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Considerable progress has been made over the past years to better understand the genetic nature and pathophysiology of brain AVM. For the actual review, a PubMed search was carried out regarding the embryology, inflammation, advanced imaging, and fluid dynamical modeling of brain AVM. Whole-genome sequencing clarified the genetic origin of sporadic and familial AVM to a large degree, although some open questions remain. Advanced MRI and DSA techniques allow for better segmentation of feeding arteries, nidus, and draining veins, as well as the deduction of hemodynamic parameters such as flow and pressure in the individual AVM compartments. Nonetheless, complete modeling of the intranidal flow structure by computed fluid dynamics (CFD) is not possible so far. Substantial progress has been made towards understanding the embryology of brain AVM. In contrast to arterial aneurysms, complete modeling of the intranidal flow and a thorough understanding of the mechanical properties of the AVM nidus are still lacking at the present time.

Objective Isocitrate dehydrogenase (IDH)-wildtype glioblastomas are the most malignant glial tumours. Median survival is only 14–16 months after diagnosis, with patients aged ≥ 65 years reportedly showing worse outcome. This study aimed to further evaluate the prognostic role of age in a homogenously treated patient cohort. Methods The study includes 132 IDH-wildtype glioblastoma patients treated between 2013 and 2017 with open resection followed by radiotherapy with concomitant and maintenance temozolomide. Patients were dichotomized into a non-elderly (MGMT) promoter methylation status were determined for each tumour. Clinical and radiological follow-up data were obtained at 6 weeks after the end of radiation therapy and thereafter in 3-month intervals. Progression-free survival (PFS) and overall survival (OS) were evaluated in univariate and multivariate cox regression analyses. Results The elderly group consisted of 58 patients (median age: 70.5 years) and the non-elderly group of 74 patients (median age: 55 years). Median pre- and postoperative operative Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group (ECOG) score and National Institutes of Stroke Scale (NIHSS) were not significantly different between the groups, but KPS and ECOG scores became significantly worse in the elderly group at 6 weeks after termination of radiation therapy. Neither PFS nor OS differed significantly between the age groups. Patients with MGMT promoter-methylated tumours survived longer. Conclusion Elderly patients in good pre- and postoperative clinical conditions may show similar outcome as younger patients when treated according to standard of care. However, elderly patients may suffer more frequently from clinical deterioration following chemoradiotherapy. In both age groups, MGMT promoter methylation was linked to longer PFS and OS.

In 1999 a visionary short article by The Wall Street Journal writers Robert Langreth and Michael Waldholz popularized the new term “personalized medicine,” that is to say, the targeting of drugs to each unique genetic profile. From today’s perspective, targeted approaches have clearly found the widest use in the antineoplastic domain. The current review was initiated to review the progress that has been made regarding the treatment of patients with advanced cancer and brain metastases. PubMed was searched for the terms brain metastasis, brain metastases, or metastatic brain in the Title/Abstract. Selection was limited to randomized controlled trial (RCT) and publication date January 2010 to February 2022. Following visual review, 51 papers on metastatic lung cancer, 12 on metastatic breast cancer, and 9 on malignant melanoma were retained and underwent full analysis. Information was extracted from the papers giving specific numbers for intracranial response rate and/or overall survival. Since most pharmacological trials on advanced cancers excluded patients with brain metastases and since hardly any information on adjuvant radiotherapy and radiosurgery is available from the pharmacological trials, precise assessment of the effect of targeted medication for the subgroups with brain metastases is difficult. Some quantitative information regarding the success of targeted pharmacological therapy is only available for patients with breast and lung cancer and melanoma. Overall, targeted approaches approximately doubled the lifespan in the subgroups of brain metastases from tumors with targetable surface receptors such as anaplastic lymphoma kinase (ALK) fusion receptor in non-small cell lung cancer or human epidermal growth factor receptor 2 (HER2)–positive breast cancer. For these types, overall survival in the situation of brain metastases is now more than a year. For receptor-negative lung cancer and melanoma, introduction of immune checkpoint blockers brought a substantial advance, although overall survival for melanoma metastasized to the brain appears to remain in the range of 6 to 9 months. The outlook for small cell lung cancer metastasized to the brain apparently remains poor. The introduction of targeted therapy roughly doubled survival times of advanced cancers including those metastasized to the brain, but so far, targeted therapy does not differ essentially from chemotherapy, therefore also facing tumors developing escape mechanisms. With the improved perspective of patients suffering from brain metastases, it becomes important to further optimize treatment of this specific patient group within the framework of randomized trials.

Purpose Intravenous and intra-arterial milrinone as a rescue measure for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) has been adopted by several groups, but so far, evidence for the clinical benefit is unclear and effect on brain perfusion is unknown. The aim of the actual analysis was to define cerebral hemodynamic effects and outcome of intravenous milrinone plus norepinephrine supplemented by intra-arterial nimodipine as a rescue strategy for DCI following aneurysmal SAH. Methods Of 176 patients with aneurysmal SAH treated at our neurosurgical department between April 2016 and March 2021, 98 suffered from DCI and were submitted to rescue therapy. For the current analysis, characteristics of these patients and clinical response to rescue therapy were correlated with hemodynamic parameters, as assessed by CT angiography (CTA) and perfusion CT. Time to peak (TTP) delay in the ischemic focus and the volume with a TTP delay of more than 4 s (T4 volume) were used as hemodynamic parameters. Results The median delay to neurological deterioration following SAH was 5 days. Perfusion CT at that time showed median T4 volumes of 40 cc and mean focal TTP delays of 2.5 ± 2.1 s in these patients. Following rescue therapy, median T4 volume decreased to 10 cc and mean focal TTP delay to 1.7 ± 1.9 s. Seventeen patients (17% of patients with DCI) underwent additional intra-arterial spasmolysis using nimodipine. Visible resolution of macroscopic vasospasm on CTA was observed in 43% patients with DCI and verified vasospasm on CTA, including those managed with additional intra-arterial spasmolysis. Initial WFNS grade, occurrence of secondary infarction, ischemic volumes and TTP delays at the time of decline, the time to clinical decline, and the necessity for additional intra-arterial spasmolysis were identified as the most important features determining neurological outcome at 6 months. Conclusion The current analysis shows that cerebral perfusion in the setting of secondary cerebral ischemia following SAH is measurably improved by milrinone and norepinephrine–based hyperdynamic therapy. A long-term clinical benefit by the addition of milrinone appears likely. Separation of the direct effect of milrinone from the effect of induced hypertension is not possible based on the present dataset.

Purpose A possible disadvantage of endovascular occlusion outside work hours is that complex procedures might expose patients to additional risk when performed in a suboptimal setting. In this prospective cohort study, we evaluated whether treatment during out of office hours is a risk factor for per-procedural complications and clinical outcome. Methods We included 471 endovascular-treated, consecutive aneurysmal subarachnoid hemorrhage patients (56.6 ± 13.1, 69% female), from two prospective observational databases which were retrospectively analyzed. Primary outcome was the occurrence of per-procedural complications. Secondary outcomes were good clinical outcome (modified ranking scale ≤ 2) and death at 6-month follow-up. We determined odds ratios (OR) with 95% confidence intervals (CI) by ordered polytomous logistic regression analysis and adjusted odds ratios (aOR) for age, World Federation of Neurosurgical Societies grade, and time to treatment. Results Most patients were treated during office hours (363/471; 77.1%). Treatment during out of office hours did not result in an increased risk of per-procedural complications (OR 0.85 (95% CI 0.53–1.37; p = 0.51). Patients treated during out of office hours displayed similar odds of good clinical outcome and death after 6 months (OR 1.14, 95% CI 0.68–1.97 and 1.16 95% CI 0.56–2.29, respectively) compared to patients treated during office hours. Conclusion In our study, endovascular coil embolization during out of office hours did not expose patients to an increased risk of procedural complications or affect functional outcome after 6 months.

