Surgical and endovascular cerebral revascularization for cerebral vasculitis with inflammatory vessel stenosis: a case series.

Autoimmune vasculitides affect the cerebral vasculature significantly in a considerable number of cases. When immunosuppressive treatments fail to prevent stenosis in cerebral vessels, treatment options for affected patients become limited. In this case series, we present four cases of pharmacoresistant vasculitis with recurrent transient ischemic attacks (TIAs) or stroke successfully treated with either extracranial-intracranial (EC-IC) bypass surgery or endovascular stenting. Both rescue treatments were effective and safe in the selected cases. Our experience suggests that cases of pharmacoresistant cerebral vasculitis with recurrent stroke may benefit from rescue revascularization in combination with maximum medical management.

mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells.

The cardiovascular risk factors, including smoking, ethanol, and oxidative stress, can induce cellular senescence. The senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase (MMPs). These pro-inflammatory molecules and MMPs promote the infiltration and accumulation of inflammatory cells in the vascular tissue, exacerbating vascular tissue inflammation. MMPs damage vascular tissue by degenerating the extracellular matrix. Consequently, these cellular and molecular events promote the initiation and progression of cardiovascular diseases. We used Rapalink-1, an mTOR inhibitor, to block ethanol-induced senescence. Rapalink-1 inhibited oxidative-stress-induced DNA damage and senescence in endothelial cells exposed to ethanol. It attenuated the relative protein expression of senescence marker P21 and improved the relative protein expression of DNA repair protein KU70 and aging marker Lamin B1. It inhibited the activation of NF-κB, MAPKs (P38 and ERK), and mTOR pathway proteins (mTOR, 4EBP-1, and S6). Moreover, Rapalink-1 suppressed ethanol-induced mRNA expression of ICAM-1, E-selectin, MCP-1, IL-8, MMP-2, and TIMP-2. Rapalink-1 also reduced the relative protein expression of MMP-2. In summary, Rapalink-1 prevented senescence, inhibited pro-inflammatory pathway activation, and ameliorated pro-inflammatory molecule expression and MMP-2.

Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases.

BACKGROUND: Smoking, alcohol abuse, and hypertension are - among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenotype (SASP). The SASP factors in feed-forward response exacerbate inflammation and cause tissue remodeling, resulting in atherosclerotic plaque formation and rupture. RESULTS: Colchicine inhibited ROS generation and mitigated oxidative stress-induced DNA damage. It dampened oxidative stress-induced endothelial cell senescence and improved the expression of DNA repair protein KU80 and aging marker Lamin B1. The drug attenuated the expression of senescence marker P21 at mRNA and protein levels. The pathway analysis showed that colchicine inhibited NF-κB and MAPKs pathways and subdued mTOR activation. Colchicine also attenuated mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, MCP-1, ICAM-1, and E-selectin. Furthermore, colchicine reduced the mRNA and protein expression of matrix metalloproteinase (MMP-2). CONCLUSION: In summary, colchicine blocked oxidative stress-induced senescence and SASP by inhibiting the activation of NF-κB and MAPKs pathways.

Endoscopic endonasal pituitary surgery: How we do it. Consensus statement on behalf of the EANS skull base section.

Introduction and research question: The use of an endoscope in skull base surgery provides a panoramic close-up view over the intracranial structures from multiple angles with excellent illumination, thus permitting greater extent of resection of tumors arising at sellar area, mostly represented by PitNet - Pituitary neuroendocrine tumors, with higher likelihood of preserving vital/intact gland tissue. For this refined specialty of neurosurgery, unique skills need to be acquired along a steep learning curve. Material and methods: EANS (European Association of Neurosurgical Societies) skull base section panelists were enrolled and 11 completed the survey: the goal was to provide a consensus statement of the endoscopic endonasal approach for pituitary adenoma surgery. Results: The survey consisted of 44 questions covering demographics data (i.e., academic/non-academic center, case load, years of experience), surgical techniques (i.e., use of neuronavigation, preoperative imaging), and follow-up management. Discussion and conclusions: In this paper we identified a series of tips and tricks at different phases of an endoscopic endonasal pituitary surgery procedure to underline the crucial steps to perform successful surgery and reduce complications: we took in consideration the principles of the surgical technique, the knowledge of the anatomy and its variations, and finally the importance of adjoining specialties experts.

