ARISE I Consensus Review on the Management of Intracranial Aneurysms.

BACKGROUND: Intracranial aneurysms (IAs) remain a challenging neurological diagnosis associated with significant morbidity and mortality. There is a plethora of microsurgical and endovascular techniques for the treatment of both ruptured and unruptured aneurysms. There is no definitive consensus as to the best treatment option for this cerebrovascular pathology. The Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts discussed best practices and the most promising approaches to improve the management of brain aneurysms. METHODS: A group of experts from academia, industry, and federal regulators convened to discuss updated clinical trials, scientific research on preclinical system models, management options, screening and monitoring, and promising novel device technologies, aiming to improve the outcomes of patients with IA. RESULTS: Aneurysm, Arteriovenous Malformation, and Chronic Subdural Hematoma Roundtable Discussion With Industry and Stroke Experts suggested the incorporation of artificial intelligence to capture sequential aneurysm growth, identify predictors of rupture, and predict the risk of rupture to guide treatment options. The consensus strongly recommended nationwide systemic data collection of unruptured IA radiographic images for the analysis and development of machine learning algorithms for rupture risk. The consensus supported centers of excellence for preclinical multicenter trials in areas such as genetics, cellular composition, and radiogenomics. Optical coherence tomography and magnetic resonance imaging contrast-enhanced 3T vessel wall imaging are promising technologies; however, more data are needed to define their role in IA management. Ruptured aneurysms are best managed at large volume centers, which should include comprehensive patient management with expertise in microsurgery, endovascular surgery, neurology, and neurocritical care. CONCLUSIONS: Clinical and preclinical studies and scientific research on IA should engage high-volume centers and be conducted in multicenter collaborative efforts. The future of IA diagnosis and monitoring could be enhanced by the incorporation of artificial intelligence and national radiographic and biologic registries. A collaborative effort between academic centers, government regulators, and the device industry is paramount for the adequate management of IA and the advancement of the field.

Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

Limb-Shaking Transient Ischemic Attacks in Patients with Carotid Occlusion or Stenosis: A Systematic Review and Individual Patient Data Meta-Analysis.

BACKGROUND: Limb-shaking transient ischemic attack (LSTIA) is a rare neurological condition which presents with involuntary jerky movements of the arm or leg, often because of carotid stenosis or occlusion. Due to the rarity of the condition, the epidemiology of LSTIA is poorly understood and the disease is frequently misdiagnosed. There is no standard treatment to date. The purpose of this study was to provide an overview of the epidemiology of LSTIA and its current treatment options. METHODS: Embase, MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials for randomized controlled trials, and Google Scholar were searched from database inception to December 30, 2023 for articles containing information on the epidemiology and treatment of LSTIA. An individual patient data meta-analysis (IPD-MA) was performed using data extracted from the included articles. Inclusion criteria were description of both the epidemiology and treatment of LSTIA in patients over the age of 18 with carotid stenosis/occlusion, confirmed by radiographic imaging. Exclusion criteria were studies focusing on pediatrics, no epidemiological data, internal carotid artery (ICA) stenosis/occlusion not radiologically confirmed, full text unavailable, full text not in English or Dutch, and non-original articles. RESULTS: Of the 8,855 articles screened, 55 articles containing 251 patients were included. Fifty articles harboring 81 patients were included in the IPD-MA, and 7 articles harboring 187 patients were included in the cohort analysis. The results of the IPD-MA showed that LSTIA was caused by unilateral ICA stenosis/occlusion in 29 patients (36%) and most often from bilateral ICA stenosis/occlusion in 52 patients (64%). Limb-shaking was unilateral in 66 patients (83%) and was accompanied by weakness in 27 patients (33%). The intervention with the highest success rate was endovascular intervention (carotid stenting or balloon angioplasty), as all 10 patients remained asymptomatic after treatment. The cohort analysis showed that LSTIA can be caused by both unilateral and bilateral carotid stenosis or occlusion. The prevalence within cohorts of TIA patients of LSTIA varied considerably from 3.5 to 29%. CONCLUSION: A large international clinical registry is warranted to gain a better understanding of the epidemiology of LSTIA. There is insufficient evidence available to suggest a standard treatment.

Validation of Novel Microsurgical Vessel Anastomosis Techniques: A Systematic Review.

