Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

Technical report: surgical preparation of human brain tissue for clinical and basic research.

BACKGROUND: The study of the distinct structure and function of the human central nervous system, both in healthy and diseased states, is becoming increasingly significant in the field of neuroscience. Typically, cortical and subcortical tissue is discarded during surgeries for tumors and epilepsy. Yet, there is a strong encouragement to utilize this tissue for clinical and basic research in humans. Here, we describe the technical aspects of the microdissection and immediate handling of viable human cortical access tissue for basic and clinical research, highlighting the measures needed to be taken in the operating room to ensure standardized procedures and optimal experimental results. METHODS: In multiple rounds of experiments (n = 36), we developed and refined surgical principles for the removal of cortical access tissue. The specimens were immediately immersed in cold carbogenated N-methyl-D-glucamine-based artificial cerebrospinal fluid for electrophysiology and electron microscopy experiments or specialized hibernation medium for organotypic slice cultures. RESULTS: The surgical principles of brain tissue microdissection were (1) rapid preparation (<1 min), (2) maintenance of the cortical axis, (3) minimization of mechanical trauma to sample, (4) use of pointed scalpel blade, (5) avoidance of cauterization and blunt preparation, (6) constant irrigation, and (7) retrieval of the sample without the use of forceps or suction. After a single round of introduction to these principles, multiple surgeons adopted the technique for samples with a minimal dimension of 5 mm spanning all cortical layers and subcortical white matter. Small samples (5-7 mm) were ideal for acute slice preparation and electrophysiology. No adverse events from sample resection were observed. CONCLUSION: The microdissection technique of human cortical access tissue is safe and easily adoptable into the routine of neurosurgical procedures. The standardized and reliable surgical extraction of human brain tissue lays the foundation for human-to-human translational research on human brain tissue.

Piezosurgery for safe and efficient petrous bone cutting in cerebellopontine angle and petroclival meningioma surgery.

Intradural petrous bone drilling has become a widespread practice, providing extended exposure in the removal of cerebellopontine angle (CPA) or petroclival tumors. Adjacent neurovascular structures are at risk, however, when drilling is performed in this deep and narrow area. Hence, this study evaluates the use of Piezosurgery (PS) as a non-rotating tool for selective bone cutting in CPA surgery. A Piezosurgery® device was used in 36 patients who underwent microsurgery for extra-axial CPA or petroclival tumors in our Neurosurgical Department between 2013 and 2019. The clinical and radiological data were retrospectively analyzed. The use of PS was evaluated with respect to the intraoperative applicability and limitations as well as efficacy and safety of the procedure. Piezosurgical petrous bone cutting was successfully performed in the removal of meningiomas or extra-axial metastases arising from the dura of the petroclival region (21 patients) or petrous bone (15 patients). PS proved to be very helpful in the deep and narrow CPA region, considerably reducing the surgeon's distress toward bone removal in close proximity to cranial nerves and vessels in comparison to common rotating drills. The use of PS was safe without injuries to neurovascular structures. Gross total resection was achieved in 67% of petroclival and 100% of petrous bone tumors. Piezosurgery proved to be an effective and safe method for selective petrous bone cutting in CPA surgery avoiding rotating power and associated risks. This technique can particularly be recommended for bone cutting in close vicinity to critical neurovascular structures.

Vertebral osteomyelitis in patients with Staphylococcus aureus bloodstream infection: Evaluation of risk factors for treatment failure.

OBJECTIVES: Staphylococcus aureus is the most common cause of pyogenic vertebral osteomyelitis (VO). Studies indicate that S. aureus VO results in poor outcome. We aimed to investigate risk factors for treatment failure in patients with Staphylococcus aureus bloodstream infection (SAB) and VO. METHODS: We conducted a post hoc-analysis of data from a German bi-center prospective SAB cohort (2006-2014). Patients were followed-up for one year. Primary outcome was treatment failure defined as relapse and/or death within one year. RESULTS: A total of 1069 patients with SAB were analyzed, with 92 VO patients. In addition to antibiotic treatment, surgery was performed in 60/92 patients. Treatment failed in 44/92 patients (death, n = 42; relapse, n = 2). Multivariable analysis revealed higher age (HR 1.04 [per year], 95%CI 1.01-1.07), Charlson comorbidity index (HR 1.20, 95%CI 1.06-1.36), presence of neurologic deficits (HR 2.53, 95%CI 1.15-5.53) and local abscess formation (HR 3.35, 95%CI 1.39-8.04) as independent risk factors for treatment failure. In contrast, surgery seemed to be associated with a favourable outcome (HR 0.45 (95%CI 0.20-0.997)). CONCLUSION: SAB patients with VO exhibit a high treatment failure rate. Red flags are older age, comorbidities, neurologic deficits and local abscess formation. Whether these patients benefit from intensified treatment (e.g. radical surgery, prolongation of antibiotics) should be investigated further.

