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.publishedVersio

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.publishedVersio

Long-term effects of conservative management of vestibular schwannoma on dizziness, balance, and caloric function

Objectives: To study the development of dizziness, caloric function, and postural sway during long-term observation of untreated vestibular schwannoma patients. Study Design: Retrospective review of a prospectively maintained longitudinal cohort. Setting: Tertiary referral hospital. Subjects and Methods: Patients with vestibular schwannoma undergoing wait-and-scan management were included—specifically, those who did not require treatment during a minimum radiologic follow-up of 1 year. Baseline data and follow-up included magnetic resonance imaging, posturography, bithermal caloric tests, and a dizziness questionnaire. Main outcomes were prevalence of moderate to severe dizziness, canal paresis, and postural instability at baseline and follow-up, as compared with McNemar’s test. Results: Out of 433 consecutive patients with vestibular schwannoma, 114 did not require treatment during follow-up and were included. Median radiologic follow-up was 10.2 years (interquartile range, 4.5 years). Age ranged from 31 to 78 years (mean, 59 years; SD, 10 years; 62% women). Median tumor volume at baseline was 139 mm3 (interquartile range, 314 mm3). This did not change during follow-up (P = .446). Moderate to severe dizziness was present in 27% at baseline and 19% at follow-up (P = .077). Postural unsteadiness was present in 17% at baseline and 21% at follow-up (P = .424). Canal paresis was present in 51% at baseline and 56% at follow-up (P = .664). Conclusions: There was no significant change in the prevalence of dizziness, postural sway, or canal paresis during conservative management of vestibular schwannoma, while tumor volume remained unchanged. This indicates a favorable prognosis in these patients with regard to vestibular symptoms.acceptedVersio

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.publishedVersio

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

Under embargo until: 2022-06-02Background 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.acceptedVersio

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

Under embargo until: 2022-04-27Background 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% 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.acceptedVersio

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.publishedVersio

Environmental contaminants in freshwater food webs, 2021

Prosjektledere: Morten Jartun, Asle ØkelsrudThis report presents monitoring data from freshwater food webs and abiotic samples from Lake Mjøsa and Femunden within the Milfersk programme. Studies and monitoring of legacy and emerging contaminants have been carried out through this programme for several years, focusing on the pelagic food web. This is the first report in the monitoring program focusing on a benthic food chain (Chironomids, ruffe, roach and perch) in addition to inputs to Lake Mjøsa by analysis of lake sediments, surface waters, stormwater, effluent and sludge from a wastewater treatment plant (WWTP). The analytical programme includes the determination of a total of ̴ 260 single components.Environmental contaminants in freshwater food webs, 2021MiljødirektoratetpublishedVersio