However, the majority of research to date has focused on investigating the effects of post-traumatic neuro-inflammation on grey matter injury rather than the consequences upon white matter (WM), which contributes greatly to cognitive dysfunction across many neurological diseases (Filly and Kelly, 2018). Herein, we will briefly discuss: (i) high mobility group box protein 1 (HMGB1) as a potential therapeutic target; (ii) the relevance of WM injury in TBI and current understanding of WM repair following injury; and (iii) perspectives on how HMGB1 may play a role

The effectiveness of virtual reality interventions for improvement of neurocognitive performance post-traumatic brain injury: a systematic review

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

Current status of websites offering information to traumatic brain injury patients and caregivers: time for reform?

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 whilst awaiting formal healthcare 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 two online search engines (GoogleTM, YahooTM), and the first 30 websites per search were assessed for eligibility. Quality (DISCERN score, JAMA Benchmark score) and readability (Flesch-Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES)) were assessed. Associations between search ranking, quality, and readability were evaluated. Results 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 FKGL and categorised as ‘Difficult’ on FRES (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 TBI patients. Herein, we highlight: (i) the importance of guidance from healthcare professionals regarding online-information seeking; (ii) recommendations for the most useful online resources available

YouTube as a neurosurgical training tool for the insertion of external ventricular drain

Objectives YouTube is the largest open-access media website and an increasingly recognised resource in Medical Education, with much content related to Neurosurgery. External Ventricular Drain (EVD) insertion is frequently undertaken by neurosurgical trainees. Online and distant learning have gained popularity during this COVID-19 pandemic more than ever. We evaluated content on YouTube as to its use as an effective open-access learning resource for EVD insertion as a key neurosurgical procedure. Methods A keyword search identified videos related to EVD insertion on 01/06/2020. Inclusion criteria was created to focus on content aimed at describing the technique of EVD insertion. An educational scoring system was devised related to the procedure of EVD insertion. Each video was scored on our educational score, JAMA Benchmark Criteria and Global Quality Score (GQS). They were subsequently categorised as effective or ineffective. Results A total of 12/700 videos met inclusion criteria. Dates posted ranged from 01/07/2012 – 24/04/2019, with views range 359 – 166,388, and mean of 30,531 (SD 49,570). Four videos (33%) were considered an effective learning resource. The cohort had a mean educational score of 6.91 (SD 3.86), with median JAMA score and GQS 2/4 (SD 0.62) and 2/5 (SD 1.6) respectively. A strong correlation was found between viewership and score (R 0.85, p < 0.005) Conclusion The majority of YouTube content on EVD insertion is an ineffective resource. Neurosurgeons and Institutions could harness YouTubes broad access by posting high-quality educational content. This is more important than ever with increasing emphasis on online training resources, YouTube included

Impact of copy number variation on human neurocognitive deficits and congenital heart defects: a systematic review

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 reduce 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 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 improvement in the quality of patient’s life

Acute subdural haematoma in the elderly- to operate or not to operate A systematic review and meta-analysis of outcomes following surgery

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, I2=73%) at discharge and 49.30% (95% CI 42.01% to 56.61%; 10 studies, 277/555 patients, I2=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, I2=45%) at discharge, and 79.25% (95% CI 72.42% to 85.37%; 8 studies, 402/511 patients, I2=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

Glycyrrhizin blocks the detrimental effects of HMGB1 on cortical neurogenesis after traumatic neuronal injury

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. View Full-Text Keywords: traumatic brain injury; neurogenesis; HMGB1; neuroinflammatio

The efficacy of cysto-peritoneal shunting for the surgical management of intracranial arachnoid cysts in the elderly: a systematic review of the literature

Background: Intracranial arachnoid cysts (AC) are benign, cerebrospinal fluid filled spaces within the arachnoid layer of the meninges. Neurosurgical intervention in children and young adults has been extensively studied, but the optimal strategy in the elderly remains unclear. Therefore, we performed a single center retrospective study combined with a systematic review of the literature to compare cystoperitoneal (CP) shunting with other surgical approaches in the elderly cohort. Methods: Retrospective neurosurgical database search between January 2005 and December 2018, and systematic review of the literature using PRISMA guidelines were performed. Inclusion criteria: Age 60 years or older, radiological diagnosis of intracranial AC, neurosurgical intervention, and neuroradiological (NOG score)/clinical outcome (COG score). Data from both sources were pooled and statistically analyzed. Results: Our literature search yielded 12 studies (34 patients), which were pooled with our institutional data (13 patients). CP shunts (7 patients; 15%), cyst fenestration (28 patients; 60%) and cyst marsupialisation/resection (10 patients; 21%) were the commonest approaches. Average duration of follow-up was 23.6, 26.9, and 9.5 months for each approach, respectively. There was no statistically significant association between choice of surgical intervention and NOG score (P = 0.417), COG score (P = 0.601), or complication rate (P = 0.955). However, CP shunting had the lowest complication rate, with only one patient developing chronic subdural haematoma. Conclusion: CP shunting is a safe and effective surgical treatment strategy for ACs in the elderly. It has similar clinical and radiological outcomes but superior risk profile when compared with other approaches. We advocate CP shunting as first line neurosurgical intervention for the management of intracranial ACs in the elderly

Interleukin-6 as a prognostic biomarker of clinical outcomes after traumatic brain injury: a systematic review

Background 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 outcome. Methods 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. Results 15 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 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 outcome, one found them to predict better outcomes, and three found no association. Greater parenchymal IL-6 was associated with better outcomes. Conclusion 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 CRD4202127120