Combined use of 3D printing and mixed reality technology for neurosurgical training: getting ready for brain surgery.

OBJECTIVE: Learning surgical skills is an essential part of neurosurgical training. Ideally, these skills are acquired to a sufficient extent in an ex vivo setting. The authors previously described an in vitro brain tumor model, consisting of a cadaveric animal brain injected with fluorescent agar-agar, for acquiring a wide range of basic neuro-oncological skills. This model focused on haptic skills such as safe tissue ablation technique and the training of fluorescence-based resection. As important didactical technologies such as mixed reality and 3D printing become more readily available, the authors developed a readily available training model that integrates the haptic aspects into a mixed reality setup. METHODS: The anatomical structures of a brain tumor patient were segmented from medical imaging data to create a digital twin of the case. Bony structures were 3D printed and combined with the in vitro brain tumor model. The segmented structures were visualized in mixed reality headsets, and the congruence of the printed and the virtual objects allowed them to be spatially superimposed. In this way, users of the system were able to train on the entire treatment process from surgery planning to instrument preparation and execution of the surgery. RESULTS: Mixed reality visualization in the joint model facilitated model (patient) positioning as well as craniotomy and the extent of resection planning respecting case-dependent specifications. The advanced physical model allowed brain tumor surgery training including skin incision; craniotomy; dural opening; fluorescence-guided tumor resection; and dura, bone, and skin closure. CONCLUSIONS: Combining mixed reality visualization with the corresponding 3D printed physical hands-on model allowed advanced training of sequential brain tumor resection skills. Three-dimensional printing technology facilitates the production of a precise, reproducible, and worldwide accessible brain tumor surgery model. The described model for brain tumor resection advanced regarding important aspects of skills training for neurosurgical residents (e.g., locating the lesion, head position planning, skull trepanation, dura opening, tissue ablation techniques, fluorescence-guided resection, and closure). Mixed reality enriches the model with important structures that are difficult to model (e.g., vessels and fiber tracts) and advanced interaction concepts (e.g., craniotomy simulations). Finally, this concept demonstrates a bridging technology toward intraoperative application of mixed reality.

Evaluation of FRESH scores in predicting outcome and quality of life after aneurysmal subarachnoid haemorrhage in a European patient cohort.

BACKGROUND: Despite aneurysmal subarachnoid haemorrhage (aSAH) patients often experiencing physical and mental disabilities impacting their quality of life (QoL), routine assessment of long-term QoL data and predictive tools are limited. This study evaluates the newly developed "functional recovery expected after subarachnoid haemorrhage" (FRESH) scores with long-term outcomes and QoL in European aSAH patients. METHODS: FRESH, FRESH-cog, and FRESH-quol scores were retrospectively obtained from aSAH patients. Patients were contacted, and the modified Rankin Scale (mRS), extended short form-36 (SF-36), and telephone interview for cognitive status (TICS) were collected and performed. The prognostic and empirical outcomes were compared. RESULTS: Out of 374 patients, 171 patients (54.1%) completed the SF-36, and 154 patients completed the TICS. The SF-36 analysis showed that 32.7% had below-average physical component summary (PCS) scores, and 39.8% had below-average mental component summary (MCS) scores. There was no significant correlation between the FRESH score and PCS (p = 0.09736), MCS (p = 0.1796), TICS (p = 0.7484), or mRS 10-82 months (average 46 months) post bleeding (p = 0.024), respectively. There was also no significant correlation found for "FRESH-cog vs. TICS" (p = 0.0311), "FRESH-quol vs. PCS" (p = 0.0204), "FRESH-quol vs. MCS" (p = 0.1361) and "FRESH-quol vs. TICS" (p = 0.1608). CONCLUSIONS: This study found no correlation between FRESH scores and validated QoL tools in a European population of aSAH patients. The study highlights the complexity of reliable long-term QoL prognostication in aSAH patients and emphasises the need for further prospective research to also focus on QoL as an important outcome parameter.

Clinical Outcome Prediction of Early Brain Injury in Aneurysmal Subarachnoid Hemorrhage: the SHELTER-Score.