Differences in intraoperative sampling during meningioma surgery regarding CNS invasion - Results of a survey on behalf of the EANS skull base section.

Introduction: and Research Question: Invasive growth of meningiomas into CNS tissue is rare but of prognostic significance. While it has entered the WHO classification as a stand-alone criterion for atypia, its true prognostic impact remains controversial. Retrospective analyses, on which the current evidence is based, show conflicting results. Discordant findings might be explained by different intraoperative sampling methodologies. Material and methods: To assess the applied sampling methods in the light of the novel prognostic impact of CNS invasion, an anonymous survey was designed and distributed via the EANS website and newsletter. The survey was open from June 5th until July 15th, 2022. Results: After exclusion of 13 incomplete responses, 142 (91.6%) datasets were used for statistical analysis. Only 47.2% of participants' institutions utilize a standardized sampling method, and 54.9% pursue a complete sampling of the area of contact between the meningioma surface and CNS tissue. Most respondents (77.5%) did not change their sampling practice after introduction of the new grading criteria to the WHO classification of 2016. Intraoperative suspicion of CNS invasion changes the sampling for half of the participants (49.3%). Additional sampling of suspicious areas of interest is reported in 53.5%. Dural attachment and adjacent bone are more readily sampled separately if tumor invasion is suspected (72.5% and 74.6%, respectively), compared to meningioma tissue with signs of CNS invasion (59.9%). Discussion and conclusions: Intraoperative sampling methods during meningioma resection vary among neurosurgical departments. There is need for a structured sampling to optimize the diagnostic yield of CNS invasion.

Update in Cushing disease: What the neurosurgeon has to KNOW, on behalf of the EANS skull base section.

Introduction: Cushing's disease is a state of chronic and excessive cortisol levels caused by a pituitary adenoma. Research question: CD is a complex entity and often entails difficulties in its diagnosis and management. For that reason, there are still controversial points to that respect. The aim of this consensus paper of the skull base section of the EANS is to review the main aspects of the disease a neurosurgeon has to know and also to offer updated recommendations on the controversial aspects of its management. Material and methods: PUBMED database was used to search the most pertinent articles published on the last 5 years related with the management of CD. A summary of literature evidence was proposed for discussion within the EANS skull base section and other international experts. Results: This article represents the consensual opinion of the task force regarding optimal management and surgical strategy in CD. Discussion and conclusion: After discussion in the group several recommendations and suggestions were elaborated. Patients should be treated by an experienced multidisciplinary team. Accurate clinical, biochemical and radiological diagnosis is mandatory. The goal of treatment is the complete adenoma resection to achieve permanent remission. If this is not possible, the treatment aims to achieving eucortisolism. Radiation therapy is recommended to patients with CD when surgical options have been exhausted. All patients in remission should be tested all life-long.

Olfactory Groove Meningiomas: Comprehensive assessment between the different microsurgical transcranial approaches and the Endoscopic Endonasal Approaches, systematic review and metanalysis on behalf of the EANS skull base section.

•OGM surgery is much more complex than a simple debate of "from above or from below" (transcranial vs endoscopic).•Lateral Sub-frontal and Superior Interhemispheric seem the most effective, superior and versatile approaches for OGM.•Minimally Invasive Transcranial approaches showed no inferiority in OGM sized <4 â€‹cm.•Endoscopic Endonasal Approaches showed inferior results in surgical and in functional outcomes for OGM.

Aggressive pituitary neuroendocrine tumors: current practices, controversies, and perspectives, on behalf of the EANS skull base section.