INTRODUCTION: Thorough validation of novel microsurgical techniques is deemed essential before their integration into clinical practice. To achieve proper validation, the design of randomized controlled trials (RCTs) should be undertaken, accompanied by the execution of comprehensive statistical analyses, including confounder adjustment and power analysis. This systematic review aims to provide an encompassing overview of the validation methodologies employed in microsurgical studies, with a specific focus on innovative vessel anastomosis techniques. METHODS: A literature search was conducted in PubMed for articles describing the validation of novel microsurgical vessel anastomosis techniques in animal or human subjects. RESULTS: The literature search yielded 6,658 articles. A total of 6,564 articles were excluded based on title and abstract. Ninety-four articles were assessed for full-text eligibility. Forty-eight articles were included in this systematic review. Out of 30 comparative studies, 9 studies validated novel modified interrupted suture techniques, 6 studies modified continuous techniques, 6 studies modified sleeve anastomosis techniques, 1 study a modified vesselotomy technique, 7 studies sutureless techniques, and 1 study a modified lymphaticovenular anastomosis technique. Twenty-eight studies contained animals (n = 1,998). Fifteen animal studies were RCTs. Two studies contained human/cadaveric subjects (n = 29). Statistical power analysis and confounder adjustment were performed in one animal study. Out of 18 noncomparative studies, 5 studies validated novel modified interrupted suture techniques, 1 study a modified continuous technique, 2 studies modified sleeve anastomosis techniques, 4 studies modified vesselotomy techniques, 4 studies sutureless techniques, and 2 studies modified lymphaticovenular anastomosis techniques. Ten studies contained animal subjects (n = 320), with two RCTs. Eight studies contained human subjects (n = 173). Statistical power analysis and confounder adjustment were performed in none of the animal or human studies. CONCLUSION: The current methods of microsurgical technique validation should be reconsidered due to poor study design. Statistical analysis including confounder adjustment and power analysis should be performed as a standard method of novel technique validation.

Causal inference and observational data.

Observational studies using causal inference frameworks can provide a feasible alternative to randomized controlled trials. Advances in statistics, machine learning, and access to big data facilitate unraveling complex causal relationships from observational data across healthcare, social sciences, and other fields. However, challenges like evaluating models and bias amplification remain.

Impact of an external ventricular shunt (EVD) handling protocol on secondary meningitis rates: a historical cohort study with propensity score matching.

BACKGROUND: External ventricular drainage (EVD) is frequently used in neurosurgical procedures for cerebrospinal fluid (CSF) drainage. It is, however, associated with high infection rates, namely secondary meningitis and ventriculitis. Based on a previous high prevalence of these infections among patients with EVDs, we have proposed and implemented a protocol in an effort to decrease the infection rate. The aim of this study was to measure the effect of hospital-wide implementation of the EVD handling protocol on secondary EVD infections. PATIENTS AND METHODS: We included 409 consecutive patients who received a new EVD for other indications than infectious pathologies from January 2000 until June 2012. Patients above 18 years of age were divided into pre- (n = 228) and post-protocol (n = 181) groups. Patient and disease demographics, as well as EVD data together with confounders for secondary meningitis were recorded in a database. Propensity score matching was then performed to create groups matched for sex, age, reason for drainage, type of shunt, time in situ and duration of surgery to place the EVD. Binomial logistic regression for confounder adjustment and regression discontinuity analyses were then performed on the matched cohort. RESULTS: Infections occurred more frequently in the pre-protocol group (23% vs 9%, p <  0.001). The incidence of infection was 33/1000 drain-days pre-protocol and 9/1000 drain-days post-protocol. Regression analysis in a propensity score-matched cohort (n = 103 in the pre- and n = 178 in the post-protocol groups) showed that the pre-protocol period was independently associated with more infections (OR 2.69; 95%-CI 1.22-5.95, p = 0.01). CONCLUSIONS: The incidence of secondary EVD infections can be reduced significantly by the implementation of a strict hospital-wide EVD handling protocol.

Trapped fourth ventricle: to stent, shunt, or fenestrate-a systematic review and individual patient data meta-analysis.

