Embolization of an Intracranial Vertebral Artery Aneurysm via the Deep Cervical Artery.

Treatment of vertebral artery aneurysms can be challenging due to the unusual vascular anatomy or unfeasibility of traditional endovascular techniques. We describe a novel approach for endovascular treatment of a ruptured intracranial vertebral artery aneurysm with bilateral vertebral artery occlusions and hypoplasia of the posterior communicating arteries. Successful coil embolization was performed using a collateral pathway for microcatheterization via anastomosis between the deep cervical artery and the vertebral artery. This case report highlights a novel alternative endovascular treatment approach for vertebrobasilar aneurysms in case of a poor vascular status with occlusion or lack of traditional endovascular access routes.

Clinical Results and Quality of Life After Transcortical Versus Transcallosal Resection of Adult Lateral and Third Ventricle Lesions: Long-Term Outcome.

BACKGROUND: Resection of intraventricular tumors can be achieved using 2 main operative approaches: transcallosal or transcortical. This study aims to describe preoperative and postoperative factors as well as quality of life (QoL) based on long-term results in these patients. METHODS: Patients underwent surgery of primary intraventricular lesions between 2007 and 2020 via a transcortical (group A) or transcallosal (group B) route. The main clinical parameters were completeness of resection, overall survival, surgical complications, postoperative neurologic deficits, and seizure rates. QoL was assessed using a modified questionnaire Short-Form 36 inventory. RESULTS: Forty patients (19 women and 21 men) met the inclusion criteria. Group A consisted of 26 patients (12 women and 14 men; median age 45.5 years ± 16.7 standard deviation) and had lower preoperative tumor volume (confounder) compared with group B (7 women and 7 men; age 50.0 ± 17.4 years). Gross total resection was achieved in 65% in group A and 71% in group B. Follow-up was 7.8 ± 3.9 years. New seizures/permanent neurologic deficits occurred in 27%/15% (group A) and 29%/29% (group B) and surgical complications in 23% of patients. Group B had a higher degree of memory impairment (21%) compared with group A (10%). QoL impairment was present in both groups mainly regarding physical role function and mental health index. CONCLUSIONS: Keeping in mind the limitations, transcallosal surgery was associated with a higher probability of neurologic deficits and memory impairment in our series. However, it had fewer surgical complications with similar gross total resection and seizure rates.

A chance to cut is a chance to cure: complete resection of an atypical neurofibroma prevents further progression to malignancy.

Plexiform neurofibromas are the hallmark of neurofibromatosis type 1 (NF1) and significantly contribute to the overall burden of disease. While surgical excision has long been the only available therapy, the MEK inhibitor (MEKi) selumetinib has been approved as a non-surgical treatment option for these tumors in 2020 (USA) and 2021 (Europe), respectively. However, selumetinib will result in tumor shrinkage only after several months of therapy and might not prevent malignant transformation of a plexiform neurofibroma that occurs with a frequency of 10-15%. Here, we demonstrate that surgical excision might be the therapy of choice in some plexiform neurofibromas despite the availability of MEKi therapy.

Loss of respiratory complex I subunit NDUFB10 affects complex I assembly and supercomplex formation.

The orchestrated activity of the mitochondrial respiratory or electron transport chain (ETC) and ATP synthase convert reduction power (NADH, FADH2) into ATP, the cell's energy currency in a process named oxidative phosphorylation (OXPHOS). Three out of the four ETC complexes are found in supramolecular assemblies: complex I, III, and IV form the respiratory supercomplexes (SC). The plasticity model suggests that SC formation is a form of adaptation to changing conditions such as energy supply, redox state, and stress. Complex I, the NADH-dehydrogenase, is part of the largest supercomplex (CI + CIII2 + CIVn). Here, we demonstrate the role of NDUFB10, a subunit of the membrane arm of complex I, in complex I and supercomplex assembly on the one hand and bioenergetics function on the other. NDUFB10 knockout was correlated with a decrease of SCAF1, a supercomplex assembly factor, and a reduction of respiration and mitochondrial membrane potential. This likely is due to loss of proton pumping since the CI P P -module is downregulated and the P D -module is completely abolished in NDUFB10 knock outs.

Efficient stabilization of therapeutic hepatitis B vaccine components by amino-acid formulation maintains its potential to break immune tolerance.

