Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Retrospective Analysis of Risk Factors for Recurrence of Chronic Subdural Haematoma after Surgery.

(1) Background: In this study, epidemiological, clinical, therapeutical, and haemostaseological variables were investigated regarding their correlation with the recurrence of chronic subdural haematomas to assess the risk of recurrence more reliably in everyday clinical practice. (2) Methods: In our retrospective study, the electronic records of 90 patients who underwent surgery for a chronic subdural haematoma at our institute between 1 January 2017 and 31 May 2021 were analysed regarding previously defined variables. (3) Results: In the patient collective, 33.33% of the 90 patients experienced a recurrence requiring treatment. The occurrence of a recurrence was not statistically significantly related to age, gender, known alcohol abuse, a specific location, extension over one or both hemispheres, the surgical method, or anticoagulant medication. However, the recurrence was statistically significantly related to haematoma width (p = 0.000007), septation (p = 0.005), and the existence of a coagulation disorder not treated with medication (p = 0.04). (4) Conclusions: In our study, the width of the haematoma, septation, and coagulation disorders not treated with medication were documented as risk factors for the occurrence of a chronic subdural haematoma. Identifying of these risk factors could help in adapting individual therapeutic concepts for chronic subdural haematomas.

Patient Satisfaction and Radiologic Assessability After Treatment of Complex Skull Defects With a Custom-Made Cranioplasty From a Thin Titanium Sheet.

OBJECTIVE: The cosmetically good coverage of skull defects is a challenge in neurosurgical clinics. In addition, the skull treated with implants and the underlying structures must remain radiologically assessable. In this examination, the postoperative courses of patients after implantation of CranioTop is described. Digital x-ray, computed tomography, and magnetic resonance images after implantation of CranioTop were evaluated with regard to their assessability. MATERIALS AND METHODS: Between 2018 and 2020, 23 titanium cranioplasties (CranioTop) were implanted to 21 patients. The intraoperative handling, the accuracy of fit, the healing process, the cosmetic result and the physical condition of the patients were examined. In addition, digital x-rays, magnetic resonance imaging, and computed tomography scans of the cranium supplied with CranioTop were examined. RESULTS: The evaluation showed good to very good results regarding patients' satisfaction. There were no severe complications; thirteen patients found the cosmetic result very good; 8 patients assessed the cosmetic result as good. Because of the low thickness and density of the CranioTop plastic there was only low formation of radial stripe artifacts (streaking) and susceptibility artifacts. The assessment of digital x-ray, computed tomography, and magnetic resonance imaging images is possible after implantation of CranioTop. CONCLUSION: The patients treated with CranioTop showed a high level of satisfaction with regard to the cosmetic result and their physical condition. Furthermore, the cranium supplied with CranioTop remains well assessable in radiologic imaging with only slight limitations in magnetic resonance imaging.

Rescuing Infected Deep Brain Stimulation Therapies in Severely Affected Patients.

(1) Background: Infections in deep brain stimulation (DBS) hardware, while an undesired complication of DBS surgeries, can be effectively addressed. Minor infections are typically treated with wound revision and IV antibiotics. However, when visible hardware infection occurs, most centers opt for complete removal, leaving the patient in a preoperative state and necessitating post-removal care. To avoid the need for such care, a novel technique was developed. (2) Methods: The electrodes are placed at the exact same spot and then led to the contralateral side. new extensions and a new generator contralateral to the infection as well. Subsequently, the infected system is removed. This case series includes six patients. (3) Results: The average duration of DBS system implantation before the second surgery was 272 days. Only one system had to be removed after 18 months due to reoccurring infection; the others remained unaffected. Laboratory alterations and pathogens were identified in only half of the patients. (4) Conclusions: The described surgical technique proves to be safe, well tolerated, and serves as a viable alternative to complete system removal. Importantly, it effectively prevents the need of post-removal care for patients.

Stereotactic Radiosurgery for Benign Cavernous Sinus Meningiomas: A Multicentre Study and Review of the Literature.

