Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation.

OBJECTIVE: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN: Multi-institutional historical cohort study. SETTING: Five tertiary care referral centers. PATIENTS: Adults ≥18 years old with sporadic VS. INTERVENTION: Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE: Microsurgery-free survival after repeat SRS. RESULTS: Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

Salvage Microsurgery Following Failed Primary Radiosurgery in Sporadic Vestibular Schwannoma.

Importance: Management of sporadic vestibular schwannoma with radiosurgery is becoming increasingly common globally; however, limited data currently characterize patient outcomes in the setting of microsurgical salvage for radiosurgical failure. Objective: To describe the clinical outcomes of salvage microsurgery following failed primary stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) among patients with sporadic vestibular schwannoma. Design, Setting, and Participants: This was a cohort study of adults (≥18 years old) with sporadic vestibular schwannoma who underwent salvage microsurgery following failed primary SRS/FSRT in 7 vestibular schwannoma treatment centers across the US and Norway. Data collection was performed between July 2022 and January 2023, with data analysis performed between January and July 2023. Exposure: Salvage microsurgical tumor resection. Main Outcomes and Measures: Composite outcome of undergoing less than gross total resection (GTR) or experiencing long-term facial paresis. Results: Among 126 patients, the median (IQR) age at time of salvage microsurgery was 62 (53-70) years, 69 (55%) were female, and 113 of 117 (97%) had tumors that extended into the cerebellopontine angle at time of salvage. Of 125 patients, 96 (76%) underwent primary gamma knife SRS, while 24 (19%) underwent linear accelerator-based SRS; the remaining patients underwent FSRT using other modalities. Postoperative cerebrospinal fluid leak was seen in 15 of 126 patients (12%), hydrocephalus in 8 (6%), symptomatic stroke in 7 (6%), and meningitis in 2 (2%). Each 1-mm increase in cerebellopontine angle tumor size was associated with a 13% increased likelihood of foregoing GTR (64 of 102 patients [63%]) or long-term postoperative House-Brackmann grade higher than I (48 of 102 patients [47%]) (odds ratio, 1.13; 95% CI, 1.04-1.23). Following salvage microsurgery, tumor growth-free survival rates at 1, 3, and 5 years were 97% (95% CI, 94%-100%), 93% (95% CI, 87%-99%), and 91% (95% CI, 84%-98%), respectively. Conclusions: In this cohort study, more than half of patients who received salvage microsurgery following primary SRS/FSRT underwent less than GTR or experienced some degree of facial paresis long term. These data suggest that the cumulative risk of developing facial paresis following primary SRS/FSRT by the end of the patient's journey with treatment approximates 2.5% to 7.5% when using published primary SRS/FSRT long-term tumor control rates.

Risk Factors for Neural-Tube Defects Detected in Utero: A Prospective Community-Based Study from Addis Ababa.

BACKGROUND: A recent community-based study from Addis Ababa identifying Neural Tube Defect (NTD) cases by ultrasound examination of pregnant women showed a higher prevalence of 17 per 1000 fetuses. The risk factors behind the high prevalence remain unclear. METHODS: Altogether 891 of the 958 women participated in the ultrasound examination. Thirteen with unaffected twin pregnancies were excluded. Among 878 singleton pregnancies, 15 NTD cases were identified. Serum Folate, vitamin B12, and homocysteine levels were measured in case-mothers and a sub-set of 28 noncase mothers. Because of the modest sample size, exact logistic regression analysis was used to estimate associations between risk factors and NTDs. RESULTS: Serum vitamin status was generally poor for participants in the study. Still, relatively higher values of folate or vitamin B12 in serum, appeared to be protective for NTD (odds ratio [OR] = 0.61 per ng/ml, 95% Confidence interval [CI]: 0.42-0.85 and OR = 0.67 per 100 pg/ml, 95% CI: 0.41-1.02, respectively). High serum homocysteine was associated with higher risk of NTD (OR = 1.3 per µmol/l, 95% CI: 1.02-1.8). Women aged 30 years or more had an OR of 3.5 (95% CI: 1.1-12) for having a NTD child, and families with NTD children had lower household income. Women in the NTD group also had more spontaneous abortions or stillbirths in previous pregnancies. Self-reported intake of folate did not appear to protect against NTDs. CONCLUSIONS: Within this high-prevalence community, poor vitamin status was identified as a risk factor for NTDs detected at ultrasound examination. Improving food security and fortification of foods or food ingredients could be alternative measures.