Background & Aims: Induction of potent, HBV-specific immune responses is crucial to control and finally cure HBV. The therapeutic hepatitis B vaccine TherVacB combines protein priming with a Modified Vaccinia virus Ankara (MVA)-vector boost to break immune tolerance in chronic HBV infection. Particulate protein and vector vaccine components, however, require a constant cooling chain for storage and transport, posing logistic and financial challenges to vaccine applications. We aimed to identify an optimal formulation to maintain stability and immunogenicity of the protein and vector components of the vaccine using a systematic approach. Methods: We used stabilizing amino acid (SAA)-based formulations to stabilize HBsAg and HBV core particles (HBcAg), and the MVA-vector. We then investigated the effect of lyophilization and short- and long-term high-temperature storage on their integrity. Immunogenicity and safety of the formulated vaccine was validated in HBV-naïve and adeno-associated virus (AAV)-HBV-infected mice. Results: In vitro analysis proved the vaccine's stability against thermal stress during lyophilization and the long-term stability of SAA-formulated HBsAg, HBcAg and MVA during thermal stress at 40 °C for 3 months and at 25 °C for 12 months. Vaccination of HBV-naïve and AAV-HBV-infected mice demonstrated that the stabilized vaccine was well tolerated and able to brake immune tolerance established in AAV-HBV mice as efficiently as vaccine components constantly stored at 4 °C/-80 °C. Even after long-term exposure to elevated temperatures, stabilized TherVacB induced high titre HBV-specific antibodies and strong CD8+ T-cell responses, resulting in anti-HBs seroconversion and strong suppression of the virus in HBV-replicating mice. Conclusion: SAA-formulation resulted in highly functional and thermostable HBsAg, HBcAg and MVA vaccine components. This will facilitate global vaccine application without the need for cooling chains and is important for the development of prophylactic as well as therapeutic vaccines supporting vaccination campaigns worldwide. Impact and implications: Therapeutic vaccination is a promising therapeutic option for chronic hepatitis B that may enable its cure. However, its application requires functional cooling chains during transport and storage that can hardly be guaranteed in many countries with high demand. In this study, the authors developed thermostable vaccine components that are well tolerated and that induce immune responses and control the virus in preclinical mouse models, even after long-term exposure to high surrounding temperatures. This will lower costs and ease application of a therapeutic vaccine and thus be beneficial for the many people affected by hepatitis B around the world.

Photosystem I light-harvesting proteins regulate photosynthetic electron transfer and hydrogen production.

Linear electron flow (LEF) and cyclic electron flow (CEF) compete for light-driven electrons transferred from the acceptor side of photosystem I (PSI). Under anoxic conditions, such highly reducing electrons also could be used for hydrogen (H2) production via electron transfer between ferredoxin and hydrogenase in the green alga Chlamydomonas reinhardtii. Partitioning between LEF and CEF is regulated through PROTON-GRADIENT REGULATION5 (PGR5). There is evidence that partitioning of electrons also could be mediated via PSI remodeling processes. This plasticity is linked to the dynamics of PSI-associated light-harvesting proteins (LHCAs) LHCA2 and LHCA9. These two unique light-harvesting proteins are distinct from all other LHCAs because they are loosely bound at the PSAL pole. Here, we investigated photosynthetic electron transfer and H2 production in single, double, and triple mutants deficient in PGR5, LHCA2, and LHCA9. Our data indicate that lhca2 and lhca9 mutants are efficient in photosynthetic electron transfer, that LHCA2 impacts the pgr5 phenotype, and that pgr5/lhca2 is a potent H2 photo-producer. In addition, pgr5/lhca2 and pgr5/lhca9 mutants displayed substantially different H2 photo-production kinetics. This indicates that the absence of LHCA2 or LHCA9 impacts H2 photo-production independently, despite both being attached at the PSAL pole, pointing to distinct regulatory capacities.

Chloroplasts require glutathione reductase to balance reactive oxygen species and maintain efficient photosynthesis.

