The value of cryoablation in orbital surgery.

Aim of this article is to give an overview of the technical background and the advantages of modern devices for different applications of cryoablation in cranio-orbital neurosurgery.The treatment of orbital lesions is complicated by the complex and potentially inapparent anatomy due to retro-orbital fat. With the help of cryoprobes different well-defined lesions such as cavernous venous malformations can be safely and effectively removed thanks to the cryoadhesive effect. Their use has been described in several different approaches including traditional lateral or transcranial orbitotomy but also anterior transconjunctival as well as transnasal endoscopic approaches. Recently, single-use devices were introduced that allow the use of cryosurgery also without the need for large investment or service costs.

MRI surveillance after translabyrinthine vestibular schwannoma resection and cochlear implantation: is it feasible?

PURPOSE: Cochlear implantation in patients with vestibular schwannomas is of increasing importance and interest. Two remaining challenges are the assessment of conduction of the cochlear nerve and the possibility of postoperative surveillance with magnetic resonance imaging. The aim of the current study was to assess follow-up imaging and determine the visibility of the internal auditory canal after vestibular schwannoma resection and cochlear implantation as well as in patients with persistent vestibular schwannomas and cochlear implants in place. Visibility of the internal auditory canal, cerebellopontine angle, and labyrinth were evaluated and graded. METHODS: For this retrospective study, 15 MR examinations of 13 patients after translabyrinthine vestibular schwannoma resection and ipsilateral cochlear implantation were included. All patients had been implanted with an MED-EL cochlear implant. Magnetic resonance imaging was carried out on a 1.5T device. All patients were prepped according to the manufacturer's recommendations. RESULTS: All 15 examinations were carried out without any adverse event during imaging, such as pain, magnet dislocation, or malfunction. The internal auditory canal and the cerebellopontine angle were sufficiently visible in all cases to allow for vestibular schwannoma follow-up. CONCLUSION: Magnetic resonance imaging surveillance of the internal auditory canal following vestibular schwannoma resection and cochlear implantation is feasible and safe with modern implants with a 1.5T magnetic resonance imaging device using metal artifact reduction sequences. Necessary follow-up imaging should not be a contraindication for cochlear implantation in patients with vestibular schwannomas.

Functional Outcome After Simultaneous Vestibular Schwannoma Resection and Cochlear Implantation With Intraoperative Cochlear Nerve Monitoring.

OBJECTIVE: Electrically evoked auditory brainstem response audiometry has emerged as a suitable option to intraoperatively assess cochlear nerve function during vestibular schwannoma resection. This study aimed to analyze the functional outcome and implant usage of patients with preserved auditory nerve responses after simultaneous translabyrinthine schwannoma resection and cochlear implantation. STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. METHODS: Patients with unilateral sporadic vestibular schwannoma underwent translabyrinthine tumor resection. Intraoperatively, electrically evoked auditory brainstem response audiometry was performed before and after tumor removal. Cochlear implantation was carried out if positive responses were detected after tumor removal indicating cochlear nerve function. Postoperatively, patients were biannually followed-up to assess aided sound field audiometry and word recognition as well as implant usage. RESULTS: Overall, 26 patients with vestibular schwannoma underwent translabyrinthine schwannoma resection. Out of these patients, 15 had positive cochlear nerve responses after tumor removal and concurrently received a cochlear implant. In 13 patients with histologically confirmed vestibular schwannoma, hearing improved by 23.7 ± 33.2 decibels and word recognition by 25.0 ± 42.4% over a mean follow-up period of 18 months. Overall, 12 included patients were regular cochlear implant users. CONCLUSION: Patients with vestibular schwannoma can benefit substantially from cochlear implantation. Intraoperative assessment of cochlear nerve function using electrically evoked auditory brainstem response audiometry can help to better identify individuals eligible for simultaneous vestibular schwannoma resection and cochlear implantation.

Toward digital histopathological assessment in surgery for central nervous system tumors using stimulated Raman histology.

