Sequential rupture of two concomitant cerebral aneurysms.

The diagnosis of multiple cerebral aneurysms in patients with a spontaneous aneurysmal subarachnoid haemorrhage is not uncommon. The incidence of rupture from a second aneurysm, whilst the patient is recovering from a first bleed is however extremely rare. We report a 21-year-old female with a WFNS grade 1 subarachnoid haemorrhage secondary to a ruptured 5mm right posterior communicating artery aneurysm which was secured with clipping. Sixteen days later, whilst an in-patient, she suffered a second SAH from a left anterior choroidal artery aneurysm which was subsequently coiled. Comparison of digital subtraction angiography showed an almost doubling of the aneurysm from 2.7x2 mm to 4.4x2.3 mm. We review the literature of previously reported simultaneous and sequential aneurysmal subarachnoid haemorrhage and add to the sparse literature on this rare phenomena.

Instant tissue field and magnetic susceptibility mapping from MRI raw phase using Laplacian enhanced deep neural networks.

Quantitative susceptibility mapping (QSM) is an MRI post-processing technique that produces spatially resolved magnetic susceptibility maps from phase data. However, the traditional QSM reconstruction pipeline involves multiple non-trivial steps, including phase unwrapping, background field removal, and dipole inversion. These intermediate steps not only increase the reconstruction time but accumulates errors. This study aims to overcome existing limitations by developing a Laplacian-of-Trigonometric-functions (LoT) enhanced deep neural network for near-instant quantitative field and susceptibility mapping (i.e., iQFM and iQSM) from raw MRI phase data. The proposed iQFM and iQSM methods were compared with established reconstruction pipelines on simulated and in vivo datasets. In addition, experiments on patients with intracranial hemorrhage and multiple sclerosis were also performed to test the generalization of the proposed neural networks. The proposed iQFM and iQSM methods in healthy subjects yielded comparable results to those involving the intermediate steps while dramatically improving reconstruction accuracies on intracranial hemorrhages with large susceptibilities. High susceptibility contrast between multiple sclerosis lesions and healthy tissue was also achieved using the proposed methods. Comparative studies indicated that the most significant contributor to iQFM and iQSM over conventional multi-step methods was the elimination of traditional Laplacian unwrapping. The reconstruction time on the order of minutes for traditional approaches was shortened to around 0.1 s using the trained iQFM and iQSM neural networks.

Diagnostic Sensitivity of Plasma Endothelin-1 for Cerebral Vasospasm After Subarachnoid Hemorrhage, a Multicentre Double-Blind Study.

The purpose of this study is to establish the diagnostic sensitivity of Endothelin-1 for risk stratification and screening of clinical vasospasm after subarachnoid hemorrhage.This is a multicentre, observational study, correlating daily blood Endothelin-1 with clinical variables. Binary logistic regression used to examine if Endothelin-1 levels could be used to predict clinical vasospasm. Bivariate modelling used to explore associations between patient characteristics and vasospasm. A Receiver Operating Curve used to explore cut-off values for Endothelin-1. Sensitivity and specificity was used to validate the cut-point found in the pilot study. A total of 96 patients were enrolled over two years. Median Endothelin-1 was higher for patients who experienced clinical vasospasm except for day-5, where median endothelin for patients without vasospasm was higher (3.6 IQR = 5.3), compared to patients with vasospasm (3.3 IQR = 8.5) although differences were not significant. The Receiver Operating Curve analysis confirmed that day-5 Endothelin-1 was not a good indicator of vasospasm, with an area under the curve of 0.506 (95% CI: 0.350-0.663, p = 0.938). The levels of Endothelin-1 in blood do not discriminate patients who may develop symptomatic vasospasm. The high variability in Endothelin-1 levels, aligns with the pathophysiological variability of most biomarkers, decreasing their ability to predict a clinical event.

Quantifying irregular pulsation of intracranial aneurysms using 4D-CTA.