Vesselplasty: a new minimally invasive approach to treat pathological vertebral fractures in selected tumor patients - preliminary results.

PURPOSE: To evaluate the effectiveness and safety of percutaneous vesselplasty in pathological vertebral fractures of the thoracolumbar spine in selected tumor patients. MATERIALS AND METHODS: Eleven pathological vertebral fractures in nine patients were treated with vesselplasty (Vessel-X®, MAXXSPINE). Nine of eleven vertebras (81.8 %) had major posterior wall deficiency (> 30 %). Clinical and radiological (CT) measures were obtained before and 3 months after the procedure. RESULTS: The mean VAS improved significantly from preoperative to postoperative (6.9 ± 2.2 to 3.7 ± 2.3; p < 0.05), as did the ODI (59.7 %± 19.2 % to 40.3 %± 24.0 %; p < 0.05). The physical component summary of the SF-36 was significantly improved by the operation (19.2 ± 8.0 to 31.0 ± 16.5; p < 0.05). Symptomatic cement leakage or other operation-associated complications were not observed. Three patients were primarily treated with concomitant minimally invasive stabilization via fixateur interne. One patient had to undergo minimally invasive stabilization via fixateur interne 4 months after vesselplasty due to further collapse of the treated vertebral body. CONCLUSION: From these preliminary results, vesselplasty appears to be a treatment option worth considering in pathological vertebral fractures, even in the case of posterior wall deficiency. Selected tumor patients might benefit from vesselplasty as a minimally invasive procedure for stabilization of the fractured vertebra, pain control, and improvement in body function and quality of life. Long-term prospective studies with a larger sample size are required to validate these results.

First experience using navigation-guided radiofrequency kyphoplasty for sacroplasty in sacral insufficiency fractures.

PURPOSE: To evaluate the efficacy and safety of navigation-guided radiofrequency kyphoplasty for sacroplasty in patients with sacral insufficiency fractures. METHODS: In this single-center retrospective observational study, four consecutive patients with sacral insufficiency fractures were treated with navigation-guided radiofrequency kyphoplasty for sacroplasty between April 2010 and May 2012. Symptom characteristics, pain duration and pain intensity were recorded for each patient. Cement extravasation was evaluated in thin-sliced and triplanar reconstructed CT scans of the sacrum. RESULTS: Four female patients with painful sacral insufficiency fractures and extensive osteopenic areas significantly improved from an average pre-treatment VAS score of 8.3 ± 0.5 to 2.3 ± 1.0 (p < 0.001) on the first postoperative day and to 1.3 ± 1.9 (p < 0.004) at follow-up (mean, 20.1 weeks). Slight cement extravasations were observed without evidence of being symptomatic. No major complications or procedure-related morbidity were noted. CONCLUSION: From the limited experience in four patients, navigation-guided radiofrequency kyphoplasty appears to be a safe and effective treatment option for sacral insufficiency fractures even though asymptomatic cement extravasation was noted. The use of navigation based on intraoperative 3 D images simplifies the positioning of the navigated bone needles via the long axis approach. The radiofrequency kyphoplasty system provides the possibility to administer a sufficient amount of bone cement with a well-defined viscosity over the entire period of the procedure leading to high security and low cement extravasation. Sacroplasty provides rapid and enduring pain relief and facilitates prompt mobilization.

Essentials and pitfalls in the treatment of CNS hemangioblastomas and von Hippel-Lindau disease.

Hemangioblastomas are rare CNS tumors, which are mostly located in the posterior fossa or spinal cord and occasionally in spinal nerves. They can occur sporadically or as a component tumor of von Hippel-Lindau (VHL) disease, an autosomal dominant tumor syndrome. The limited awareness of several pitfalls in the therapy of these rare lesions results in delayed or suboptimal treatment for many of these patients, especially those with VHL disease. The University of Freiburg serves as a reference center for patients with VHL disease and hemangioblastomas. The current therapeutic strategies for hemangioblastoma patients and typical pitfalls are presented here.