The cerebellum is historically implicated in motor coordination, but accumulating modern evidence indicates involvement in non-motor domains, including cognition, emotion, and language. This correlates with the symptoms observed in postoperative cerebellar mutism syndrome (CMS). Profound knowledge of cerebellar functional topography and tractography is important when approaching cerebellar tumors, as surgical trauma to relevant structures of cerebellar pathways plays a role in the pathogenesis of CMS. The aim of this systematic review is to provide a concise overview of relevant modern neuroimaging data and cerebellar functional tracts with regard to neurosurgical procedures.

Objective Symptomatic spine metastases are found in about 10% of patients with cancer. As the long-term survival of patients with carcinoma rises, the number of patients with symptomatic spine metastases is also increasing. In our tertiary referral center, patients usually present rapidly progressive neurologic disorders, which require an urgent treatment decision. Treatment options include extensive 360° stabilizations. These complex interventions are not always readily available. We examined the extent to which the patient population benefited from decompressive surgery without stabilization. We hypothesize that patients benefit from merely dorsal decompression, which preserves stability when they experience symptomatic spine metastases. Methods We performed a retrospective analysis of electronic patient data from 19 patients, who were treated for symptomatic spine metastases by hemilaminectomy between 2009 and 2017. We evaluated the preoperative and postoperative neurologic functions using the American Spinal Injury Association (ASIA) Impairment Scale. A comparative literature analysis was carried out to assess the Spinal Neoplastic Instability Score, Tokuhashi score, and Tomita score. Results Nine participants had prostate cancer, 4 had mammary carcinoma, 3 had bronchial carcinoma, and 3 had other cancers. The median preoperative ASIA score was C, postoperatively, the score significantly improved to D (sign test P = 0.002). None of the patients needed stabilization within the follow-up period of up to 56 months. Conclusions In our patient population, minimal intervention could significantly improve neurologic disorders. This outcome was seen over the whole study period. Even though different scoring systems suggest stabilization, our results show that spinal decompression alone might be indicated as well.

Objective With the introduction of the 5-aminolevulinic acid (5-ALA) technique, surgical neuro-oncology has made a major advance. 5-ALA fluorescence–guided resection of malignant glioma results in more complete surgical resections and subsequently prolonged survival. However, it remains uncertain how light intensities of the blue light source and 5-ALA–derived fluorescence intensities of the illuminated tissue are connected. The aim of the present study was to compare light intensities of different blue light sources and protoporphyrin (PpIX) fluorescence intensities of PpIX solutions with defined concentrations after illumination with different light sources. Material and Methods The light spectrum of 7 different blue light sources and the fluorescence intensity of 2 PpIX solutions (0.15 μg/mL and 5 μg/mL) were quantified after illumination. We compared the Zeiss OPMI Pentero microscope, the Zeiss OPMI Pentero 900 microscope, the Leica M530 OH6 microscope, an endoscope equipped with the 5-ALA technique, a mini-spectrometer equipped with a multi-channel light-emitting diode (LED) source emitting monochromatic light, a modified commercially available LED head lamp, and a commercially available unmodified UV-LED lamp. PpIX fluorescence was quantified in a standardized setup using a mini-spectrometer. Results Maximum light intensities of the evaluated light sources were reached at different wavelengths. All tested devices were able to detect PpIX-induced fluorescence. However, the intensity of PpIX fluorescence of the differently concentrated PpIX solutions (0.15 μg/mL and 5 μg/mL) was significantly dependent on the light source used. Conclusions Intensity of the 5-ALA–derived fluorescence is related to the light source used.

5-ALA fluorescence-guided surgery (FGS) is a major advance in neuro-oncological surgery. So far, Protoporphyrin IX (PpIX)-fluorescence has been observed in about half of cerebral metastases resected with routinely equipped microscopes during 5-ALA FGS. The aim of the present pilot study was to quantify PpIX-induced fluorescence of cerebral metastases with a spectrometer. We hypothesize that non-fluorescing metastases under the operating microscope may have spectrometrically measurable levels of fluorescence. A second aim was to analyze correlations between quantified 5-ALA fluorescence and histology or primary tumor type, respectively. Standard FGS was performed in all patients. The fluorescence intensity of the metastasis was semi-quantitatively determined in vivo by a senior surgeon using a special surgical microscope equipped for FGS. A systematic spectrometric ex vivo evaluation of tumor specimens and PpIX-induced fluorescence was performed using a spectrometer connected by optic fibers to a handheld probe. Quantification of 5-ALA-derived fluorescence was measured in a standardized manner with direct contact between mini-spectrometer and metastasis. The difference between the maximum PpIX-fluorescence at 635 nm and the baseline fluorescence was defined as the PpIX fluorescence intensity of the metastasis and given in arbitrary units (AU). Diagnosis of a cerebral metastasis was confirmed by histopathological analysis. A total of 29 patients with cerebral metastases were included. According to neuropathological analysis, 11 patients suffered from non-small cell lung cancer, 10 patients from breast cancer, 6 patients from cancer originating in the gastro-intestinal tract, 1 patient suffered from a malignant melanoma and one patient from renal cancer. The mean age was 63 years (37–81 years). 15 patients were female, 14 patients male. 13 cerebral metastases were considered as ALA-positive by the surgeon. In nine metastases, 5-ALA fluorescence was not visible to the naked eye and could only be detected using the spectrometer. The threshold for an ALA signal rated as “positive” by the surgeon was PpIX fluorescence above 1.1 × 106 AU. The mean PpIX fluorescence of all analyzed cerebral metastases was 1.29 × 106 ± 0.23 × 106 AU. After quantification, we observed a significant difference between the mean 5-ALA-derived fluorescence in NSCLC and breast cancer metastases (Mean Diff: − 1.2 × 106; 95% CI of difference: − 2.2 × 106 to − 0.15 × 106; Sidak-adjusted p = 0.026). In our present pilot series, about half of cerebral metastases showed a 5-ALA fluorescence invisible to the naked eye. Over 50% of these non-fluorescent metastases show a residual 5-ALA fluorescence which can be detected and quantified using a spectrometer. Moreover, the quantified 5-ALA signal significantly differed with respect to the primary tumor of the corresponding cerebral metastasis. Further studies should evaluate the predictive value of the 5-ALA signal and if a quantified 5-ALA signal enables a reliable intraoperative differentiation between residual tumor tissue and edematous brain—in particular in metastases with a residual fluorescence signal invisible to the naked eye.