Trapped or isolated fourth ventricle (TFV) is a rare but critical neurosurgical condition, mostly occurring in pediatric patients, caused by a blockage of the in- and outlets of the fourth ventricle. The purpose of this study is to review all available data on the treatment options of TFV and to compare their safety, efficacy, and durability. MEDLINE, Embase, and Google Scholar were searched from inception to September 13, 2022, for prospective or retrospective cohorts, case-control studies, case series or case reports, reporting detailing outcomes of TFV patients, treated with an endoscopic-, microsurgical-, shunt placement,- or hybrid approaches to TFV. All authors were contacted to provide individual patient data. Eighty-seven articles (314 patients) were included in the individual patient data meta-analysis (IPD) and 9 (151 patients) in the cohort meta-analysis. The IPD revealed that primary endoscopic (aOR 0.21; [95% CI 0.08-0.57]) and microsurgical interventions (aOR 0.21; [95% CI 0.05-0.82]) were associated with a significantly lower revision rate, compared to shunt placement, when adjusted for confounders. Endoscopy was also associated with a significantly higher rate of clinical improvement (aOR 4.56; [95% CI 1.2-18]). The meta-analysis revealed no significant difference in revision rate between the endoscopic (0.33 [95% CI 0.0-0.52]) and shunt group (0.44 [95% CI 0.0-1.0]). Endoscopy should be considered as the first-line treatment of TFV due to its superior efficacy, durability, and similar safety, compared to shunt placement and its minimally invasive nature. Microsurgery should be considered as a second treatment option, due to its similar clinical outcomes and revision rate as endoscopy, but it is more invasive in nature.

Early surgery versus conservative treatment in patients with traumatic intracerebral hematoma: a CENTER-TBI study.

PURPOSE: Evidence regarding the effect of surgery in traumatic intracerebral hematoma (t-ICH) is limited and relies on the STITCH(Trauma) trial. This study is aimed at comparing the effectiveness of early surgery to conservative treatment in patients with a t-ICH. METHODS: In a prospective cohort, we included patients with a large t-ICH (< 48 h of injury). Primary outcome was the Glasgow Outcome Scale Extended (GOSE) at 6 months, analyzed with multivariable proportional odds logistic regression. Subgroups included injury severity and isolated vs. non-isolated t-ICH. RESULTS: A total of 367 patients with a large t-ICH were included, of whom 160 received early surgery and 207 received conservative treatment. Patients receiving early surgery were younger (median age 54 vs. 58 years) and more severely injured (median Glasgow Coma Scale 7 vs. 10) compared to those treated conservatively. In the overall cohort, early surgery was not associated with better functional outcome (adjusted odds ratio (AOR) 1.1, (95% CI, 0.6-1.7)) compared to conservative treatment. Early surgery was associated with better outcome for patients with moderate TBI and isolated t-ICH (AOR 1.5 (95% CI, 1.1-2.0); P value for interaction 0.71, and AOR 1.8 (95% CI, 1.3-2.5); P value for interaction 0.004). Conversely, in mild TBI and those with a smaller t-ICH (< 33 cc), conservative treatment was associated with better outcome (AOR 0.6 (95% CI, 0.4-0.9); P value for interaction 0.71, and AOR 0.8 (95% CI, 0.5-1.0); P value for interaction 0.32). CONCLUSIONS: Early surgery in t-ICH might benefit those with moderate TBI and isolated t-ICH, comparable with results of the STITCH(Trauma) trial.

Comparison of Large Animal Models for Acute Ischemic Stroke: Which Model to Use?

Translation of acute ischemic stroke research to the clinical setting remains limited over the last few decades with only one drug, recombinant tissue-type plasminogen activator, successfully completing the path from experimental study to clinical practice. To improve the selection of experimental treatments before testing in clinical studies, the use of large gyrencephalic animal models of acute ischemic stroke has been recommended. Currently, these models include, among others, dogs, swine, sheep, and nonhuman primates that closely emulate aspects of the human setting of brain ischemia and reperfusion. Species-specific characteristics, such as the cerebrovascular architecture or pathophysiology of thrombotic/ischemic processes, significantly influence the suitability of a model to address specific research questions. In this article, we review key characteristics of the main large animal models used in translational studies of acute ischemic stroke, regarding (1) anatomy and physiology of the cerebral vasculature, including brain morphology, coagulation characteristics, and immune function; (2) ischemic stroke modeling, including vessel occlusion approaches, reproducibility of infarct size, procedural complications, and functional outcome assessment; and (3) implementation aspects, including ethics, logistics, and costs. This review specifically aims to facilitate the selection of the appropriate large animal model for studies on acute ischemic stroke, based on specific research questions and large animal model characteristics.

