Long-term outcome after decompressive hemicraniectomy for malignant middle cerebral artery infarction.

BACKGROUND: Although decompressive hemicraniectomy (DHC) is a lifesaving treatment strategy for patients with malignant middle cerebral artery infarction (mMCAi), only one in four patients achieves low to moderate post-stroke disability according to previous studies. However, the short follow-up periods in prior studies could have overestimated the poor clinical prognosis. This study therefore examined the long-term outcome after DHC for mMCAi. METHODS: We retrospectively included all patients who had undergone DHC after mMCAi at the University Hospital Graz between 2006 and 2019. Demographics, clinical data and complications were collected from electronic clinical patient records. To investigate long-term prognosis, all patients were followed up to 14 years after stroke including quality of life (QOL) assessment. Post-stroke disability was rated according to the modified Rankin Scale (mRS). RESULTS: Of 47 patients that had undergone DHC for mMCAi, follow-up data were available in 40 patients (mean age: 48 years; 40% female). Six months after the mMCAi, 14 patients had died (35%) and nine (23%) had a low to moderate post-stroke disability (mRS 0-3). Of 26 stroke survivors, half (50%) showed further mRS improvement (≥ 1 point) during the long-term follow-up period (mean follow-up time: 8 years). At last follow-up, 17 patients had achieved an mRS score of ≤ 3 (65% versus 35% after 6 months; p = 0.008) and 55% had no signs of depression and anxiety, and 50% no signs of pain or discomfort in QOL assessment. CONCLUSION: This study shows substantial long-term improvement of functional disability and reasonable QOL in mMCAi patients after DHC.

Twenty-Three Months Repetitive Transcranial Magnetic Stimulation of the Primary Motor Cortex for Refractory Trigeminal Neuralgia: A Single-Case Study.

Treatment refractory or recurrent trigeminal neuralgia (TN) is a severe chronic pain illness. Single-session repetitive transcranial magnetic stimulation (rTMS) has been shown to elicit analgesic effects in several craniofacial pain syndromes, including TN. However, the safety and long-term effect of multi-session rTMS for TN have yet to be fully explored. In this study, we present a case of a patient with medical treatment-refractory TN after microvascular decompression. The patient volunteered to undergo 73 sessions of 10 Hz rTMS over 23 months. Neurovagination was used for precise localization and stimulation of the hand and face representation at the left motor cortex. The numeric pain intensity scores derived using the visual analog scale served as a daily index of treatment efficacy. The patient experienced a significant weekly reduction in pain scores, cumulating in 70.89% overall pain relief. The medication dosages were reduced and then discontinued toward the end of the intervention period. No severe adverse events were reported. From our results, we can conclude that the longitudinal multi-session application of rTMS over the hand and face area of M1 is a safe and effective method for producing long-lasting pain relief in TN. Using rTMS may thus prove helpful as an adjunct to conventional methods for treating pain in TN.

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017-2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017-2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

Preservation of nasal turbinates in endoscopic, anterior skull base surgery-yes, we can!

OBJECTIVE: To evaluate the frequency, type and indications of nasal turbinate (NT) resection during endoscopic, anterior skull base surgery and to analyze factors that may have an impact on the need of NT removal. METHODS: In this retrospective cohort study, 306 subjects (150 males and 156 females, mean age 55.4 ± 15.3 years) who underwent multidisciplinary, transnasal, endoscopic tumor surgery of the anterior skull base using 4-handed techniques between 2011 and 2019 at the Department of Otorhinolaryngology, Medical University of Graz, were included. RESULTS: In the majority of interventions (n = 281/306; 91.8%), all NT were preserved. Significant factors influencing the need of NT resections turned out to be type of endoscopic approach (p < 0.001; V = 0.304), sagittal (p = 0.003; d = 0.481) and transversal (p = 0.017; d = 0.533) tumor diameter, tumor type (p < 0.001; V = 0.355) and tumor location (p < 0.001; V = 0.324). CONCLUSIONS: NT can be preserved in the majority of patients undergoing tumor resection in anterior, transnasal, skullbase surgery and routine resection of NT should be avoided. Variables that have an impact on the need of NT resections are types of endoscopic approaches, sagittal and transversal tumor extension and tumor type. These factors should be considered in planning of surgery and preoperative information of patients.

Comparing the Impact of Multi-Session Left Dorsolateral Prefrontal and Primary Motor Cortex Neuronavigated Repetitive Transcranial Magnetic Stimulation (nrTMS) on Chronic Pain Patients.