Study design Retrospective analysis of anonymized malpractice claims. Summary of background data Spine surgery is considered a high-risk specialty with regards to malpractice claims. However, limited data is available for Germany. We analyzed the rate, subject, and legal outcome of malpractice claims faced by spine surgeons in one of the largest Medical Council coverage areas in Germany, representing 60,000 physicians and a population of 10 million. Methods Analysis of all malpractice claims regarding spinal surgeries completed by the Review Board of the North Rhine Medical Council (NRMC) from 2012 to 2016. Claim merit, content, and actual treatment errors were reviewed. Severity of damage was graded from negligible (1) to death (6). Results A total of 8,381 malpractice cases were reviewed by the NRMC from 2012 to 2016. Four percent (340 cases: 181 females, 159 males) pertained to patients undergoing spinal surgery with 94.7% of patients undergoing inhospital treatment and 5.3% as outpatients. Malpractice claims most frequently involved neurosurgery (48.5%) and orthopedic surgery (37.6%). Trauma surgery was involved in 9.1% and other specialties in 4.8%. Actual treatment errors were found in 89 of 340 cases (26.2%).Of those, 81 resulted in treatment-associated health impairment. Negligible and/or temporary impairment was found in 49.3%. Negligible to moderate but permanent damage was observed in 39.5%. Nine patients suffered severe permanent damage or death (11.1%). The treated diagnosis was degenerative disc disease in 34 patients (41.9%), spinal canal stenosis in 13 (16%), vertebral body fractures in 10 (12.3%), spondylolisthesis in 6 (7.4%), and other diagnoses accounting for the remaining 18 (22.2%). Errors involved actual surgical treatment in 40.7%, surgical indication and preoperative workup in 28.4%, postoperative treatment in 25.9%, and patient consent in 4.9%. Conclusions Spinal surgery claims account for 4% of all claims reviewed by the NRMC in the 5-year period from 2012 to 2016. Eighty-nine (26.2%) were deemed justified. The majority of treatment errors (59.3%) occurred during workup, indication and consent, or during postoperative care. Errors during actual surgery were responsible for 40.7% of all treatment-associated damages. Understanding the distribution and content of claims is key to improving patient satisfaction not only by honing surgical skills, but also by improving pre- and postoperative communication and care.

Malignant stroke occurs in a subgroup of patients suffering from ischemic cerebral infarction and is characterized by neurological deterioration due to progressive edema, raised intracranial pressure, and cerebral herniation. Decompressive craniectomy (DC) is a surgical technique aiming to open the “closed box” represented by the non-expandable skull in cases of refractory intracranial hypertension. It is a valuable modality in the armamentarium to treat patients with malignant stroke: the life-saving effect has been proven for both supratentorial and infratentorial DC in virtually all age groups. This leaves physicians with the difficult task to decide who will require early or preemptive surgery and who might benefit from postponing surgery until clear evidence of deterioration evolves. Together with the patient’s relatives, physicians also have to ascertain whether the patient will have acceptable disability and quality of life in his or her presumed perception, based on preoperative predictions. This complex decision-making process can only be managed with interdisciplinary efforts and should be supported by continued research in the age of personalized medicine.

Background Randomized trials on spontaneous lobar intracerebral hemorrhage (ICH) provided no convincing evidence of the superiority of surgical treatment. Since recruitment in the trials was under the premise of equipoise, a selection bias toward patients who did not need surgery or were in hopeless condition must be suspected. The aim of the actual analysis was to compare outcome and patient profile of an unselected hospital series with recent randomized trials and to develop a prognostic model. Methods Of 821 patients with spontaneous ICH managed at the neurosurgical department of the University Hospital Düsseldorf between 2013 and 2018, 159 had lobar bleedings. Patient characteristics, hematoma volume, treatment modality, and 6-month survival were compared with STICH II and the subset of lobar hemorrhage in the MISTIE III trial. In addition, a prognostic model for 6-month survival in our patients was developed using a random forest classifier. Results One hundred and seven patients were managed by surgical evacuation of the hematoma and 52 without surgical evacuation. Median hemorrhage volume in our surgical cohort was 66 and 42 mL in the conservative cohort, compared with 38 and 36 mL in the STICH II trial, and 46 and 47 mL in the surgical and conservative MISTIE III lobar hemorrhage subset. Median initial Glasgow Coma Scale (GCS) score was 12 in our surgical group and 11 in the conservative group, compared with 13 in the STICH II cohorts and 12 in the MISTIE III lobar hemorrhage subset. Median age in our surgical and conservative cohorts was 73 and 74 years, respectively, compared with 65 years in both STICH II cohorts and 68 years in the MISTIE II subsets. Twenty-nine percent of our surgical cohort and 55% of our conservatively managed patients deceased within the first 6 months, compared with 18 and 24%, respectively, in STICH II and 17 and 24% in the MISTIE III subset. Our prognostic model identified large hemorrhage volumes and low admission GCS score as main unfavorable prognostic factors for 6-month survival. The random forest classifier achieved a predictive accuracy of 78% and an area under curve (AUC)- value of 88% regarding survival at 6 months, on a test set independent of the training set. Conclusions In comparison with our surgical group, the STICH II and MISTIE III cohorts, recruited under the premise of physician equipoise, underrepresented patients with large ICHs. The cohorts in the randomized trials were therefore biased toward patients with a favorable perspective under conservative management. Initial hematoma volume and admission GCS were the main prognostic factors in our patients.

Objectives: Lennox-Gastaut syndrome (LGS) is among the most severe epileptic and developmental encephalopathies. A meta-analysis was performed to evaluate the effectiveness of adjunctive vagus nerve stimulation (VNS Therapy) in patients with LGS. Materials & Methods: PubMed database was queried (January 1997 to September 2018) to identify publications reporting on the efficacy of VNS Therapy in patients with LGS, with or without safety findings. Primary endpoint of the meta-analysis was the proportion of responders (≥50% reduction in seizure frequency). Random-effects analysis was used to calculate weighted mean estimates and confidence intervals. Heterogeneity was evaluated by statistical tests including I2. Results: Of 2752 citations reviewed, 17 articles (480 patients) were eligible including 10 retrospective studies and seven prospective studies. A random-effects model produced a pooled proportion of 54% (95% confidence intervals [CI]: 45%, 64%) of patients with LGS who responded to adjunctive VNS Therapy (p for heterogeneity

Contains fulltext : 225137.pdf (Publisher’s version ) (Open Access) Inconsistency in outcome parameters for delayed cerebral ischemia (DCI) makes it difficult to compare results between mouse studies, in the same way inconsistency in outcome parameters in human studies has for long obstructed adequate comparison. The absence of an established definition may in part be responsible for the failed translational results. The present article proposes a standardized definition for DCI in experimental mouse models, which can be used as outcome measure in future animal studies. We used a consensus-building approach to propose a definition for "experimental secondary ischemia" (ESI) in experimental mouse subarachnoid hemorrhage that can be used as an outcome measure in preclinical studies. We propose that the outcome measure should be as follows: occurrence of focal neurological impairment or a general neurological impairment compared with a control group and that neurological impairment should occur secondarily following subarachnoid hemorrhage (SAH) induction compared with an initial assessment following SAH induction. ESI should not be used if the condition can be explained by general anesthesia or if other means of assessments sufficiently explain function impairment. If neurological impairment cannot reliably be evaluated, due to scientific setup. Verification of a significant secondary impairment of the cerebral perfusion compared with a control group is mandatory. This requires longitudinal examination in the same animal. The primary aim is that ESI should be distinguished from intervention-related ischemia or neurological deficits, in order establish a uniform definition for experimental SAH in mice that is in alignment with outcome measures in human studies.