OBJECTIVE: Intraoperative neuropathological assessment with conventional frozen sections supports the neurosurgeon in optimizing the surgical strategy. However, preparation and review of frozen sections can take as long as 45 minutes. Stimulated Raman histology (SRH) was introduced as a novel technique to provide rapid high-resolution digital images of unprocessed tissue samples directly in the operating room that are comparable to conventional histopathological images. Additionally, SRH images are simultaneously and easily accessible for neuropathological judgment. Recently, the first study showed promising results regarding the accuracy and feasibility of SRH compared with conventional histopathology. Thus, the aim of this study was to compare SRH with conventional H&E images and frozen sections in a large cohort of patients with different suspected central nervous system (CNS) tumors. METHODS: The authors included patients who underwent resection or stereotactic biopsy of suspected CNS neoplasm, including brain and spinal tumors. Intraoperatively, tissue samples were safely collected and SRH analysis was performed directly in the operating room. To enable optimal comparison of SRH with H&E images and frozen sections, the authors created a digital databank that included images obtained with all 3 imaging modalities. Subsequently, 2 neuropathologists investigated the diagnostic accuracy, tumor cellularity, and presence of diagnostic histopathological characteristics (score 0 [not present] through 3 [excellent]) determined with SRH images and compared these data to those of H&E images and frozen sections, if available. RESULTS: In total, 94 patients with various suspected CNS tumors were included, and the application of SRH directly in the operating room was feasible in all cases. The diagnostic accuracy based on SRH images was 99% when compared with the final histopathological diagnosis based on H&E images. Additionally, the same histopathological diagnosis was established in all SRH images (100%) when compared with that of the corresponding frozen sections. Moreover, the authors found a statistically significant correlation in tumor cellularity between SRH images and corresponding H&E images (p < 0.0005 and R = 0.867, Pearson correlation coefficient). Finally, excellent (score 3) or good (2) accordance between diagnostic histopathological characteristics and H&E images was present in 95% of cases. CONCLUSIONS: The results of this retrospective analysis demonstrate the near-perfect diagnostic accuracy and capability of visualizing relevant histopathological characteristics with SRH compared with conventional H&E staining and frozen sections. Therefore, digital SRH histopathology seems especially useful for rapid intraoperative investigation to confirm the presence of diagnostic tumor tissue and the precise tumor entity, as well as to rapidly analyze multiple tissue biopsies from the suspected tumor margin. A real-time analysis comparing SRH images and conventional histological images at the time of surgery should be performed as the next step in future studies.

Combined Open Surgical and Endoscopic Approach for Management of a Meningoencephalocele After Iatrogenic Perforation of the Anterior Skull Base in a Young Infant.

Traumatic iatrogenic perforation of the anterior skull base is a rare complication following endonasal intubation in preterm infants. Subsequent meningoencephaloceles with concomitant cerebrospinal fluid (CSF) fistulas bear the risk of severe complications, therefore early diagnosis and closure of the skull defect are crucial. However, there is no consensus on the management of such cases of meningoencephaloceles. This case report presents a sophisticated approach of open brain surgery in combination with endonasal endoscopy. A 15-month-old girl presented with a meningoencephalocele and a CSF fistula due to iatrogenic perforation of the left anterior skull base during attempted endonasal intubation after birth. Difficult nasal breathing and an increasing diameter of the skull base defect on imaging controls indicated surgical management. Close multidisciplinary collaboration was essential for diagnosis and decision upon treatment. Open neurosurgical resection and CSF fistula closure combined with endonasal endoscopic removal of the excised meningoencephalocele was performed. Our case report shows that this combined open surgical and endonasal endoscopic approach is a safe procedure in favor of the postoperative outcome and follow-up of the patient.

[Vestibular schwannoma: Diagnosis-Therapy-Aftercare]. / Vestibularisschwannome: Diagnose ­ Therapie ­ Nachsorge.

Vestibular schwannomas can severely impair the quality of life of patients. Next to impaired hearing function, facial palsy is perceived as particularly disturbing in this context. Varying growth rates of these benign tumors complicate a prediction of functional impairment of cranial nerves. Therefore, a regular update on current therapeutic strategies and alternative treatment options is relevant for both physicians and patients.

Triamcinolone acetonide can be detected in cerebrospinal fluid after intratympanic injection.

Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to deliver gene therapy agents, or biologics to the inner ear. Further diversion from the middle ear and perilymph to blood circulation and cerebrospinal fluid via the cochlear aqueduct are one of the limiting factors and so far not understood well enough. In this study, intratympanically applied triamcinolone acetonide was determined in cerebrospinal fluid. Additionally, perilymph was sampled through the round window membrane as well as at the lateral semicircular canal to determine drug levels. Of the twenty-one included patients, triamcinolone acetonide was quantifiable in cerebrospinal fluid in 43% at very low levels (range 0 ng/ml-6.2 ng/ml) which did not correlate with perilymph levels. Drug levels at the two different perilymph sampling sites were within a range of 13.5 ng/ml to 1180.0 ng/ml. Results suggest an equal distribution of triamcinolone acetonide to semicircular canals, which might support the use of triamcinolone acetonide as a treatment option for vestibular pathologies such as Menièrés disease. On the other hand, the distribution to cerebrospinal fluid might be limiting current approaches in gene therapy where a central distribution is unwanted.