Thiol-based redox-regulation is vital for coordinating chloroplast functions depending on illumination and has been throroughly investigated for thioredoxin-dependent processes. In parallel, glutathione reductase (GR) maintains a highly reduced glutathione pool, enabling glutathione-mediated redox buffering. Yet, how the redox cascades of the thioredoxin and glutathione redox machineries integrate metabolic regulation and detoxification of reactive oxygen species remains largely unresolved because null mutants of plastid/mitochondrial GR are embryo-lethal in Arabidopsis thaliana. To investigate whether maintaining a highly reducing stromal glutathione redox potential (EGSH ) via GR is necessary for functional photosynthesis and plant growth, we created knockout lines of the homologous enzyme in the model moss Physcomitrella patens. In these viable mutant lines, we found decreasing photosynthetic performance and plant growth with increasing light intensities, whereas ascorbate and zeaxanthin/antheraxanthin levels were elevated. By in vivo monitoring stromal EGSH dynamics, we show that stromal EGSH is highly reducing in wild-type and clearly responsive to light, whereas an absence of GR leads to a partial glutathione oxidation, which is not rescued by light. By metabolic labelling, we reveal changing protein abundances in the GR knockout plants, pinpointing the adjustment of chloroplast proteostasis and the induction of plastid protein repair and degradation machineries. Our results indicate that the plastid thioredoxin system is not a functional backup for the plastid glutathione redox systems, whereas GR plays a critical role in maintaining efficient photosynthesis.

Algorithm-Based Liquid Formulation Development Including a DoE Concept Predicts Long-Term Viral Vector Stability.

Specifically tailored amino acid-based formulations were previously shown to have a high potential to avoid stress-mediated degradation of complex molecules such as monoclonal antibodies and viral vectors. By using adenovirus 5 (Ad5) as a model, we studied whether such formulations may also efficiently protect viral vectors in thermal stress experiments and during long-term liquid storage. Algorithm-based amino acid preselection using an excipient database and subsequent application of design of experiments (DoE) in combination with a 37°C challenging model enabled the prediction of long-term storage stability of Ad5. By statistical analysis of the Ad5 infectivity, amino acids with significant influence on Ad5 stability were detected after 2 and 3 weeks of liquid storage at 37°C. Ad5 formulations comprising positively selected amino acids did not reveal any loss of infectivity after 24 months in liquid storage at 5°C. By contrast, a 2 log reduction after 3 months and complete loss of infectivity after 18 months was observed with a standard viral vector formulation. By an optimization round, we designed a simple and well-balanced formulation avoiding MgCl2, previously considered essential in Ad5 formulations. This work demonstrates the efficacy of an algorithm-based development approach in the formulation development for viral vectors.

Modulation of ABA responses by the protein kinase WNK8.

Abscisic acid (ABA) regulates growth and developmental processes in response to limiting water conditions. ABA functions through a core signaling pathway consisting of PYR1/PYL/RCAR ABA receptors, type 2C protein phosphatases (PP2Cs), and SnRK2-type protein kinases. Other signaling modules might converge with ABA signals through the modulation of core ABA signaling components. We have investigated the role of the protein kinase WNK8 in ABA signaling. WNK8 interacted with PP2CA and PYR1, phosphorylated PYR1 in vitro, and was dephosphorylated by PP2CA. A hypermorphic wnk8-ct Arabidopsis mutant allele suppressed ABA and glucose hypersensitivities of pp2ca-1 mutants during young seedling development, and WNK8 expression in protoplasts suppressed ABA-induced reporter gene expression. We conclude that WNK8 functions as a negative modulator of ABA signaling.

Surgical Anatomy of the Orbit in Human Cadavers-An Endoscopic Pictorial Documentation.

Background The aim of our study was a pictorial documentation of the anatomical structures of the orbit. Methods We performed a transmaxillary endoscopic approach in nine formalin-fixed human heads. We identified and documented the anatomy of the inferior part of the orbit. Results The first intraorbital anatomical landmark was the inferior rectus muscle, from which important structures medially and laterally could be identified. Anatomical structures and their relation to each other were documented and presented as illustrative figures. Conclusion Knowledge of the topographic anatomy of the inferior part of the orbit could be sufficiently imparted by our illustrations. The presented transmaxillary approach allowed a wide overview of the anatomical structures located in the inferior part of the orbit. Our pictorial documentation may provide neurosurgeons more safety and the opportunity to become familiar with the endoscopic anatomy.

[Fluorescence Cholangiography in Comparison to Radiographic Cholangiography During Laparoscopic Cholecystectomy]. / ICG-Fluoreszenzcholangiografie im Vergleich zur konventionellen Röntgencholangiografie im Rahmen einer laparoskopischen Cholezystektomie.