Background De novo aneurysm formation after completely occluded aneurysms via clipping or coiling has not been well studied. Although known to occur several years after initial aneurysm management, the natural history of de novo aneurysms is obscure. We investigated the formation of new aneurysms in patients who had previously undergone treatment of intracranial aneurysms. Methods In a retrospective, single-institutional series, eligible patients who had undergone treatment of ruptured cerebral aneurysms from 2000 to 2011 were included. The primary outcome measure was the development of de novo aneurysms during long-term follow-up. Results Overall, 130 patients (63% women) who had undergone microsurgical clipping (n = 63; 48.5%) or endovascular coiling (n = 67%; 51.5%) for ruptured aneurysms were included. The average follow-up time for our cohort was 10 ± 2.7 years. De novo aneurysms occurred in 10 of 130 patients (7.7%), with a mean time of 7.9 years for aneurysm detection. No association between the formation of de novo aneurysms and the location of the treated aneurysms, smoking status, hypertension, age, or gender was found. Follow-up imaging studies were performed every 2 years. De novo aneurysms had formed in 2 patients within 2–5 years, 7 patients after 5–10 years, and 1 patient after 10 years of follow-up. In 2 of 10 patients, the de novo aneurysm had ruptured and led to subarachnoid haemorrhage. Conclusion The rate of de novo aneurysm occurrence was 7.6%, with a mean time to development of 7.9 years. This underscores the significance of long-term monitoring of patients with intracranial aneurysms. In our series, most new aneurysms had occurred after 5 years of follow-up.

Limitations in genetic stability and recapitulating accurate physiological disease properties challenge the utility of patient-derived (PD) cancer models for reproducible and translational research. A portfolio of isogenic human induced pluripotent stem cells (hiPSCs) with different pan-cancer relevant oncoprotein signatures followed by differentiation into lineage-committed progenitor cells was genetically engineered. Characterization on molecular and biological level validated successful stable genetic alterations in pluripotency state as well as upon differentiation to prove the functionality of our approach. Meanwhile proposing core molecular networks possibly involved in early dysregulation of stem cell homeostasis, the application of our cell systems in comparative substance testing indicates the potential for cancer research such as identification of augmented therapy resistance of stem cells in response to activation of distinct oncogenic signatures.

Bow hunter's syndrome is a rare clinical condition. It is caused by dynamic compression of the vertebral artery (VA) either at the level of the transverse foramina (V2 segment) or at the atlantoaxial level (V3 segment). We report a 54-year-old man with typical bow hunter's syndrome caused by compression at the level of C6/C7. He was successfully treated by anterolateral VA decompression without a need for stabilization. We present preoperative imaging (magnetic resonance imaging, computed tomographic angiography, and dynamic angiography) and a high-quality intraoperative video detailing each step of the surgical technique (high-definition video with annotations and audio track of the Doppler ultrasound used as intraoperative control). Furthermore, postoperative imaging and a video of the clinical outcome are presented. Adequate management of bow hunter's syndrome requires good pathophysiologic understanding of the disease and careful clinical examination. Dynamic angiography confirms the exact site of VA compression. Surgical decompression is the treatment of the cause. Surgical techniques include VA decompression by an anterolateral approach (V2 or V3) or a posterior approach (V3). Some authors advocate stand-alone stabilization, which is, however, only an indirect treatment and results in significant loss of head motion. Other nonsurgical treatments such as orthesis, medical therapy, or endovascular stenting have been only anecdotally reported. Bow hunter's syndrome is best treated by VA decompression. This may safely be achieved by good anatomic knowledge and a straightforward surgical technique. Here, the anterolateral approach is presented in detail in a high-definition surgical instruction video.

Objective To evaluate a new surgical tool combining suction and monopolar neurostimulation (stimulation sucker) for cerebellopontine angle (CPA) tumors. The usefulness for continuous (time) and dynamic (space) facial nerve mapping was studied. Methods Patients operated on with the stimulation sucker for a CPA tumor between April 2016 and May 2017 in a tertiary care center were identified. Clinical charts were retrospectively evaluated. The minimum follow-up time of patients was 12 months. Results The study population included 17 patients with tumor (6 women and 11 men). The age range was from 2 to 77 years (mean age, 45.7 years; standard error of the mean, 22.7 years). Most CPA tumors were large (Koos grade 4) vestibular schwannomas (n = 10); other pathologies included petrous meningioma (n = 1), metastasis (n = 1), medulloblastoma (n = 2), ependymoma (n = 2), and pilocytic astrocytoma (n = 1). One patient with trigeminal neuralgia served as the normal control subject. No complications because of the stimulation sucker were encountered. Clinical and radiologic outcomes compared favorably with institutional experience and literature. The stimulation sucker allowed for continuous (time) mapping of the facial nerve at the site of resection (space). This real-time feedback allowed early identification of the facial nerve. Handling and ergonomy were excellent and workflow improved. The shortcomings compared with a bayonet-shaped bipolar probe were decreased visibility of neurovascular structures and lower spatial discrimination. The new device did not simplify delicate at the brainstem and on the nerve. We think it should be considered as a complementary tool in the surgeon's armamentarium. Conclusions Until now, nerve damage as assessed by neuromonitoring (e.g., facial nerve electromyography, motor evoked potential) served as surrogate for nerve function. This concept should be challenged. The studied stimulation sucker detected the facial nerve earlier than conventional techniques, preventing harm by surgical trauma. A larger, prospective study is warranted to better define its role in CPA surgery.

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.

Randomized controlled trials (RCTs) are gold standard for comparing treatment modalities. Recently, RCTs transformed ischemic stroke care by first proving benefit of decompressive craniectomy (DC) and later of interventional mechanical thrombectomy. Aim of this study was to explore the impact of RCTs on neurosurgical practice. RCTs investigating DC and thrombectomy were identified. Annual numbers of DCs for ischemic stroke between 2000 and 2017 were determined and correlated with publication dates of RCTs. The initial RCTs demonstrating efficacy of DC were published in 2007, followed by an increase in DC numbers between 2008 and 2009. The first RCTs on mechanical thrombectomy were published in 2014 and 2015, with a decline in DCs observed between 2015 and 2016. There is a close temporal relationship between publication of these RCTs and changes in neurosurgical practice. Dynamics of annual DCs appear to correlate with the publication of RCTs. Significantly positive results of surgical and interventional RCTs were translated into clinical practice with a latency of 1 year, as reflected by shifts in annual DC numbers.