Aggressive pituitary neuroendocrine tumors (APT) account for 10% of pituitary tumors. Their management is a rapidly evolving field of clinical research and has led pituitary teams to shift toward a neuro-oncological-like approach. The new terminology "Pituitary neuroendocrine tumors" (PitNet) that was recently proposed to replace "pituitary adenomas" reflects this change of paradigm. In this narrative review, we aim to provide a state of the art of actual knowledge, controversies, and recommendations in the management of APT. We propose an overview of current prognostic markers, including the recent five-tiered clinicopathological classification. We further establish and discuss the following recommendations from a neurosurgical perspective: (i) surgery and multi-staged surgeries (without or with parasellar resection in symptomatic patients) should be discussed at each stage of the disease, because it may potentialize adjuvant medical therapies; (ii) temozolomide is effective in most patients, although 30% of patients are non-responders and the optimal timeline to initiate and interrupt this treatment remains questionable; (iii) some patients with selected clinicopathological profiles may benefit from an earlier local radiotherapy and/or chemotherapy; (iv) novel therapies such as VEGF-targeted therapies and anti-CTLA-4/anti-PD1 immunotherapies are promising and should be discussed as 2nd or 3rd line of treatment. Finally, whether neurosurgeons have to operate on "pituitary adenomas" or "PitNets," their role and expertise remain crucial at each stage of the disease, prompting our community to deal with evolving concepts and therapeutic resources.

Ciprofloxacin enhances phototoxicity of 5-aminolevulinic acid mediated photodynamic treatment for chordoma cell lines.

BACKGROUND: Chordoma are uncommon aggressive tumors of the skeleton. Surgical resection is often subtotal and adjuvant treatment possibilities are limited as chordomas are highly chemo- and radioresistant. In the present study we examined the impact of 5-ALA PDT on different human chordoma cell lines. Furthermore, we investigated the variation of two parameters: (1.) 5-ALA incubation time and (2.) supplemental use of ciprofloxacin as iron chelator. METHODS: Experiments were realized in vitro with three different human chordoma cell lines: U-CH2, U-CH2B and U-CH14. After pre-incubation for 24 h with various concentrations of ciprofloxacin (1.5 - 5.0 µg/ml), different amounts of 5-ALA (15 - 50 µg/ml) were applied to the cells either for a brief (4 h) or a long (6 h) incubation time. Subsequently cells were exposed to photodynamic radiation. Cell viability was exploited by WST-1 assay. Thus, for each of the three cell lines, two drug combinations (ciprofloxacin plus 5-ALA and 5-ALA only) and two incubation times (short, 4 h and long, 6 h) were tested. Negative control groups were also examined. RESULTS: Supplemental use of ciprofloxacin led to increased cell death in each of the cell lines. Different 5-ALA incubation times (4 h vs. 6 h) showed no significant differences in cell viability except for U-CH2. CONCLUSION: Ciprofloxacin as an ordinary applied antibiotic, enhanced the effect of 5-ALA PDT on different human chordoma cell lines in vitro. The impact was dependent on the dose of ciprofloxacin-5-ALA. There were no notable differences for the tested 5-ALA incubation times. In human chordoma cell lines 5-ALA PDT may effectively be amended by ciprofloxacin.

Quantification of PpIX-fluorescence of cerebral metastases: a pilot study.

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; Sidák-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.

Is the Intensity of 5-Aminolevulinic Acid-Derived Fluorescence Related to the Light Source?

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.

Risk factors for in-brain local progression in elderly patients after resection of cerebral metastases.

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.

Compression Syndromes of the Vertebral Artery at the Craniocervical Junction.

Compression syndromes of the vertebral artery that occur at the craniocervical junction are extremely rare causes of haemodynamic insufficiency of the posterior cerebral circulation. The aetiology of the compression syndrome may be a malformation, trauma, tumour, infection or degenerative pathology. This may lead to dynamic vertebral artery occlusion where the vessel courses around the atlas and the axis-the so-called V3 segment. This in turn may result in insufficient collateral flow to the posterior fossa. The clinical picture is a vertebrobasilar insufficiency syndrome of variable expression ranging from vertigo to posterior fossa stroke. The typical clinical presentation is syncope occurring during rotation of the head, also known as 'bow hunter's syndrome'. The workup is based on dynamic angiography and computed tomography angiography. The treatment of choice is surgical vascular decompression, resulting in a good clinical outcome. However, in some instances, atlantoaxial fusion may be indicated. Alternatively, conservative and endovascular options have to be considered in inoperable patients.