BACKGROUND: The reported incidence rate of bile duct injury (BDI) during laparoscopic cholecystectomy (LC) is 0.3%. However, routine use of intraoperative cholangiography (IOC) is a controversial, due to the additional cost and radiation exposure. The aim of this study was to assess the application of fluorescence cholangiography (FC) in comparison to IOC and to LC without any intraoperative imaging. MATERIALS AND METHODS: This prospective study included 230 patients undergoing LC in our institution. The subjects were divided into two groups. In the first group, with 170 patients, both FC and IOC were performed following a standardised protocol. In second group, with 60 patients, FC was compared to LC without any intraoperative imaging. The data were then analysed with respect to procedure time and identification of predefined anatomical structures. RESULTS: The mean age and body mass index in the first group were 54.4 ± 15.7 years and 27.9 ± 5.7 kg/m², respectively. The mean operative time was 67.6 ± 23.3 min. FC was performed more rapidly than IOC (1.5 ± 0.9 vs.7.3 ± 5.0 min) and visualised the cystic duct (DC) in 67.5% of patients and the common bile duct (DHC) in 66.2% of patients before dissection of Calot's triangle. During dissection, DC and DHC were detected in 95.9% and 71.2% of patients, respectively. BMI > 25 kg/m² and male gender significantly reduced the identification rate of DC before dissection of Calot's triangle. Bile leakage from the liver bed after cholecystectomy was found in 3 cases (1.8%) by FC. In 2 patients (1.2%), IOC visualised the DC joining directly to the right hepatic duct. In 1 of these 2 cases (0.6%), the anatomical variation was identified first by FC. Intraductal filling defects were detected in 9 patients (5.3%) using IOC, compared to 1 patient (0.6%) using FC. In the second group, the visualisation rates of DC and DHC were 80.0 and 53.3%, respectively, with FC and 60.0 and 43.3%, respectively, during LC without any imaging. Surgeons confirmed an increase in safety in 70.0% of patients using FC. CONCLUSION: FC is a simple procedure for non-invasive real-time visualisation of bile duct anatomy during LC. Earlier identification of biliary anomalies and bile leakage increases the operative safety and enables immediate care. In obese patients, FC has limited validity.

A Modified Mini-Pterional (Subfrontal-Suprapterional) Approach to MCA Bifurcation Aneurysms with Minimal Dissection of the Temporal Muscle.

There are a number of different surgical approaches in middle cerebral artery (MCA) aneurysm surgery. Evolution from the classical pterional approach towards smaller modified approaches took place over the years. In the present report, we describe a new modified approach in the treatment of MCA aneurysms, which is almost exclusively subfrontal. A modified approach was used on three patients with MCA bifurcation aneurysms. Craniotomy was subfrontal and suprapterional with minimal dissection of the temporal muscle and no drilling of the pterion. In all three cases, after establishing proximal control and dissecting the M1 carefully, retraction of the frontal lobe elevated the sylvian fissure and allowed opening of the fissure. The aneurysm could be identified easily and clips were applied. There was no infection and complete aneurysm clipping was achieved in all 3 patients. The described minimal craniotomy to the MCA through a subfrontal-suprapterional approach allows dissection of peripheral MCA bifurcation aneurysms without any problems.

The value of intraoperative ultrasonography during the resection of relapsed irradiated malignant gliomas in the brain.

PURPOSE: The aim of this study was to investigate whether intraoperative ultrasonography (IOUS) helped the surgeon navigate towards the tumor as seen in preoperative magnetic resonance imaging and whether IOUS was able to distinguish between tumor margins and the surrounding tissue. METHODS: Twenty-five patients suffering from high-grade gliomas who were previously treated by surgery and radiotherapy were included. Intraoperatively, two histopathologic samples were obtained a sample of unequivocal tumor tissue (according to anatomical landmarks and the surgeon's visual and tactile impressions) and a small tissue sample obtained using a navigated needle when the surgeon decided to stop the resection. This specimen was considered to be a boundary specimen, where no tumor tissue was apparent. The decision to take the second sample was not influenced by IOUS. The effect of IOUS was analyzed semi-quantitatively. RESULTS: All 25 samples of unequivocal tumor tissue were histopathologically classified as tumor tissue and were hyperechoic on IOUS. Of the boundary specimens, eight were hypoechoic. Only one harbored tumor tissue (P=0.150). Seventeen boundaries were moderately hyperechoic, and these samples contained all possible histological results (i.e., tumor, infiltration, or no tumor). CONCLUSION: During surgery performed on relapsed, irradiated, high-grade gliomas, IOUS provided a reliable method of navigating towards the core of the tumor. At borders, it did not reliably distinguish between remnants or tumor-free tissue, but hypoechoic areas seldom contained tumor tissue.