The conserved stem cell signaling network canonical Wingless (WNT) plays important roles in development and disease. Aberrant activation of this pathway has been linked to tumor progression and resistance to therapy. Industry and academia have substantially invested in developing substances, which can efficiently and specifically block the WNT signaling pathway. However, a clear clinical proof of the efficacy of this approach is still missing. Studies on the metabolomics dysregulation of cancer cells have led to innovations in oncological diagnostics. In addition, modulation of cancer cell metabolome is at the base of promising clinical oncology trials currently underway. While onco-protein activation can have profound metabolic outcomes, the involvement of stem cell signals, such as the WNT pathway, in tumor cell metabolomics is yet insufficiently characterized.We determined live cell metabolism and bioenergetics in pathophysiological relevant, WNT-dependent glioblastoma stem cell (GSC) models. We quantified those parameters in cells with canonical WNT activity and in isogenic cells where WNT activity had been inhibited by short hairpin RNA against β-catenin. Furthermore, we applied computational analysis of RNA sequencing to verify our functional findings in independent GSCs cohorts.The investigated collection of disease models allows the separation in tumors with low, moderate and high base line metabolic activity. Suppression of canonical WNT signaling led to significant reduction of total, mitochondrial, and glycolytic ATP production rates. Elevated canonical WNT transcription signature in GSCs positively correlated with transcription levels of mitochondrial ATP synthesis, whereas non-canonical WNT gene expression signature did not.The applied disease modeling technology allows the recapitulation of inter-tumoral heterogeneous metabolic properties of glioblastoma. Our data show for the first time that inhibition of canonical WNT signaling in alive GSCs functionally correlates with energy inhibition and glucose homeostasis. As this correlation occurs in GSCs from different transcriptional or epigenetic transcriptional subtypes, our results suggest that developing therapies directed against glycolysis/ATP-synthesis may be a promising strategy to overcome therapy resistance due to inter-tumoral heterogeneity and offers starting point to impair downstream signal WNT.

Objective Shunt surgery is common in pediatric neurosurgery and is associated with relevant complication rates. We aimed to compare previously published metrics in a single data set and propose the Negative Shunt Revision Rate (NSRR), defined as proportion of shunt explorations revealing a properly working system, as a new quality metric. Methods Retrospective analysis of our shunt surgery activity in 2015 was performed. Demographic, clinical, and radiologic variables were extracted from electronic medical notes. Surgical Activity Rate, Revision Quotient, 30-day shunt malfunction rate, 90-day global shunt revision rate, Preventable Shunt Revision Rate, and novel NSRR were calculated. Results Of 60 shunt operations analyzed, 18 (39%) were new shunt insertions, and 42 (70%) were revisions. Median age was 18 months (range, 0.03–204 months), and main etiologies were posthemorrhagic (n = 16; 41%), congenital (n = 11; 28%), and tumor-associated (n = 8; 21%) hydrocephalus. Within 90 days after index surgery, 13 shunt failures occurred, predominantly owing to proximal failure (n = 6; 46%). Surgical Activity Rate was 0.127, Revision Quotient was 2.333, 30-day shunt malfunction rate was 0.166, 90-day global shunt revision rate was 21.7%, and Preventable Shunt Revision Rate was 38.5%. NSRR was 7.1%. Conclusions Our results correlate with published values and offer measurement of quality that can be compared across studies and considered patient-oriented, easily measurable, and potentially modifiable. We propose NSRR as a new quality metric, covering an aspect of shunt surgery that was not addressed previously.

Objective To compare fluorescence intensity of tumor specimens, as measured by a fluorescence-guided surgery microscope and a spectrometer, to evaluate tumor infiltration of dura mater around meningiomas with help of these 2 different 5-aminolevulinic acid (5-ALA)-based fluorescence tools, and to correlate fluorescence intensity with histopathologic data. Material and Methods In a clinical series, meningiomas were resected by 5-ALA fluorescence-guided surgery. Fluorescence intensity was semiquantitatively rated by the surgeon at predefined points. Biopsies were harvested and fluorescence intensity measured by a spectrometer and histopathologically analyzed. Sampling was realized at the level of the dura in a centrifugal direction. Results A total of 104 biopsies (n = 13 tumors) were analyzed. Specificity and sensitivity of the microscope were 0.96 and 0.53 and of the spectrometer 0.95 and 0.93, respectively. Fluorescence intensity as measured by the spectrometer was correlated to histologically confirmed tumor burden. In a centrifugal direction, tumor burden and fluorescence intensity continuously decreased (along the dural tail). Below a threshold value of 639 arbitrary units no tumor was histologically detectable. Conclusions At the level of the dura the spectrometer was highly sensitive for detection of meningioma cells. The surgical microscope showed false negative results and missed residual tumor cells in more than one half of the cases. The complementary use of both fluorescence tools may improve resection quality.

Chordomas are very rare tumors of the skull base and the sacrum. They show infiltrating and destructive growth and are known to be chemo- and radio-resistant. After surgical resection, the recurrence rate is high and overall survival limited. As current adjuvant treatments are ineffective, new treatment concepts are urgently needed. 5-aminolevulinic acid-based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. However, it is unknown so far, whether chordomas accumulate protoporphyrin IX (PPIX) after application of 5-ALA and whether they are sensitive to subsequent 5-ALA based PDT.The immortalized human chordoma cells U-CH2 were used as in vitro model. After incubation for 4h or 6h with different 5-ALA concentrations, PPIX accumulation was determined by flow cytometry. To assess sensitivity to PDT, chordoma cells were incubated at 30.000cells/well (high cell density) or 15.000cells/well (low cell density) with graded doses of 5-ALA (0-50μg/ml) in 96-well plates and subsequently exposed to laser light of 635nm wavelength (18.75J/cmU-CH2 cells dose-dependently accumulated PPIX (ANOVA; p0.0001). PPIX fluorescence was significantly higher, when cells were incubated with 5-ALA for 6h compared to 4h at higher 5-ALA concentrations (ANOVA/Bonferroni; p≤0.05 for≥30μg/ml 5-ALA). For both cell densities, a 5-ALA dose-dependent decline in viability was observed (ANOVA; p0.0001). Viability was significantly lower at higher 5-ALA concentrations, when 30.000 cells/wells were treated compared to 15.000cells/well (ANOVA/Bonferroni; p≤0.001 for≥30μg/ml 5-ALA). LD50 was 30.25μg/ml 5-ALA.The human UCH-2 cell line was a very useful in vitro model to study different effects of 5-ALA based PDT. For the first time, it could be shown that human chordoma cells may be destroyed by 5-ALA/PDT.

Objectives Elevated blood glucose is frequently detected early after aneurysmal subarachnoid hemorrhage (aSAH) and is considered a risk factor for poor neurological outcome. However it remains unclear whether hyperglycemia is caused by the SAH ictus or reflects a pre-existing hyperglycemic metabolism. In a prospective register we analysed glycated haemoglobin levels (HbA1c) in patients with aSAH and its influence on outcome. Patients and methods Between July 2012 and July 2014, 87 patients with confirmed aSAH were included (NCT02081820). Within 72 h HbA1c levels were assessed as a measure for hyperglycemic metabolism preceding aSAH. Blood glucose levels were recorded upon admission. Patient outcome was recorded after 6 months using modified Rankin scale (mRS). Results HbA1c levels did not correlate with initial neurological status (p = 0.338, r = 0.104). On the contrary, initial blood glucose levels correlated significantly with neurological status at admission (p = 0.001, r = 0.341). Additionally, HbA1c levels failed to show a significant influence on the occurrence of delayed cerebral ischemia (DCI) (p = 0.400) or outcome after 6 months (p = 0.790). Conclusion A pre-existing hyperglycemic metabolism does not contribute to the severity of aSAH or influences the quality of neurological recovery. Hyperglycemia after aSAH correlates with initial neurological status and patient outcome and is potentially attributable to the metabolic changes induced by the brain injury after the hemorrhage.