BACKGROUND: Despite intensive research on preventing and treating vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH), mortality and morbidity rates remain high. Early brain injury (EBI) has emerged as possibly the major significant factor in aSAH pathophysiology, emphasizing the need to investigate EBI-associated clinical events for improved patient management and decision-making. This study aimed to identify early clinical and radiological events within 72 h after aSAH to develop a conclusive predictive EBI score for clinical practice. METHODS: This retrospective analysis included 561 consecutive patients with aSAH admitted to our neurovascular center between 01/2014 and 09/2022. Fourteen potential predictors occurring within the initial 72 h after hemorrhage were analyzed. The modified Rankin Scale (mRS) score at 6 months, discretized to three levels (0-2, favorable; 3-5, poor; 6, dead), was used as the outcome variable. Univariate ordinal regression ranked predictors by significance, and forward selection with McFadden's pseudo-R2 determined the optimal set of predictors for multivariate proportional odds logistic regression. Collinear parameters were excluded, and fivefold cross-validation was used to avoid overfitting. RESULTS: The analysis resulted in the Subarachnoid Hemorrhage Associated Early Brain Injury Outcome Prediction score (SHELTER-score), comprising seven clinical and radiological events: age (0-4 points), World Federation of Neurosurgical Societies (0-2.5 points), cardiopulmonary resuscitation (CPR) (2 points), mydriasis (1-2 points), midline shift (0.5-1 points), early deterioration (1 point), and early ischemic lesion (2 points). McFadden's pseudo-R2 = 0.339, area under the curve for death or disability 0.899 and 0.877 for death. A SHELTER-score below 5 indicated a favorable outcome (mRS 0-2), 5-6.5 predicted a poor outcome (mRS 3-5), and ≥ 7 correlated with death (mRS 6) at 6 months. CONCLUSIONS: The novel SHELTER-score, incorporating seven clinical and radiological features of EBI, demonstrated strong predictive performance in determining clinical outcomes. This scoring system serves as a valuable tool for neurointensivists to identify patients with poor outcomes and guide treatment decisions, reflecting the great impact of EBI on the overall outcome of patients with aSAH.

Management of non-vestibular schwannomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section Part III: Lower cranial nerve schwannomas, jugular foramen (CN IX, X, XI) and hypoglossal schwannoma (XII).

BACKGROUND: Non-vestibular schwannomas are relatively rare, with trigeminal and jugular foramen schwannomas being the most common. This is a heterogenous group which requires detailed investigation and careful consideration to management strategy. The optimal management for these tumours remains unclear, and there are several controversies. The aim of this paper is to provide insight into the main principles defining management and surgical strategy, in order to formulate a series of recommendations. METHODS: A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumours on a European perspective. To achieve this, the task force performed an extensive systematic review in this field and had discussions within the group. This article is the third of a three-part series describing non-vestibular schwannomas (IX, X, XI, XII). RESULTS: A summary of literature evidence was proposed after discussion within the EANS skull base section. The constituted task force dealt with the practice patterns that exist with respect to preoperative radiological investigations, ophthalmological assessments, optimal surgical and radiotherapy strategies and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the treatment of non-vestibular schwannomas. For each of these tumours, the management paradigm is shifting towards the compromise between function preservation and progression free survival.

Management of non-vestibular schwannomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section. Part I: oculomotor and other rare non-vestibular schwannomas (I, II, III, IV, VI).

BACKGROUND: Non-vestibular schwannomas are relatively rare, with trigeminal and jugular foramen schwannomas being the most common. This is a heterogeneous group which requires detailed investigation and careful consideration to management strategy. The optimal management for these tumours remains unclear, and there are several controversies. The aim of this paper is to provide insight into the main principles defining management and surgical strategy, in order to formulate a series of recommendations. METHODS: A task force was created by the EANS skull base section along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumours on a European perspective. To achieve this, the task force performed an extensive systematic review in this field and had discussions within the group. This article is the first of a three-part series describing non-vestibular schwannomas (I, II, III, IV, VI). RESULTS: A summary of literature evidence was proposed after discussion within the EANS skull base section. The constituted task force dealt with the practice patterns that exist with respect to pre-operative radiological investigations, ophthalmological assessments, optimal surgical and radiotherapy strategies and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the treatment of non-vestibular schwannomas. For each of these tumours, the management of these patients is complex, and for those which are symptomatic tumours, the paradigm is shifting towards the compromise between function preservation and progression-free survival.