Repetitive transcranial stimulation (rTMS) has been shown to produce an analgesic effect and therefore has a potential for treating chronic refractory pain. However, previous studies used various stimulation parameters (including cortical targets), and the best stimulation protocol is not yet identified. The present study investigated the effects of multi-session 20 Hz (2000 pulses) and 5 Hz (1800 pulses) rTMS stimulation of left motor cortex (M1-group) and left dorsolateral prefrontal cortex (DLPFC-group), respectively. The M1-group (n = 9) and DLPFC-group (n = 7) completed 13 sessions of neuronavigated stimulation, while a Sham-group (n = 8) completed seven sessions of placebo stimulation. The outcome was measured using the German Pain Questionnaire (GPQ), Depression, Anxiety and Stress Scale (DASS), and SF-12 questionnaire. Pain perception significantly decreased in the DLPFC-group (38.17%) compared to the M1-group (56.11%) (p ≤ 0.001) on the later sessions. Health-related quality of life also improved in the DLPFC-group (40.47) compared to the Sham-group (35.06) (p = 0.016), and mental composite summary (p = 0.001) in the DLPFC-group (49.12) compared to M1-group (39.46). Stimulation of the left DLPFC resulted in pain relief, while M1 stimulation was not effective. Nonetheless, further studies are needed to identify optimal cortical target sites and stimulation parameters.

Trends and outcomes for non-elective neurosurgical procedures in Central Europe during the COVID-19 pandemic.

The world currently faces the novel severe acute respiratory syndrome coronavirus 2 pandemic. Little is known about the effects of a pandemic on non-elective neurosurgical practices, which have continued under modified conditions to reduce the spread of COVID-19. This knowledge might be critical for the ongoing second coronavirus wave and potential restrictions on health care. We aimed to determine the incidence and 30-day mortality rate of various non-elective neurosurgical procedures during the COVID-19 pandemic. A retrospective, multi-centre observational cohort study among neurosurgical centres within Austria, the Czech Republic, and Switzerland was performed. Incidence of neurosurgical emergencies and related 30-day mortality rates were determined for a period reflecting the peak pandemic of the first wave in all participating countries (i.e. March 16th-April 15th, 2020), and compared to the same period in prior years (2017, 2018, and 2019). A total of 4,752 emergency neurosurgical cases were reviewed over a 4-year period. In 2020, during the COVID-19 pandemic, there was a general decline in the incidence of non-elective neurosurgical cases, which was driven by a reduced number of traumatic brain injuries, spine conditions, and chronic subdural hematomas. Thirty-day mortality did not significantly increase overall or for any of the conditions examined during the peak of the pandemic. The neurosurgical community in these three European countries observed a decrease in the incidence of some neurosurgical emergencies with 30-day mortality rates comparable to previous years (2017-2019). Lower incidence of neurosurgical cases is likely related to restrictions placed on mobility within countries, but may also involve delayed patient presentation.

Correction to: Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebocontrolled, randomised, double blind, multi-centre study.

After publication of our article [1] the authors have notified us that one of the names has been incorrectly spelled.

Efficacy of Ronopterin (VAS203) in Patients with Moderate and Severe Traumatic Brain Injury (NOSTRA phase III trial): study protocol of a confirmatory, placebo-controlled, randomised, double blind, multi-centre study.

BACKGROUND: Traumatic brain injury is a leading cause of death and disability worldwide. The nitric oxide synthase inhibitor Ronopterin was shown to improve clinical outcome by enhancing neuroprotection in a phase IIa trial. METHODS/DESIGN: The NOSTRA phase III trial (Ronopterin in traumatic brain injury) is a multi-centre, prospective, randomised, double-blinded, placebo-controlled, phase III trial in Europe. It aims at determining whether the administration of Ronopterin compared to placebo improves neurological outcome in patients with moderate or severe traumatic brain injury at 6 months after injury. The trial is designed to recruit patients between 18 and 60 years of age with moderate or severe traumatic brain injury (Glasgow Coma Scale score ≥ 3) and requiring insertion of an intracranial pressure probe. Trial patients will receive a 48-h intravenous infusion of either Ronopterin or placebo starting at the earliest 6 h and at the latest 18 h after injury. The primary outcome will be the extended Glasgow Outcome Score (eGOS) at 6 months. Secondary outcomes will include the Quality of Life Index (QOLIBRI) at 6 months after the injury and the eGOS at 3 months after the injury. Additionally, effects on mortality, intracranial pressure and cerebral perfusion pressure are evaluated. DISCUSSION: The trial aims to provide evidence on the efficacy and safety of Ronopterin in patients with traumatic brain injury. TRIAL REGISTRATION: EudraCT, 2013-003368-29. Registered on 9 March 2016. ClinicalTrials.gov, NCT02794168. Registered on 8 June 2016. Protocol version 14.0 from 05 November 2018.

