A Multidisciplinary Skull Base Board for Tumour and Non-Tumour Diseases: Initial Experiences.

The skull base is the area where various cancerous and non-cancerous diseases occur and represents the intersection of several medical fields. The key is an integrated treatment by specialists of multiple disciplines. We prospectively analysed patients with a skull base disease between August 2022 and 2023 and presented to the Multidisciplinary Skull Base Board (MDT-SB), which takes place once a month hybridly (in-person and remotely). Thirty-nine patients (median age of 58.2 years) were included, of which twelve (30.8%) had a benign tumour, twelve (30.8%) had a malignant tumour, five had an infection (12.8%), and ten (25.6%) had other diseases. For each patient, at least two otorhinolaryngologists, a neurosurgeon, and a neuroradiologist, as well as an infectious disease specialist, a paediatrician, an oculoplastic surgeon, a maxillofacial surgeon, and a pathologist were involved in 10%, 8%, 8%, 3%, and 3% of cases, respectively. In fifteen patients (38%), the MDT-SB suggested surgical treatment; in fourteen (36%), radiological follow-ups; in five (13%), non-surgical treatments; in two, conservative treatments (5%); in two (5%), surgical and conservative treatments; and in one (3%), a biopsy. Non-cancerous and cancerous diseases of the skull base in adults and children should be presented to the MDT-SB, which consists of at least an otolaryngologist, a neurosurgeon, and a neuroradiologist.

COVID-19 and Surgical Practice in Slovenia: Managing the Crisis in Neurosurgery during the COVID-19 Pandemic.

Worldwide, the novel coronavirus disease 2019 (COVID-19) has become a significant threat to global health. Worldwide, COVID-19 has affected the health service also in Slovenia. During this time, neurosurgery is facing difficulties in its service, both in emergency and elective surgeries. In the article, we describe the anti-COVID-19 measures taken at our neurosurgical department in a medical centre in Ljubljana, Slovenia, and analysed and compared the number of emergency and elective neurosurgical procedures during the time of the pandemic.

Clinical infections in neurosurgical oncology: An overview.

Central nervous system (CNS) infections are urgent conditions with high morbidity and mortality. Bacteria, viruses, parasites or fungi can cause them. Intracranial infections after craniotomies are an important complication of treatment, especially in oncological patients that are already immunologically compromised due to the disease and treatment. The consequence of CNS infections in oncological patients includes longer treatment with antibiotics, additional surgical procedures, higher treatment costs and poorer treatment outcomes. Additionally, the management of primary pathology may be prolonged or postponed as a result of the active infection. By introducing new and improved protocols, tightening controls on their implementation, constantly educating the entire team involved in patient treatment and educating both patients and relatives, the incidence of infections can be reduced effectively.

Atypical Skull-Base Osteomyelitis: Comprehensive Review and Multidisciplinary Management Viewpoints.

Atypical skull-base osteomyelitis is a rare but fatal disease that usually involves infection of the ethmoid, sphenoid, occipital, or temporal bones that form the skull base. Unlike typical (so-called otogenic), atypical skull-base osteomyelitis has no otogenic cause. Instead, some authors call atypical skull-base osteomyelitis sinonasal, since the infection most often originates from the nose and paranasal sinuses. Diagnosing and treating this disease is challenging. To assist in managing atypical skull-base osteomyelitis, a review of the most recent literature, with patient cases and multidisciplinary perspectives from otolaryngologists, neurosurgeons, radiologists, infectious disease specialists, pathologists, and clinical microbiologists, is provided in this paper.

Awake craniotomy for operative treatment of brain gliomas - experience from University Medical Centre Ljubljana.