Management of non-vestibular schwannomas in adult patients: a systematic review and consensus statement on behalf of the EANS skull base section Part II: Trigeminal and facial nerve schwannomas (CN V, VII).

BACKGROUND: Non-vestibular schwannomas are relatively rare, with trigeminal and jugular foramen schwannomas being the most common. This is a heterogenous group which requires detailed investigation and careful consideration to management strategy. The optimal management for these tumours remains unclear and there are several controversies. The aim of this paper is to provide insight into the main principles defining management and surgical strategy, in order to formulate a series of recommendations. METHODS: A task force was created by the EANS skull base section committee along with its members and other renowned experts in the field to generate recommendations for the surgical management of these tumours on a European perspective. To achieve this, the task force performed an extensive systematic review in this field and had discussions within the group. This article is the second of a three-part series describing non-vestibular schwannomas (V, VII). RESULTS: A summary of literature evidence was proposed after discussion within the EANS skull base section. The constituted task force dealt with the practice patterns that exist with respect to pre-operative radiological investigations, ophthalmological assessments, optimal surgical and radiotherapy strategies, and follow-up management. CONCLUSION: This article represents the consensually derived opinion of the task force with respect to the treatment of trigeminal and facial schwannoma. The aim of treatment is maximal safe resection with preservation of function. Careful thought is required to select the appropriate surgical approach. Most middle fossa trigeminal schwannoma tumours can be safely accessed by a subtemporal extradural middle fossa approach. The treatment of facial nerve schwannoma remains controversial.

Asymmetry of P1 and vertebral arteries is not related to basilar tip aneurysm development or rupture.

OBJECTIVE: Lately, morphological parameters of the surrounding vasculature aside from aneurysm size, specific for the aneurysm location, e.g., posterior cerebral artery angle for basilar artery tip aneurysms, could be identified to correlate with the risk of rupture. We examined further image-based morphological parameters of the aneurysm surrounding vasculature that could correlate with the growth or the risk of rupture of basilar artery tip aneurysms. METHODS: Data from 83 patients with basilar tip aneurysms (27 not ruptured; 56 ruptured) and 100 control patients were assessed (50 without aneurysms and 50 with aneurysms of the anterior circle of Willis). Anatomical parameters of the aneurysms were assessed and analyzed, as well as of the surrounding vasculature, namely the asymmetry of P1 and the vertebral arteries. RESULTS: Patients with basilar tip aneurysm showed no significant increase in P1 or vertebral artery asymmetry compared with the control patients or patients with aneurysms of the anterior circulation, neither was there a significant difference in asymmetry between cases with ruptured and unruptured aneurysms. Furthermore, we observed no significant correlations between P1 asymmetry and the aneurysm size or number of lobuli in the aneurysms. CONCLUSION: We observed no significant difference in aneurysm size, rupture, or lobulation associated with P1 or vertebral artery (surrounding vasculature) asymmetry. Therefore, the asymmetry of the surrounding vessels does not seem to be a promising morphological parameter for the evaluation of probability of rupture and growth in basilar tip aneurysms in future studies.

Transcranial Doppler Ultrasound, Perfusion Computerized Tomography, and Cerebral Angiography Identify Different Pathological Entities and Supplement Each Other in the Diagnosis of Delayed Cerebral Ischemia.

