Survival and quality of life after CSF diversion in adult patients with leptomeningeal metastasis-associated hydrocephalus: a systematic review and meta-analysis.

OBJECTIVE: Leptomeningeal metastasis (LM) is associated with altered CSF flow dynamics in 50%-70% of patients. Approximately 1%-5% of patients develop symptomatic LM-associated hydrocephalus (LM-H), which adversely impacts quality of life (QOL), functional status, and overall survival (OS). There is equipoise for CSF diversion procedures in LM-H. This systematic review and meta-analysis aimed to assess the effect of CSF diversion on OS and QOL in this context. METHODS: This systematic review was conducted according to the PRISMA guidelines. PubMed/Medline, Embase, Web of Science, and Scopus were searched for articles that evaluated the role of CSF diversion for LM-H due to systemic cancer in adult patients. A meta-analysis was conducted using random effects models, with mean differences and 95% CIs reported. Bias was assessed using the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. RESULTS: Ten eligible studies with a total of 494 patients were included. Two studies reported multivariate HRs for median OS, suggesting no significant effect of shunting on OS (pooled HR 0.42, 95% CI 0.09-1.94, p = 0.27). A difference between preoperative and postoperative Karnofsky Performance Status of mean 17.6 points (95% CI 10.44-24.68, p < 0.0001) was calculated from 4 studies. Across all studies, a symptomatic improvement rate of 67%-100% was observed, with high rates of improvement for headaches and nausea and lower rates for cranial nerve palsies. Complication rates across 9 studies ranged from 0% to 21.1%. CONCLUSIONS: Based on the present findings, shunting does not improve OS but does relieve symptoms, suggesting that individuals who exhibit certain symptoms should be considered for CSF diversion. The present findings prompt the generation of a standardized decision-making tool and a critical analysis of the individual patient risk-benefit ratio. Implementation of these will optimize surgical management of LM-H patients.

Moving towards a unified classification of glioblastomas utilizing artificial intelligence and deep machine learning integration.

Glioblastoma a deadly brain cancer that is nearly universally fatal. Accurate prognostication and the successful application of emerging precision medicine in glioblastoma relies upon the resolution and exactitude of classification. We discuss limitations of our current classification systems and their inability to capture the full heterogeneity of the disease. We review the various layers of data that are available to substratify glioblastoma and we discuss how artificial intelligence and machine learning tools provide the opportunity to organize and integrate this data in a nuanced way. In doing so there is the potential to generate clinically relevant disease sub-stratifications, which could help predict neuro-oncological patient outcomes with greater certainty. We discuss limitations of this approach and how these might be overcome. The development of a comprehensive unified classification of glioblastoma would be a major advance in the field. This will require the fusion of advances in understanding glioblastoma biology with technological innovation in data processing and organization.

Safety and efficacy of brain biopsy: Results from a single institution retrospective cohort study.

Introduction: Brain biopsy provides important histopathological diagnostic information for patients with new intracranial lesions. Although a minimally invasive technique, previous studies report an associated morbidity and mortality between 0.6% and 6.8%. We sought to characterise the risk linked to this procedure, and to establish the feasibility of instigating a day-case brain biopsy pathway at our institution. Materials and methods: This single-centre retrospective case series study included neuronavigation guided mini craniotomy and frameless stereotactic brain biopsies carried out between April 2019 and December 2021. Exclusion criteria were interventions performed for non-neoplastic lesions. Demographic data, clinical and radiological presentation, type of biopsy, histology and complications in the post-operative period were recorded. Results: Data from 196 patients with a mean age of 58.7 years (SD+/-14.4 years) was analysed. 79% (n=155) were frameless stereotactic biopsies and 21% (n=41) neuronavigation guided mini craniotomy biopsies. Complications resulting in acute intracerebral haemorrhage and death, or new persistent neurological deficits were observed in 2% of patients (n=4; 2 frameless stereotactic; 2 open). Less severe complications or transient symptoms were noted in 2.5% of cases (n=5). 8 patients had minor haemorrhages in the biopsy tract with no clinical ramifications. Biopsy was non-diagnostic in 2.5% (n=5) of cases. Two cases were subsequently identified as lymphoma. Other reasons included insufficient sampling, necrotic tissue, and target error. Discussion and conclusion: This study demonstrates that brain biopsy is a procedure with an acceptably low rate of severe complications and mortality, in line with previously published literature. This supports the development of day-case pathway allowing improved patient flow, reducing the risk of iatrogenic complications associated with hospital stay, such as infection and thrombosis.

