Prolonged course of brain edema and neurological recovery in a translational model of decompressive craniectomy after closed head injury in mice.

Background: The use of decompressive craniectomy in traumatic brain injury (TBI) remains a matter of debate. According to the DECRA trial, craniectomy may have a negative impact on functional outcome, while the RescueICP trial revealed a positive effect of surgical decompression, which is evolving over time. This ambivalence of craniectomy has not been studied extensively in controlled laboratory experiments. Objective: The goal of the current study was to investigate the prolonged effects of decompressive craniectomy (both positive and negative) in an animal model. Methods: Male mice were assigned to the following groups: sham, decompressive craniectomy, TBI and TBI followed by craniectomy. The analysis of functional outcome was performed at time points 3d, 7d, 14d and 28d post trauma according to the Neurological Severity Score and Beam Balance Score. At the same time points, magnetic resonance imaging was performed, and brain edema was analyzed. Results: Animals subjected to both trauma and craniectomy presented the exacerbation of the neurological impairment that was apparent mostly in the early course (up to 7d) after injury. Decompressive craniectomy also caused a significant increase in brain edema volume (initially cytotoxic with a secondary shift to vasogenic edema and gliosis). Notably, delayed edema plus gliosis appeared also after decompression even without preceding trauma. Conclusion: In prolonged outcomes, craniectomy applied after closed head injury in mice aggravates posttraumatic brain edema, leading to additional functional impairment. This effect is, however, transient. Treatment options that reduce brain swelling after decompression may accelerate neurological recovery and should be explored in future experiments.

Metastases to the pituitary gland: insights from the German pituitary tumor registry.

Metastatic involvement of the pituitary gland is a rare but clinically significant phenomenon, that often poses diagnostic and therapeutic challenges. The aim of this study was to provide a comprehensive analysis of the origin of pituitary metastases using data from the German Pituitary Tumor Registry, one of the globally largest collections of pituitary pathology specimens. Here, we report data from a retrospective analysis of patients with metastases to the pituitary registered between 1990 and 2022. Out of 17,896 pituitary cases in the registry during this period, a total of 96 metastases to the pituitary gland were identified, accounting for 0.5% of all pituitary tumors in the registry. The mean age of the patients was 64 years. Breast cancer was identified as the primary tumor in 25% of total cases (n = 24/96) and in 50% of female patients. The second most prevalent primary tumor was lung cancer (18.75%, n = 18/96), followed by renal cell carcinoma (14.58%, n = 14/96). In comparison to current meta-analyses, this cohort shows a higher prevalence of metastases originating from the kidney. Furthermore, in contrast to the existing literature, no case of primary thyroid tumor was identified. Our study highlights the importance of pituitary metastases as a differential diagnosis in patients presenting with pituitary tumors.

A minimally invasive tubular retractor-assisted retropleural approach for thoracic disc herniations - case series and technical note.

PURPOSE: Thoracic disc herniations are uncommon and carry a high risk for neurological deterioration. Traditional surgical approaches include thoracotomy, costotransversectomy or posterior approaches with considerable morbidity. In this technical note with case series, we describe a minimally invasive tubular retractor-assisted retropleural approach for simple and less invasive microsurgical exploration of thoracic disc herniations from a lateral angle. METHODS: Surgical technique consisted of partial rib resection and retropleural dissection followed by the placement of a tubular retractor (METRx Tubes, Medtronic) for an anterior-lateral exposure of the disc and neuroforamen. Epidemiological, clinical and surgical patient data were acquired. RESULTS: Between 2017 and 2020, six patients were surgically treated using the minimally invasive tubular retractor-assisted retropleural approach. Microsurgical exposure of the disc and neural structures was achieved from a lateral direction without requiring thoracotomy or lung deflation. Control imaging confirmed resection in all cases without relevant residuum. As postoperative complications, one dural injury and one postoperative pneumothorax occured. No neurologic deterioration or recurrence occurred during a median follow-up of 3 months. CONCLUSION: The described tubular retractor-assisted retropleural exposure serves as a feasible minimally invasive microsurgical approach to the anterior-lateral thoracic spine.

Preoperative angiographic considerations and neurological outcome after surgical treatment of intradural spinal hemangioblastoma: a multicenter retrospective case series.