INTRODUCTION: There is still controversial discussion of the value of transcranial Doppler (TCD) in predicting vasospasms in patients with aneurysmal SAH (aSAH). A newer method of predicting a delayed ischemic deficit (DCI) is CT perfusion (CTP), although it is not quite understood which kind of perfusion deficit is detected by this method since it seems to also identifying microcirculatory disturbances. We compared the TCD and CTP values with angiography and evaluated TCD and CTP changes before and after patients received intra-arterial spasmolytic therapy. MATERIAL AND METHODS: Retrospective analysis of TCD, CTP, and angiographies of N = 77 patients treated from 2013 to 2016. In 38 patients intra-arterial spasmolysis had been performed, and in these cases TCD and CTP data were compared before and after lysis. Thirty-nine patients had a pathological CTP but no angiographically seen vasospasm. RESULTS: There was no correlation between the known thresholds of mean transit time (MTT) in CTP and vasospasm or with mean velocities in TCD and vasospasm. After spasmolysis in patients with vasospasms, only the MTT showed significant improvement, whereas TCD velocities and Lindegaard index remained unaffected. CONCLUSION: TCD and CTP seem to identify different pathological entities of DCI and should be used supplementary in order to identify as many patients as possible with vasospasms after aSAH.

Surgical management for large vestibular schwannomas: a systematic review, meta-analysis, and consensus statement on behalf of the EANS skull base section.

BACKGROUND AND OBJECTIVE: The optimal management of large vestibular schwannomas continues to be debated. We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of this problem from a European perspective. MATERIAL AND METHODS: A systematic review of MEDLINE database, in compliance with the PRISMA guidelines, was performed. A subgroup analysis screening all surgical series published within the last 20 years (January 2000 to March 2020) was performed. Weighted summary rates for tumor resection, oncological control, and facial nerve preservation were determined using meta-analysis models. This data along with contemporary practice patterns were discussed within the task force to generate consensual recommendations regarding preoperative evaluations, optimal surgical strategy, and follow-up management. RESULTS: Tumor classification grades should be systematically used in the perioperative management of patients, with large vestibular schwannomas (VS) defined as > 30 mm in the largest extrameatal diameter. Grading scales for pre- and postoperative hearing (AAO-HNS or GR) and facial nerve function (HB) are to be used for reporting functional outcome. There is a lack of consensus to support the superiority of any surgical strategy with respect to extent of resection and use of adjuvant radiosurgery. Intraoperative neuromonitoring needs to be routinely used to preserve neural function. Recommendations for postoperative clinico-radiological evaluations have been elucidated based on the surgical strategy employed. CONCLUSION: The main goal of management of large vestibular schwannomas should focus on maintaining/improving quality of life (QoL), making every attempt at facial/cochlear nerve functional preservation while ensuring optimal oncological control, thereby allowing to meet patient expectations. Despite the fact that this analysis yielded only a few Class B evidences and mostly expert opinions, it will guide practitioners to manage these patients and form the basis for future clinical trials.

Barrel Stave Osteotomy Decompression for Acute Brain Injury in Infants: Technical Note.

Decompressive craniectomy (DC) is rarely required in infants, but when performed several aspects should be considered: These youngest patients are vulnerable to blood loss and cranial reconstruction can be challenging due to skull growth and bone flap resorption. On the other hand, infants have thin and flexible bone and osteogenic potential. The authors propose a technique which makes use of these unique aspects by achieving decompression with the craniofacial method of barrel stave osteotomy, aiming to achieve adequate DC, limit perioperative risks and facilitate subsequent cranial reconstruction.

Is it all a matter of size? Impact of maximization of surgical resection in cerebral tumors.

The oncological impact of cytoreductive surgery for malignant glioma has been analyzed in a few prospective, randomized studies; however, the impact of different cytoreductive surgical techniques of cerebral tumors remains controversial. Despite retrospective analyses revealing an oncological impact of complete surgical resection in cerebral metastases and low-grade glioma, the oncological impact of further extension of resection to a supramarginal resection remains disputable lacking high-grade evidence: supramarginal resections have yet to be analyzed in malignant glioma. Although extension of resection towards a supramarginal resection was thought to improve outcome and prevent malignant transformation in low-grade glioma, the rate of (temporary) deficits was higher than 50% in recent retrospective studies, and the oncological impact and long-term results have to be analyzed in further (prospective and controlled) studies. Cerebral metastases show a growth pattern different from glioma with less and more locally limited brain invasion. Therefore, local control may be achieved by extension of resection after complete lesionectomy of cerebral metastases. Therefore, supramarginal resection may be a promising approach but must be evaluated in further studies.