Establishment of clival chordoma cell line MUG-CC1 and lymphoblastoid cells as a model for potential new treatment strategies.

Chordomas are rare malignant tumors that develop from embryonic remnants of the notochord and arise only in the midline from the clivus to the sacrum. Surgery followed by radiotherapy is the standard treatment. As chordomas are resistant to standard chemotherapy, further treatment options are urgently needed. We describe the establishment of a clivus chordoma cell line, MUG-CC1. The cell line is characterized according to its morphology, immunohistochemistry, and growth kinetics. During establishment, cell culture supernatants were collected, and the growth factors HGF, SDF-1, FGF2, and PDGF analyzed using xMAP(®) technology. A spontaneous lymphoblastoid EBV-positive cell line was also developed and characterized. MUG-CC1 is strongly positive for brachyury, cytokeratin, and S100. The cell line showed gains of the entire chromosomes 7, 8, 12, 13, 16, 18, and 20, and high level gains on chromosomes 1q21-1q24 and 17q21-17q25. During cultivation, there was significant expression of HGF and SDF-1 compared to continuous chordoma cell lines. A new, well-characterized clival chordoma cell line, as well as a non-tumorigenic lymphoblastoid cell line should serve as an in vitro model for the development of potential new treatment strategies for patients suffering from this disease.

Rare case of a primary intracranial chondrosarcoma.

BACKGROUND: Intracranial chondrosarcomas comprise 6% of all skull base neoplasms and account for 0.15% of all intracranial tumors. They are potentially fatal, invading the brain and elevating intracranial pressure by progressive enlargement. Diplopia and headache are the most common clinical symptoms. Previous data indicate a particularly aggressive behavior of intracranial chondrosarcomas. CASE REPORT: A 17-year-old female patient presented to the hospital with focal seizures. A magnetic resonance imaging (MRI) scan revealed a brain tumor located in the right meso-temporal region. Total tumor resection, followed by conformal proton therapy was performed. The tumor displayed a chondroid differentiation, and accordingly, a chondrosarcoma was diagnosed. At follow-up investigation two years after the resection of the tumor, the patient was in a good general state of health and no tumor recurrence had occurred. DISCUSSION AND CONCLUSION: Intracranial chondrosarcoma is a differential diagnosis for intracranial tumors of the skull base. State-of-the-art therapy should comprise of surgical resection and adjuvant radiotherapy. Previously published data about intracranial chondrosarcomas indicate the extreme aggressiveness of this tumor entity.

Vivostat®: an autologous fibrin sealant as useful adjunct in endoscopic transnasal CSF-leak repair.

The benefit of fibrin glue for reduction of postoperative CSF-leaks after endoscopic skull base surgery is not clearly evident in literature. However, its use is supposed to be beneficial in fixing grafting material. As of today there is no specific data available for otolaryngological procedures. A retrospective data analysis at a tertiary care referral center on 73 patients treated endoscopically transnasally for CSF-leaks at the ENT-department Graz between 2009 and 2012 was performed. Primary closure rate between conventional fibrin glue and autologous fibrin glue were analyzed. The Vivostat(®) system was used in 33 CSF-leak closures and in 40 cases conventional fibrin glue was used. Comparing the two methods the primary closure rate using the autologous Vivostat(®) system was 75.8 and 85.0 % with conventional fibrin glue. The secondary closure the rates were 90.9 % with Vivostat(®) 92.5 % with conventional fibrin glue. The Vivosat(®) system is a useful adjunct in endoscopic CSF-leak closure. Its advantages over conventional fibrin glue are its application system for fixation of grafting material particularly in underlay techniques. Despite this advantage it cannot replace grafting material or is a substitute for proper endoscopic closure which is reflected by the closure rates.

Feasibility of piezoelectric endoscopic transsphenoidal craniotomy: a cadaveric study.