Surgical treatment outcome of children with neural-tube defect: A prospective cohort study in a high volume center in Addis Ababa, Ethiopia.

Introduction: Prevalence of neural tube defects (NTD) is high thus many children are born with a neural tube defect in Addis Ababa, and surgical closure is a commonly performed procedure at the pediatric neurosurgical specialty center. Research question: The primary aim is to study the outcomes in children undergoing surgical closure of NTDs and to identify risk factors for readmission, complications and mortality. Material and methods: Single-center prospective study of all surgically treated NTDs from April 2019 to May 2020. Results: A total of 228 children, mean age 11 days (median 4) underwent surgery during the study period. There were no in-hospital deaths. Perioperatively 11 (4.8%) children developed wound complications, none of them needed surgery and there was no perioperative mortality. The one-year follow-up rate was 62.7% (143/228) and neurological status remained stable since discharge in all. The readmission and reoperation rates were 38 % and 8 % and risk factors for readmission were hydrocephalus (80%) and open defects (88%). Hydrocephalus (P = 0.05) and younger age (P = 0.02) were identified as risk factors for mortality. The wound-related complication rate was 55% at and was associated with large defects (P = 0.04) and delayed closure due to late hospital presentation (P = 0.01). Discussion and conclusion: The study reveals good perioperative surgical outcome and further need for systematic improvement in treatment and follow-up of NTD patients especially with hydrocephalus. We identified risk factors for wound-related complications, readmission and mortality.

Rationale for the Development of a Novel Clinical Grading Scale for Postoperative Facial Nerve Function: Results of a Multidisciplinary International Working Group.

OBJECTIVE: The objective of the current study was to present the results of an international working group survey identifying perceived limitations of existing facial nerve grading scales to inform the development of a novel grading scale for assessing early postoperative facial paralysis that incorporates regional scoring and is anchored in recovery prognosis and risk of associated complications. STUDY DESIGN: Survey. SETTING: A working group of 48 multidisciplinary clinicians with expertise in skull base, cerebellopontine angle, temporal bone, or parotid gland surgery. RESULTS: House-Brackmann grade is the most widely used system to assess facial nerve function among working group members (81%), although more than half (54%) agreed that the system they currently use does not adequately estimate the risk of associated complications, such as corneal injury, and confidence in interrater and intrarater reliability is generally low. Simplicity was ranked as the most important attribute of a novel postoperative facial nerve grading system to increase the likelihood of adoption, followed by reliability and accuracy. There was widespread consensus (91%) that the eye is the most critical facial region to focus on in the early postoperative setting. CONCLUSIONS: Members were invited to submit proposed grading systems in alignment with the objectives of the working group for subsequent validation. From these data, we plan to develop a simple, clinically anchored, and reproducible staging system with regional scoring for assessing early postoperative facial nerve function after surgery of the skull base, cerebellopontine angle, temporal bone, or parotid gland.

Upfront Radiosurgery vs a Wait-and-Scan Approach for Small- or Medium-Sized Vestibular Schwannoma: The V-REX Randomized Clinical Trial.

