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Ralf Dirk Rothoerl and Alexander Brawanski

✓ After the development of deep hypothermia and circulatory arrest for cardiothoracic procedures in the late 1950s, this technique was adopted by several neurosurgeons as an aid to complex cranial surgery. Woodhall and colleagues described its first use for a neurosurgical procedure in 1960. Although their case did not involve a cerebrovascular procedure, the technique was subsequently used for the surgical treatment of cerebrovascular lesions, especially complex and giant aneurysms as well as large and solid hemangioblastomas. At the beginning, incorporation of this technique into common neurosurgical practice was impeded by several factors. For example, postbypass coagulopathy had been a serious source of morbidity. Furthermore, the need for cooperation among multiple subspecialities and the requirements for expensive equipment had further limited the availability of this technique. Subsequent improvements in the technique and advances in the equipment designed for cardiopulmonary bypass have led to its more widespread use starting in the 1980s. Hypothermic circulatory arrest has been described in several reports as a safe and useful tool in the treatment of large and giant aneurysms. Nevertheless, improvements in endovascular procedures and further refinement in skull base surgical techniques have limited the indications for circulatory arrest and deep hypothermia. The authors describe the history of hypothermia and circulatory arrest, its implementation in cerebrovascular surgery, and the changes in indications for and results of its use over time.

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Martin Proescholdt, Marsha Merrill, Eva-Maria Stoerr, Annette Lohmeier, Wolfgang Dietmaier and Alexander Brawanski


In craniopharyngiomas, cystic growth causes pressure on vital structures of the adjacent brain, leading to significant morbidity. However, the molecular pathogenesis of this cyst formation remains unknown. Carbonic anhydrase IX (CA IX) is a tumor-associated, hypoxia-inducible enzyme, which can cause fluid production and development of cysts. The authors investigated CA IX expression in craniopharyngiomas and its correlation with the extent of cyst formation. In addition, the major pathways of CA IX regulation, hypoxia and p53 mutation, were analyzed.


Expression of CA IX was analyzed in 20 craniopharyngioma patients by means of in situ hybridization and immunohistochemistry. Preoperative imaging was used to quantify cyst volume. To analyze putative hypoxic induction of CA IX, immunohistochemical staining for HIF-1α and VEGF was performed. Since p53 negatively regulates CA IX expression, we also analyzed the tumors for p53 mutation by direct sequencing.


Significant CA IX was found in 85% of the 20 cases. The extent of CA IX expression was significantly correlated with cyst volume. HIF-1α expression was largely absent in all tissue samples, whereas moderate VEGF expression was present in a subset of cases but without correlation to cyst volume. No p53 mutation was found in any of the analyzed tumors.


Carbonic anhydrase IX, which is virtually absent in normal brain, is significantly upregulated in craniopharyngiomas and shows a significant association with cyst size. The mechanisms of regulation remain unknown, since neither hypoxia nor p53 appears to play a role. These results indicate that inhibition of CA IX may be a potential target for the adjuvant treatment in patients with cystic craniopharyngiomas.

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Christoph P. Beier, Arndt Hartmann, Chris Woertgen, Alexander Brawanski and Ralf D. Rothoerl

✓ Symptomatic gout tophi of the spine are a rare but well-characterized complication of tophaceous gout. The authors report the case of a 29-year-old previously healthy man who presented with L-5 radiculopathy. Lumbar magnetic resonance (MR) imaging revealed a 4.5 × 4.5 × 2.8—cm large gout tophus mimicking a malignant spinal tumor or abscess. The tophus completely destroyed both L-4 and L-5 facet joints and the left L-4 lamina and spread epidurally from L-3 to L-5, compressing the left L-5 nerve root. There has been no similar case reported so far with respect to the extent of bone destruction. The authors describe the case history and present intraoperative, MR imaging, and histological findings.

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Naureen Keric, Christian Doenitz, Amer Haj, Izabela Rachwal-Czyzewicz, Mirjam Renovanz, Dominik M. A. Wesp, Stephan Boor, Jens Conrad, Alexander Brawanski, Alf Giese and Sven R. Kantelhardt


Recent studies have investigated the role of spinal image guidance for pedicle screw placement. Many authors have observed an elevated placement accuracy and overall improvement of outcome measures. This study assessed a bi-institutional experience following introduction of the Renaissance miniature robot for spinal image guidance in Europe.


The medical records and radiographs of all patients who underwent robot-guided implantation of spinal instrumentation using the novel system (between October 2011 and March 2015 in Mainz and February 2014 and February 2016 in Regensburg) were reviewed to determine the efficacy and safety of the newly introduced robotic system. Screw position accuracy, complications, exposure durations to intraoperative radiation, and reoperation rate were assessed.