AutoScore-Ordinal: an interpretable machine learning framework for generating scoring models for ordinal outcomes.

BACKGROUND: Risk prediction models are useful tools in clinical decision-making which help with risk stratification and resource allocations and may lead to a better health care for patients. AutoScore is a machine learning-based automatic clinical score generator for binary outcomes. This study aims to expand the AutoScore framework to provide a tool for interpretable risk prediction for ordinal outcomes. METHODS: The AutoScore-Ordinal framework is generated using the same 6 modules of the original AutoScore algorithm including variable ranking, variable transformation, score derivation (from proportional odds models), model selection, score fine-tuning, and model evaluation. To illustrate the AutoScore-Ordinal performance, the method was conducted on electronic health records data from the emergency department at Singapore General Hospital over 2008 to 2017. The model was trained on 70% of the data, validated on 10% and tested on the remaining 20%. RESULTS: This study included 445,989 inpatient cases, where the distribution of the ordinal outcome was 80.7% alive without 30-day readmission, 12.5% alive with 30-day readmission, and 6.8% died inpatient or by day 30 post discharge. Two point-based risk prediction models were developed using two sets of 8 predictor variables identified by the flexible variable selection procedure. The two models indicated reasonably good performance measured by mean area under the receiver operating characteristic curve (0.758 and 0.793) and generalized c-index (0.737 and 0.760), which were comparable to alternative models. CONCLUSION: AutoScore-Ordinal provides an automated and easy-to-use framework for development and validation of risk prediction models for ordinal outcomes, which can systematically identify potential predictors from high-dimensional data.

Hypertensive primary intraventricular hemorrhage: a systematic review.

Primary intraventricular hemorrhage (PIVH) is a special subtype of intraventricular hemorrhage (IVH) without a hemorrhagic parenchymal component. Different conditions may cause this uncommon hemorrhage including trauma, vascular anomalies, coagulation disorders, and others. Frequently, PIVH is associated with structural vascular anomalies such as aneurysms, arteriovenous malformations, and dural fistulas. Traditionally, hypertension has been considered a predisposing factor for PIVH. A wide variety of studies have been published describing patients with PIVH; however, studies describing exclusively patients with hypertensive PIVH are lacking in the literature. For this reason, the features of PIVH secondary to hypertension are not well described. The purpose of this study is to analyze and describe the characteristics of hypertensive PIVH. A PubMed and Scopus search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed to include studies reporting patients with hypertensive PIVH. The search yielded 19 articles reporting retrospective case series. The diagnosis of hypertensive PIVH should be established in patients meeting the following criteria: (a) elevation of blood pressure is observed at admission, (b) a cerebral angiography is negative for vascular anomalies, and (c) other causes of intracranial hemorrhage are ruled out. The prognosis is poorer in patients who present with low Glasgow Coma Score (GCS), old age, hydrocephalus, or more extensive intraventricular bleeding. The results of this study show that hypertension is the most common cause of PIVH, followed by hemorrhage caused by vascular anomalies. Hypertension may be a direct cause of PIVH, but also it may be a predisposing factor for bleeding in cases of an associated vascular anomaly.

Comparative effectiveness of intracranial hypertension management guided by ventricular versus intraparenchymal pressure monitoring: a CENTER-TBI study.