Sandwich Wound Closure Reduces the Risk of Cerebrospinal Fluid Leaks in Posterior Fossa Surgery.

Posterior fossa surgery is demanding and hides a significant number of obstacles starting from the approach to the wound closure. The risk of cerebrospinal fluid (CSF) leakage in posterior fossa surgery given in the literature is around 8%. The present study aims to introduce a sandwich closure of the dura in posterior fossa surgery, which reduces significantly the number of CSF leaks (3.8%) in the patients treated in our department. Three hundred and ten patients treated in our hospital in the years 2009-2013 for posterior fossa pathologies were retrospectively evaluated. The dura closure method was as following: lyophilized dura put under the dura and sealed with fibrin glue and sutures, dura adapting stitches, TachoSil® (Takeda Pharma A/S, Roskilde, Denmark), Gelfoam® (Pfizer Inc., New York, NY, USA) and polymethylmethacrylate (osteoclastic craniotomy). The incidence of postsurgical complications associated with the dural closure like CSF leakage, infections, bleeding is evaluated. Only 3.8% of patients developed CSF leakage and only 0.5% needed a second surgery for CSF leakage closure. Two percent had a cerebellar bleeding with no need for re-operation and 3% had a wound infection treated with antibiotics. The sandwich wound closure we are applying for posterior fossa surgery in our patients correlates with a significant reduction of CSF leaks compared to the literature.

Laparoscopic insertion of the peritoneal catheter in ventriculoperitoneal shunting. Review of 405 consecutive cases.

BACKGROUND: Based upon our excellent previous experience with 151 adult patients and 39 children whom had the peritoneal catheter in ventriculoperitoneal shunting placed laparoscopically, we continued following this technique as a first-line-procedure in ventriculoperitoneal shunting. Now we analyzed our experience with additional 405 cases for a better comprehension of the complications, advantages and disadvantages of this procedure on this high number of patients. A strict interdisciplinary setting with the maximum of medical intraoperative competence was our goal and therefore better results. MATERIAL AND METHODS: N = 405 patients with intraperitoneal shunt insertion from the years 2006-2013 (Follow-up period ranges from 2 to 9 years with a 5,9-year mean follow-up period) were retrospectively analyzed with a special focus on the possible peritoneal catheter complications after laparoscopical shunt insertion. In our department all the peritoneal catheters in ventriculoperitoneal shunting are inserted laparoscopically, when there is no contraindication for this technique. RESULTS: We had 0% peritoneal catheter misplacement rate with help of the laparoscopic technique. In two cases (0.49%) injury of the small bowel could be repaired immediately with no further action required. In two cases umbilical hernias have been accidently discovered and the repair of the hernias took place in the same surgical session. As this technique helps us to control the shunt position intraperitoneally by direct laparoscopic vision, the patients spared an extra radiation exposure, to control the position of the peritoneal catheter. A diagnostic laparoscopy is also possible if needed. The time of the operation is shortened in comparison with the needed time, which is mentioned in literature, for the open laparotomy and of course the needed anesthesia and its possible risks and complications decreased. CONCLUSION: No revision surgeries were required because of any misplacement of the peritoneal catheter, no additional technique related risks compared to the open surgical technique, no abdominal x-rays were needed, the operation time is shortened and the dose of anesthesia needed is decreased and of course its possible side effects' rate is also decreased. Another great benefit of this technique is the possibility of accidental diagnosis of intra-abdominal pathologies. Also, if a surgical treatment of this accidentally discovered intra-abdominal pathologies is needed, it can take place in the same surgical session. No prolonged surgery time as the laparoscopic technique is much easier, controllable and fast.

Resolution of a periodontoid rheumatoid pannus mass in an elderly patient treated with a rigid cervical collar: A case report and literature review.

In patients with C2 rheumatoid pannus with spinal cord compression the treatment of choice is extensive surgery either through a transoral resection of the dens axis or a dorsal stabilisation, or both. We present a case of an 11-mm rheumatoid pannus with significant compression of the spinal cord, which failed surgical treatment with respect to dorsal stabilisation. Therefore, rigid cervical collar for 8 weeks followed by soft collar for another 4 weeks was chosen as a treatment option. During the follow-up period of 1 year, the pannus reduced significantly and the spinal cord decompressed. In cases where surgery is not an option or is technically very demanding, the alternative of cervical collar immobilisation is a satisfying option.