OBJECTIVE: Endoscopic transsphenoidal approach has become the gold standard for surgical treatment of treating pituitary adenomas or other lesions in that area. Opening of bony skull base has been performed with burrs, chisels, and hammers or standard instruments like punches and circular top knives. The creation of primary bone flaps-as in external craniotomies-is difficult.The piezoelectric osteotomes used in the present study allows creating a bone flap for endoscopic transnasal approaches in certain areas. The aim of this study was to prove the feasibility of piezoelectric endoscopic transnasal craniotomies. Study Design. Cadaveric study. METHODS: On cadaveric specimens (N = 5), a piezoelectric system with specially designed hardware for endonasal application was applied and endoscopic transsphenoidal craniotomies at the sellar floor, tuberculum sellae, and planum sphenoidale were performed up to a size of 3-5 cm(2). RESULTS: Bone flaps could be created without fracturing with the piezoosteotome and could be reimplanted. Endoscopic handling was unproblematic and time required was not exceeding standard procedures. CONCLUSION: In a cadaveric model, the piezoelectric endoscopic transsphenoidal craniotomy (PETC) is technically feasible. This technique allows the surgeon to create a bone flap in endoscopic transnasal approaches similar to existing standard transcranial craniotomies. Future trials will focus on skull base reconstruction using this bone flap.

Acute subdural hematoma without subarachnoid hemorrhage or intraparenchymal hematoma caused by rupture of a posterior communicating artery aneurysm: case report and review of the literature.

BACKGROUND: Acute subdural hematoma without subarachnoid hemorrhage or intraparenchymal hematoma is rare. CASE REPORT: We report on a 47-year-old women without previous trauma who presented with an acute subdural hematoma without subarachnoid hemorrhage. The hematoma was evacuated immediately. Further evaluation with a cerebral four-vessel angiography revealed a left-sided posterior communicating artery aneurysm that was occluded by endovascular embolization. The patient recovered without neurological deficit. CONCLUSIONS: Ruptured intracranial aneurysm should be considered as a cause of nontraumatic subdural hematoma. Immediate subdural hematoma removal after aneurysm coiling can be performed in such patients, even those in poor neurological condition.

Does insulin-like growth factor 1 receptor (IGF-1R) targeting provide new treatment options for chordomas? A retrospective clinical and immunohistochemical study.

AIMS: The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a potential target for specific inhibition in chordomas. METHODS AND RESULTS: Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed IGF-2. Semi-quantitative analyses revealed a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042). CONCLUSIONS: IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1 expression is much stronger than IGF-2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting, particularly if they suffer from large and surgically non-resectable chordomas.

Intraoperative medialization of medial rectus muscle as a new endoscopic technique for approaching intraconal lesions.

BACKGROUND: Intraconal tumors of the orbit are rare entities and surgical treatment is challenging. Endoscopic transnasal approaches to the orbit offer a new perspective for surgery, although only few reports exist in literature. This study displays the Graz experience with endoscopic approaches to intraorbital tumors between 2006 and 2010 introducing a novel endoscopic technique for temporary medialization of the medial rectus muscle facilitating access to the orbital cone. METHODS: A retrospective analysis of patients' charts was performed. RESULTS: For approaches to intraconal lesions a special endoscopic temporary medialization technique of the medial rectus muscle through applying transseptal sutures was developed. Six patients (four male and two female patients) have been included in this study presenting with intraconal/intraorbital tumors. Three patients underwent endoscopic surgery for two hemangiomas and one Schwannoma, respectively, and three patients were successfully biopsied endoscopically revealing one malignant melanoma, one malignant lymphoma, and one optic glioma each. Both hemangiomas were completely resected without any deterioration of vision. The Schwannoma was partially resected with postoperative imaging showing no tumor progression within 3 months. No intraoperative complications occurred. Five cases were performed with computer assisted surgery using CT/MR fusion navigation. CONCLUSION: Although technically challenging, the endoscopic approach to the orbit, even for intraconal lesions with medialization of the medial rectus muscle, can be safe and promising for well-selected cases. Good postoperative results and sufficient material acquisition for proper histological examination can be obtained. Advantages are good visualization of the surgical field and avoidance of external scars. Limitations to endoscopic techniques are tumors in the lateral superior and lateral inferior quadrant of the orbit.

Quantitative analysis of cyclooxygenase 2 in the posterior longitudinal ligament of cervical spondylotic myelopathy.