OBJECTIVE: To compare outcomes between patients with primary external ventricular device (EVD)-driven treatment of intracranial hypertension and those with primary intraparenchymal monitor (IP)-driven treatment. METHODS: The CENTER-TBI study is a prospective, multicenter, longitudinal observational cohort study that enrolled patients of all TBI severities from 62 participating centers (mainly level I trauma centers) across Europe between 2015 and 2017. Functional outcome was assessed at 6 months and a year. We used multivariable adjusted instrumental variable (IV) analysis with "center" as instrument and logistic regression with covariate adjustment to determine the effect estimate of EVD on 6-month functional outcome. RESULTS: A total of 878 patients of all TBI severities with an indication for intracranial pressure (ICP) monitoring were included in the present study, of whom 739 (84%) patients had an IP monitor and 139 (16%) an EVD. Patients included were predominantly male (74% in the IP monitor and 76% in the EVD group), with a median age of 46 years in the IP group and 48 in the EVD group. Six-month GOS-E was similar between IP and EVD patients (adjusted odds ratio (aOR) and 95% confidence interval [CI] OR 0.74 and 95% CI [0.36-1.52], adjusted IV analysis). The length of intensive care unit stay was greater in the EVD group than in the IP group (adjusted rate ratio [95% CI] 1.70 [1.34-2.12], IV analysis). One hundred eighty-seven of the 739 patients in the IP group (25%) required an EVD due to refractory ICPs. CONCLUSION: We found no major differences in outcomes of patients with TBI when comparing EVD-guided and IP monitor-guided ICP management. In our cohort, a quarter of patients that initially received an IP monitor required an EVD later for ICP control. The prevalence of complications was higher in the EVD group. PROTOCOL: The core study is registered with ClinicalTrials.gov , number NCT02210221, and the Resource Identification Portal (RRID: SCR_015582).

Reduction of the Number of Live Animals Used for Microsurgical Skill Acquisition: An Experimental Randomized Noninferiority Trial.

BACKGROUND: Live animals have been used for decades as one of the many training models for developing surgical skills. Microsurgery in particular relies on training for skill acquisition and maintenance, using live animal models, especially rats (murine models). Efforts are underway to reduce the number of rats sacrificed to achieve this objective. METHODS: A group of students with minimal microsurgical experience, after having gone through a basic microsurgical course, were randomly split into three equal groups, all three groups following a 24-week standard training program based on low- and medium-fidelity training models with standardized murine training days. In addition to the standard training regimen, each participant performed supplementary training on live rats every 4, 6, or 8 weeks. According to the training program, the procedures have been performed on chicken legs, flower petals, and rats, each procedure being blindly assessed and evaluated using validated models and scales. The primary evaluated outcome was the Stanford Microsurgery and Resident Training (SMaRT) scale result of the final rat anastomosis performed by each group, for which the tested hypothesis was one of noninferiority. The secondary outcomes were represented by the final rat anastomosis time, final chicken leg anastomosis result and time, and the final petal score. RESULTS: After the 24th week, no differences were observed between the three groups regarding their microsurgical skills, as measured by the aforementioned surgical outcomes. All participants improved significantly during the study (mean [standard deviation] 19 ± 4 points on the SMaRT scale), with no significant differences between the groups, p < 0.001 for noninferiority. CONCLUSION: A training regimen based on low- and moderate-fidelity models, with the addition of training on a live rat every 8 weeks was noninferior to a training regimen that used a live rat every 6 weeks and also noninferior to a training regimen that used a live rat every 4 weeks.

Unruptured Arteriovenous Malformations: Do We Have an Answer After the Final Follow-Up of ARUBA? A Bayesian Viewpoint.

Brain arteriovenous malformations (bAVMs) are vascular lesions that carry significant morbidity and mortality risk upon rupture. bAVM rupture causes either intracerebral or intraventricular hemorrhage, or both. In 2014, the first results of the ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) were published in The Lancet, causing a paradigm shift in clinical practice and suggesting the superiority of medical treatment in terms of mortality or stroke compared with any intervention designed to obliterate the AVM. In 2020, the final results of the ARUBA trial were published. In this Viewpoint, we critically review the clinical equipoise behind the trial, highlight issues regarding external validity, and place the results of the trial in the context of other results in scientific literature of bAVMs using Bayesian inference. ARUBA is a trial of decision-making, and only proper knowledge of the nuances of its interpretation within the broader context of bAVM research can lead to proper decision-making when confronted with patients with unruptured bAVMs.

Deep Cerebral Perforators: Anatomical Distribution and Clinical Symptoms: An Overview.