BACKGROUND: Awake craniotomy is a neurosurgical technique that allows neurophysiological testing with patient cooperation during the resection of brain tumour in regional anaesthesia. This allows identification of vital functional (i.e. eloquent) brain areas during surgery and avoidance of their injury. The aim of the study was to present clinical experience with awake craniotomy for the treatment of gliomas at the University Medical Centre Ljubljana from 2015 to 2019. PATIENTS AND METHODS: Awake craniotomy was considered in patients with a gliomas near or within the language brain areas, in all cases of insular lesions and selected patients with lesions near or within primary motor brain cortex. Each patient was assessed before and after surgery. RESULTS: During the 5-year period, 24 awake craniotomies were performed (18 male and 6 female patients; average age 41). The patient's cooperation, discomfort and perceived pain assessed during the awake craniotomy were in majority of the cases excellent, slight, and moderate, respectively. After surgery, mild neurological worsening was observed in 13% (3/24) of patients. Gross total resection, in cases of malignant gliomas, was feasible in 60% (6/10) and in cases of low-grade gliomas in 29% (4/14). The surgery did not have important negative impact on functional status or quality of life as assessed by Karnofsky score and Short-Form 36 health survey, respectively (p > 0.05). CONCLUSIONS: The results suggest that awake craniotomy for treatment of gliomas is feasible and safe neurosurgical technique. The proper selection of patients, preoperative preparation with planning, and cooperation of medical team members are necessary for best treatment outcome.

The Cytotoxic Effects of Cannabidiol and Cannabigerol on Glioblastoma Stem Cells May Mostly Involve GPR55 and TRPV1 Signalling.

Glioblastoma (GBM) is one of the most aggressive cancers, comprising 60-70% of all gliomas. The large G-protein-coupled receptor family includes cannabinoid receptors CB1, CB2, GPR55, and non-specific ion receptor protein transporters TRPs. First, we found up-regulated CNR1, GPR55, and TRPV1 expression in glioma patient-derived tissue samples and cell lines compared with non-malignant brain samples. CNR1 and GPR55 did not correlate with glioma grade, whereas TRPV1 negatively correlated with grade and positively correlated with longer overall survival. This suggests a tumour-suppressor role of TRPV1. With respect to markers of GBM stem cells, preferred targets of therapy, TRPV1 and GPR55, but not CNR1, strongly correlated with different sets of stemness gene markers: NOTCH, OLIG2, CD9, TRIM28, and TUFM and CD15, SOX2, OCT4, and ID1, respectively. This is in line with the higher expression of TRPV1 and GPR55 genes in GSCs compared with differentiated GBM cells. Second, in a panel of patient-derived GSCs, we found that CBG and CBD exhibited the highest cytotoxicity at a molar ratio of 3:1. We suggest that this mixture should be tested in experimental animals and clinical studies, in which currently used Δ9-tetrahydrocannabinol (THC) is replaced with efficient and non-psychoactive CBG in adjuvant standard-of-care therapy.

Problematics of neurosurgical service during the COVID-19 pandemic in Slovenia.

The novel coronavirus disease 2019 (COVID-19) is an ongoing disease caused by severe acute respiratory syndrome coronavirus-2 that still poses an important and urgent threat to global health. In Slovenia, the epidemic was declared on March 12th, 2020, and since then COVID-19 has had a great impact on our health system. The field of neurosurgery in particular has been experiencing difficulties in both elective and emergency service. In this article, we described epidemiologic protocols and the effect that the COVID-19 pandemic had on the surgical practice and workflow of the Department of Neurosurgery at the University Medical Centre Ljubljana. We analyzed and compared the number of elective and emergency neurosurgical procedures in a 2-year period before and during the pandemic. We recorded a drop in cases mostly on account of elective procedures whilst emergency service remained relatively unaffected.

Clinical Applications of Poly-Methyl-Methacrylate in Neurosurgery: The In Vivo Cranial Bone Reconstruction.