Importance: Current guidelines for treating small- to medium-sized vestibular schwannoma recommend either upfront radiosurgery or waiting to treat until tumor growth has been detected radiographically. Objective: To determine whether upfront radiosurgery provides superior tumor volume reduction to a wait-and-scan approach for small- to medium-sized vestibular schwannoma. Design, Setting, and Participants: Randomized clinical trial of 100 patients with a newly diagnosed (<6 months) unilateral vestibular schwannoma and a maximal tumor diameter of less than 2 cm in the cerebellopontine angle as measured on magnetic resonance imaging. Participants were enrolled at the Norwegian National Unit for Vestibular Schwannoma from October 28, 2014, through October 3, 2017; 4-year follow-up ended on October 20, 2021. Interventions: Participants were randomized to receive either upfront radiosurgery (n = 50) or to undergo a wait-and-scan protocol, for which treatment was given only upon radiographically documented tumor growth (n = 50). Participants underwent 5 annual study visits consisting of clinical assessment, radiological examination, audiovestibular tests, and questionnaires. Main Outcomes and Measures: The primary outcome was the ratio between tumor volume at the trial end at 4 years and baseline (V4:V0). There were 26 prespecified secondary outcomes, including patient-reported symptoms, clinical examinations, audiovestibular tests, and quality-of-life outcomes. Safety outcomes were the risk of salvage microsurgery and radiation-associated complications. Results: Of the 100 randomized patients, 98 completed the trial and were included in the primary analysis (mean age, 54 years; 42% female). In the upfront radiosurgery group, 1 participant (2%) received repeated radiosurgery upon tumor growth, 2 (4%) needed salvage microsurgery, and 45 (94%) had no additional treatment. In the wait-and-scan group, 21 patients (42%) received radiosurgery upon tumor growth, 1 (2%) underwent salvage microsurgery, and 28 (56%) remained untreated. For the primary outcome of the ratio of tumor volume at the trial end to baseline, the geometric mean V4:V0 was 0.87 (95% CI, 0.66-1.15) in the upfront radiosurgery group and 1.51 (95% CI, 1.23-1.84) in the wait-and-scan group, showing a significantly greater tumor volume reduction in patients treated with upfront radiosurgery (wait-and-scan to upfront radiosurgery ratio, 1.73; 95% CI, 1.23-2.44; P = .002). Of 26 secondary outcomes, 25 showed no significant difference. No radiation-associated complications were observed. Conclusion and relevance: Among patients with newly diagnosed small- and medium-sized vestibular schwannoma, upfront radiosurgery demonstrated a significantly greater tumor volume reduction at 4 years than a wait-and-scan approach with treatment upon tumor growth. These findings may help inform treatment decisions for patients with vestibular schwannoma, and further investigation of long-term clinical outcomes is needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02249572.

Growth dynamics of incidental meningiomas: A prospective long-term follow-up study.

Background: There is no consensus on the management of incidental meningiomas. The literature on long-term growth dynamics is sparse and the natural history of these tumors remains to be illuminated. Methods: We prospectively assessed long-term tumor growth dynamics and survival rates during active monitoring of 62 patients (45 female, mean age 63.9 years) harboring 68 tumors. Clinical and radiological data were obtained every 6 months for 2 years, annually until 5 years, then every second year. Results: The natural progression of incidental meningiomas during 12 years of monitoring was growth (P < .001). However, mean growth decelerated at 1.5 years and became insignificant after 8 years. Self-limiting growth patterns were seen in 43 (63.2%) tumors, non-decelerating in 20 (29.4%) and 5 (7.4%) were inconclusive due to  ≤ 2 measurements. Decelerating growth persisted once established. Within 5 years, 38 (97.4%) of 39 interventions were initiated. None developed symptoms prior to intervention. Large tumors (P < .001) involving venous sinuses (P = .039) grew most aggressively. Since inclusion 19 (30.6%) patients have died of unrelated causes and 2 (3%) from grade 2 meningiomas. Conclusion: Active monitoring seems a safe and appropriate first-line management of incidental meningiomas. Intervention was avoided in  > 40% with indolent tumors in this cohort. Treatment was not compromised by tumor growth. Clinical follow-up seems sufficient beyond 5 years if self-limiting growth is established. Steady or accelerating growth warrant monitoring until they reach a stable state or intervention is initiated.

Prevalence of neural tube defects among pregnant women in Addis Ababa: a community-based study using prenatal ultrasound examination.