Anatomical evaluation of intracranial aneurysm rupture risk in patients with multiple aneurysms.

In patients with aneurysmal subarachnoid hemorrhage (aSAH) and multiple aneurysms, there is a need to objectively identify the ruptured aneurysm. Additionally, studying the intra-individual rupture risk of multiple aneurysms eliminates extrinsic risk factors and allows a focus on anatomical factors, which could be extrapolated to patients with single aneurysms too. Retrospective bi-center study (Department of Neurosurgery of the University Hospital Duesseldorf and Bern) on patients with multiple aneurysms and subarachnoid hemorrhage caused by the rupture of one of them. Parameters investigated were height, width, neck, shape, inflow angle, diameter of the proximal and distal arteries, width/neck ratio, height/width ratio, height/neck ratio, and localization. Statistical analysis and logistic regressions were performed by the R program, version 3.4.3. N = 186 patients with aSAH and multiple aneurysms were treated in either department from 2008 to 2016 (Bern: 2008-2016, 725 patients and 100 multiple aneurysms, Duesseldorf: 2012-2016, 355 patients, 86 multiple aneurysms). The mean age was 57 years. N = 119 patients had 2 aneurysms, N = 52 patients had 3 aneurysms, N = 14 had 4 aneurysms and N = 1 had 5 aneurysms. Eighty-four percent of ruptured aneurysms were significantly larger than the largest unruptured. Multilobularity of ruptured aneurysms was significantly higher than in unruptured. Metric variables describing the geometry (height, width, etc.) and shape are the most predictive for rupture. One or two of them alone are already reliable predictors. Ratios are completely redundant in saccular aneurysms.

Open Microsurgical Dorsal Root Ganglion Lead Placement.

INTRODUCTION: Dorsal root ganglion stimulation (DRG) is a new but well-established neuromodulation technique allowing new indications and superiority to pre-existing stimulation techniques such as spinal cord stimulation in selected pain etiologies. Previous surgical procedures in the implantation area pose a challenge for the percutaneous technique and are therefore considered contraindications for DRG stimulation surgery. We describe the successful open DRG electrode placement in two patients with previous surgeries suffering from severe radiculopathy due to foraminal stenosis. METHODS: Percutaneous implantation attempts failed and an open laminotomy/foraminotomy followed by open lead placement was performed. Leads and loops were placed under the microscope, lead location was verified by x-ray during surgery. Leads and loops were kept in position with fibrin glue and fibrin sealant patches. No special tool was required for open lead placement. RESULTS: In both patients, surgery resulted in lead and loop placement resembling the results seen in percutaneous technique. Programming and stimulation results are similar to observations made following percutaneous techniques in one patient significantly lower stimulation amplitudes were necessary. In 18 and 12 months follow-up, respectively, lead location and paresthesia coverage were stable. CONCLUSION: The option of open electrode placement should be taken into account following unsuccessful percutaneous lead placement. A combination of fibrin sealant patch and fibrin glue may be a good option for stabilization of the lead and specially of the strain relief loops in open placement. Knowledge of basic spinal surgery techniques and experience in percutaneous DRG stimulation is necessary to perform this procedure.

Various shades of red-a systematic analysis of qualitative estimation of ALA-derived fluorescence in neurosurgery.

5-Aminolevulinic acid (5-ALA)-fluorescence-guided resection is well established in many neuro-oncologic centers. Different classifications of 5-ALA-induced fluorescence have been reported. The aim of the systematic analysis was to evaluate the frequency of graduations, definitions, and designations of 5-ALA-induced fluorescence qualities. A systematic database search of PubMed was performed to identify studies reporting (1) on 5-ALA fluorescence-guided either spinal or cranial surgery, (2) on qualitative estimation and/or categorization of 5-ALA-induced fluorescence, (3) in English, and (4) were published as peer-reviewed original studies. Totally, 93 studies were identified. Different classification systems of 5-ALA-induced fluorescence were found. Over 60 % of the included studies used a dichotomized categorization of 5-ALA-induced fluorescence and 27.5 % of studies distinguished two different intensities of 5-ALA fluorescent tissue in addition to non-fluorescing tissue. More than 50 % of studies explicitly defined criteria for categorization of 5-ALA-induced fluorescence. The major limitation of the present analysis might be that it mainly comprises data from retrospective, uncontrolled, non-randomized trials. However, a precise definition of each 5-ALA-induced fluorescence quality is essential. Although dichotomized classification is the most common and simple graduation system, it may not be suitable for every clinical or scientific task. A three-level 5-ALA-induced fluorescence classification with precise definition of each fluorescence quality and their correlation with histological features would be more useful and reproducible in these cases.