BACKGROUND: Biomaterials and biotechnology are becoming increasingly important fields in modern medicine. For cranial bone defects of various aetiologies, artificial materials, such as poly-methyl-methacrylate, are often used. We report our clinical experience with poly-methyl-methacrylate for a novel in vivo bone defect closure and artificial bone flap development in various neurosurgical operations. METHODS: The experimental study included 12 patients at a single centre in 2018. They presented with cranial bone defects after various neurosurgical procedures, including tumour, traumatic brain injury and vascular pathologies. The patients underwent an in vivo bone reconstruction from poly-methyl-methacrylate, which was performed immediately after the tumour removal in the tumour group, whereas the trauma and vascular patients required a second surgery for cranial bone reconstruction due to the bone decompression. The artificial bone flap was modelled in vivo just before the skin closure. Clinical and surgical data were reviewed. RESULTS: All patients had significant bony destruction or unusable bone flap. The tumour group included five patients with meningiomas destruction and the trauma group comprised four patients, all with severe traumatic brain injury. In the vascular group, there were three patients. The average modelling time for the artificial flap modelling was approximately 10 min. The convenient location of the bone defect enabled a relatively straightforward and fast reconstruction procedure. No deformations of flaps or other complications were encountered, except in one patient, who suffered a postoperative infection. CONCLUSIONS: Poly-methyl-methacrylate can be used as a suitable material to deliver good cranioplasty cosmesis. It offers an optimal dural covering and brain protection and allows fast intraoperative reconstruction with excellent cosmetic effect during the one-stage procedure. The observations of our study support the use of poly-methyl-methacrylate for the ad hoc reconstruction of cranial bone defects.

Management of neurosurgical patients during coronavirus disease 2019 pandemics: The Ljubljana, Slovenia experience.

The novel coronavirus disease 2019 (COVID-19) is an emerging disease, caused by severe acute respiratory syndrome coronavirus-2. It bears unique biological characteristics, clinical symptoms and imaging manifestations, therefore presenting an important and urgent threat to global health. As a result, a new public health crisis arose, threatening the world with the spread of the 2019 novel coronavirus. Despite the maximal worldwide public health responses aimed at containing the disease and delaying its spread, many countries have been confronted with a critical care crisis, and even more, countries will almost certainly follow. In Slovenia, the COVID-19 has struck the health system immensely and among all the specialities, neurosurgery has also been experiencing difficulties in the service, not only in regular, elective surgeries but especially during emergencies. The management of these neurosurgical patients has become more difficult than ever. We describe our protocol in the management of neurosurgical patients in the University Medical Centre Ljubljana, Slovenia and how neurosurgical pathology was tackled during the pandemics.

Selective dorsal rhizotomy: short-term results and early experiences with a newly established surgical treatment in Slovenia.

BACKGROUND: Spasticity is characterised by an atypical increase of muscle tone, affecting normal movements and interfering with the patient quality of life. The medicines may limit the effects of the disease and selective dorsal rhizotomy (SDR) can be used for selected cases or cases refractory to medicine. We present the surgical technique and the short-term results of this newly established surgical treatment in Slovenia. METHODS: A retrospective analysis was performed of all patients that underwent the SDR from 2017 to 2019. The median follow-up was of 10 months. The following data have been collected: aetiology of spasticity, age at SDR, number of sectioned lumbar rootlets L1-S2, intraoperative disappearance of the H-reflex and intraoperative preservation of the bulbocavernosus reflex. The motor functions of all children have been classified by the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88). Twelve children underwent SDR, the median age at surgery was 9.6 years (min 3.9-max 16 years). RESULTS: A mean of 57.8% of dorsal rootlets L2-S1 have been cut, while at level L1 50% of the dorsal roots have been routinely sectioned. The median amount of S2 rootlets cut was 14.3%. Postoperatively, we observed a sudden decrease in muscle tone. In all patients, there was an improvement of the muscle tone and of the gait pattern. The GMFM improved from 187.8 to 208.3 after a follow-up of 6 months. CONCLUSIONS: There was no complication in terms of wound healing, cerebrospinal fluid fistula of neurological dysfunctions. Despite the relatively short follow-up, our early results confirm the efficacy of the SDR.