PURPOSE: The primary aim of this study was to estimate the prevalence of NTDs at ultrasound examination in communities of Addis Ababa and secondarily to provide a description of the dysmorphology of the NTD cases. METHODS: We enrolled 958 pregnant women from 20 randomly selected health centers in Addis Ababa during the period from October 1, 2018, to April 30, 2019. Of these 958 women, 891 had an ultrasound examination after enrollment, with a special focus on NTDs. We estimated the prevalence of NTDs and compared it with previously reported hospital-based birth prevalence estimates from Addis Ababa. RESULTS: Among 891 women, 13 had twin pregnancies. We identified 15 NTD cases among 904 fetuses, corresponding to an ultrasound-based prevalence of 166 per 10,000 (95% CI: 100-274). There were no NTD cases among the 26 twins. Eleven had spina bifida (122 per 10,000, 95% CI: 67-219). Among the 11 fetuses with spina bifida, three had a cervical and one had a thoracolumbar defect while the anatomical site for 7 was not registered. Seven of the 11 spina bifida defects had skin covering, while two of the cervical lesions were uncovered. CONCLUSION: We report a high prevalence of NTDs among pregnancies in communities of Addis Ababa based on screening by ultrasound. The prevalence was higher than in previous hospital-based studies in Addis, and the prevalence of spina bifida was particularly high.

Surgical treatment and outcome of chronic subdural hematoma: a comparative study between Ethiopia and Norway.

BACKGROUND: Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions. Here, we studied differences in demographics, treatment, and outcome for CSDH patients in low-income (Ethiopia) and high-income (Norway) countries and assessed potential outcome determinants. METHODS: We included patients from Addis Ababa University Hospitals (AAUH) and Haukeland University Hospital (HUH) who had surgery for CSDH (2013-2017). Patients were included prospectively in Ethiopia and retrospectively in Norway. RESULTS: We enrolled 314 patients from AAUH and 284 patients from HUH, with a median age of 60 and 75 years, respectively. Trauma history was more common in AAUH (72%) than in HUH patients (64.1%). More patients at HUH (45.1%) used anticoagulants/antiplatelets than at AAUH (3.2%). Comorbidities were more frequent in HUH (77.5%) than in AAUH patients (30.3%). Burr hole craniostomy under local anesthesia and postoperative drainage was the standard treatment in both countries. Postoperative CT scanning was more common at HUH (99.3%) than at AAUH (5.2%). Reoperations were more frequent at HUH (10.9%) than at AAUH (6.1%), and in both countries, mostly due to hematoma recurrence. Medical complications were more common at HUH (6.7%) than at AAUH (1.3%). The 1-year mortality rate at HUH was 7% and at AAUH 3.5%. At the end of follow-up (> 3 years), the Glasgow Outcome Scale Extended (GOSE) score was 8 in 82.9% of AAUH and 46.8% of HUH patients. CONCLUSION: The surgical treatment was similar at AAUH and HUH. The poorer outcome in Norway could largely be explained by age, comorbidity, medication, and complication rates.

Salvage radiosurgery following subtotal resection of vestibular schwannomas: does timing influence tumor control?

OBJECTIVE: The goal of microsurgical resection of vestibular schwannoma (VS) is gross-total resection (GTR) to provide oncological cure. However, a popular strategy is to halt the resection if the surgical team feels the risk of cranial nerve injury is imminent, achieving a maximally safe subtotal resection (STR) instead. The tumor remnant can then be treated with stereotactic radiosurgery (SRS) once the patient has recovered from the immediate postoperative period, or it can be followed with serial imaging and treated with SRS in a delayed fashion if residual tumor growth is seen. In this study, the authors evaluated the efficacy of this multimodality approach, particularly the influence of timing and dose of SRS on radiological tumor control, need for salvage treatment, and cranial nerve function. METHODS: VS patients treated with initial microsurgery and subsequent radiosurgery were retrospectively included from two tertiary treatment centers and dichotomized depending on whether SRS was given upfront (defined as before 12 months) or later. Radiological tumor control was defined as less than 20% tumor volume expansion and oncological tumor control as an absence of salvage treatment. Facial and cochlear nerve functions were assessed after surgery, at the time of SRS, and at last follow-up. Finally, a systematic literature review was conducted according to PRISMA guidelines. RESULTS: A total of 110 VS patients underwent SRS following microsurgical resection, with a mean preradiosurgical tumor volume of 2.2 cm3 (SD 2.5 cm3) and mean post-SRS follow-up time of 5.8 years (SD 4.1 years). The overall radiological tumor control and oncological tumor control were 77.3% and 90.9%, respectively. Thirty-five patients (31.8%) received upfront SRS, while 75 patients (68.2%) were observed for a minimum of 12 months prior to SRS. The timing of SRS did not influence the radiological tumor control (p = 0.869), the oncological tumor control (p = 0.560), or facial nerve (p = 0.413) or cochlear nerve (p = 0.954) function. An escalated marginal dose (> 12 Gy) was associated with greater tumor shrinkage (p = 0.020) and superior radiological tumor control (p = 0.020), but it did not influence the risk of salvage treatment (p = 0.904) or facial (p = 0.351) or cochlear (p = 0.601) nerve deterioration. CONCLUSIONS: Delayed SRS after close observation of residuals following STR is a safe alternative to upfront SRS regarding tumor control and cranial nerve preservation in selected patients.