PURPOSE: Intradural spinal hemangioblastomas are rare highly hypervascularized benign neoplasms. Surgical resection remains the treatment of choice, with a significant risk of postoperative neurological deterioration. Due to the tumor infrequency, scientific evidence is scarce and limited to case reports and small case series. METHODS: We performed a retrospective multicenter study including five high-volume neurosurgical centers analyzing patients surgically treated for spinal hemangioblastomas between 2006 and 2021. We assessed clinical status, surgical data, preoperative angiograms, and embolization when available. Follow-up records were analyzed, and logistic regression performed to assess possible risk factors for neurological deterioration. RESULTS: We included 60 patients in Germany and Austria. Preoperative angiography was performed in 30% of the cases; 10% of the patients underwent preoperative embolization. Posterior tumor location and presence of a syrinx favored gross total tumor resection (93.8% vs. 83.3% and 97.1% vs. 84%). Preoperative embolization was not associated with postoperative worsening. The clinical outcome revealed a transient postoperative neurological deterioration in 38.3%, depending on symptom duration and preoperative modified McCormick grading, but patients recovered in most cases until follow-up. CONCLUSION: Spinal hemangioblastoma patients significantly benefit from early surgical treatment with only transient postoperative deterioration and complete recovery until follow-up. The performance of preoperative angiograms remains subject to center disparities.

In vivo imaging in experimental spinal cord injury - Techniques and trends.

Introduction: Traumatic Spinal Cord Injury (SCI) is one of the leading causes of disability in the world. Treatment is limited to supportive care and no curative therapy exists. Experimental research to understand the complex pathophysiology and potential mediators of spinal cord regeneration is essential to develop innovative translational therapies. A multitude of experimental imaging methods to monitor spinal cord regeneration in vivo have developed over the last years. However, little literature exists to deal with advanced imaging methods specifically available in SCI research. Research Question: This systematic literature review examines the current standards in experimental imaging in SCI allowing for in vivo imaging of spinal cord regeneration on a neuronal, vascular, and cellular basis. Material and Methods: Articles were included meeting the following criteria: experimental research, original studies, rodent subjects, and intravital imaging. Reviewed in detail are microstructural and functional Magnetic Resonance Imaging, Micro-Computed Tomography, Laser Speckle Imaging, Very High Resolution Ultrasound, and in vivo microscopy techniques. Results: Following the PRISMA guidelines for systematic reviews, 689 articles were identified for review, of which 492 were sorted out after screening and an additional 104 after detailed review. For qualitative synthesis 93 articles were included in this publication. Discussion and Conclusion: With this study we give an up-to-date overview about modern experimental imaging techniques with the potential to advance the knowledge on spinal cord regeneration following SCI. A thorough knowledge of the strengths and limitations of the reviewed techniques will help to optimally exploit our current experimental armamentarium in the field.

Navigation accuracy and assessability of carbon fiber-reinforced PEEK instrumentation with multimodal intraoperative imaging in spinal oncology.

Radiolucent carbon-fiber reinforced PEEK (CFRP) implants have helped improve oncological follow-up and radiation therapy. Here, we investigated the performance of 3D intraoperative imaging and navigation systems for instrumentation and precision assessment of CFRP pedicle screws across the thoraco-lumbar spine. Thirty-three patients with spinal tumors underwent navigated CFRP instrumentation with intraoperative CT (iCT), robotic cone-beam CT (rCBCT) or cone-beam CT (CBCT) imaging. Two different navigation systems were used for iCT-/rCBCT- and CBCT-based navigation. Demographic, clinical and outcome data was assessed. Four blinded observers rated image quality, assessability and accuracy of CFRP pedicle screws. Inter-observer reliability was determined with Fleiss` Kappa analysis. Between 2018 and 2021, 243 CFRP screws were implanted (iCT:93, rCBCT: 99, CBCT: 51), of which 13 were non-assessable (iCT: 1, rCBCT: 9, CBCT: 3; *p = 0.0475; iCT vs. rCBCT). Navigation accuracy was highest using iCT (74%), followed by rCBCT (69%) and CBCT (49%) (*p = 0.0064; iCT vs. CBCT and rCBCT vs. CBCT). All observers rated iCT image quality higher than rCBCT/CBCT image quality (*p < 0.01) but relevant pedicle breaches were reliably identified with substantial agreement between all observers regardless of the imaging modality. Navigation accuracy for CFRP pedicle screws was considerably lower than expected from reports on titanium implants and CT may be best for reliable assessment of CFRP materials.

Severe Traumatic Brain Injury in children-paradigm of decompressive craniectomy compared to a historic cohort.