Recent studies have suggested that irregular pulsation of intracranial aneurysm during the cardiac cycle may be potentially associated with aneurysm rupture risk. However, there is a lack of quantification method for irregular pulsations. This study aims to quantify irregular pulsations by the displacement and strain distribution of the intracranial aneurysm surface during the cardiac cycle using four-dimensional CT angiographic image data. Four-dimensional CT angiography was performed in 8 patients. The image data of a cardiac cycle was divided into approximately 20 phases, and irregular pulsations were detected in four intracranial aneurysms by visual observation, and then the displacement and strain of the intracranial aneurysm was quantified using coherent point drift and finite element method. The displacement and strain were compared between aneurysms with irregular and normal pulsations in two different ways (total and stepwise). The stepwise first principal strain was significantly higher in aneurysms with irregular than normal pulsations (0.20±0.01 vs 0.16±0.02, p=0.033). It was found that the irregular pulsations in intracranial aneurysms usually occur during the consecutive ascending or descending phase of volume changes during the cardiac cycle. In addition, no statistically significant difference was found in the aneurysm volume changes over the cardiac cycle between the two groups. Our method can successfully quantify the displacement and strain changes in the intracranial aneurysm during the cardiac cycle, which may be proven to be a useful tool to quantify intracranial aneurysm deformability and aid in aneurysm rupture risk assessment.

Time-of-Flight MRA of Intracranial Aneurysms with Interval Surveillance, Clinical Segmentation and Annotations.

Intracranial aneurysms (IAs) are present in 2-6% of the global population and can be catastrophic upon rupture with a mortality rate of 30-50%. IAs are commonly detected through time-of-flight magnetic resonance angiography (TOF-MRA), however, this data is rarely available for research and training purposes. The provision of imaging resources such as TOF-MRA images is imperative to develop new strategies for IA detection, rupture prediction, and surgical training. To support efforts in addressing data availability bottlenecks, we provide an open-access TOF-MRA dataset comprising 63 patients, of which 24 underwent interval surveillance imaging by TOF-MRA. Patient scans were evaluated by a neuroradiologist, providing aneurysm and vessel segmentations, clinical annotations, 3D models, in addition to 3D Slicer software environments containing all this data for each patient. This dataset is the first to provide interval surveillance imaging for supporting the understanding of IA growth and stability. This dataset will support computational and experimental research into IA dynamics and assist surgical and radiology training in IA treatment.

Intracranial ependymoma in an adult patient with multiple primary malignancies.

The incidence of multiple primary malignancies (MPM) is increasing, and therefore, it has become highly important for clinicians to consider the concept of MPM when treating oncology patients. In this case report, we follow the clinical course of a patient diagnosed with a new intracranial lesion, an ependymoma, on a background of MPM. We explore the barriers implicating the delay in her diagnosis, dissect the challenges in managing her disease and emphasise the importance of social determinants in optimising her care.

Anti-inflammatory interleukin 1 receptor antagonist concentration in plasma correlates with blood-brain barrier integrity in the primary lesion area in traumatic brain injury patients.