According to current evidence, adding decompressive craniectomy (DC) to best medical therapy reduces case fatality rate of malignant middle cerebral artery infarction by 50–75%. There is currently little information available regarding the outcome of subgroups, in particular of patients with extensive infarctions exceeding the territory of the middle cerebral artery. The records of 101 patients with large hemispheric infarctions undergoing DC were retrospectively reviewed. Twenty-seven patients had additional ACA and/or PCA infarcts. Sequential CTs were used for postoperative follow-up. Intracranial pressure (ICP) was monitored via a ventricular catheter in comatose patients. The main aim of treatment was to keep midline shift below 10 mm and ICP below 20 mmHg. If midline shift increased despite preceding DC, repeat surgery with removal of clearly necrotic tissue was considered. For the current analysis, Glasgow Coma Scale (GCS) at 14 days and modified Rankin Scale (mRS) at 3 months were used as outcome parameters. mRS 2 and 3 were defined as “moderate disability”, mRS 4 as “severe disability”, and mRS 5 and 6 as “poor outcome”. These outcome parameters were correlated to age, gender, side, vascular territory, and time delay after stroke, GCS at the time of decompression, maximum ICP, maximum midline shift, and delay of maximum shift. The median age of the 39 female and 62 male patients was 56 years (range, 5–79 years). Overall, 12 patients died in the acute stage (11.9%). Twenty-three (22.8%) patients recovered to moderate disability at 3 months (mRS ≤ 3), 45 (44.6%) to severe disability and 33 (32.6%) suffered a poor outcome (mRS 5 or 6). Twenty patients (19.8%) required additional necrosectomy due to secondary increasing midline shift and/or intracranial hypertension. Patients recovering to moderate disability at 3 months were in the median 10 years younger than patients with less favorable outcome (P

Posterior reversible encephalopathy syndrome (PRES) is a clinico-neuroradiological syndrome associated with various clinical conditions, such as headache, encephalopathy, and seizures. It is reversible if a prompt diagnosis is made and treatment undertaken. We report a 52-year-old male with hypertensive crisis. Progressing somnolence and an unresponsive left pupil occurred. MRI revealed an intra-axial hyperintensity of the cerebellum and brainstem and occlusive hydrocephalus suggestive of encephalitis or a tumor. Because of the life-threatening clinical picture, posterior fossa decompression was performed. Histopathology failed to identify any pathology. After decompression, the edema improved immediately. Under life-threatening conditions, a decompressive craniectomy in PRES seems to achieve the same results as supportive treatment.

Objectives The pathophysiology of traumatic brain injury (TBI) largely involves the brains vascular structural integrity. We analyzed the value of an intraoperative cortical indocyanine green (ICG) angiography in patients with severe TBI and acute subdural hematoma who underwent decompressive craniectomy. Methods ICG-derived fluorescence curves of cortex and cerebral vessels were recorded by the use of software integrated into a surgical microscope in 10 patients. The maximum intensity, rise time (RT), time to peak, and residual fluorescence intensity (FI) were estimated from cortical arteries, the parenchyma, and veins. Results ICG-derived fluorescence parameters were correlated with the short-term outcome 3 months after discharge. Five patients had a favorable and 5 an unfavorable outcome. Patients with a favorable outcome showed a significant longer RT in the arteries and a trend towards a significant longer RT in the veins. Overall mean residual FI was 47.5 ± 6.8% for the arteries, 45.0 ± 7% for the parenchyma and 57.6 ± 6% for the veins. The residual FI of the parenchyma and the veins was significantly greater in patients with an unfavorable clinical outcome. Conclusions Patients with an unfavorable clinical outcome showed an altered shape of the ICG-derived fluorescence curve, a shorter increase of the ICG-derived fluorescence intensity in the cortical arteries, and significantly greater residual fluorescence intensity. These observations are likely a correlate of an increased intracranial pressure, a capillary leak, and venous congestion. Intraoperative quantification of the ICG-derived fluorescence might help to appreciate the clinical outcome in patients with severe TBI.

Introduction Sudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy. One aspect not included in current models of SUDEP is the role of increased intracranial pressure (ICP) which can be observed immediately upon seizure activity in neurosurgical practice. Methods We conducted a systematic review of the occurrence of edema in patients with epilepsy reported to have died of sudden death who underwent brain autopsy or postmortem brain imaging and discuss how increased ICP may contribute to clinical features of SUDEP. Results 19 eligible studies comprising a total of 623 patients were identified. Edema—mostly mild or moderate—was reported in 17% of cases and 74% of studies. 1% (n = 6) of the overall cases were clearly identified as having Dravet syndrome or an SCN1A mutation. In these patients, edema was found in 4 (67%) of cases. Conclusion Edema is regularly found in patients with epilepsy classified to have died from SUDEP. We argue that seizures preceding SUDEP may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to sudden death of patients with epilepsy. Furthermore, we hypothesize that mild edema may especially progress to severe edema in patients with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations., Seizures may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to SUDEP. We hypothesize that mild edema may especially progress to severe edema in certain patients e.g. those with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations.

Clinical prediction models in neurosurgery are increasingly reported. These models aim to provide an evidence-based approach to the estimation of the probability of a neurosurgical outcome by combining 2 or more prognostic variables. Model development and model reporting are often suboptimal. A basic understanding of the methodology of clinical prediction modeling is needed when interpreting these models. We address basic statistical background, 7 modeling steps, and requirements of these models such that they may fulfill their potential for major impact for our daily clinical practice and for future scientific work.

Vaccination therapy using tumour antigen-loaded, autologous dendritic cells (DC) is a promising therapeutic approach alongside standard treatment for glioblastoma (GBM). However, reliable diagnostic criteria regarding therapy monitoring are not established. Here, we analysed the impact of additionalWe analysed data of GBM patients who received DC vaccination therapy. Following MRI diagnosis of tumour recurrence, additional static and dynamicBetween 2003 and 2016, 5 patients were identified who received DC vaccination andDespite the small patients number our results indicate an additional impact of

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.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.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.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.

Reported data regarding the relation between the incidence of spontaneous subarachnoid hemorrhage (SAH) and weather conditions are conflicting and do so far not allow prognostic models. Admissions for spontaneous SAH (ICD I60.*) 2009–2018 were retrieved form our hospital data base. Historical meteorological data for the nearest meteorological station, Dusseldorf Airport, was retrieved from the archive of the Deutsche Wetterdienst (DWD). Airport is in the center of our catchment area with a diameter of approximately 100 km. Pearson correlation matrix between mean daily meteorological variables and the daily admissions of one or more patients with subarachnoid hemorrhage was calculated and further analysis was done using deep learning algorithms. For the 10-year period from January 1, 2009 until December 31, 2018, a total of 1569 patients with SAH were admitted. No SAH was admitted on 2400 days (65.7%), 1 SAH on 979 days (26.7%), 2 cases on 233 days (6.4%), 3 SAH on 37 days (1.0%), 4 in 2 days (0.05%), and 5 cases on 1 day (0.03%). Pearson correlation matrix suggested a weak positive correlation of admissions for SAH with precipitation on the previous day and weak inverse relations with the actual mean daily temperature and the temperature change from the previous days, and weak inverse correlations with barometric pressure on the index day and the day before. Clustering with admission of multiple SAH on a given day followed a Poisson distribution and was therefore coincidental. The deep learning algorithms achieved an area under curve (AUC) score of approximately 52%. The small difference from 50% appears to reflect the size of the meteorological impact. Although in our data set a weak correlation of the probability to admit one or more cases of SAH with meteorological conditions was present during the analyzed time period, no helpful prognostic model could be deduced with current state machine learning methods. The meteorological influence on the admission of SAH appeared to be in the range of only a few percent compared with random or unknown factors.