PURPOSE: Traumatic brain injury (TBI) is one of the leading causes of death and disability in children. Medical therapy remains limited, and decompressive craniectomy (DC) is an established rescue therapy in case of elevated intracranial pressure (ICP). Much discussion deals with clinical outcome after severe TBI treated with DC, while data on the pediatric population is rare. We report our experience of treating severe TBI in two different treatment setups at the same academic institution. METHODS: Forty-eight patients (≤ 16 years) were hospitalized with severe TBI (GCS ≤ 8 points) between 2008 and 2018 in a pediatric intensive care unit (ICU) at a specialized tertiary pediatric care center. Data on treatment, clinical status, and outcome was retrospectively analyzed. Outcome data included Glasgow Outcome Scale (GOS) at 3-, 12-, and 36-month follow-up. Data was compared to a historic cohort with 53 pediatric severe TBI patients treated at the same institution in a neurointensive care unit between 1996 and 2007. Ethical approval was granted (EA2/076/21). RESULTS: Between 2008 and 2018, 11 patients were treated with DC. Compared to the historic cohort, patients were younger and GCS was worse, while in-hospital mortality and clinical outcome remained similar. A trend towards more aggressive EVD placement and the internal paradigm change for treatment in a specialized pediatric ICU was observed. CONCLUSIONS: In children with severe TBI treated over two decades, clinical outcome was comparable and mostly favorable in two different treatment setups. Consequent therapy is warranted to maintain the positive potential for favorable outcome in children with severe TBI.

Therapeutic Approaches Targeting Vascular Repair After Experimental Spinal Cord Injury: A Systematic Review of the Literature.

Traumatic spinal cord injury (SCI) disrupts the spinal cord vasculature resulting in ischemia, amplification of the secondary injury cascade and exacerbation of neural tissue loss. Restoring functional integrity of the microvasculature to prevent neural loss and to promote neural repair is an important challenge and opportunity in SCI research. Herein, we summarize the course of vascular injury and repair following SCI and give a comprehensive overview of current experimental therapeutic approaches targeting spinal cord microvasculature to diminish ischemia and thereby facilitate neural repair and regeneration. A systematic review of the published literature on therapeutic approaches to promote vascular repair after experimental SCI was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. The MEDLINE databases PubMed, Embase, and OVID MEDLINE were searched using the keywords "spinal cord injury," "angiogenesis," "angiogenesis inducing agents," "tissue engineering," and "rodent subjects." A total of 111 studies were identified through the search. Five main therapeutic approaches to diminish hypoxia-ischemia and promote vascular repair were identified as (1) the application of angiogenic factors, (2) genetic engineering, (3) physical stimulation, (4) cell transplantation, and (5) biomaterials carrying various factor delivery. There are different therapeutic approaches with the potential to diminish hypoxia-ischemia and promote vascular repair after experimental SCI. Of note, combinatorial approaches using implanted biomaterials and angiogenic factor delivery appear promising for clinical translation.

Surgical management of spinal metastases involving the cervicothoracic junction: results of a multicenter, European observational study.

OBJECTIVE: Surgical management of spinal metastases at the cervicothoracic junction (CTJ) is highly complex and relies on case-based decision-making. The aim of this multicentric study was to describe surgical procedures for metastases at the CTJ and provide guidance for clinical and surgical management. METHODS: Patients eligible for this study were those with metastases at the CTJ (C7-T2) who had been consecutively treated in 2005-2019 at 7 academic institutions across Europe. The Spine Instability Neoplastic Score, neurological function, clinical status, medical history, and surgical data for each patient were retrospectively assessed. Patients were divided into four surgical groups: 1) posterior decompression only, 2) posterior decompression and fusion, 3) anterior corpectomy and fusion, and 4) anterior corpectomy and 360° fusion. Endpoints were complications, surgical revision rate, and survival. RESULTS: Among the 238 patients eligible for inclusion this study, 37 were included in group 1 (15%), 127 in group 2 (53%), 18 in group 3 (8%), and 56 in group 4 (24%). Mechanical pain was the predominant symptom (79%, 189 patients). Surgical complications occurred in 16% (group 1), 20% (group 2), 11% (group 3), and 18% (group 4). Of these, hardware failure (HwF) occurred in 18% and led to surgical revision in 7 of 8 cases. The overall complication rate was 34%. In-hospital mortality was 5%. CONCLUSIONS: Posterior fusion and decompression was the most frequently used technique. Care should be taken to choose instrumentation techniques that offer the highest possible biomechanical load-bearing capacity to avoid HwF. Since the overall complication rate is high, the prevention of in-hospital complications seems crucial to reduce in-hospital mortality.