The impact of cerebral metastases growth pattern on neurosurgical treatment.

The surgical resection of cerebral metastases is one key element in a multimodal therapy of brain oligometastatic patients. Standard surgery alone is often not sufficient to achieve local control. Various reasons have been discussed including microscopic and macroscopic tumor rests after surgery and different growth patterns of cerebral metastases: In this review, we assessed the surgical standard technique and then analyzed the growth pattern of cerebral metastases and discussed its oncologic impact and new strategies in the surgical management of cerebral metastases. A major percentage of cerebral metastases are not sharply delimitated but show an irregular tumor-brain interface or even an infiltrative growth pattern. Different patterns of adjacent brain invasions have been described and may correlate with the prognosis of patients with cerebral metastasis. Even metastases of the same histological subtype and the same origin show a heterogeneous brain invasion pattern. Future therapeutic strategies might have to take this heterogeneity into account. An infiltrative growth pattern of cerebral metastases might be one reason for their extraordinary high local recurrence rate and might have an influence on the individual overall survival. An intraoperative detection of residual tumor and development of more radical surgical techniques is therefore an important neurooncological challenge and might result in better tumor control. Supramarginal resection of cerebral metastases is a promising approach.

An introduction to the pathophysiology of aneurysmal subarachnoid hemorrhage.

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI) would mean that future therapies should address EBI more specifically. If the mechanisms following SAH display no causal pathophysiological connection but are rather evoked by the subarachnoid blood and its degradation production, multiple treatment strategies addressing the different pathophysiological mechanisms are required. The discrepancy between experimental and clinical SAH could be one reason for unsuccessful translational results.

Increased mortality of patients with aneurysmatic subarachnoid hemorrhage caused by prolonged transport time to a high-volume neurosurgical unit.

BACKGROUND: Time has shown to be a relevant factor in the prognosis for a multitude of clinical conditions. The current analysis aimed to establish whether delayed admission to specialized care is a risk factor for increased mortality in case of high-grade aneurysmal subarachnoid hemorrhage. MATERIAL AND METHODS: Consecutive patients with aneurysmal subarachnoid hemorrhage were enrolled retrospectively if they had a World Federation of Neurological Surgeons Grading System grade of 5. Predictor variables for in-hospital mortality reflecting demographic, spatial, temporal treatment, and neurological factors were recorded from hospital medical records and emergency physicians' reports. We performed statistical analysis on the influence between the predictor variables and in-hospital mortality. RESULTS: The study included 61 patients with an average age of 58 years. The overall in-hospital mortality rate was 28% (17/61 patients). A delayed transport to specialized neurosurgical care was associated with increased in-hospital mortality. Transportation time was mainly prolonged in cases where an alternative diagnosis was made by the emergency physician. Mortality was highest in patients with cardiovascular complications of subarachnoid hemorrhage. CONCLUSION: Delayed admission to specialized care is associated with a higher mortality rate in patients with high-grade aneurysmal subarachnoid hemorrhage. Accompanying non-neurosurgical, mainly cardiac complications might be a significant factor leading to delayed admission. The emergency physician should be aware that cardiovascular abnormalities are a relevant complication and sometimes the first identified clinical feature of high-grade subarachnoid hemorrhage.

Demographic distribution of hospital admissions for brain arteriovenous malformations in Germany--estimation of the natural course with the big-data approach.