Long-Term Outcome and Comparison of Treatment Modalities of Temporal Bone Paragangliomas.

INTRODUCTION: Temporal bone paragangliomas are rare tumors with high vascularization and usually benign entity. A variety of modalities, including gross total resection, subtotal resection, conventional or stereotactic radiotherapy including gamma-knife, embolization, and wait-and-scan strategy can be considered. The aim of this study was to compare long-term outcomes of different primary treatment modalities in temporal bone paragangliomas. MATERIALS AND METHODS: Patients with temporal bone paragangliomas treated between 1976 and 2018 at a tertiary referral center were retrospectively analyzed in this study. Collected patient data of 42 years were analyzed and long-term results including interdisciplinary management were assessed. Patient outcomes were compared within the different therapy modalities according to tumor control rate and complications. Clinical characteristics, radiological imaging, tumor extent and location (according to Fisch classification), symptoms, and follow-up were evaluated and a descriptive analysis for each treatment modality was performed. Tumor recurrence or growth progression and respective cranial nerve function before and after therapy were described. RESULTS: A total of 59 patients were treated with a single or combined treatment modality and clinical follow-up was 7 (13) years (median, interquartile range). Of the included patients 45 (76%) were female and 14 (24%) male (ratio 3:1) with a patient age range from 18 to 83 years. Total resection was performed on 31 patients, while 14 patients underwent subtotal resection. Eleven patients were treated with conventional primary radiotherapy or gamma-knife radiosurgery. Pulsatile tinnitus (n = 17, 29%) and hearing impairment (n = 16, 27%) were the most common symptoms in our patient group. Permanent lower cranial nerve deficits were observed only in patients with large tumors (Fisch C and D, n = 14, 24%). Among the 45 patients who were treated surgically, 88% of patients with Fisch A and B paragangliomas had no recurrent disease, while no tumor growth was perceived in 83% of patients with Fisch C and D paragangliomas. CONCLUSION: In conclusion, we propose surgery as a treatment option for patients with small tumors, due to a high control rate and less cranial nerve deficits compared to larger tumors. Although patients with Fisch C and D temporal bone paraganglioma can be treated surgically, only subtotal resections are possible in many cases. Additionally, frequent occurrence of cranial nerve deficits in those patients and tumor growth progression in long-term follow-up examinations make a combination of the therapy modalities or a primary radiotherapy more suitable in larger tumors.

Clinical Outcome and Technical Nuances After Resection of Orbital Cavernous Venous Malformations-A Single-Center Experience.

BACKGROUND: Cavernous venous malformations (CVMs) represent the most common benign intraorbital lesions. Enlarging or symptomatic CVMs (progressive proptosis or visual disturbances) are treated by surgical resection. For this, a variety of different surgical approaches have been described. The aim of this study was to present a contemporary series of orbital CVMs treated via open microsurgical approaches. METHODS: In this study, patients who underwent resection of orbital CVMs between 2002 and 2019 were included. Presenting symptoms were noted and neuro-ophthalmologic examinations performed pre- and postoperatively. For surgical resection, the location of the orbital CVM and its relation to the orbital anatomy led to decision-making for appropriate approaches. A comparison between anatomical location and surgical outcome was performed. RESULTS: Overall, 35 patients with orbital CVMs were included. Most common presenting symptoms were progressive proptosis (43%) and visual disturbances (34%). Most common location was the lateral quadrant (37%) followed by the superior quadrant (20%). A subfrontal craniotomy was performed in 40% of cases followed by a supraorbital craniotomy including the orbital rim in 34% of cases. For surgical excision, a cryo-probe was used in 30 patients, and complete resection was feasible in all cases. Location of a CVM within the superior quadrant was associated with improved postoperative recovery of visual acuity. No differences for clinical outcomes were observed depending on the surgical approach. CONCLUSIONS: Resection of orbital CVMs is indicated in patients with visual disturbances or progressive proptosis. In these, microsurgical approaches can be used with minimal morbidity for complete removal of these well-circumscribed lesions.

Cerebrolysin after moderate to severe traumatic brain injury: prospective meta-analysis of the CAPTAIN trial series.