Cavernous sinus meningiomas (CSMs) remain a surgical challenge due to the intimate involvement of their contained nerves and blood vessels. Stereotactic radiosurgery (SRS) is a safe and effective minimally invasive alternative for the treatment of small- to medium-sized CSMs. Objective: To assess the medium- to long-term outcomes of SRS for CSMs with respect to tumour growth, prevention of further neurological deterioration and improvement of existing neurological deficits. This multicentric study included data from 15 European institutions. We performed a retrospective observational analysis of 1222 consecutive patients harbouring 1272 benign CSMs. All were treated with Gamma Knife stereotactic radiosurgery (SRS). Clinical and imaging data were retrieved from each centre and entered into a common database. All tumours with imaging follow-up of less than 24 months were excluded. Detailed results from 945 meningiomas (86%) were then analysed. Clinical neurological outcomes were available for 1042 patients (85%). Median imaging follow-up was 67 months (mean 73.4, range 24-233). Median tumour volume was 6.2 cc (+/-7), and the median marginal dose was 14 Gy (+/-3). The post-treatment tumour volume decreased in 549 (58.1%), remained stable in 336 (35.6%) and increased in only 60 lesions (6.3%), yielding a local tumour control rate of 93.7%. Only 27 (2.8%) of the 60 enlarging tumours required further treatment. Five- and ten-year actuarial progression-free survival (PFS) rates were 96.7% and 90.1%, respectively. Tumour control rates were higher for women than men (p = 0.0031), and also for solitary sporadic meningiomas (p = 0.0201). There was no statistically significant difference in outcome for imaging-defined meningiomas when compared with histologically proven WHO Grade-I meningiomas (p = 0.1212). Median clinical follow up was 61 months (mean 64, range 6-233). Permanent morbidity occurred in 5.9% of cases at last follow-up. Stereotactic radiosurgery is a safe and effective method for treating benign CSM in the medium term to long term.

Load-Bearing Capacity and Design Advantages of a Custom-Made, Thin Pure-Titanium Cranioplasty (CranioTop).

BACKGROUND: Adequate and stable coverage of cranial contour and continuity defects of any origin is a common challenge in neurosurgical clinics. This study presents the results of investigations concerning the mechanical load-bearing capacity and design advantages of custom-made implants made from a thin, pure-titanium sheet (CranioTop) (CLinstruments, Attendorn, Germany) for covering complex cranial defects. METHODS: In 9 test series, the stability of three differently shaped and sized thin titanium sheet implants was tested using vertical, uniaxial compression with 3 different compression stamps, to investigate the behaviour of these implants in relation to punctiform as well as planar forces. RESULTS: All 9 model implants showed elastic behavior in the synchronously recorded force/displacement diagrams at an impression of up to 2 mm. The forces at 2 mm deformation were between 170.1 and 702.7 Newton. CONCLUSION: Cranioplasty using CranioTop is a stable procedure for covering skull defects, even those of large dimensions. An added advantage is the significant reduction in effort required to prepare the area of the bone margins compared to other current techniques of cranioplasty.

Virtual reality-based evaluation of neurovascular conflict for the surgical planning of microvascular decompression in trigeminal neuralgia patients.

OBJECTIVE: Trigeminal neuralgia (TN) is a lightning bolt of violent, electrifying, and stinging pain, often secondary to the neurovascular conflict (NVC). The vessels involved in NVC are mostly arteries and rarely veins. Evaluation of NVC in the deep infratentorial region is inseparably connected with cranial imaging. We retrospectively analyzed the potential influence of three-dimensional (3D) virtual reality (VR) reconstructions compared to conventional magnetic resonance imaging (MRI) scans on the evaluation of NVC for the surgical planning of microvascular decompression in patients with TN. METHODS: Medical files were retrospectively analyzed regarding patient- and disease-related data. Preoperative MRI scans were retrospectively visualized via VR software to detect the characteristics of NVC. A questionnaire of experienced neurosurgeons evaluated the influence of VR visualization technique on identification of anatomical structures involved in NVC and on surgical strategy. RESULTS: Twenty-four patients were included and 480 answer sheets were evaluated. Compared to conventional MRI, image presentation using 3D-VR modality significantly influenced the identification of the affected trigeminal nerve (p = 0.004), the vascular structure involved in the NVC (p = 0.0002), and the affected side of the trigeminal nerve (p = 0.005). CONCLUSIONS: In patients with TN caused by NVC, the reconstruction of conventional preoperative MRI scans and the spatial and anatomical presentation in 3D-VR models offers the possibility of increased understanding of the anatomy and even more the underlying pathology, and thus influences operation planning and strategy.

Impact of Virtual Reality in Arterial Anatomy Detection and Surgical Planning in Patients with Unruptured Anterior Communicating Artery Aneurysms.