Optimising trajectory planning for stereotactic brain tumour biopsy using artificial intelligence: a systematic review of the literature.

PURPOSE: Despite advances in technology, stereotactic brain tumour biopsy remains challenging due to the risk of injury to critical structures. Indeed, choosing the correct trajectory remains essential to patient safety. Artificial intelligence can be used to perform automated trajectory planning. We present a systematic review of automated trajectory planning algorithms for stereotactic brain tumour biopsies. METHODS: A PRISMA adherent systematic review was conducted. Databases were searched using keyword combinations of 'artificial intelligence', 'trajectory planning' and 'brain tumours'. Studies reporting applications of artificial intelligence (AI) to trajectory planning for brain tumour biopsy were included. RESULTS: All eight studies were in the earliest stage of the IDEAL-D development framework. Trajectory plans were compared through a variety of surrogate markers of safety, of which the minimum distance to blood vessels was the most common. Five studies compared manual to automated planning strategies and favoured automation in all cases. However, this comes with a significant risk of bias. CONCLUSIONS: This systematic review reveals the need for IDEAL-D Stage 1 research into automated trajectory planning for brain tumour biopsy. Future studies should establish the congruence between expected risk of algorithms and the ground truth through comparisons to real world outcomes.

Data-driven spatio-temporal modelling of glioblastoma.

Mathematical oncology provides unique and invaluable insights into tumour growth on both the microscopic and macroscopic levels. This review presents state-of-the-art modelling techniques and focuses on their role in understanding glioblastoma, a malignant form of brain cancer. For each approach, we summarize the scope, drawbacks and assets. We highlight the potential clinical applications of each modelling technique and discuss the connections between the mathematical models and the molecular and imaging data used to inform them. By doing so, we aim to prime cancer researchers with current and emerging computational tools for understanding tumour progression. By providing an in-depth picture of the different modelling techniques, we also aim to assist researchers who seek to build and develop their own models and the associated inference frameworks. Our article thus strikes a unique balance. On the one hand, we provide a comprehensive overview of the available modelling techniques and their applications, including key mathematical expressions. On the other hand, the content is accessible to mathematicians and biomedical scientists alike to accommodate the interdisciplinary nature of cancer research.

Cerebral cavernous malformation: Management, outcomes, and surveillance strategies - A single centre retrospective cohort study.

BACKGROUND: Cerebral cavernous malformations (CCM) may undergo a period of clinical and/or radiographical surveillance that precedes or follows definitive treatment. There are no international guidelines on the optimal surveillance strategy. This study describes the surveillance strategies at our centre and explore the related clinical outcomes. METHODS: We performed a retrospective study of adult patients with CCMs referred to a neurovascular service over an 8-year period, to determine the frequency and type of surveillance, intervention, and explore the associated outcomes. We report our findings adhering to STROBE guidelines. RESULTS: 133 patients (Male:Female 73:60; men age 42 years; range 12-82) were included. CCMs were identified in patients first presenting with symptomatic intracerebral haemorrhage (42.11%); headache, focal neurological deficit, or seizure without haemorrhage (41.35%); or, as an incidental finding (16.54%). The most common CCM location was supratentorial (59.40%), followed by brain stem (21.80%), cerebellum (10.53%) and basal ganglia (6.02%). Of the 133 patients, 77 patients (57.89%) were managed conservatively, 49 patients (36.84%) were managed by surgical resection alone, and seven patients (5.26%) were managed with stereotactic radiosurgery (SRS). Patients follow-up had a mean duration of 65.94 months, and varied widely (SD = 52.59; range 0-265), for a total of 730.83 person-years of follow up. During surveillance, 16 patients suffered an ICH equating to a bleeding rate of 2.19 per 100 patient years. CCMs that increased in size had a higher bleeding rate (p = 8.58 ×10-4). There were 8 (6.02%) cases where routine clinic review or MRI resulted in a change in management. CONCLUSIONS: Our single centre retrospective study supports existing literature relating to presentation and sequalae of CCM, with an increase in CCM size being associated with higher rates of detected bleeding. There remains heterogeneity, even within a single centre, on the frequency and modality of surveillance. Further, there are no international guidelines or high-quality data that recommends the optimal duration and frequency of surveillance, and its effect on clinical outcomes. This is a future research direction.