INTRODUCTION: This prospective meta-analysis summarizes results from the CAPTAIN trial series, evaluating the effects of Cerebrolysin for moderate-severe traumatic brain injury, as an add-on to usual care. MATERIALS AND METHODS: The study included two phase IIIb/IV prospective, randomized, double-blind, placebo-controlled clinical trials. Eligible patients with a Glasgow Coma Score (GCS) between 6 and 12 received study medication (50 mL of Cerebrolysin or physiological saline solution per day for ten days, followed by two additional treatment cycles with 10 mL per day for 10 days) in addition to usual care. The meta-analysis comprises the primary ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses based on multivariate, directional tests. RESULTS: A total 185 patients underwent meta-analysis (mean admission GCS = 10.3, mean age = 45.3, and mean Baseline Prognostic Risk Score = 2.8). The primary endpoint, a multidimensional ensemble of functional and neuropsychological outcome scales indicated a "small-to-medium" sized effect in favor of Cerebrolysin, statistically significant at Day 30 and at Day 90 (Day 30: MWcombined = 0.60, 95%CI 0.52 to 0.66, p = 0.0156; SMD = 0.31; OR = 1.69; Day 90: MWcombined = 0.60, 95%CI 0.52 to 0.68, p = 0.0146; SMD = 0.34, OR = 1.77). Treatment groups showed comparable safety and tolerability profiles. DISCUSSION: The meta-analysis of the CAPTAIN trials confirms the safety and efficacy of Cerebrolysin after moderate-severe TBI, opening a new horizon for neurorecovery in this field. Integration of Cerebrolysin into existing guidelines should be considered after careful review of internationally applicable criteria.

Simultaneous Vestibular Schwannoma Resection and Cochlear Implantation Using Electrically Evoked Auditory Brainstem Response Audiometry for Decision-making.

OBJECTIVE: The aim of the study was to evaluate the predictive value regarding postoperative hearing benefit of electrically evoked auditory brainstem response audiometry in sporadic vestibular schwannoma patients undergoing simultaneous tumor resection and cochlear implantation. DESIGN: Patients were included in a prospective study conducted between October 2016 and January 2019. SETTING: The study was conducted at a tertiary care center. PARTICIPANTS: Subjects with unilateral sporadic vestibular schwannoma were screened for study participation. Patients underwent translabyrinthine vestibular schwannoma resection and cochlear implantation simultaneously. INTERVENTION: Electrically evoked brainstem response audiometry was performed during surgery before and after tumor removal using an intracochlear test electrode to objectively evaluate nerve conduction. MAIN OUTCOME MEASURE: Electrically evoked brainstem response audiometry results were correlated with postoperative sound field audiometry, word recognition tests, and speech reception thresholds. Quality of life was assessed before and 12 months after translabyrinthine tumor removal and cochlear implantation. RESULTS: Five patients, three male and two female, were included in the study and followed for at least 1 year after implantation. Three of the five patients are daily cochlear implant users with open set speech recognition. Two individuals with negative intraoperative electrically evoked auditory brainstem response results showed no auditory perception with cochlear implant. CONCLUSIONS: Simultaneous translabyrinthine vestibular schwannoma resection and cochlear implantation with intraoperative electrically evoked auditory brainstem response measurements is a feasible and promising option for sporadic vestibular schwannoma patients. Preservation of electrically evoked auditory brainstem responses seems to predict good subsequent hearing outcomes.

Development and assessment of competency-based neurotrauma course curriculum for international neurosurgery residents and neurosurgeons.

OBJECTIVE: Traumatic brain injuries (TBIs) are a significant disease burden worldwide. It is imperative to improve neurosurgeons' training during and after their medical residency with appropriate neurotrauma competencies. Unfortunately, the development of these competencies during neurosurgeons' careers and in daily practice is very heterogeneous. This article aimed to describe the development and evaluation of a competency-based international course curriculum designed to address a broad spectrum of needs for taking care of patients with neurotrauma with basic and advanced interventions in different scenarios around the world. METHODS: A committee of 5 academic neurosurgeons was involved in the task of building this course curriculum. The process started with the identification of the problems to be addressed and the subsequent performance needed. After this, competencies were defined. In the final phase, educational activities were designed to achieve the intended learning outcomes. In the end, the entire process resulted in competency and outcomes-based education strategy, including a definition of all learning activities and learning outcomes (curriculum), that can be integrated with a faculty development process, including training. Further development was completed by 4 additional academic neurosurgeons supported by a curriculum developer specialist and a project manager. After the development of the course curriculum, template programs were developed with core and optional content defined for implementation and evaluation. RESULTS: The content of the course curriculum is divided into essentials and advanced concepts and interventions in neurotrauma care. A mixed sample of 1583 neurosurgeons and neurosurgery residents attending 36 continuing medical education activities in 30 different cities around the world evaluated the course. The average satisfaction was 97%. The average usefulness score was 4.2, according to the Likert scale. CONCLUSIONS: An international competency-based course curriculum is an option for creating a well-accepted neurotrauma educational process designed to address a broad spectrum of needs that a neurotrauma practitioner faces during the basic and advanced care of patients in different regions of the world. This process may also be applied to other areas of the neurosurgical knowledge spectrum. Moreover, this process allows worldwide standardization of knowledge requirements and competencies, such that training may be better benchmarked between countries regardless of their income level.