Purpose: Blood-brain barrier (BBB) dysregulation and pro-inflammatory signalling molecules are secondary factors that have been associated with injury severity and long-term clinical outcome following traumatic brain injury (TBI). However, the association between BBB permeability and inflammation is unknown in human TBI patients. In this study, we investigated whether BBI integrity as measured by Dynamic Contrast-Enhanced (DCE) Magnetic Resonance Imaging (MRI) correlates with plasma levels of immunological markers following TBI. Methods: Thirty-two TBI patients recruited from a neurosurgical unit were included in the study. Structural three-dimensional T1-weighted and DCE-MRI images were acquired on a 3T MRI at the earliest opportunity once the participant was sufficiently stable after patient admission to hospital. Blood sampling was performed on the same day as the MRI. The location and extents of the haemorrhagic and contusional lesions were identified. Immunological biomarkers were quantified from the participants' plasma using a multiplex immunoassay. Demographic and clinical information, including age and Glasgow Coma Scale (GCS) were also collected and the immunological biomarker profiles were compared across controls and the TBI severity sub-groups. Contrast agent leakiness through blood-brain barriers (BBB) in the contusional lesions were assessed by fitting DCE-MRI using Patlak model and BBB leakiness characteristics of the participants were correlated with the immunological biomarker profiles. Results: TBI patients showed reduced plasma levels of interleukin (IL)-1ß, IFN-γ, IL-13, and chemokine (C-C motif) ligands (CCL)2 compared to controls and significantly higher levels of platelet-derived growth factor (PDGF-BB), IL-6, and IL-8. BBB leakiness of the contusional lesions did not significantly differ across different TBI severity sub-groups. IL-1ra levels significantly and positively correlated with the contusional lesion's BBB integrity as measured with DCE-MRI via an exponential curve relationship. Discussion: This is the first study to combine DCE-MRI with plasma markers of inflammation in acute TBI patients. Our finding that plasma levels of the anti-inflammatory cytokine IL-1ra correlated negatively with increased leakiness of the BBB.

Properties and Implementation of 3-Dimensionally Printed Models in Spine Surgery: A Mixed-Methods Review With Meta-Analysis.

OBJECTIVE: Spine surgery addresses a wide range of spinal pathologies. Potential applications of 3-dimensional (3D) printed in spine surgery are broad, encompassing education, planning, and simulation. The objective of this study was to explore how 3D-printed spine models are implemented in spine surgery and their clinical applications. METHODS: Methods were combined to create a scoping review with meta-analyses. PubMed, EMBASE, the Cochrane Library, and Scopus databases were searched from 2011 to 7 September 2021. Results were screened independently by 2 reviewers. Studies utilizing 3D-printed spine models in spine surgery were included. Articles describing drill guides, implants, or nonoriginal research were excluded. Data were extracted according to reporting guidelines in relation to study information, use of model, 3D printer and printing material, design features of the model, and clinical use/patient-related outcomes. Meta-analyses were performed using random-effects models. RESULTS: Forty articles were included in the review, 3 of which were included in the meta-analysis. Primary use of the spine models included preoperative planning, education, and simulation. Six printing technologies were utilized. A range of substrates were used to recreate the spine and regional pathology. Models used for preoperative and intraoperative planning showed reductions in key surgical performance indicators. Generally, feedback for the tactility, utility, and education use of models was favorable. CONCLUSIONS: Replicating realistic spine models for operative planning, education, and training is invaluable in a subspeciality where mistakes can have devastating repercussions. Future study should evaluate the cost-effectiveness and the impact spine models have of spine surgery outcomes.

Reproducibility of the computational fluid dynamic analysis of a cerebral aneurysm monitored over a decade.

Computational fluid dynamics (CFD) simulations are increasingly utilised to evaluate intracranial aneurysm (IA) haemodynamics to aid in the prediction of morphological changes and rupture risk. However, these models vary and differences in published results warrant the investigation of IA-CFD reproducibility. This study aims to explore sources of intra-team variability and determine its impact on the aneurysm morphology and CFD parameters. A team of four operators were given six sets of magnetic resonance angiography data spanning a decade from one patient with a middle cerebral aneurysm. All operators were given the same protocol and software for model reconstruction and numerical analysis. The morphology and haemodynamics of the operator models were then compared. The segmentation, smoothing factor, inlet and outflow branch lengths were found to cause intra-team variability. There was 80% reproducibility in the time-averaged wall shear stress distribution among operators with the major difference attributed to the level of smoothing. Based on these findings, it was concluded that the clinical applicability of CFD simulations may be feasible if a standardised segmentation protocol is developed. Moreover, when analysing the aneurysm shape change over a decade, it was noted that the co-existence of positive and negative values of the wall shear stress divergence (WSSD) contributed to the growth of a daughter sac.