The anatomic distribution of the deep cerebral perforators is considered either a given or subject to enormous variability. Most published overviews on this topic only report findings from a limited number of anatomic dissections, and no attempt has been made to date to provide a comprehensive overview of all published data. A comprehensive literature search was performed on MEDLINE, Embase, and Google Scholar with the help of an information specialist. Three types of studies were included: (1) articles that described the anatomy and distribution territories of perforator groups arising from the arteries of the circle of Willis; (2) studies that evaluated the anatomy of the deep cerebral perforators using imaging techniques; and (3) studies that evaluated either microsurgically or radiologically confirmed perforator occlusion and reported the (magnetic resonance imaging-confirmed) distribution territory of the infarction together with a description of the clinical symptoms associated as a result of the infarction. A total of 2715 articles were screened and 53 were included. Of these, 40 dealt with the anatomic and imaging anatomy of perforator groups (37 reported results of dissections and 3 results of imaging studies), with a total of 2421 hemispheres investigated. Another 13 articles with 680 patients were included that evaluated perforator infarction territories. The deep cerebral perforator distribution shows large variability with poor concordance rates among reported studies, with the exception of the posterior communicating and anterior choroidal artery perforators. Despite the assumption that cerebral perforator anatomy is a given, studies show large variability in the anatomic distribution of various perforator groups. Perforator anatomy and relationships between perforator groups, as well as potential collateral circulation in these territories should be prioritized as a research topic in cerebrovascular disease in the near future.

How I do it: proximal control in parkinson's triangle for a very large paraclinoid aneurysm.

BACKGROUND: Paraclinoid aneurysms, especially when they are large, can be quite difficult to treat, both endovascularly and through microsurgical clip reconstruction. There are many possibilities to approach this region surgically, and most hinge on total or partial removal of the anterior clinoid process. Gaining proximal control may be a challenge when space is limited, which is why Parkinson's triangle may be a viable alternative in some cases. METHODS: We describe in a stepwise fashion the steps used to reconstruct a very large paraclinoid aneurysm. We first attempted to gain proximal control in the carotid cave and later in Parkinson's triangle because of limited manoeuvrability. CONCLUSION: Proximal control in Parkinson's triangle can be a safe alternative when the post-clinoidal segment of the internal carotid artery (ICA) is short and working space is limited in paraclinoid aneurysm microsurgical clip reconstruction.

Traumatic axonal injury (TAI): definitions, pathophysiology and imaging-a narrative review.

INTRODUCTION: Traumatic axonal injury (TAI) is a condition defined as multiple, scattered, small hemorrhagic, and/or non-hemorrhagic lesions, alongside brain swelling, in a more confined white matter distribution on imaging studies, together with impaired axoplasmic transport, axonal swelling, and disconnection after traumatic brain injury (TBI). Ever since its description in the 1980s and the grading system by Adams et al., our understanding of the processes behind this entity has increased. METHODS: We performed a scoping systematic, narrative review by interrogating Ovid MEDLINE, Embase, and Google Scholar on the pathophysiology, biomarkers, and diagnostic tools of TAI patients until July 2020. RESULTS: We underline the misuse of the Adams classification on MRI without proper validation studies, and highlight the hiatus in the scientific literature and areas needing more research. In the past, the theory behind the pathophysiology relied on the inertial force exerted on the brain matter after severe TBI inducing a primary axotomy. This theory has now been partially abandoned in favor of a more refined theory involving biochemical processes such as protein cleavage and DNA breakdown, ultimately leading to an inflammation cascade and cell apoptosis, a process now described as secondary axotomy. CONCLUSION: The difference in TAI definitions makes the comparison of studies that report outcomes, treatments, and prognostic factors a daunting task. An even more difficult task is isolating the outcomes of isolated TAI from the outcomes of severe TBI in general. Targeted bench-to-bedside studies are required in order to uncover further pathways involved in the pathophysiology of TAI and, ideally, new treatments.

The Double Stitch Everting Technique in the End-to-Side Microvascular Anastomosis: Validation of the Technique Using a Randomized N-of-1 Trial.