Anterior-communicating artery (ACoA) aneurysms have diverse configurations and anatomical variations. The evaluation and operative treatment of these aneurysms necessitates a perfect surgical strategy based on review of three-dimensional (3D) angioarchitecture using several radiologic imaging methods. We analyzed the influence of 3D virtual reality (VR) reconstructions versus conventional computed tomography angiography (CTA) scans on the identification of vascular anatomy and on surgical planning in patients with unruptured ACoA aneurysms. Medical files were retrospectively analyzed regarding patient- and disease-related data. Preoperative CTA scans were retrospectively reconstructed to 3D-VR images and visualized via VR software to detect the characteristics of unruptured ACoA aneurysms. A questionnaire was used to evaluate the influence of VR on the identification of aneurysm morphology and relevant arterial anatomy and on surgical strategy. Twenty-six patients were included and 520 answer sheets were evaluated. The 3D-VR modality significantly influenced detection of the aneurysm-related vascular structure (p = 0.0001), the recommended head positioning (p = 0.005), and the surgical approach (p = 0.001) in the planning of microsurgical clipping. Thus, reconstruction of conventional preoperative CTA scans into 3D images and the spatial presentation in VR models enabled greater understanding of the anatomy and pathology, provided realistic haptic feedback for aneurysm surgery, and influenced operation planning and strategy.

Comparison of stand-alone cage and cage-with-plate for monosegmental cervical fusion and impact of virtual reality in evaluating surgical results.

OBJECTIVES: After ventral decompression of monosegmental cervical spondylotic stenosis, a stand-alone cage (SC) or cage-with-plate (CP) can be inserted for fusion. Postoperative radiological evaluation can be achieved using different imaging modalities. We retrospectively compared complications, as well as clinical and radiological outcomes for both fusion techniques, and analyzed the possible role of virtual reality (VR) in evaluating the postoperative results. PATIENTS AND METHODS: One hundred seventeen patients were included (SC/CP: 54/63). Complications, as well as clinical and radiological outcomes of both fusion techniques were compared. Computed tomography (CT) scans were visualized via VR to measure the smallest cross-sectional area of the intervertebral neuroforamen in the lateral resection region, and to assess the degree of the intersegmental ossification. RESULTS: There were no significant differences between the two fusion techniques regarding perioperative complication rates, fusion rates, or pain parameter (visual analogue scale (VAS) of arm pain, neck disability index). However, advantages regarding subsidence, kyphosis, and VAS of neck pain were found when using the CP versus SC. Using the VR technique, there was no significant difference between the two fusion techniques in the mean size of the cross-sectional area at the end of follow-up. CONCLUSION: Due to the long-term advantages of CP fusion, we prefer a monosegmental cervical spinal fusion using CP. Reconstruction of postsurgical two-dimensional CT images into three-dimensional images, and the spatial and anatomical presentation in VR models, improved the evaluation of these postoperative results.

Early autologous cranioplasty: complications and identification of risk factors using virtual reality visualisation technique.

Background: Cranioplasty (CP) of autologous bone flap after decompressive craniectomy (DC) is known to be associated with a high complication rate, particularly bone flap resorption (BFR). In a retrospective study, we used a novel virtual reality (VR) visualisation technique to identify and evaluate risk factors associated with CP.Method: Twenty-five patients underwent early autologous CP. All complications were recorded. Cranial computed tomography scans were visualised via the VR software to access the fitting accuracy of the bone flap (bone flap size, gap width at trepanation cutting edge, extent of osteoclastic extension).Results: An overall complication rate of 44% was seen, and BFR was the most common (36%). Only 'osteoclastic extension of trepanation' (p = .04) was a significant risk factor for BFR. The factors 'indication for DC' (p = .09) and 'size of bone flap' (p = .09) had a tendency towards influencing the rate of BFR, while 'age' (p = .68), 'time interval between DC and CP' (p = 1.00), and 'gap width' (p = .50) were not considered to influence the BFR rate.Conclusions: DC and subsequent CP is a complication-prone procedure. Therefore, it is relevant to identify and quantify probable risk factors for the most common complications, such as BFR. Here, we found that the extent of osteoclastic extension may impair the patient's healing process. Our investigation was made considerably easier by using the novel VR visualisation technique, which allows parallax free measurements of distances in 3D space.

Virtual Reality-Based Evaluation of Surgical Planning and Outcome of Monosegmental, Unilateral Cervical Foraminal Stenosis.