Efficacy and safety of cerebrolysin in neurorecovery after moderate-severe traumatic brain injury: results from the CAPTAIN II trial.

INTRODUCTION: The objective of this trial was to evaluate the efficacy and safety of Cerebrolysin in treating patients after moderate to severe traumatic brain injury (TBI) as an adjunct to standard care protocols. The trial was designed to investigate the clinical effects of Cerebrolysin in the acute (neuroprotective) stage and during early and long-term recovery as part of a neurorestorative strategy. MATERIALS AND METHODS: The study was a phase IIIb/IV single-center, prospective, randomized, double-blind, placebo-controlled clinical trial. Eligible patients with a Glasgow Coma Score (GCS) between 7 and 12 received study medication (50 ml of Cerebrolysin or physiological saline solution per day for 10 days, followed by two additional treatment cycles with 10 ml per day for 10 days) in addition to standard care. We tested ensembles of efficacy criteria for 90, 30, and 10 days after TBI with a priori ordered hypotheses using a multivariate, directional test, to reflect the global status of patients after TBI. RESULTS: The study enrolled 142 patients, of which 139 underwent formal analysis (mean age = 47.4, mean admission GCS = 10.4, and mean Baseline Prognostic Risk Score = 2.6). The primary endpoint, a multidimensional ensemble of 13 outcome scales, indicated a "small-to-medium"-sized effect in favor of Cerebrolysin, statistically significant at day 90 (MWcombined = 0.59, 95% CI 0.52 to 0.66, P = 0.0119). Safety and tolerability observations were comparable between treatment groups. CONCLUSION: Our trial confirms previous beneficial effects of the multimodal, biological agent Cerebrolysin for overall outcome after moderate to severe TBI, as measured by a multidimensional approach. Study findings must be appraised and aggregated in conjunction with existing literature, as to improve the overall level of insight regarding therapeutic options for TBI patients. The widely used pharmacologic intervention may benefit from a large-scale observational study to map its use and to establish comparative effectiveness in real-world clinical settings.

Single-stage bone resection and cranioplastic reconstruction: comparison of a novel software-derived PEEK workflow with the standard reconstructive method.

The combined resection of skull-infiltrating tumours and immediate cranioplastic reconstruction predominantly relies on freehand-moulded solutions. Techniques that enable this procedure to be performed easily in routine clinical practice would be useful. A cadaveric study was developed in which a new software tool was used to perform single-stage reconstructions with prefabricated implants after the resection of skull-infiltrating pathologies. A novel 3D visualization and interaction framework was developed to create 10 virtual craniotomies in five cadaveric specimens. Polyether ether ketone (PEEK) implants were manufactured according to the bone defects. The image-guided craniotomy was reconstructed with PEEK and compared to polymethyl methacrylate (PMMA). Navigational accuracy and surgical precision were assessed. The PEEK workflow resulted in up to 10-fold shorter reconstruction times than the standard technique. Surgical precision was reflected by the mean 1.1±0.29mm distance between the virtual and real craniotomy, with submillimetre precision in 50%. Assessment of the global offset between virtual and actual craniotomy revealed an average shift of 4.5±3.6mm. The results validated the 'elective single-stage cranioplasty' technique as a state-of-the-art virtual planning method and surgical workflow. This patient-tailored workflow could significantly reduce surgical times compared to the traditional, intraoperative acrylic moulding method and may be an option for the reconstruction of bone defects in the craniofacial region.

Safety and Efficacy of TachoSil (Absorbable Fibrin Sealant Patch) Compared With Current Practice for the Prevention of Cerebrospinal Fluid Leaks in Patients Undergoing Skull Base Surgery: A Randomized Controlled Trial.