Quality of life reporting in the management of posterior fossa tumours: A systematic review.

Introduction: Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of current QoL instruments used for adult PFTs. Aim of this review is to outline the QoL reporting in the management of PFTs and measure participation level. Methods: This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis. A search strategy to identify adult patients with PFTs who took part in QoL metrics was conducted. Observational and experimental studies published from 1990 to date were included. Studies with a sample size less than 10 and performance measures such as Karnofsky Performance Status were not considered. Results: A total of 116 studies were included in the final analysis. Vestibular schwannomas were the most common tumour pathology (n = 23,886, 92.6%) followed by pilocytic astrocytomas (n = 657, 2.5%) and meningiomas (n = 437, 1.7%) Twenty-five different QoL measures were used in the study pool. SF-36 was the most common (n = 55, 17 47.4%) QoL metric in the whole study pool, followed by the Penn Acoustic Neuroma QoL scale (n = 24, 20.7%) and Dizziness Handicap Inventory (n = 16, 13.8%). Seventy-two studies reported less-than 100% participation in QoL evaluation. The commonest reason for non-participation was a lack of response (n = 1,718, 60.8%), incomplete questionnaires (n = 268, 9.4%) and cognitive dysfunction (n = 258, 9.1%). Conclusion: Informed clinical decision-making in PFT patients requires the development of specific QoL outcomes. Core outcome sets, and minimal clinically important differences (MCID) are essential for these metrics to show clinically significant improvements in patient QoL.

Injury programs shape glioblastoma.

Glioblastoma is the most common and aggressive primary brain cancer in adults and is almost universally fatal due to its stark therapeutic resistance. During the past decade, although survival has not substantially improved, major advances have been made in our understanding of the underlying biology. It has become clear that these devastating tumors recapitulate features of neurodevelopmental hierarchies which are influenced by the microenvironment. Emerging evidence also highlights a prominent role for injury responses in steering cellular phenotypes and contributing to tumor heterogeneity. This review highlights how the interplay between injury and neurodevelopmental programs impacts on tumor growth, invasion, and treatment resistance, and discusses potential therapeutic considerations in view of these findings.

Cystic glioblastoma: A systematic review and meta-analysis of characteristics and outcomes.

Introduction: Cystic glioblastoma is a well-recognised clinical entity but the characteristics and role of these cystic components in determining clinical outcome remains poorly understood. Research question: To determine whether (1) there is a prognostic significance to a glioblastoma having a cystic component and (2) whether the presence of cyst, and its prognosis relative to non-cystic glioblastoma, relates to patient demographics and other tumour characteristics. Material & methods: A systematic review and meta-analysis was conducted in accordance to PRISMA guidelines. Articles with histological and/or radiological diagnosis of cystic glioblastoma that reported on survival outcome and/or characteristics of cystic glioblastomas mentioned were included. Meta-analysis was performed and presented using random effect model. Results: Twenty studies met the inclusion criteria, and nine studies were included in the meta-analysis (374 glioblastoma patients with cystic components and 2477 glioblastoma patients without cystic components above 18 years of age). Search result did not yield any Level I evidence. There is statistically significant survival benefit in cystic over non-cystic glioblastomas (HR â€‹= â€‹0.81, 95%CI 0.70-0.93, p â€‹= â€‹0.004, I2 â€‹= â€‹50%). Studies reported younger average patient age, larger tumor size and slower tumor growth velocity in cystic glioblastoma. No significant difference in gender ratio and IDH-1 and MGMT methylation status between cystic and non-cystic glioblastoma were reported. Discussion & conclusion: Presence of cyst in glioblastoma tumor is associated with improved overall survival outcome. Etiology of cystic entities and why they might confer survival benefits remained to be determined, and future studies examining how to best treat cystic glioblastomas would be clinically valuable.

Neurosurgical experience of managing optic pathway gliomas.