Of the 413 surgeries that used robotic guidance, 406 were via a minimally invasive approach. In 7 cases the surgeon switched to conventional screw placement, using a midline approach, due to referencing problems. A total of 2067 screws were implanted using robotic guidance, and 1857 screws were evaluated by postoperative CT. Of the 1857 screws, 1799 (96.9%) were classified as having an acceptable or good position, whereas 38 screws (2%) showed deviations of 3–6 mm and 20 screws (1.1%) had deviations > 6 mm. Nine misplaced screws, implanted in 7 patients, required revision surgery, yielding a screw revision rate of 0.48% of the screws and 7 of 406 (1.7%) of the patients. The mean ± SD per-patient intraoperative fluoroscopy exposure was 114.4 (± 72.5) seconds for 5.1 screws on average and any further procedure required. Perioperative and direct postoperative complications included hemorrhage (2 patients, 0.49%) and wound infections necessitating surgical revision (20 patients, 4.9%).


The hexapod miniature robotic device proved to be a safe and robust instrument in all situations, including those in which patients were treated on an emergency basis. Placement accuracy was high; peri- and early postoperative complication rates were found to be lower than rates published in other series of percutaneous screw placement techniques. Intraoperative radiation exposure was found to be comparable to published values for other minimally invasive and conventional approaches.

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Christoph Metz, Matthias Holzschuh, Thomas Bein, Christian Woertgen, Anton Frey, Irmgard Frey, Kai Taeger and Alexander Brawanski

✓ Cerebral and extracerebral effects of moderate hypothermia (core temperature 32.5°C–33.0°C) were prospectively studied in 10 patients with severe closed head injury (Glasgow Coma Scale score, < 7) in the intensive care unit of a university hospital. Hypothermia was induced by cooling the patient's body surface with water-circulating blankets. Before cooling, a conventional intracranial pressure (ICP) reduction therapy was applied, which remained unchanged throughout the study. Cerebral blood flow (CBF), cerebral metabolic rates for oxygen (CMRO2) and lactate (CMRL), and ICP were simultaneously measured prior to inducing hypothermia, after obtaining hypothermia, after 24 hours of hypothermia, and after rewarming. With respect to extracerebral effects, supplemental investigations were conducted 24 and 72 hours after rewarming. The median delay between injury and induction of hypothermia was 16 hours.

Hypothermia reduced CMRO2 by 45% (p < 0.01), whereas CBF did not change significantly. Before cooling, six patients had elevated CMRL indicating cerebral ischemia. Cooling normalized CMRL in all patients (p < 0.01). The intracranial hypertension present prior to cooling declined markedly during hypothermia (p < 0.01) without significant rebound effects after rewarming. Cardiac index decreased by 18% after hypothermia was reached (p < 0.05), recovered at 24 hours of hypothermia, and surpassed baseline values after rewarming. Platelet counts dropped continuously up to 24 hours after rewarming (p < 0.01). Plasma coagulation tests did not show significant worsening. Creatinine clearance decreased during cooling (p < 0.01) and recovered by 24 hours after rewarming. Twenty-four hours after cooling had begun, eight patients had elevated serum lipase activity (p < 0.01) and four of them acquired pancreatitis. Rewarming normalized both pancreatic alterations. Seven patients made a good recovery; one survived severely disabled; and two patients died.

Moderate hypothermia is effective in preventing secondary brain damage while reducing cerebral ischemia. However, there are potentially hazardous side effects that require additional monitoring.

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Victor E. Staartjes, Morgan Broggi, Costanza Maria Zattra, Flavio Vasella, Julia Velz, Silvia Schiavolin, Carlo Serra, Jiri Bartek Jr., Alexander Fletcher-Sandersjöö, Petter Förander, Darius Kalasauskas, Mirjam Renovanz, Florian Ringel, Konstantin R. Brawanski, Johannes Kerschbaumer, Christian F. Freyschlag, Asgeir S. Jakola, Kristin Sjåvik, Ole Solheim, Bawarjan Schatlo, Alexandra Sachkova, Hans Christoph Bock, Abdelhalim Hussein, Veit Rohde, Marike L. D. Broekman, Claudine O. Nogarede, Cynthia M. C. Lemmens, Julius M. Kernbach, Georg Neuloh, Oliver Bozinov, Niklaus Krayenbühl, Johannes Sarnthein, Paolo Ferroli, Luca Regli, Martin N. Stienen and FEBNS


Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient’s risk of experiencing any functional impairment.


The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated.


In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69–0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69–0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at


Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.