Three-dimensional (3D) printing for post-traumatic orbital reconstruction, a systematic review and meta-analysis.

The purpose of this study was to determine if three-dimensional (3D) printed orbit models and preoperative plate contouring provides benefit over traditional surgical reconstruction of orbit fractures. This systematic review and meta-analysis searched five databases to identify cases of 3D printing for orbital fracture reconstruction. Primary outcomes were resolution of diplopia and enophthalmos, orbital volume symmetry and operation duration. Meta-analyses were used to calculate log odds ratios (OR) for diplopia and enophthalmos and absolute mean difference for orbital volume. A total of 58 articles describing 906 patient cases were included. A single article for each of diplopia and enophthalmos compared 3D printing with traditional management, which prevented answering the primary research question. However, pre-post meta-analysis showed that postoperative groups were less likely to have diplopia (n = 747, log OR = -2.35, 95%CI -1.72 to -2.98, p < 0.001, I2 = 10.91%) and enophthalmos (n = 486, log OR = -2.47, 95%CI -1.95 to -2.99, p < 0.001, I2 = 11.33%) than preoperatively. Mean orbital volume did not differ between the repaired and uninjured orbits (n = 290, mean difference = -0.13 cm3, 95%CI -0.48 to 0.22, p = 0.472, I2 = 9.48%). Pooled mean operation duration for orbital reconstruction with 3D printing was 67.70 minutes (standard error [SE] = 4.24 minutes). Orbital reconstruction combined with 3D printing adequately restores orbital volume symmetry and improves diplopia and enophthalmos. Due to a lack of controlled studies, it remains unclear what contribution 3D printing alone makes to these results. Three-dimensional printing is likely a safe, accurate and effective adjunct; however, further controlled studies are required.

Intracranial perianeurysmal cysts: case series and review of the literature.

BACKGROUND: Intracranial perianeurysmal cysts are a rare finding associated with cerebral aneurysms. Patients may present with symptoms secondary to mass effect from perianeurysmal cysts requiring drainage. These lesions can masquerade as neoplasms if dedicated vascular imaging is not performed, leading to misdiagnosis. METHOD: A retrospective search of our database was done for intracranial aneurysms that have been treated between 1998 and 2020. A literature search was then performed on PubMed and Google Scholar with the search terms 'aneurysm', 'intracranial/intracerebral', 'cyst', and 'perianeurysmal cyst'. Patient demographics, aneurysms and cysts characteristics were then summarized as a table and in the discussion. RESULTS: Three cases where intracranial aneurysm had associated perianeurysmal cysts were found in our database. Combined with the available literature a total of 19 cases of perianeurysmal cysts have thus far been reported since this entity was first described in 2002. A significant number of perianeurysmal cysts (5/19) required intervention. In 5/19 cases the patient presented with a perianeurysmal cyst without a history of subarachnoid hemorrhage. Of the 10 cases where aneurysm follow-up was reported there were 5 cases where there was aneurysm recurrence necessitating re-treatment. CONCLUSION: Significant variability exists in the patient demographics, aneurysm and cyst characteristics of perianeurysmal cysts. This suggests that there is no single unified etiology and pathogenesis. These lesions are a rare finding and at present do not appear to carry diagnostic or prognostic significance. Management of perianeurysmal cysts is case-dependent and intervention should be considered when treating the related aneurysm, especially in patients with secondary symptoms.

Circadian Rhythmicity of Vital Signs at Intensive Care Unit Discharge and Outcome of Traumatic Brain Injury.