Genetic alterations associated with malignant transformation of sporadic vestibular schwannoma.

INTRODUCTION: Malignant peripheral nerve sheath tumor of the vestibulocochlear nerve (VN-MPNST) is exceedingly rare and carries a poor prognosis. Little is known about its underlying genetics and in particular the process of malignant transformation. There is an ongoing debate on whether the transformation is initiated by ionizing radiation. We present here the analysis and comparison of two post-radiation VN-MPNST and one undergoing spontaneous transformation. METHODS: Four tumors from three patients (radiation-naïve vestibular schwannoma before (VS) and after (VN-MPNST) malignant transformation in addition to two post-radiation VN-MPNST) were subjected to DNA whole-genome microarray and whole-exome sequencing and tumor-specific mutations were called. Mutational signatures were characterized using MuSiCa. RESULTS: The tumor genomes were characterized predominantly by copy-number aberrations with 36-81% of the genome affected. Even the VS genome was grossly aberrated. The spontaneous malignant transformation was characterized by a near-total whole-genome doubling, disappearance of NF2 mutation and new mutations in three cancer-related genes (GNAQ, FOXO4 and PDGFRB). All tumors had homozygous loss of the tumor suppressor CDKN2A. Neither mutational signature nor copy number profile was associated with ionizing radiation. CONCLUSION: The VN-MPNST genome in our cases is characterized by large copy-number aberrations and homozygous deletion of CDKN2A. Our study demonstrates a VS with genetic alterations similar to its malignant counterpart, suggesting the existence of premalignant VS. No consistent mutational signature was associated with ionizing radiation.

The SH3PXD2A-HTRA1 fusion transcript is extremely rare in Norwegian sporadic vestibular schwannoma patients.

INTRODUCTION: Vestibular schwannoma (VS) is a benign intracranial tumor in which the underlying genetics is largely uncertain, apart from mutations in the tumor suppressor gene NF2. Alternative tumorigenic mechanisms have been proposed, including a recurrent in-frame fusion transcript of the HTRA1 and SH3PXD2A genes. The gene product of the SH3PXD2A-HTRA1 fusion has been shown to promote proliferation, invasion and resistance to cell death in vitro and tumor growth in vivo. The aim of this study was to replicate the findings and to investigate the frequency of this fusion gene in another cohort of vestibular schwannoma patients. METHODS: The SH3PXD2A-HTRA1 transcript was synthesized in vitro using PCR and used as a positive control to assess the sensitivity of a real-time PCR assay. This real-time PCR assay was used to search for the presence of the fusion transcript in 121 Norwegian sporadic VS patients. RESULTS: The real-time PCR assay showed a high sensitivity and was able to detect as low as ~ 5 copies of the fusion transcript. Out of the 121 investigated tumors, only 1 harbored the SH3PXD2A-HTRA1 fusion. CONCLUSION: Even though the SH3PXD2A-HTRA1 fusion has been shown to be a driver of tumorigenesis, our results suggest that it is a rare event in our VS patients. Further investigation is warranted in order to elucidate whether our results represent an extreme, and if the fusion is present also in other neoplasms.

EANO guideline on the diagnosis and management of meningiomas.