BACKGROUND: Foraminal cervical nerve root compression can be caused by lateral disk herniation or osteophyte formation of the vertebrae. Improved diagnosis and evaluation can be achieved using different imaging techniques: radiographs, computed tomography (CT), and magnetic resonance imaging. We retrospectively evaluated the potential influence of a virtual reality (VR) visualization technique on surgery planning and evaluation of postoperative results in patients with monosegmental, unilateral osseous cervical neuroforaminal stenosis. METHODS: Seventy-three patients were included. Ventral decompression of the neuroforamen was performed in 41 patients, dorsal decompression in 32 patients. Patients' files were evaluated. CT scans were visualized via VR software to measure the smallest cross-sectional area of the intervertebral neuroforamen in the lateral resection region. A questionnaire evaluated the influence of VR technique on surgical planning and strategy. RESULTS: The VR-technique had a moderate influence on the choice of the approach (ventral or dorsal), a significant influence on the ventral approach strategy, and no influence on the positioning of the patient or the dorsal approach strategy. A significant difference was found in the size of the smallest cross-sectional area of the intervertebral neuroforamen in the lateral resection region between ventral and dorsal approaches, with no correlation to the clinical outcome. CONCLUSIONS: Reconstruction of pre- and postoperative 2D-CT images of the cervical spine into 3D images, and the spatial and anatomical reconstructions in VR models, can be helpful in planning surgical approaches and treatment strategies for patients with cervical foraminal stenoses, and for evaluation of their postoperative results.

5-ALA Fluorescence in Native Pituitary Adenoma Cell Lines: Resection Control and Basis for Photodynamic Therapy (PDT)?

OBJECTIVE: Pituitary adenomas (PA), especially invasive ones, are often not completely resectable. Usage of 5-aminolevulinic acid (5-ALA) for fluorescence guided surgery could improve the rate of total resection and, additionally, open the doors for photodynamic therapy (PDT) in case of unresectable or partially resected PAs. The aim of this study was to investigate the uptake of 5-ALA and the effect of 5-ALA based PDT in cell lines. METHODS: GH3 and AtT-20 cell lines were incubated with different concentrations of 5-ALA, protoporphyrin IX (PPIX) fluorescence was measured by flow cytometry and fluorescencespectrometry. WST-1 assays were performed to determine the surviving fraction of cells after PDT. PPIX fluorescence intensities and PDT effect of the pituitary adenoma cells were compared to U373MG, a well-known glioblastoma cell line. RESULTS: Both cell lines showed a 5-ALA dependent intracellular PPIX fluorescence. Significant differences after 24hrs of incubation were observed in AtT-20 cells in comparison to GH3. Regardless of the incubation or metabolism time, there was a proliferation inhibiting effect after PDT, with no statistical significance. CONCLUSION: Since GH3 cells showed a heterogenous uptake of 5-ALA in the flow cytometry profile, but not constantly high concentrations they might have a 5-ALA efflux mechanism, which still needs to be determined. In the case of AtT-20, the cells might need a longer time for the uptake due to their size or slow metabolism. We showed that the different cell lines have different uptake and metabolism mechanisms, which needs to be further investigated. The general uptake of 5-ALA allows the possibility of resection control and PDT for pituitary adenomas. But, the role of PDT for unresectable pituitary adenomas deserves further investigations.

Chemotaxis of MDCK-F cells toward fibroblast growth factor-2 depends on transient receptor potential canonical channel 1.

Movement toward the source of a chemoattractant gradient is a basic cellular property in health and disease. Enhanced migration during metastasis involves deregulated growth factor signaling. Growth factor stimulation and cell migration converge both on the important second messenger Ca(2+). To date, the molecular identification of Ca(2+) entry pathways activated by growth factors during chemotaxis is still an open issue. We investigated the involvement of the nonselective Ca(2+) channel TRPC1 (transient receptor potential canonical 1) in FGF-2 guided chemotaxis by means of time-lapse video microscopy and by functional Ca(2+) measurements. To specifically address TRPC1 function in transformed MDCK cells we altered the expression levels by siRNA or overexpression. We report that TRPC1 channels are required for the orientation of transformed MDCK cells in FGF-2 gradients because TRPC1 knockdown or pharmacological blockade prevented chemotaxis. Stimulation with FGF-2 triggered an immediate Ca(2+) influx via TRPC1 channels that depended on phospholipase C and phosphatidylinositol 3-kinase signaling. Impeding this Ca(2+) influx abolished chemotaxis toward FGF-2. This functional connection correlated with clustering of FGF receptors and TRPC1 channels as was observed by immunolabeling. These findings show the important interplay between growth factor signaling and Ca(2+) influx in chemotaxis.