Surgical treatment and neurological outcome of infiltrating intramedullary astrocytoma WHO II-IV: a multicenter retrospective case series.

INTRODUCTION: Primary malignant spinal astrocytomas present rare oncological entities with limited median survival and rapid neurological deterioration. Evidence on surgical therapy, adjuvant treatment, and neurological outcome is sparse. We aim to describe the treatment algorithm and clinical features on patients with infiltrating intramedullary astrocytomas graded WHO II-IV. METHODS: The following is a multicentered retrospective study of patients treated for spinal malignant glioma WHO II-IV in five high-volume neurosurgical departments from 2008 to 2019. Pilocytic astrocytomas were excluded. We assessed data on surgical technique, perioperative neurological status, adjuvant oncological therapy, and clinical outcome. RESULTS: 40 patients were included (diffuse astrocytoma WHO II n = 11, anaplastic astrocytoma WHO III n = 12, WHO IV n = 17). Only 40% were functionally independent before surgery, most patients presented with moderate disability (47.5%). Most patients underwent a biopsy (n = 18, 45%) or subtotal tumor resection (n = 15, 37.5%), and 49% of the patients deteriorated after surgery. Patients with WHO III and IV tumors were treated with combined radiochemotherapy. Median overall survival (OS) was 46.5 months in WHO II, 25.7 months in WHO III, and 7.4 months in WHO IV astrocytomas. Preoperative clinical status and WHO significantly influenced the OS, and the extent of resection did not. CONCLUSION: Infiltrating intramedullary astrocytomas WHO II-IV present rare entities with dismal prognosis. Due to the high incidence of surgery-related neurological impairment, the aim of the surgical approach should be limited to obtaining the histological tissue via a biopsy or, tumor debulking in cases with rapidly progressive severe preoperative deficits.

Metastatic dissemination patterns of different primary tumors to the spine and other bones.

Metastatic spine disease (MSD) is a severe event in cancer patients. Experimental data indicate that bone metastasis is mostly mediated by blood flow-dependent, passive arrest of circulating tumor cells to the bone metastatic niche (BMN). Here, we have set out to test these experimental observations in a clinical, human setting to improve our understanding of MSD. 507 patients, treated on spinal metastases in our institution from 2005 to 2015 were retrospectively evaluated. We identified 259 patients with accessible staging reports of the skeleton before and at initial diagnosis of MSD. Data analysis comprised localizations of bone metastases, underlying malignancy and time to development of MSD. Dissemination pattern of bone metastasis was correlated with red bone marrow (RBM) content of the respective bone as a measure of blood flow. Spinal metastases occurred most frequently in lung cancer (21%), prostate cancer (19%), and breast cancer (12%). At the diagnosis of MSD, majority of patients have multiple extra-spinal bone metastases (2/3). The distribution of metastases to extra-spinal bones and to the spine is mostly proportional to the RBM content of the involved bone. Corresponding to the high RBM content, thoracic spine, pelvic bones and ribs represent a predilection site for bone metastasis. We confirm a distinct preference of cancer types to metastasize to bones. When it comes to bone metastases all primaries show uniform distribution pattern, which supports the hypothesis of a predominantly blood flow-dependent distribution of tumor cells and passive arrest to the BMN rather than a spine-specific homing mechanism.

Brain Edema Formation and Functional Outcome After Surgical Decompression in Murine Closed Head Injury Are Modulated by Acetazolamide Administration.

Acetazolamide (ACZ), carbonic anhydrase inhibitor, has been successfully applied in several neurosurgical conditions for diagnostic or therapeutic purposes. Furthermore, neuroprotective and anti-edematous properties of ACZ have been postulated. However, its use in traumatic brain injury (TBI) is limited, since ACZ-caused vasodilatation according to the Monro-Kellie doctrine may lead to increased intracranial blood volume / raise of intracranial pressure. We hypothesized that these negative effects of ACZ will be reduced or prevented, if the drug is administered after already performed decompression. To test this hypothesis, we used a mouse model of closed head injury (CHI) and decompressive craniectomy (DC). Mice were assigned into following experimental groups: sham, DC, CHI, CHI+ACZ, CHI+DC, and CHI+DC+ACZ (n = 8 each group). 1d and 3d post injury, the neurological function was assessed according to Neurological Severity Score (NSS) and Beam Balance Score (BBS). At the same time points, brain edema was quantified by MRI investigations. Functional impairment and edema volume were compared between groups and over time. Among the animals without skull decompression, the group additionally treated with acetazolamide demonstrated the most severe functional impairment. This pattern was reversed among the mice with decompressive craniectomy: CHI+DC treated but not CHI+DC+ACZ treated animals showed a significant neurological deficit. Accordingly, radiological assessment revealed most severe edema formation in the CHI+DC group while in CHI+DC+ACZ animals, volume of brain edema did not differ from DC-only animals. In our CHI model, the response to acetazolamide treatment varies between animals with decompressive craniectomy and those without surgical treatment. Opening the cranial vault potentially creates an opportunity for acetazolamide to exert its beneficial effects while vasodilatation-related risks are attenuated. Therefore, we recommend further exploration of this potentially beneficial drug in translational research projects.