Surgery of Small Anterior Skull Base Meningiomas by Endoscopic 5-Aminolevulinic Acid Fluorescence Guidance: First Clinical Experience.

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.

Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection technique was first introduced for malignant glioma. However, the impact of the 5-ALA fluorescence behaviour of cerebral metastases is still unclear. Aim of this study was to determine the impact of PpIX-fluorescence on the local progression-free and overall survival. MATERIALS AND METHODS: A secondary analysis was performed and included an updated follow-up of 136 patients comprised in two previous studies. Additionally, 82 new patients were included. All patients underwent surgical resection of cerebral metastasis and intraoperative estimation of 5-ALA-induced fluorescence. The 5-ALA fluorescence behaviour of cerebral metastases was correlated with the rate of local recurrences, the local progression-free and overall survival. RESULTS: 218 patients suffering from cerebral metastatic spread fulfilled the inclusion criteria and were analysed: complete surgical resection could be achieved in 123/218 patients (56.4%). Dichotomised degree of surgical resection (complete vs. incomplete or questionable complete resection) was not related to dichotomized 5-ALA fluorescence of cerebral metastases (p = 0.66). 51 patients (23.4%) developed a local in-brain progression within or at the border of the resection cavity. Of these, 8 patients showed a PpIX-fluorescent metastasis. There was a trend towards a correlation between a higher local in-brain progression in PpIX-non-fluorescent metastases (p = 0.03). Median time to local in-brain progression was 4 ± 11 months. PpIX-fluorescent and PpIX-non-fluorescent metastases showed a significantly different progression-free survival (p = 0.01). PpIX-positive and -negative metastases showed a significantly different overall survival (20 and 14 months respectively; p = 0.006). CONCLUSION: The 5-ALA fluorescence behaviour was related to the local progression-free and the overall survival in the present retrospective series and might be considered a prognostic marker. Further studies are required to appreciate the oncological impact of the 5-ALA induced fluorescence behaviour of cerebral metastases.

Continuous and Dynamic Facial Nerve Mapping During Surgery of Cerebellopontine Angle Tumors: Clinical Pilot Series.

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.

Bow Hunter's Syndrome Caused by Compression of the Subaxial Vertebral Artery: Surgical Technique of Anterolateral Decompression (video).

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.

Predictors for a further local in-brain progression after re-craniotomy of locally recurrent cerebral metastases.

Treatment of recurrent cerebral metastases is an emerging challenge due to the high local failure rate after surgery or radiosurgery and the improved prognosis of patients with malignancies. A total of 36 patients with 37 metastases who underwent surgery for a local in-brain progression of a cerebral metastasis after previous metastasectomy were retrospectively analyzed. Degree of surgical resection on an early postoperative MRI within 72 h after surgery was correlated with the local in-brain progression rate and overall survival. Complete surgical resection of locally recurrent cerebral metastases as confirmed by early postoperative MRI could only be achieved in 37.8%. Detection of residual tumor tissue on an early MRI following recurrent metastasis surgery correlated with further local in-brain progression when defining a significance level of p = 0.05 but not after Sidák or Bonferroni significance level correction for multiple testing: However, definite local tumor control could finally be achieved in 91.9% after adjuvant therapy. Overall survival after recurrent metastasectomy was significantly higher as predicted by diagnosis-specific graded prognostic assessment (12.9 ± 2.3 vs. 8.4 ± 0.7 months; p < 0.0001). However, our series involved a limited number of heterogeneous patients. A larger, prospective, and controlled study is required. Considering the adequate local tumor control achieved in the vast majority of patients, surgery of recurrent metastases may represent one option in a multi-modal treatment approach of patients suffering from locally recurrent cerebral metastases.

5-ALA-Induced Fluorescence in Leptomeningeal Dissemination of Spinal Malignant Glioma.