BACKGROUND: Physiological functions with circadian rhythmicity are often disrupted during illness. OBJECTIVE: To assess the utility of circadian rhythmicity of vital signs in predicting outcome of traumatic brain injury (TBI). METHODS: A retrospective single-center cohort study of adult intensive care unit (ICU) patients with largely isolated TBI to explore the relationship between the circadian rhythmicity of vital signs during the last 24 hours before ICU discharge and clinical markers of TBI severity and score on the Glasgow Outcome Scale 6 months after injury (GOS-6). RESULTS: The 130 study participants had a median age of 39.0 years (IQR, 23.0-59.0 years), a median Glasgow Coma Scale score at the scene of 8.0 (IQR, 3.0-13.0), and a median Rotterdam score on computed tomography of the head of 3 (IQR, 3-3), with 105 patients (80.8%) surviving to hospital discharge. Rhythmicity was present for heart rate (30.8% of patients), systolic blood pressure (26.2%), diastolic blood pressure (20.0%), and body temperature (26.9%). Independent predictors of a dichotomized GOS-6 ≥4 were the Rotterdam score (odds ratio [OR], 0.38 [95% CI, 0.18-0.81]; P = .01), Glasgow Coma Scale score at the scene (OR, 1.22 [95% CI, 1.05-1.41]; P = .008), age (OR, 0.95 [95% CI, 0.92-0.98]; P = .003), oxygen saturation <90% in the first 24 hours (OR, 0.19 [95% CI, 0.05-0.73]; P = .02), serum sodium level <130 mmol/L (OR, 0.20 [95% CI, 0.05-0.70]; P = .01), and active intracranial pressure management (OR, 0.16 [95% CI, 0.04-0.62]; P = .008), but not rhythmicity of any vital sign. CONCLUSION: Circadian rhythmicity of vital signs at ICU discharge is not predictive of GOS-6 in patients with TBI.

Original sound compositions reduce anxiety in emergency department patients: a randomised controlled trial.

OBJECTIVE: To determine whether emergency department (ED) patients' self-rated levels of anxiety are affected by exposure to purpose-designed music or sound compositions with and without the audio frequencies of embedded binaural beat. DESIGN, SETTING AND PARTICIPANTS: Randomised controlled trial in an ED between 1 February 2010 and 14 April 2010 among a convenience sample of adult patients who were rated as category 3 on the Australasian Triage Scale. INTERVENTIONS: All interventions involved listening to soundtracks of 20 minutes' duration that were purpose-designed by composers and sound-recording artists. Participants were allocated at random to one of five groups: headphones and iPod only, no soundtrack (control group); reconstructed ambient noise simulating an ED but free of clear verbalisations; electroacoustic musical composition; composed non-musical soundtracks derived from audio field recordings obtained from natural and constructed settings; sound composition of audio field recordings with embedded binaural beat. All soundtracks were presented on an iPod through headphones. Patients and researchers were blinded to allocation until interventions were administered. State-trait anxiety was self-assessed before the intervention and state anxiety was self-assessed again 20 minutes after the provision of the soundtrack. MAIN OUTCOME MEASURE: Spielberger State-Trait Anxiety Inventory. RESULTS: Of 291 patients assessed for eligibility, 170 patients completed the pre-intervention anxiety self-assessment and 169 completed the post-intervention assessment. Significant decreases (all P < 0.001) in anxiety level were observed among patients exposed to the electroacoustic musical composition (pre-intervention mean, 39; post-intervention mean, 34), audio field recordings (42; 35) or audio field recordings with embedded bianaural beats (43; 37) when compared with those allocated to receive simulated ED ambient noise (40; 41) or headphones only (44; 44). CONCLUSION: In moderately anxious ED patients, state anxiety was reduced by 10%-15% following exposure to purpose-designed sound interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN 12608000444381.