BACKGROUND: Optic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3-5% of all pediatric brain tumors. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumors results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other eloquent brain structures typically precludes complete resection or optimal radiation dosing without incurring significant neurological injury. There are various surgical interventions that can be performed in relation to these lesions including biopsy, cerebrospinal fluid diversion, and partial or radical resection, but their role is a source of debate. This study catalogues our surgical experience and patient outcomes in order to support decision-making in this challenging pathology. METHODS: A retrospective review of all cases of OPGs treated in a single center from July 1990 to July 2020. Data was collected on patient demographics, radiographic findings, pathology, and management including surgical interventions. Outcome data included survival, visual function, endocrine, and hypothalamic dysfunction. RESULTS: One hundred twenty-one patients with OPG were identified, and 50 of these patients underwent a total of 104 surgical procedures. These included biopsy (31), subtotal or gross total resection (20 operations in 17 patients), cyst drainage (17), Ommaya reservoir insertion (9), or cerebrospinal fluid diversion (27). During the study period, there was 6% overall mortality, 18% hypothalamic dysfunction, 20% endocrine dysfunction, and 42% had some cognitive dysfunction. At diagnosis 75% of patients had good or moderate visual function in at least one eye, and overall, this improved to 83% at the end of the study period. In comparison the worst eye had good or moderate visual function in 56%, and this reduced to 53%. Baseline and final visual function were poorer in patients who had a surgical resection, but improvements in vision were still found-particularly in the best eye. DISCUSSION/CONCLUSION: OPG are debilitating childhood tumor that have lifelong consequences in terms of visual function and endocrinopathies/hypothalamic dysfunction; this can result in substantial patient morbidity. Decisions regarding management and the role of surgery in this condition are challenging and include cerebrospinal fluid diversion, biopsy, and in highly select cases cystic decompression or surgical resection. In this paper, we review our own experience, outcomes, and surgical philosophy.

A randomized controlled trial of the X-Stop interspinous distractor device versus laminectomy for lumbar spinal stenosis with 2-year quality-of-life and cost-effectiveness outcomes.

OBJECTIVE: Lumbar spinal stenosis (LSS) is a common and debilitating condition that is increasing in prevalence in the world population. Surgical decompression is often standard treatment when conservative measures have failed. Interspinous distractor devices (IDDs) have been proposed as a safe alternative; however, the associated cost and early reports of high failure rates have brought their use into question. The primary objective of this study was to determine the cost-effectiveness and long-term quality-of-life (QOL) outcomes after treatment of LSS with the X-Stop IDD compared with surgical decompression by laminectomy. METHODS: A multicenter, open-label randomized controlled trial of 47 patients with LSS was conducted; 21 patients underwent insertion of the X-Stop device and 26 underwent laminectomy. The primary outcomes were monetary cost and QOL measured using the EQ-5D questionnaire administered at 6-, 12-, and 24-month time points. RESULTS: The mean monetary cost for the laminectomy group was £2712 ($3316 [USD]), and the mean cost for the X-Stop group was £5148 ($6295): £1799 ($2199) procedural cost plus £3349 mean device cost (£2605 additional cost per device). Using an intention-to-treat analysis, the authors found that the mean quality-adjusted life-year (QALY) gain for the laminectomy group was 0.92 and that for the X-Stop group was 0.81. The incremental cost-effectiveness ratio was -£22,145 (-$27,078). The revision rate for the X-Stop group was 19%. Five patients crossed over to the laminectomy arm after being in the X-Stop group. CONCLUSIONS: Laminectomy was more cost-effective than the X-Stop for the treatment of LSS, primarily due to device cost. The X-Stop device led to an improvement in QOL, but it was less than that in the laminectomy group. The use of the X-Stop IDD should be reserved for cases in which a less-invasive procedure is required. There is no justification for its regular use as an alternative to decompressive surgery. Clinical trial registration no.: ISRCTN88702314 (www.isrctn.com).

Atlantoaxial rotatory fixation in childhood: a staged management strategy incorporating manipulation under anaesthesia.