BACKGROUND: 5-Aminolevulinic acid (5-ALA)-fluorescence-guided resection of malignant glioma is well established in many neuro-oncology departments. In addition, the use of 5-ALA has been reported for cerebral metastases, meningioma, and spinal tumors. We report a case of a patient with a leptomeningeal spread of a K27M-mutated spinal anaplastic astrocytoma (World Health Organization° [WHO] III), which was detected by its faint 5-ALA-induced fluorescence. CASE DESCRIPTION: A 26-year-old female patient with an incomplete resection of a spinal astrocytoma (WHO II) at Th1-Th3 was treated with adjuvant combined radiotherapy/chemotherapy. After 4 years the patient suffered from a progressive paraplegia. Magnetic resonance imaging of the central nervous system showed no local progression of the spinal astrocytoma but an extensive disseminated leptomeningeal tumor formation. The cerebrospinal fluid of the patient obtained by lumbar puncture showed no indication of malignant cells in the cytopathologic examination. An open biopsy with preoperative administered 5-ALA with excision of the sensory nerve root from the cauda equina was performed. The biopsy showed a clearly light pink 5-ALA-induced fluorescence. The histopathologic examination confirmed a leptomeningeal spread of a K27M-mutated anaplastic astrocytoma (WHO° III) without R132H-IDH1 mutation. CONCLUSIONS: Previous application of 5-ALA might intraoperatively help to visualize and identify leptomeningeal spread.

Effect of augmentation techniques on the failure of pedicle screws under cranio-caudal cyclic loading.

PURPOSE: Augmentation of pedicle screws is recommended in selected indications (for instance: osteoporosis). Generally, there are two techniques for pedicle screw augmentation: inserting the screw in the non cured cement and in situ-augmentation with cannulated fenestrated screws, which can be applied percutaneously. Most of the published studies used an axial pull out test for evaluation of the pedicle screw anchorage. However, the loading and the failure mode of pullout tests do not simulate the cranio-caudal in vivo loading and failure mechanism of pedicle screws. The purpose of the present study was to assess the fixation effects of different augmentation techniques (including percutaneous cement application) and to investigate pedicle screw loosening under physiological cyclic cranio-caudal loading. METHODS: Each of the two test groups consisted of 15 vertebral bodies (L1-L5, three of each level per group). Mean age was 84.3 years (SD 7.8) for group 1 and 77.0 years (SD 7.00) for group 2. Mean bone mineral density was 53.3 mg/cm3 (SD 14.1) for group 1 and 53.2 mg/cm3 (SD 4.3) for group 2. 1.5 ml high viscosity PMMA bone cement was used for all augmentation techniques. For test group 1, pedicles on the right side of the vertebrae were instrumented with solid pedicle screws in standard fashion without augmentation and served as control group. Left pedicles were instrumented with cannulated screws (Viper cannulated, DePuy Spine) and augmented. For test group 2 pedicles on the left side of the vertebrae were instrumented with cannulated fenestrated screws and in situ augmented. On the right side solid pedicle screws were augmented with cement first technique. Each screw was subjected to a cranio-caudal cyclic load starting at 20-50 N with increasing upper load magnitude of 0.1 N per cycle (1 Hz) for a maximum of 5000 cycles or until total failure. Stress X-rays were taken after cyclic loading to evaluate screw loosening. RESULTS: Test group 1 showed a significant higher number of load cycles until failure for augmented screws compared to the control (4030 cycles, SD 827.8 vs. 1893.3 cycles, SD 1032.1; p < 0.001). Stress X-rays revealed significant less screw toggling for the augmented screws (5.2°, SD 5.4 vs. 16.1°, SD 5.9; p < 0.001). Test group 2 showed 3653.3 (SD 934) and 3723.3 (SD 560.6) load cycles until failure for in situ and cement first augmentation. Stress X-rays revealed a screw toggling of 5.1 (SD 1.9) and 6.6 (SD 4.6) degrees for in situ and cement first augmentation techniques (p > 0.05). CONCLUSION: Augmentation of pedicle screws in general significantly increased the number of load cycles and failure load comparing to the nonaugmented control group. For the augmentation technique (cement first, in situ augmented, percutaneously application) no effect could be exhibited on the failure of the pedicle screws. By the cranio-caudal cyclic loading failure of the pedicle screws occurred by screw cut through the superior endplate and the characteristic "windshield-wiper effect", typically observed in clinical practice, could be reproduced.