BACKGROUND: Estimation of the natural history of arteriovenous malformations based on short-term observation is potentially biased by multiple factors. Retrieval of demographic information of all AVM patients of national data pools and comparison with the national demographic profile might be another way to approach the natural history. MATERIALS AND METHODS: Upon request, the German Federal Statistical Office provided the numbers of patients admitted in Germany from 2009 through 2013 with ICD Q28.2 (brain AVM) as primary discharge diagnosis, and the corresponding age distribution. Age-related admission rates of AVM were calculated by comparison with the German demographic distribution. RESULTS: A total of 6527 patients were hospitalized from 2009-2013 with brain AVM (Q28.2) as the principal diagnosis. Age-specific admission rate during the first year of life was high with 19.0/100,000 during the 5-year study period, corresponding to a yearly admission rate of 3.8 per 100,000 babies. Apart from the high admission rate during the first year of life, the admission rate was low, but steadily increasing during first decades of life reaching a plateau with 11.1/100,000 in the age group 30-34 years, corresponding to an annual admission rate of 2.2/100,000. After the age of 30-34 years, admission rates decreased continuously, reaching 0 in the age group 90-95 years. The lifetime risk of admission in terms of admission per 100,000 age-matched people was calculated by retrograde integration of the admission rates. At the age of 1 year, the cumulative number of future admissions for AVM during lifetime amounted to 131.3/100,000 children. For the older age groups, the chance of future admission for AVM decreased as expected, reaching 43.8/100,000 by the age of 50 and 0 by the age of 90. CONCLUSIONS: Despite some open issues, the current data suggests that achieving old age with an untreated brain AVM is unlikely. Furthermore, the data support the concept that most brain AVMs are not necessarily a congenital entity but develop during the first decades of life.

Uptake and tracer kinetics of O-(2-(18)F-fluoroethyl)-L-tyrosine in meningiomas: preliminary results.

PURPOSE: O-(2-[(18)F]Fluoroethyl)-L-tyrosine ((18)F-FET) is a well-established PET tracer for the imaging of cerebral gliomas, but little is known about (18)F-FET uptake in meningiomas. The aim of this study was to explore (18)F-FET kinetics and tumour-to-background contrast in meningiomas of various histologies. METHODS: A group of 24 patients with suspected cerebral meningioma on MRI/CT had an additional dynamic (18)F-FET PET scan prior to surgery. Time-activity curves (TAC) of (18)F-FET uptake in the tumours and tumour-to-brain ratios (TBR) for early (3 - 14 min after injection) and late (18)F-FET uptake (20 - 40 min after injection) were analysed and compared with histological subtypes and WHO grade. (18)F-FET uptake in critical structures in the skull base was also evaluated in terms of tumour-to-tissue (T/Tis) ratio. RESULTS: TBR of (18)F-FET uptake in meningiomas was significantly higher in the early phase than in the late phase (3.5 ± 0.8 vs. 2.2 ± 0.3; P < 0.001). The difference in TBR between low-grade meningiomas (WHO grade I, 18 patients) and high-grade meningiomas (WHO grade II or III, 6 patients) was significant in the late phase of (18)F-FET uptake (2.1 ± 0.2 vs. 2.5 ± 0.2, P = 0.003) while there was no significant difference in the early phase. ROC analysis showed that TBR of (18)F-FET uptake in the late phase had significant power to differentiate low-grade from high-grade meningiomas (AUC 0.87 ± 0.18, sensitivity 83 %, specificity 83 %, optimal cut-off 2.3; P < 0.01). Evaluation of TAC yielded three different curve patterns of (18)F-FET PET uptake. Combination of TBR (cut-off value 2.3) and TAC pattern slightly improved the differentiation of high-grade from low-grade meningiomas (accuracy 92 %; P = 0.001). Analysis of background radioactivity in the skull base indicated that (18)F-FET uptake may be helpful in distinguishing meningioma tissue in the late phase. T/Tis ratios were >1.2 in all patients for the periorbita, sphenoidal sinus, pituitary gland, tentorium, bone and brain, in more than 90 % of patients for the mucosa and dura, but in only 63 % of patients for the cavernous sinus. CONCLUSION: (18)F-FET PET may provide additional information for noninvasive grading of meningiomas and possibly for the discrimination of tumour in critical areas of the skull base. A further evaluation of (18)F-FET PET in meningiomas appears to be justified.