AIMS: The aims were to evaluate the safety of manipulation under anaesthesia (MUA) for atlantoaxial rotatory fixation (AARF) and the relative efficacy of rigid collar vs halo-body orthosis (HBO) in avoiding relapse and the need for open surgery. METHODS: Cases of CT-verified AARF treated by MUA were identified from a neurosurgical operative database. Demographic details, time to presentation and aetiology of AARF were ascertained through case note review. Cases were divided according to method of immobilisation after successful reduction, either rigid collar (group 1) or HBO (group 2). The primary outcome measure was relapse requiring open surgical arthrodesis. RESULTS: Thirty-three patients (2.2-12.7 years) satisfied inclusion criteria. Time to presentation varied from 1 day to 18 months. There were 19 patients in group 1 and 14 in group 2. There were no adverse events associated with MUA. 9/19 (47%) patients in group 1 resolved without need for further treatment compared with 10/14 (71%) in group 2 (p = 0.15). Of the 10 patients who failed group 1 treatment, four resolved after HBO. A total of ten patients (30%) failed treatment and required open surgery. CONCLUSIONS: MUA is a safe procedure for AARF where initial conservative measures have failed. MUA followed by immobilisation avoids the need for open surgery in over two thirds of cases. Immobilisation by cervical collar appears equally effective to HBO as an initial management, and so a step-wise approach may be reasonable. Delayed presentation may be a risk factor for relapse and need for open surgery.

Comparison between outcomes of endovascular and surgical treatments of ruptured anterior communicating artery aneurysms.

INTRODUCTION: The natural history and optimal treatment of previously ruptured anterior communicating artery (ACOM) aneurysms that recur is unknown. This study looks at rates of complications and recurrences of ruptured ACOM aneurysms treated endovascularly and surgically. MATERIALS AND METHODS: A retrospective observational study of all patients presenting to a single tertiary neurosurgical centre with the first presentation of subarachnoid haemorrhage (SAH) secondary to a ruptured ACOM aneurysm. Data was collected from November 2012 to September 2018 and included baseline demographics, aneurysm characteristics, management, complications, follow-up imaging, and clinical outcomes. RESULTS: 137 patients were included in the study. 113 aneurysms were coiled and 19 were clipped. Management decisions were taken by the multidisciplinary team based on aneurysm morphology or the presence of a haematoma exerting mass effect. There were 187.5 patient-years of follow-up, with a median of 3 years (range 0-73 months). Rates of vasospasm, infarction, CSF diversion, rebleed, length of stay, and functional outcome were not significantly different in the two cohorts. There was a statistically significant increase in the risk of ACOM recurrence in the coiled group when compared to the clipped group at one year (p = .0433). 15 patients required further treatment at a median time of 16 months. In a subgroup group analysis of coiled aneurysms, there was no statistical differences in rates of rebleeding or the functional outcome in those that had aneurysm recurrence and those that did not. CONCLUSIONS: This study suggests patients with aneurysms treated by endovascular coiling have an increased risk of recurrence versus those treated with clipping. However, the risk of rebleed was not statistically significant. The prevention and impact of recurrence and residual aneurysms remains incompletely understood. Hence, treatment decisions should be taken by patients after they have been given carefully considered recommendations from the multi-disciplinary team.

Systematic review of the nonsurgical management of atlantoaxial rotatory fixation in childhood.

OBJECTIVE: Atlantoaxial rotatory fixation (AARF) is an acquired fixed abnormality of C1-2 joint rotation associated with torticollis in childhood. If the condition is left uncorrected, patients are at risk for developing C1-2 fusion with permanent limitation in the cervical range of movement, cosmetic deformity, and impact on quality of life. The management of AARF and the modality of nonsurgical treatment are poorly defined in both primary care and specialized care settings, and the optimal strategy is not clear. This systematic review aims to examine the available evidence to answer key questions relating to the nonsurgical management of AARF. METHODS: A systematic review was performed using the following databases: PubMed, MEDLINE, Healthcare Management Information Consortium (HMIC), EMCare, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), British Nursing Index (BNI), and Allied and Complementary Medicine Database (AMED). Search criteria were created and checked independently among the authors. All articles with a radiological diagnosis of AARF and primary outcome data that met the study inclusion criteria were included and analyzed by the authors. RESULTS: Search results did not yield any level I evidence such as a meta-analysis or randomized controlled trial. The initial search yielded 724 articles, 228 of which were screened following application of the core exclusion criteria. A total of 37 studies met the full criteria for inclusion in this review, consisting of 4 prospective studies and 33 retrospective case reviews. No articles directly compared outcomes between modalities of nonsurgical management. Six studies compared the outcome of AARF based on duration of symptoms before initiation of treatment. Comparative analysis of studies was hindered by the wide variety of treatment modalities described and the heterogeneity of outcome data. CONCLUSIONS: The authors did not identify any level I evidence comparing different nonsurgical management approaches for AARF. There were few prospective studies, and most studies were uncontrolled, nonrandomized case series. Favorable outcomes were often reported regardless of treatment methods, with early treatment of AARF tending to yield better outcomes independent of the treatment modality. There is a lack of high-quality data, and further research is required to determine the optimal nonsurgical treatment strategy.