BACKGROUND: The double stitch everting (DSE) technique, in which time is won by leaving the needle inside the vessel wall in-between stitching, is a modification of the end-to-side (ETS) anastomosis in the interest of reducing anastomosis time. This ensures proper wall eversion, intima-to-intima contact, and improved suture symmetry. METHODS: We designed an N-of-1 randomized trial with each microsurgeon as their own control. We included 10 microsurgeons of different levels of experience who were then asked to perform classic and DSE ETS anastomoses on the chicken leg and rat femoral models. Every anastomosis was cut and evaluated using blinded assessment. Two-way analysis of variance (ANOVA) and multivariable logistic regression were used to analyze the results and for confounder adjustment. RESULTS: A total of 210 anastomoses were performed, of which 177 on the chicken leg and 43 on the rat femoral artery and vein. From the 210 anastomoses, 111 were performed using the classic technique and 99 using the DSE technique. The mean anastomosis time was 28.8 ± 11.3 minutes in the classic group and 24.6 ± 12 minutes in the DSE group (p < 0.001, t-test). There was a significant reduction (p < 0.001, two-way ANOVA) in the number of mistakes when using the DSE technique (mean 5.5 ± 2.6) compared with those using the classic technique (mean 7.7 ± 3.4). CONCLUSION: The DSE technique for ETS anastomoses improves anastomoses times in experienced and moderately experienced microsurgeons while also improving or maintaining suture symmetry and lowering the number of mistakes.

The ethical and legal status of neurosurgical guidelines: the neurosurgeon's golden fleece or Achilles' heel?

Neurosurgical guidelines are fundamental for evidence-based practice and have considerably increased both in number and content over the last decades. Yet, guidelines in neurosurgery are not without limitations, as they are overwhelmingly based on low-level evidence. Such recommendations have in the past been occasionally overturned by well-designed randomized controlled trials (RCTs), demonstrating the volatility of poorly underpinned evidence. Furthermore, even RCTs in surgery come with several limitations; most notably, interventions are often insufficiently standardized and assume a homogeneous patient population, which is not always applicable to neurosurgery. Lastly, guidelines are often outdated by the time they are published and smaller fields such as neurosurgery may lack a sufficient workforce to provide regular updates. These limitations raise the question of whether it is ethical to use low-level evidence for guideline recommendations, and if so, how strictly guidelines should be adhered to from an ethical and legal perspective. This article aims to offer a critical approach to the ethical and legal status of guidelines in neurosurgery. To this aim, the authors discuss: 1) the current state of neurosurgical guidelines and the evidence they are based on; 2) the degree of implementation of these guidelines; 3) the legal status of guidelines in medical disciplinary cases; and 4) the ethical balance between confident and critical use of guidelines. Ultimately, guidelines are neither laws that should always be followed nor purely academic efforts with little practical use. Every patient is unique, and tailored treatment defined by the surgeon will ensure optimal care; guidelines play an important role in creating a solid base that can be adhered to or deviated from, depending on the situation. From a research perspective, it is inevitable to rely on weaker evidence initially in order to generate more robust evidence later, and clinician-researchers have an ethical duty to contribute to generating and improving neurosurgical guidelines.

Corticosteroid treatment compared with surgery in chronic subdural hematoma: a systematic review and meta-analysis.

BACKGROUND: There is an ongoing debate on the role of corticosteroids in the treatment of chronic subdural hematoma (CSDH). This study aims to evaluate the effectiveness of corticosteroids for the treatment of CSDH compared to surgery. METHOD: A systematic search was performed in relevant databases up to January 2019 to identify RCTs or observational studies that compared at least two of three treatment modalities: the use of corticosteroids as a monotherapy (C), corticosteroids as an adjunct to surgery (CS), and surgery alone (S). Outcome measures were good neurological outcome, need for reintervention, mortality, and complications. Effect estimates were pooled and presented as relative risk (RR) with 95% confidence interval (95%CI). RESULTS: Of 796 initially identified studies, 7 were included in the meta-analysis. Risk of bias was generally high. There were no differences in good neurological outcome between treatment modalities. The need for reintervention varied between 4 and 58% in C, 4-12% in CS, and 7-26% in S. The need for reintervention was lower in CS compared with C (RR 3.34 [95% CI 1.53-7.29]; p < 0.01) and lower in CS compared with S (RR 0.44 [95% CI 0.27-0.72]; p < 0.01). Mortality varied between 0 and 4% in C, 0-13% in CS, and 0-44% in S. Mortality was lower in CS compared with S (RR 0.39 [95% CI 0.25-0.63]; p < 0.01). There were no differences in complications between treatment modalities. CONCLUSIONS: This meta-analysis suggests that the addition of corticosteroids to surgery might be effective in the treatment of CSDH. However, the results must be interpreted with caution in light of the serious risk of bias of the included studies. This study stresses the need for large randomized trials to investigate the use of corticosteroids in the management of CSDH.