Meningiomas are the most common intracranial tumors. Yet, only few controlled clinical trials have been conducted to guide clinical decision making, resulting in variations of management approaches across countries and centers. However, recent advances in molecular genetics and clinical trial results help to refine the diagnostic and therapeutic approach to meningioma. Accordingly, the European Association of Neuro-Oncology (EANO) updated its recommendations for the diagnosis and treatment of meningiomas. A provisional diagnosis of meningioma is typically made by neuroimaging, mostly magnetic resonance imaging. Such provisional diagnoses may be made incidentally. Accordingly, a significant proportion of meningiomas, notably in patients that are asymptomatic or elderly or both, may be managed by a watch-and-scan strategy. A surgical intervention with tissue, commonly with the goal of gross total resection, is required for the definitive diagnosis according to the WHO classification. A role for molecular profiling including gene panel sequencing and genomic methylation profiling is emerging. A gross total surgical resection including the involved dura is often curative. Inoperable or recurrent tumors requiring treatment can be treated with radiosurgery, if the size or the vicinity of critical structures allows that, or with fractionated radiotherapy (RT). Treatment concepts combining surgery and radiosurgery or fractionated RT are increasingly used, although there remain controversies regard timing, type, and dosing of the various RT approaches. Radionuclide therapy targeting somatostatin receptors is an experimental approach, as are all approaches of systemic pharmacotherapy. The best albeit modest results with pharmacotherapy have been obtained with bevacizumab or multikinase inhibitors targeting vascular endothelial growth factor receptor, but no standard of care systemic treatment has been yet defined.

Comparing the impact of upfront radiosurgery versus expectation in vestibular schwannoma (the V-REX study): protocol for a randomised, observer-blinded, 4-year, parallel-group, single-centre, superiority study.

INTRODUCTION: The optimal management of small-sized to medium-sized vestibular schwannoma (VS) is a matter of controversy. Clinical results of the prevailing treatment modalities (microsurgery, stereotactic radiosurgery (SRS), and conservative management (CM)) are documented, but comparative studies are few, and none are randomised or blinded. Upfront radiosurgery, or a careful follow-up by MRI with subsequent treatment on growth, are two strategies used at many centres. The present study aims at comparing these strategies by randomising individuals with newly diagnosed tumours to either upfront SRS or initial CM. METHODS AND ANALYSIS: The Vestibular Schwannoma: Radiosurgery or Expectation study is designed as a randomised, controlled, observer-blinded, single-centre superiority trial with two parallel groups. Eligible patients will be randomised using sequentially numbered opaque sealed envelopes, and the radiosurgery group will undergo standard Gamma Knife Radiosurgery (GKRS) within 2 months following randomisation. The primary endpoint is tumour growth measured as volume ratio V4years/Vbaseline and volume doubling time, evaluated by annual T1 contrast MRI volumetric analysis. Secondary endpoints include symptom and sign development measured by clinical examination, audiovestibular tests, and by patient's responses to standardised validated questionnaires. In addition, the patient's working status, and the health economics involved with both strategies will be evaluated and compared. All outcome assessments will be performed by blinded observers. Power analysis indicates that 100 patients is sufficient to demonstrate the effect of GKRS on tumour volume. ETHICS AND DISSEMINATION: The trial has ethical approval from the Regional Ethical Committee (23503) and funding from The Western Norway Regional Health Authority. Trial methods and results will be reported according to the Consolidated Standards of Reporting Trials 2010 guidelines in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Clinical trials: NCT02249572. Haukeland University Hospital record: 2014/314. Regional Ethical Committee (REC West): 23 503. The Western Norway Regional Health Authority: 912 281.

Prospective Study of Surgery for Traumatic Brain Injury in Addis Ababa, Ethiopia: Surgical Procedures, Complications, and Postoperative Outcomes.