Management of concussion in soccer.

BACKGROUND: When participating in contact sports, (mild) head trauma is a common incident-observed in both professional and amateur sports. When head trauma results in transient neurological impairment, a sports-related concussion has occurred. Acute concussion, repetitive concussions, as well as cumulative "sub-concussive" head impacts may increase the risk of developing cognitive and behavioral deficits for athletes, as well as accelerated cerebral degeneration. While this concept has been well established for classic contact sports like American Football, Rugby, or Boxing, there is still an awareness gap for the role of sports-related concussion in the context of the world's most popular sport-Soccer. METHODS: Here, we review the relevance of sport-related concussion for Soccer as well as its diagnosis and management. Finally, we provide insight into future directions for research in this field. RESULTS: Soccer fulfills the criteria of a contact sport and is characterized by a high incidence of concussion. There is ample evidence that these events cause functional and structural cerebral disorders. Furthermore, heading, as a repeat sub-concussive impact, has been linked to structural brain changes and neurocognitive impairment. As a consequence, recommendations for the diagnosis and management of concussion in soccer have been formulated by consensus groups. In order to minimize the risk of repetitive concussion in soccer the rapid and reliable side-line diagnosis of concussion with adoption of a strict remove-from-play protocol is essential, followed by a supervised, graduated return-to-play protocol. Recent studies, however, demonstrate that adherence to these recommendations by players, coaches, clubs, and officials is insufficient, calling for stricter enforcement. In addition, future research to solidify the pathophysiological relevance of concussion for soccer athletes seems to be needed. Advanced neuroimaging and neurochemical biomarker analyses (e.g. S100ß, tau and neurofilament light (NfL)) may assist in detecting concussion-related structural brain changes and selecting athletes at risk for irreversible damage. CONCLUSION: Sports-related concussion represents a genuine neurosurgical field of interest. Given the high socioeconomic relevance, neurosurgeons should get involved in prevention and management of concussion in soccer.

Changes in Posttraumatic Brain Edema in Craniectomy-Selective Brain Hypothermia Model Are Associated With Modulation of Aquaporin-4 Level.

Both hypothermia and decompressive craniectomy have been considered as a treatment for traumatic brain injury. In previous experiments we established a murine model of decompressive craniectomy and we presented attenuated edema formation due to focal brain cooling. Since edema development is regulated via function of water channel proteins, our hypothesis was that the effects of decompressive craniectomy and of hypothermia are associated with a change in aquaporin-4 (AQP4) concentration. Male CD-1 mice were assigned into following groups (n = 5): sham, decompressive craniectomy, trauma, trauma followed by decompressive craniectomy and trauma + decompressive craniectomy followed by focal hypothermia. After 24 h, magnetic resonance imaging with volumetric evaluation of edema and contusion were performed, followed by ELISA analysis of AQP4 concentration in brain homogenates. Additional histopathological analysis of AQP4 immunoreactivity has been performed at more remote time point of 28d. Correlation analysis revealed a relationship between AQP4 level and both volume of edema (r 2 = 0.45, p < 0.01, **) and contusion (r 2 = 0.41, p < 0.01, **) 24 h after injury. Aggregated analysis of AQP4 level (mean ± SEM) presented increased AQP4 concentration in animals subjected to trauma and decompressive craniectomy (52.1 ± 5.2 pg/mL, p = 0.01; *), but not to trauma, decompressive craniectomy and hypothermia (45.3 ± 3.6 pg/mL, p > 0.05; ns) as compared with animals subjected to decompressive craniectomy only (32.8 ± 2.4 pg/mL). However, semiquantitative histopathological analysis at remote time point revealed no significant difference in AQP4 immunoreactivity across the experimental groups. This suggests that AQP4 is involved in early stages of brain edema formation after surgical decompression. The protective effect of selective brain cooling may be related to change in AQP4 response after decompressive craniectomy. The therapeutic potential of this interaction should be further explored.