Decompressive craniectomy (DC) is an established neurosurgical emergency technique. Patient selection, optimal timing, and technical aspects related to DC and subsequent cranioplasty remain subjects of debate. For children, the overall degree of evidence is low, compared with randomized controlled trials (RCTs) in adults. Here, we present a detailed retrospective analysis of pediatric DC, covering the primary procedure and cranioplasty. Results are analyzed and discussed in the light of modern scientific evidence, and conclusions are drawn to stimulate future research. The main indication for DC in children is traumatic brain injury (TBI). Primary and secondary DC is performed with similar frequency. Outcome appears to be better than that in adults, although long-term complications (especially bone flap resorption after autologous cranioplasty) are more common in children. Overt clinical signs of cerebral herniation prior to DC are predictors of poor outcome. We conclude that DC is an important option in the armamentarium to treat life-threatening intracranial hypertension, but further research is warranted, preferentially in a multicenter prospective registry.

Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology.

Background: The invasiveness and risk of thromboembolic complications of catheter angiography underline the need for alternative imaging modalities in patients following intracranial aneurysm (IA) repair. However, the overall image quality of existing noninvasive imaging modalities, such as single-energy CT angiography (SE-CTA), compromises its value in this respect. Objective: We prospectively investigated the value of a novel dual-energy CTA (DE-CTA) scanner and algorithm for assessing the degree of occlusion and parent vessel patency in patients following IA repair. Methods: A prospective cohort of 17 patients underwent DE-CTA imaging following surgical or endovascular IA repair. This dataset was matched with an identical historical cohort of 17 patients, who underwent IA repair and SE-CTA imaging. Beam-hardening artifacts, as a measure for objective imaging quality were analyzed based on the volume of a prolate ellipsoid, whereas subjective imaging quality at the IA site and corresponding parent vessels was rated by 2 independent neuroradiologists on a scale from 4 (excellent, no artifacts) to 1 (poor, severe artifacts). Results: Objective DE-CTA image quality was markedly higher, compared to SE-CTA in patients undergoing surgical (0.77 ± 0.23 vs. 10.91 ± 1.88 mL, respectively; p < 0.001) or endovascular (32.36 ± 10.62 vs. 107.63 ± 24.51 mL, respectively; p = 0.026) IA repair. Subjective image quality for DE-CTA was significantly improved compared to SE-CTA in the surgical group but not in the endovascular group. The calculated dose values for DE-CTA in our study remain markedly below the legally required radiation dose limits. Conclusion: The imaging quality of DE-CTA, especially for patients undergoing surgical IA repair, is distinctly superior, compared to SE-CTA imaging. Therefore, DE-CTA may serve as a noninvasive alternative for assessing the IA occlusion rate and parent vessel patency.

Background Incomplete resection of pituitary adenomas may result in recurrence. As adjuvant irradiation is not riskless, alternative treatment options should be investigated. 5-aminolevulinic acid based photodynamic therapy (5-ALA based PDT) showed promising results for malignant gliomas. The present study examined the efficacy of 5-ALA PDT in vitro on benign pituitary adenoma cell cultures. Methods In group I experiments were performed on immortalized rat pituitary adenoma cells (GH3). The cultured cells were treated with different 5-ALA concentrations ranging from 7.5–16.5 μg/ml. In Group II human pituitary adenoma cell cultures were obtained from surgically resected adenoma tissue ( n = 15). These were incubated with 5-ALA concentrations from 12.5–100 μg/ml. The concentration ranges had been determined in preliminary dose-finding tests. For both groups incubation time was four hours and PDT was performed by exposition to laser light (635 nm, 625 s, 18.75 J/cm 2 ). Cell viability was examined by WST-1 assay. Results In both groups PDT showed a 5-ALA concentration-dependent effect on cell death. In group I lower 5-ALA concentrations were necessary to destroy all cells as compared to group II. Moreover, in group II, the different subtypes of human adenomas showed different sensitivities to 5-ALA-based PDT (secreting vs . non-secreting). Especially corticotroph adenomas were highly sensitive to 5-ALA PDT. Conclusions The GH3 cell line was an useful in vitro model to optimize different PDT parameters. Human pituitary adenoma cells could also be killed by 5-ALA PDT, however this required higher 5-ALA concentrations. Furthermore, the results suggested different 5-ALA sensitivities between different human adenoma cell types. More experiments are necessary to confirm these preliminary results.

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.

Background Integrity of intervertebral disks may influence, and be influenced by, the maintenance of hydrostatic pressures inside the nucleus pulposus. Disk degeneration causes decreased pressures, leading to overload and injury of the annulus fibrosus, increasing the risk of disk herniation. Diskectomies to treat disk herniation can cause further loss of hydrostatic pressures resulting in worsening degeneration. This study investigated the impact of opening the annulus on intradiscal pressure and whether implantation of an annular closure device (ACD) can restore physiologic pressures. Methods The pressure responses under unconstrained moments in concert with axial compressive loads of nine human cadaver lumbar disks were biomechanically tested at baseline, immediately following posterior annulotomy, and immediately following implantation of the ACD. Results The analysis of variance indicated a significant difference in the pressure response (p = 0.0001) among the three rounds of testing. Specifically, the post hoc Bonferroni test revealed that the pressure response after diskectomy was significantly different when compared with baseline (p Conclusion Our findings suggest that restoration of annular integrity during diskectomy with implantation of the tested ACD may restore pressures closer to preoperative levels. Whether or not restoring pressures to preoperative levels has any clinical benefit or effect on the rate of degeneration is an area for further clinical research.

Intracranial metastases are the most frequent brain tumor with recurrence rates after treatment of around 40–60%. Age is still considered a determinant of treatment and prognosis in this pathology. Recent studies analyzing the impact of metastasectomy in elderly patients focused on reporting perioperative mortality and morbidity rates but not on the evaluation of oncological outcome parameters. Aim of this study is to determine risk factors for in-brain local recurrence after brain surgery in this sub-population. From October 2009 until September 2016 all patients aged 65 years and above with histopathologically confirmed metastasis after surgical resection were retrospectively studied. Clinical, radiological and perioperative information was collected and statistically analysed. Follow-up consisted of clinical and radiological assessment every 3-months following surgery. 78 patients were included, of these 50% were female (39 patients). Median age was 71 years (66–83). Early postoperative-MRI verified a complete surgical resection in 41 patients (52.6%) and showed a tumor-remnant in 15 patients (19.2%). In 22 patients the MRI result was inconclusive (28.2%). None of the patients experienced severe complications due to surgery. The median postoperative NIHSS was adequate 1 ± 1.4 (0–6), nonetheless, insignificantly improved in comparison to the preoperative NIHSS (p = 0.16). A total of 20 patients (25.6%) presented local recurrence. The only statistically significant factor for development of local in-brain recurrence after resection of cerebral metastases in patients above 65 years of age was a tumor-remnant in the early postoperative MRI (p = 0.00005). Median overall survival was 13 months. Local in-brain recurrence after surgical resection of a cerebral metastasis in patients above 65 years of age was 25.6%. In our analysis, tumor-remnant in early postoperative MRI is the only risk factor for local in-brain recurrence. Oncological parameters in the present cohort do not seem to differ from recent phase III studies with non-geriatric patients. Nevertheless, controlled studies on the impact of metastasectomy in elderly patients delivering high quality reliable data are required.