Diffuse Spinal Leptomeningeal Spread of a Pilocytic Astrocytoma in a 3-year-old Child.

Pilocytic astrocytomas correspond to low-grade gliomas and therefore metastasize exceedingly rare. However, pilocytic astrocytomas are able to and leptomeningeal dissemination may be seen. What are the treatment options of these cases? We present a case report of a 3-year-old child with a pilocytic astrocytoma of the optic chiasm with leptomeningeal dissemination of the spinal meninges. Partial resection of the cerebral tumor has been performed. Since the leptomeningeal dissemination was seen all over the spinal meninges, the child did not undergo further surgical treatment. A wait and watch strategy were followed. Chemotherapy was initiated, if a 25% tumor growth was seen. Leptomeningeal dissemination of a pilocytic astrocytoma is seen so infrequently that no standard therapy is established. Since these metastases may occur even up to 2 decades after primary tumor resection, long-term follow-up is indicated. In case of spinal metastases, surgical treatment should be performed if feasible. Otherwise observation should be possessed and/or chemotherapy should be initiated.

Oribital apex syndrome caused by aspergilloma in an immunocompromised patient with cutaneous lymphoma: A case report of a rare entity.

A 57-year-old man with a history of chemotherapy because of cutaneous lymphoma presented with an orbital apex syndrome. The cranial computed tomography scan revealed a tumour in the orbital apex, extending intradurally. With a suspected diagnosis of a neoplastic lesion, the patient underwent orbital surgery with optic nerve decompression. Histology revealed an aspergilloma. No other foci were seen and treatment with antifungals was started. In immunocompromised patients with intracranial tumours, infection is always a major consideration in the differential diagnosis, even if the reason for immunosuppression (in this case chemotherapy) dates back several months. Misdiagnosing an orbital apex lesion as a cancer and treating patients primarily with corticosteroids can be life threatening. Removal or biopsy of such lesions is essential in further treatment since antifungals have to be administered as fast as possible.

Can Break-Dance Break Your Neck? C1/C2 Luxation with a Combined Dens Fracture Without Neurological Deficits in an 11-Year Old Boy After a Break-Dance Performance.

Atlantoaxial dislocation in children is a very rare condition. We present the case of a dislocation happened during a break-dance maneuver. The purpose of this report is describing dangers of break-dancing and discussing the treatment we chose. The patient was followed up until 12 months after surgery. Magnetic resonance imaging and computed tomography of the cervical spine were evaluated. Translaminar fixation of C1/C2 had been performed after manual reposition under X-ray illumination. After a 12-month follow-up, the patient shows a stable condition without neurological dysfunction. He is not allowed to perform any extreme sports.

German Cranial Reconstruction Registry (GCRR): protocol for a prospective, multicentre, open registry.

INTRODUCTION: Owing to increasing numbers of decompressive craniectomies in patients with malignant middle cerebral artery infarction, cranioplastic surgery becomes more relevant. However, the current literature mainly consists of retrospective single-centre (evidence class III) studies. This leads to a wide variability of technical approaches and clinical outcomes. To improve our knowledge about the key elements of cranioplasty, which may help optimising clinical treatment and long-term outcome, a prospective multicentre registry across Germany, Austria and Switzerland will be established. METHODS: All patients undergoing cranioplastic surgery in participating centres will be invited to join the registry. Technical methods, materials, medical history, adverse events and clinical outcome measures, including modified Rankin scale and EQ-5D, will be assessed at several time points. Patients will be accessible to inclusion either at initial decompressive surgery or when cranioplasty is planned. Scheduled monitoring will be carried out at time of inclusion and subsequently at time of discharge, if any readmission is necessary, and at follow-up presentation. Cosmetic results and patient satisfaction will also be assessed. Collected data will be managed and statistically analysed by an independent biometric institute. The primary endpoint will be mortality, need for operative revision and neurological status at 3 months following cranioplasty. ETHICS AND DISSEMINATION: Ethics approval was obtained at all participating centres. The registry will provide reliable prospective evidence on surgical techniques, used materials, adverse events and functional outcome, to optimise patient treatment. We expect this study to give new insights in the treatment of skull defects and to provide a basis for future evidence-based therapy regarding cranioplastic surgery. TRIAL REGISTRATION NUMBER: This trial is indexed in the German Clinical Trials Register (DRKS-ID: DRKS00007931). The Universal Trial Number (UTN) is U1111-1168-7425.