Treatment of a middle cerebral artery aneurysm in the setting of Loeys-Dietz syndrome: Case report and review of literature.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder with associated systemic vasculopathies including intracranial arterial aneurysm formation and dissections. LDS is a relatively less well-known entity compared with other connective tissue disorders, such as Ehlers-Danlos or Marfan syndrome, and consequently experience in the management of the associated intracranial aneurysms is suboptimal. We present a case of surgical clipping of a middle cerebral artery aneurysm in a patient with LDS. A 46-year-old female with LDS (type III) was found to have a right middle cerebral artery (MCA) bifurcation aneurysm following vascular screening. The decision was made to surgically clip the aneurysm after consultation in our neurovascular multidisciplinary team meeting. A standard right pterional craniotomy was performed and the aneurysm was secured with 2 straight Sugita clips. The temporal M2 branch was noted to be thin walled and this prompted application of the second tandem clip, rather than risk re-positioning the initial clip. In our case, the MCA aneurysm neck was robust enough to take a clip without any complications, and therefore we suggest that the presence of LDS is not an absolute contra-indication to perform open craniotomy and clipping.

Detection of clustered anomalies in single-voxel morphometry as a rapid automated method for identifying intracranial aneurysms.

Unruptured intracranial aneurysms (UIAs) are prevalent neurovascular anomalies which, in rare circumstances, rupture to cause a catastrophic subarachnoid haemorrhage. Although surgical management can reduce rupture risk, the majority of UIAs exist undiscovered until rupture. Current clinical practice in the detection of UIAs relies heavily on manual radiological review of standard imaging modalities. Recent computer-aided UIA diagnoses can sensitively detect and measure UIAs within cranial angiograms but remain limited to low specificities whose output also requires considerable radiologist interpretation not amenable to broad screening efforts. To address these limitations, we have developed a novel automatic pipeline algorithm which inputs medical images and outputs detected UIAs by characterising single-voxel morphometry of segmented neurovasculature. Once neurovascular anatomy of a specified resolution is segmented, correlations between voxel-specific morphometries are estimated and spatially-clustered outliers are identified as UIA candidates. Our automated solution detects UIAs within magnetic resonance angiograms (MRA) at unmatched 86% specificity and 81% sensitivity using 3 min on a conventional laptop. Our approach does not rely on interpatient comparisons or training datasets which could be difficult to amass and process for rare incidentally discovered UIAs within large MRA files, and in doing so, is versatile to user-defined segmentation quality, to detection sensitivity, and across a range of imaging resolutions and modalities. We propose this method as a unique tool to aid UIA screening, characterisation of abnormal vasculature in at-risk patients, morphometry-based rupture risk prediction, and identification of other vascular abnormalities.

Blood-brain barrier dysfunction significantly correlates with serum matrix metalloproteinase-7 (MMP-7) following traumatic brain injury.

OBJECTIVES: To determine if radiological evidence of blood brain barrier (BBB) dysfunction, measured using Dynamic Contrast Enhanced MRI (DCE-MRI), correlates with serum matrix metalloproteinase (MMP) levels in traumatic brain injury (TBI) patients, and thereby, identify a potential biomarker for BBB dysfunction. PATIENTS AND METHODS: 20 patients with a mild, moderate, or severe TBI underwent a DCE-MRI scan and BBB dysfunction was interpreted from KTrans. KTrans is a measure of capillary permeability that reflects the efflux of gadolinium contrast into the extra-cellar space. The serum samples were concurrently collected and later analysed for MMP-1, -2, -7, -9, and -10 levels using an ELISA assay. Statistical correlations between MMP levels and the KTrans value were calculated. Multiple testing was corrected using the Benjamin-Hochberg method to control the false-discovery rate (FDR). RESULTS: Serum MMP-1 values ranged from 1.5 to 49.6 ng/ml (12 ± 12.7), MMP-2 values from 58.3 to 174.1 ng/ml (109.5 ± 26.7), MMP-7 from 1.5 to 31.5 ng/mL (10 ± 7.4), MMP-9 from 128.6 to 1917.5 ng/ml (647.7 ± 749.6) and MMP-10 from 0.1 to 0.6 ng/mL (0.3 ± 0.2). Non-parametric Spearman correlation analysis on the data showed significant positive relationship between KTrans and MMP-7 (r = 0.55, p < 0.01). Correlations were also found between KTrans and MMP-1 (r = 0.74, p < 0.0002) and MMP-2 (r = 0.5, p < 0.025) but the actual MMP values were not above reference ranges, limiting the interpretation of results. Statistically significant correlations between KTrans and either MMP-9 or -10 were not found. CONCLUSION: This is the first study to show a correlation between DCE measures and MMP values in patients with a TBI. Our results support the suggestion that serum MMP-7 may be considered as a peripheral biomarker quantifying BBB dysfunction in TBI patients.