BACKGROUND: Traumatic brain injury (TBI) is an important cause of trauma-related mortality and morbidity in Ethiopia. There are significant resource limitations along the entire continuum of care, and little is known about the neurosurgical activity and patient outcomes. METHODS: All surgically treated TBI patients at the 4 teaching hospitals in Addis Ababa, Ethiopia were prospectively registered from October 2012 to December 2016. Data registration included surgical procedures, complications, reoperations, discharge outcomes, and mortality. RESULTS: A total of 1087 patients were included. The most common procedures were elevation of depressed skull fractures (49.5%) and craniotomies (47.9%). Epidural hematoma was the most frequent indication for a craniotomy (74.7%). Most (77.7%) patients were operated within 24 hours of admission. The median hospital stay for depressed skull fracture operations or craniotomies was 4 days. Decompressive craniectomy was only done in 10 patients. Postoperative complications were seen in 17% of patients, and only 3% were reoperated. Cerebrospinal fluid leak was the most common complication (7.9%). The overall mortality was 8.2%. Diagnosis, admission Glasgow Coma Scale (GCS) score, surgical procedure, and complications were significant predictors of discharge GCS score (P < 0.01). Age, admission GCS score, and length of hospital stay were significantly associated with mortality (P ≤ 0.005). CONCLUSIONS: The injury panorama, surgical activity, and outcome are significantly influenced by patient selection due to deficits within both prehospital and hospital care. Still, the neurosurgical services benefit a large number of patients in the greater Addis region and are qualitatively comparable with reports from high-income countries.

Prospective Study of Surgery for Traumatic Brain Injury in Addis Ababa, Ethiopia: Trauma Causes, Injury Types, and Clinical Presentation.

BACKGROUND: Traumatic brain injury (TBI) is a public health problem in Ethiopia. More knowledge about the epidemiology and neurosurgical management of TBI patients is needed to identify possible focus areas for quality improvement and preventive efforts. METHODS: This prospective cross-sectional study (2012-2016) was performed at the 4 teaching hospitals in Addis Ababa, Ethiopia. All surgically treated TBI patients were included, and data on clinical presentation, injury types, and trauma causes were collected. RESULTS: We included 1087 patients (mean age 29 years; 8.7% females; 17.1% <18 years old). Only 15.5% of TBIs were classified as severe (Glasgow Coma Scale score 3-8). Depressed skull fracture (44.9%) and epidural hematoma (39%) were the most frequent injuries. Very few patients had polytrauma (3.1%). Assault was the most common injury mechanism (69.9%) followed by road traffic accidents (15.8%) and falls (8.1%). More than 80% of patients came from within 200 km of the hospitals, but the median time to admission was 24 hours. Most assault victims (80.4%) were injured >50 km from the hospitals, whereas 46% of road traffic accident victims came from the urban area. Delayed admission was associated with higher Glasgow Coma Scale scores and nonsevere TBI (P < 0.01). CONCLUSIONS: The injury panorama, delayed admission, and small number of operations performed for severe TBI are linked to a substantial patient selection bias both before and after hospital admission. Our results also suggest that there should be a geographical framework for tailored guidelines, preventive efforts, and development of prehospital and hospital services.

Postural Sway Predicts Growth in Untreated Vestibular Schwannoma: A Retrospective Volumetric Study.

BACKGROUND: One in three vestibular schwannomas (VS) will grow within 3 years after diagnosis, but no reliable baseline parameter has been found to predict such growth. OBJECTIVE: To determine if postural sway is associated with growth of untreated VS. METHODS: Patients with newly diagnosed sporadic VS assigned to a wait-and-scan protocol were identified from a prospectively maintained database. Postural sway was measured by posturography at baseline and patients were classified as steady or unsteady. Observer-blinded volumetric tumor measurements were performed on the diagnostic MRI and a 3-year control MRI. Tumor growth quantified as relative growth (%) and volume-doubling time (VDT and VDT-1) were investigated as dependent variables against baseline parameters. RESULTS: Out of 204 VS patients, 53 (26%) were classified as unsteady on the platform at baseline. Median tumor volume was 0.32 cm3 (range 0.02-4.79), and 51% demonstrated significant growth within 3 years. Unsteady patients had significantly faster-growing tumors, with a mean relative growth of 172.5% compared to 79.5% in steady patients (p < 0.006). Seventy-seven percent of unsteady patients had >20% volume increase, compared to 42% in steady patients (p < 0.001). Mean VDT-1 was 0.65 doublings per year for unsteady patients, and 0.22 for steady patients (p < 0.001). Multivariate regression analysis including demographic and clinical parameters showed an OR of 5.6 (95% CI 2.6, 11.8) for growth in unsteady patients. CONCLUSIONS: This is the first demonstrated association between a measurable parameter and future growth in untreated VS. Our findings may help clinicians identify patients with a higher risk for tumor growth and provide closer monitoring or early treatment.