BACKGROUND: Cervical spondylotic myelopathy (CSM), in part, results from degeneration of the posterior longitudinal ligament (PLL), which mechanically compresses the spinal cord. Much research was done on the ossification of PLL, but not concerning the non-ossifying degeneration of cervical PLL. The degeneration of cervical PLL may be related to inflammation. The aim of this study was to elucidate the pathological features of the PLL and the role of cyclooxygenase 2 (COX-2) in the degeneration of the PLL in CSM. METHODS: A total of 23 PLL specimens were collected during surgery from patients with CSM for the histological and immunohistochemical (type II collagen and Ki-67) study. For the control group 14 cervical PLL autopsy specimens were investigated in the same manner. mRNA expression of COX-2 was quantitatively measured by real-time reverse transcription-polymerase chain reaction (RT-PCR) from 18 PLL specimens of patients with CSM and 18 PLL specimens of autopsy cases. Immunohistochemistry was used to evaluate the cellular location of COX-2 in PLL. RESULTS: A distinct amount of fibrotic area, chondrometaplastic tissue and calcification were found in the PLL of the patient group, compared with the control group. Type II collagen was apparent around chondrometaplastic cells. Ki-67 positive reaction was less than 5%. A COX-2 positive reaction was found in 9 of the patient specimens (39.1%) in which the COX-2 was released from vascular endothelial cells in the PLL. However, such reactions were not found in the control group. Real-time PCR showed that the mRNA expression level of COX-2 in the patient group was significantly higher than that in the control group (P < 0.01). CONCLUSIONS: Chondrometaplastic tissue producing type II collagen was identified as the most predominant pathological feature in the degenerative PLL. The higher expression of COX-2 might be related to degeneration of the PLL in CSM.

Endoscopic rhino-neurosurgical approach for non-adenomatous sellar and skull base lesions.

OBJECTIVE: Since endoscopic endonasal transsphenoidal surgery requires skills of both neurosurgeons and otorhinolaryngologists, and the nose is the primary corridor of approach, we favour the term `endoscopic rhino-neurosurgery` and report on our interdisciplinary experience treating non-adenomatous lesions with skull base extension. METHODS: Between 2004 and 2009, 58 patients with 21 different disease patterns underwent endoscopic rhino-neurosurgical procedures. Mean age was 39.9 years, 50% were female. Seven had undergone prior surgery. Clinically, 34.5% presented with visual field deficits and with nerve palsies. Preoperatively, 62.1% showed a normal pituitary function. RESULTS: Mean follow-up was 13.1 months. The surgical goal depended on type of lesion; the intended extent of resection was achieved in 81%. Recovery from visual field deficits occurred in 80%. Neither deteriorated nor new cranial nerve palsies were observed. A normal endocrinological function could be maintained in 94.4%. Permanent diabetes insipidus occurred in 7 patients. Surgical complications included cerebrospinal fluid (CSF) leaks in 6 patients and meningitis in 4. All complications were managed successfully. There was no surgery-related mortality. CONCLUSION: The endoscopic rhino-neurosurgical approach is applicable for a wide variety of lesions comprising sella and skull base. As our data prove, this technique can be performed with satisfying results in non-adenomatous lesions as well.

Aggressive inverted papilloma with intracranial invasion and short malignization time.

Inverted papillomas (IP) are considered benign lesions with a prevalence up to 4% among all sinunasal tumors; however, invasive growth and varying tendency for malignization are reported in literature. We report the case of a 69-year-old woman suffering from a large, aggressively growing IP invading the orbit, skull base, and frontal lobe of the brain. Within only 3 months' time the papilloma showed transformation into an invasive carcinoma, leaving surgical therapy in vain due to explosive recurrence. Intracranial and intraorbital expansion by IP is possible despite histology not showing signs of malignancy initially. In "regular" IP close endoscopic follow-up is mandatory to not overlook recurrence harboring malignancy.

European position paper on endoscopic management of tumours of the nose, paranasal sinuses and skull base.

Tumours affecting the nose, paranasal sinuses and adjacent skull base are fortunately rare. However, they pose significant problems of management due their late presentation and juxtaposition to important anatomical structures such eye and brain. The increasing application of endonasal endoscopic techniques to their excision offers potentially similar scales of resection but with reduced morbidity. The present document is intended to be a state-of-the art review for any specialist with an interest in this area 1. to update their knowledge of neoplasia affecting the nose, paranasal sinuses and adjacent skull base; 2. to provide an evidence-based review of the diagnostic methods; 3. to provide an evidence-based review of endoscopic techniques in the context of other available treatments; 4. to propose algorithms for the management of the disease; 5. to propose guidance for outcome measurements for research and encourage prospective collection of data. The importance of a multidisciplinary approach, adherence to oncologic principles with intent to cure and need for long-term follow-up is emphasised.