BACKGROUND: Cerebrospinal fluid (CSF) leakage associated with incomplete sealing of the dura mater is a major complication of intradural procedures. OBJECTIVE: To compare the efficacy and safety of adjunctive TachoSil (Takeda Pharma A/S, Roskilde, Denmark) with current practice for the prevention of postoperative CSF leaks in patients undergoing elective skull base surgery involving dura mater closure. METHODS: Patients were intraoperatively randomized to TachoSil or current practice immediately before primary dura closure by suturing ± duraplasty. Choice of adjunctive treatment in the current practice group was at the surgeon's discretion. Primary efficacy endpoint was occurrence of clinically evident verified postoperative CSF leak or clinically evident pseudomeningocele within 7 weeks after surgery or treatment failure (third application of trial treatment or use of other treatment). RESULTS: A total of 726 patients were randomized to TachoSil (n = 361) or current practice (n = 365). More current practice patients had sutures plus duraplasty for primary dura closure compared with TachoSil (49.6% vs 35.7%) and fewer had sutures only (45.5% vs 63.2%). The primary endpoint of estimated leak rate favored TachoSil with events in 25 (6.9%) patients vs 30 (8.2%) current practice patients; however, this was not statistically significant (odds ratio: 0.82; 95% confidence interval: 0.47, 1.43; P = .485). Both treatments were well tolerated with similar frequency of adverse events. CONCLUSION: Very low rates of postoperative CSF leaks can be achieved in patients undergoing skull base surgery of various indications. Although the study did not meet its primary endpoint, TachoSil appears to be safe and effective for the prevention of CSF leaks and associated complications.

Cerebrolysin Asian Pacific trial in acute brain injury and neurorecovery: design and methods.

Traumatic brain injury (TBI) is one of the leading causes of injury-related death. In the United States alone, an estimated 1.7 million people sustain a TBI each year, and approximately 5.3 million people live with a TBI-related disability. The direct medical costs and indirect costs such as lost productivity of TBIs totaled an estimated $76.5 billion in the U.S. in the year 2000. Improving the limited treatment options for this condition remains challenging. However, recent reports from interdisciplinary working groups (consisting primarily of neurologists, neurosurgeons, neuropsychologists, and biostatisticians) have stated that to improve TBI treatment, important methodological lessons from the past must be taken into account in future clinical research. An evaluation of the neuroprotection intervention studies conducted over the last 30 years has indicated that a limited understanding of the underlying biological concepts and methodological design flaws are the major reasons for the failure of pharmacological agents to demonstrate efficacy. Cerebrolysin is a parenterally-administered neuro-peptide preparation that acts in a manner similar to endogenous neurotrophic factors. Cerebrolysin has a favorable adverse effect profile, and several meta-analyses have suggested that Cerebrolysin is beneficial as a dementia treatment. CAPTAIN is a randomized, double-blind, placebo-controlled, multi-center, multinational trial of the effects of Cerebrolysin on neuroprotection and neurorecovery after TBI using a multidimensional ensemble of outcome scales. The CAPTAIN trial will be the first TBI trial with a 'true' multidimensional approach based on full outcome scales, while avoiding prior weaknesses, such as loss of information through "dichotomization," or unrealistic assumptions such as "normal distribution."

The Comprehensive AOCMF Classification: Skull Base and Cranial Vault Fractures - Level 2 and 3 Tutorial.

The AOCMF Classification Group developed a hierarchical three-level craniomaxillofacial classification system with increasing level of complexity and details. The highest level 1 system distinguish four major anatomical units, including the mandible (code 91), midface (code 92), skull base (code 93), and cranial vault (code 94). This tutorial presents the level 2 and more detailed level 3 systems for the skull base and cranial vault units. The level 2 system describes fracture location outlining the topographic boundaries of the anatomic regions, considering in particular the endocranial and exocranial skull base surfaces. The endocranial skull base is divided into nine regions; a central skull base adjoining a left and right side are divided into the anterior, middle, and posterior skull base. The exocranial skull base surface and cranial vault are divided in regions defined by the names of the bones involved: frontal, parietal, temporal, sphenoid, and occipital bones. The level 3 system allows assessing fracture morphology described by the presence of fracture fragmentation, displacement, and bone loss. A documentation of associated intracranial diagnostic features is proposed. This tutorial is organized in a sequence of sections dealing with the description of the classification system with illustrations of the topographical skull base and cranial vault regions along with rules for fracture location and coding, a series of case examples with clinical imaging and a general discussion on the design of this classification.