Gamma Knife Radiosurgery does not alter the copy number aberration profile in sporadic vestibular schwannoma.

INTRODUCTION: Ionizing radiation is a known etiologic factor in tumorigenesis and its role in inducing malignancy in the treatment of vestibular schwannoma has been debated. The purpose of this study was to identify a copy number aberration (CNA) profile or specific CNAs associated with radiation exposure which could either implicate an increased risk of malignancy or elucidate a mechanism of treatment resistance. METHODS: 55 sporadic VS, including 18 treated with Gamma Knife Radiosurgery (GKRS), were subjected to DNA whole-genome microarray and/or whole-exome sequencing. CNAs were called and statistical tests were performed to identify any association with radiation exposure. Hierarchical clustering was used to identify CNA profiles associated with radiation exposure. RESULTS: A median of 7 (0-58) CNAs were identified across the 55 VS. Chromosome 22 aberration was the only recurrent event. A median aberrant cell fraction of 0.59 (0.25-0.94) was observed, indicating several genetic clones in VS. No CNA or CNA profile was associated with GKRS. CONCLUSION: GKRS is not associated with an increase in CNAs or alteration of the CNA profile in VS, lending support to its low risk. This also implies that there is no major issue with GKRS treatment failure being due to CNAs. In agreement with previous studies, chromosome 22 aberration is the only recurrent CNA. VS consist of several genetic clones, addressing the need for further studies on the composition of cells in this tumor.

EANO guideline on the diagnosis and treatment of vestibular schwannoma.

The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular schwannoma task force of the European Association of Neuro-Oncology assessed the data available in the literature and composed a set of recommendations for health care professionals. The radiological diagnosis of vestibular schwannoma is made by magnetic resonance imaging. Histological verification of the diagnosis is not always required. Current treatment options include observation, surgical resection, fractionated radiotherapy, and radiosurgery. The choice of treatment depends on clinical presentation, tumor size, and expertise of the treating center. In small tumors, observation has to be weighed against radiosurgery, in large tumors surgical decompression is mandatory, potentially followed by fractionated radiotherapy or radiosurgery. Except for bevacizumab in neurofibromatosis type 2, there is no role for pharmacotherapy.

A prospective study of the natural history of incidental meningioma-Hold your horses!

BACKGROUND: The number of incidental meningiomas has increased because of the increased availability of neuroimaging. Lack of prospective data on the natural history makes the optimal management unclear. We conducted a 5-year prospective study of incidental meningiomas to identify risk factors for tumor growth. METHODS: Sixty-four of 70 consecutive patients with incidental meningioma were included. Clinical and radiological status was obtained at 0, 0.5, 1, 1.5, 2, 3, 4, and 5 years. GammaPlan and mixed linear regression modeling were utilized for volumetric analysis with primary endpoint tumor growth. RESULTS: None of the patients developed tumor-related symptoms during the study period, although 48 (75%) tumors increased (>15%), 13 (20.3%) remained unchanged, and 3 (4.7%) decreased (>15%) in volume. Mean time to growth was 2.2 years (range, 0.5-5.0 years).The growth pattern was quasi-exponential in 26%, linear in 17%, sigmoidal in 35%, parabolic in 17%, and continuous reduction in 5%. There was significant correlation among growth rate, larger baseline tumor volume (P < .001), and age in years (<55 y: 0.10 cm3/y, 55-75 y: 0.24 cm3/y, and >75 y: 0.85 cm3/y). CONCLUSION: The majority of meningiomas will eventually grow. However, more than 60% display a self-limiting growth pattern. Our study provides level-2 evidence that asymptomatic tumors can be safely managed utilizing serial imaging until persistent radiological and/or symptomatic growth.