Acute Mountain Sickness Following Incremental Trekking to High Altitude: Correlation With Plasma Vascular Endothelial Growth Factor Levels and the Possible Effects of Dexamethasone and Acclimatization Following Re-exposure.

Purpose: The recognition and treatment of high-altitude illness (HAI) is increasingly important in global emergency medicine. High altitude related hypobaric hypoxia can lead to acute mountain sickness (AMS), which may relate to increased expression of vascular endothelial growth factor (VEGF), and subsequent blood-brain barrier (BBB) compromise. This study aimed to establish the relationship between AMS and changes in plasma VEGF levels during a high-altitude ascent. VEGF level changes with dexamethasone, a commonly used AMS medication, may provide additional insight into AMS. Methods: Twelve healthy volunteers ascended Mt Fuji (3,700 m) and blood samples were obtained at distinct altitudes for VEGF analysis. Oxygen saturation (SPO2) measurements were also documented at the same time-point. Six out of the 12 study participants were prescribed dexamethasone for a second ascent performed 48 h later, and blood was again collected to establish VEGF levels. Results: Four key VEGF observations could be made based on the data collected: (i) the baseline VEGF levels between the two ascents trended upwards; (ii) those deemed to have AMS in the first ascent had increased VEGF levels (23.8-30.3 pg/ml), which decreased otherwise (23.8-30.3 pg/ml); (iii) first ascent AMS participants had higher VEGF level variability for the second ascent, and similar to those not treated with dexamethasone; and (iv) for the second ascent dexamethasone participants had similar VEGF levels to non-AMS first ascent participants, and the variability was lower than for first ascent AMS and non-dexamethasone participants. SPO2 changes were unremarkable, other than reducing by around 5% irrespective of whether measurement was taken for the first or second ascent. Conclusion: First ascent findings suggest a hallmark of AMS could be elevated VEGF levels. The lack of an exercise-induced VEGF level change strengthened the notion that elevated plasma VEGF was brain-derived, and related to AMS.

Publisher Correction: A reference collection of patient-derived cell line and xenograft models of proneural, classical and mesenchymal glioblastoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An unusual presentation of a solitary benign giant neurofibroma. Case report.

The authors report on a 34-year-old man who presented with acute enlargement of an extraspinal mass secondary to a hemorrhage following minor trauma. The mass had been present from birth, had slowly enlarged over time, and previous imaging had suggested an extraspinal fibrolipoma measuring 10 x 6 x 4 cm. Following minor trauma (scratching the skin overlying the tumor), the mass rapidly enlarged to approximately double in size over a period of 4 hours. A CT scan and MR imaging confirmed an extraspinal tumor that was 15 x 11 x 11 cm, with an associated acute hematoma of similar dimensions. The patient was taken to the operating room for hematoma evacuation and tumor resection. Histopathological investigation identified a benign, diffuse neurofibroma with associated dysplastic blood vessels exhibiting irregular areas of tunica media and sinusoidal-like vascular channels. To the authors' knowledge, a solitary giant neurofibroma in a patient without neurofibromatosis presenting with acute enlargement secondary to hemorrhage following minor trauma has not been previously described. The authors suggest that the source of the acute hemorrhage may be related to the neurofibroma-associated vascular dysplasia and the resultant increased vascular fragility.