The main aim in treatment of aneurysmal subarachnoid haemorrhage (aSAH) is prevention of rebleeding because rebleeding carries a high risk of poor outcome including death. Some studies have advocated ultra-early treatment (

Currently, there is no known time frame when the patients are the most responsive during awake craniotomy. The aim of this work is therefore to determine when the patient has the shortest reaction time and so to extrapolate the optimal time window for cortical mapping. In this analytic observational study, our group has recorded the reaction times of 35 patients undergoing an awake craniotomy and compared them with the preoperative baseline. The operations were performed according to a "sleep-awake-awake" protocol. Data collection was performed in parallel with standard methods for evaluation of language and cognitive functions. The preoperative reaction times of our patient cohort (average ± SD = 510 ± 124 ms) were significantly shorter than those measured during the operation 786 ± 280 ms, p .001. A one-factor ANOVA within subjects showed a significant increase in reaction times; p .001. Post hoc comparisons on a Bonferroni-corrected α-error level of .05 showed significant differences between the reaction speed during the 0-10 min time frame and the preoperative baseline, as well as the intraoperative reaction times during the 20-30 min, 30-40 min, and the t 40 min time frames. In conclusion, measurement of intraoperative reaction speed seems to be a technically feasible method that is well tolerated by the patients. The intraoperative reaction speed performance was shown to be significantly slower than on the day before the operation. The patients seem to be the slowest directly after extubation and gradually wake up during the awake phase. The poorest wakefulness is demonstrated during the first 20 min after extubation.

The key to becoming an expert in a surgical field is mainly practice and perseverance. The old-fashioned system of teaching from one older person to a younger one, by simple demonstration, imitation, and practice, cannot be replaced in the surgical field by more modern didactic tools. Structured and explicit concepts, however, can accelerate the learning process. Structured concepts consist of a system of specifics-for example, types of aneurysms in the field of vascular pathology-and standard operating procedures. It is important to realize that the teaching requirements of the surgical disciplines differ substantially from those of the conservative disciplines. The number of procedures performed is probably the most critical factor for competence. At our center we have used the target number of 100 microsurgical aneurysm cases treated under supervision before sufficient competence is considered to have been achieved for independent surgery. Following initial training a certain amount of practice is required to remain current or competent. The proficiency requirements accepted in aviation could be seen as a guide for proficiency requirements in neurosurgery. In aviation, a minimum of 12 per year is specified for most critical procedures.

Background Minimally invasive surgery of small skull base meningiomas is technically challenging. We report the role of endoscopic 5-aminolevulinic acid fluorescence guidance (e-5-ALA-FGS) for small and deep-seated anterior skull base meningiomas. Methods We report the cases of 2 patients. The first case was a small olfactory groove meningioma resected via a trans-eyebrow, subfrontal approach. The second case was a clinoid meningioma with invasion of the optic canal resected via a small frontolateral approach. Intraoperative documentation demonstrated the usefulness of 5-ALA endoscopy. In either case, residual fluorescing tumor tissue was detected. No complication was encountered. The clinical and radiological outcomes were good. No regrowth had occurred after 54 and 17 months of follow-up, respectively. Results Residual meningioma tissue on the far side of a keyhole approach (e.g., in the olfactory groove or at the optic canal) can be difficult to visualize. Visualization can be improved by use of an endoscope. To date, fluorescence guidance with a microscope was limited by insufficient fluorescence signals in deep corridors. With a specially equipped 5-ALA fluorescence endoscope, one can combine the advantages of both endoscopic vision and fluorescence guidance. The results of present report have demonstrated the usefulness of 5-ALA endoscopy for difficult to visualize areas. Conclusion Endoscopic 5-ALA fluorescence guidance was shown to be feasible when resecting small and deep-seated skull base meningiomas via minimally invasive approaches. Based on this proof of principle, we encourage its evaluation for the middle or posterior fossa (e.g., internal auditory canal) and other difficult areas (e.g., behind neurovascular structures or the brainstem). The sensitivity and specificity of this method should be prospectively and systematically investigated.

There is limited data regarding malpractice claims in pediatric neurosurgery. Aim of this study was to analyze the rate, subject, and outcome of malpractice claims faced by pediatric neurosurgeons. We analyzed malpractice claims in pediatric neurosurgical patients assigned to the review board of North Rhine Medical Council from 2012 to 2016. Claims were categorized as “medical error” or “adverse event, no medical error.” Severity was graded from negligible (grade 1) to death (grade 6). Of 391 pediatric malpractice claims, seven (1.8%) concerned pediatric neurosurgery. Claims were related to cranial surgery (N = 5), spinal surgery (N = 1), and a neuro-interventional procedure (N = 1). Of operative cases, three were shunt operations, two were cranioplasty procedures, and one was a spinal fusion. Complications of medical care (adverse events) had occurred in all cases. A medical error was detected in only one case. Severity of damage was grade 2 (transient minor) in three, grade 3 (transient major) in one, and grade 5 (permanent major) in three cases, respectively. Pediatric neurosurgery accounted for 1.8% of all pediatric malpractice claims. In 14% of these claims, a medical error was confirmed. Malpractice claim rate thus appears to be lower than expected for a high-risk specialty. , adverse events were confirmed in all cases, a negligent medical error was rare. Adverse event rate appears to be a predictor for malpractice claim burden, highlighting the importance of surgical checklists, standard operating procedures and morbidity and mortality surveillance.

Craniocerebral disproportion (CCD) can occur as a sequela after shunting in early infancy. It can be understood as a disorder closely related to slit ventricle syndrome and chronic overdrainage syndrome. Here, we present two exemplary cases and summarize the pathophysiological, diagnostic, and therapeutic approaches to CCD. Two premature babies underwent shunting for posthemorrhagic hydrocephalus and presented in later childhood with recurrent episodes of symptomatic raised intracranial pressure (ICP) at 2 and 8 years of age, respectively. Both patients had unchanged ventricular size on cranial imaging and fulfilled the clinical diagnostic criteria of CCD. After confirming shunt patency, ICP monitoring was performed to diagnose intermittent intracranial hypertension. Different treatment pathways were pursued: While readjustment of a programmable shunt valve was sufficient to alleviate the raised ICP in the first case, a cranial expansion surgery was necessary in the second case. Both children were treated successfully after thorough assessment and careful choice of treatment approaches. This review provides detailed insight into CCD and highlights the importance of individual and critical decision-making in these complex patients.