An Exit Strategy for Resuming Nonemergency Neurosurgery after Severe Acute Respiratory Syndrome Coronavirus 2: A United Kingdom Perspective.

INTRODUCTION: Substantial healthcare resources have been diverted to manage the effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, and nonemergency neurosurgery has been effectively closed. As we begin to emerge from the crisis, we will need to manage the backlog of nonemergency neurosurgical patients whose treatment has been delayed and remain responsive to further possible surges of SARS-CoV-2 infections. METHODS: In the present study, we aimed to identify the core themes and challenges that will limit resumption of a normal neurosurgical service after the SARS-CoV-2 pandemic and to provide pragmatic advice and solutions that could be of utility to clinicians seeking to resume nonemergency neurosurgical care. We reviewed the relevant international policies, a wide range of journalistic and media sources, and expert opinion documents to address the stated aims. RESULTS: We have presented and discussed a range of factors that could become potential barriers to resuming full elective neurosurgical provision and important steps that must be completed to achieve pre-SARS-CoV-2 surgical capacity. We also explored how these challenges can be overcome and outlined the key requirements for a successful neurosurgical exit strategy from the pandemic. CONCLUSION: The performance of nonemergency neurosurgery can start once minimum criteria have been fulfilled: 1) a structured prioritization of surgical cases; 2) virus infection incidence decreased sufficiently to release previously diverted healthcare resources; 3) adequate safety criteria met for patients and staff, including sufficient personal protective equipment and robust testing availability; and 4) maintenance of systems for rapid communication at organizational and individual levels.

Craniectomy size for subdural haematomas and the impact on brain shift and outcomes.

BACKGROUND: Midline shift in trauma relates to the severity of head injury. Large craniectomies are thought to help resolve brain shift but can be associated with higher rates of morbidity. This study explores the relationship between craniectomy size and subtemporal decompression for acute subdural haematomas with the resolution of brain compression and outcomes. No systematic study correlating these measures has been reported. METHOD: A retrospective study of all adult cases of acute subdural haematomas that presented to a Major Trauma Centre and underwent a primary decompressive craniectomy between June 2008 and August 2013. Data collection included patient demographics and presentation, imaging findings and outcomes. All imaging metrics were measured by two independent trained assessors. Compression was measured as midline shift, brainstem shift and cisternal effacement. RESULTS: Thirty-six patients with mean age of 36.1 ± 12.5 (range 16-62) were included, with a median follow-up of 23.5 months (range 2.2-109.6). The median craniectomy size was 88.7 cm2 and the median subtemporal decompression was 15.0 mm. There was significant post-operative resolution of shift as measured by midline shift, brainstem shift and cisternal effacement score (all p < .00001). There was no mortality, and the majority of patients made a good recovery with 82.8% having a Modified Rankin Score of 2 or less. There was no association between craniectomy size or subtemporal decompression and any markers of brain shift or outcome (all R2 < 0.05). CONCLUSIONS: This study suggests that there is no clear relationship between craniectomy size or extent of subtemporal decompression and resolution of brain shift or outcome. Further studies are needed to assess the relative efficacy of large craniectomies and the role of subtemporal decompression.

Loss of highwire Protects Against the Deleterious Effects of Traumatic Brain Injury in Drosophila Melanogaster.

Traumatic brain injury is a major global cause of death and disability. Axonal injury is a major underlying mechanism of TBI and could represent a major therapeutic target. We provide evidence that targeting the axonal death pathway known as Wallerian degeneration improves outcome in a Drosophila Melanogaster model of high impact trauma. This cell-autonomous neurodegenerative pathway is initiated following axon injury, and in Drosophila, involves activity of the E3 ubiquitin ligase highwire. We demonstrate that a loss-of-function mutation in the highwire gene rescues deleterious effects of a traumatic injury, including-improved functional outcomes, lifespan, survival of dopaminergic neurons, and retention of synaptic proteins. This data suggests that highwire represents a potential therapeutic target in traumatic injury.