The Endplate Role in Degenerative Disc Disease Research: The Isolation of Human Chondrocytes from Vertebral Endplate-An Optimised Protocol.

BACKGROUND: Degenerative disc disease is a progressive and chronic disorder with many open questions regarding its pathomorphological mechanisms. In related studies, in vitro organ culture systems are becoming increasingly essential as a replacement option for laboratory animals. Live disc cells are highly appealing to study the possible mechanisms of intervertebral disc (IVD) degeneration. To study the degenerative processes of the endplate chondrocytes in vitro, we established a relatively quick and easy protocol for isolating human chondrocytes from the vertebral endplates. METHODS: The fragments of human lumbar endplates following lumbar fusion were collected, cut, ground and partially digested with collagenase I in Advanced DMEM/F12 with 5% foetal bovine serum. The sediment was harvested, and cells were seeded in suspension, supplemented with special media containing high nutrient levels. Morphology was determined with phalloidin staining and the characterisation for collagen I, collagen II and aggrecan with immunostaining. RESULTS: The isolated cells retained viability in appropriate laboratory conditions and proliferated quickly. The confluent culture was obtained after 14 days. Six to 8 h after seeding, attachments were observed, and proliferation of the isolated cells followed after 12 h. The cartilaginous endplate chondrocytes were stable with a viability of up to 95%. Pheno- and geno-typic analysis showed chondrocyte-specific expression, which decreased with passages. CONCLUSIONS: The reported cell isolation process is simple, economical and quick, allowing establishment of a viable long-term cell culture. The availability of a vertebral endplate cell model will permit the study of cell properties, biochemical aspects, the potential of therapeutic candidates for the treatment of disc degeneration, and toxicology studies in a well-controlled environment.

Neurosurgical Approaches to Brain Tissue Harvesting for the Establishment of Cell Cultures in Neural Experimental Cell Models.

In recent decades, cell biology has made rapid progress. Cell isolation and cultivation techniques, supported by modern laboratory procedures and experimental capabilities, provide a wide range of opportunities for in vitro research to study physiological and pathophysiological processes in health and disease. They can also be used very efficiently for the analysis of biomaterials. Before a new biomaterial is ready for implantation into tissues and widespread use in clinical practice, it must be extensively tested. Experimental cell models, which are a suitable testing ground and the first line of empirical exploration of new biomaterials, must contain suitable cells that form the basis of biomaterial testing. To isolate a stable and suitable cell culture, many steps are required. The first and one of the most important steps is the collection of donor tissue, usually during a surgical procedure. Thus, the collection is the foundation for the success of cell isolation. This article explains the sources and neurosurgical procedures for obtaining brain tissue samples for cell isolation techniques, which are essential for biomaterial testing procedures.

Do neurosurgeons follow the guidelines? A world-based survey on severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is going to be the third-leading cause of death worldwide, according to the WHO. Two European surveys suggested that adherence to brain trauma guidelines is poor. No study has compared compliance between low- (LMICs) and high-income (UHICs) countries. Hence, this study aimed to investigate differences in the management of severe TBI patients, comparing low- and high-income, and adherence to the BTF guidelines. METHODS: A web-based survey was spread through the Global Neuro Foundation, different neurosurgical societies, and social media. RESULTS: A total of 803 neurosurgeons participated: 70.4 from UHICs and 29.6% from LMICs. Hypertonic was administered as an early measure by the 73% and 65% of the responders in LMICs and UHICs, respectively (P=0.016). An invasive intracranial pressure monitoring was recommended by the 66% and 58% of the neurosurgeons in LMICs and UHICs, respectively (P<0.001). Antiseizure drugs (P<0.001) were given most frequently in LMICs as, against recommendations, steroids (87% vs. 61% and 86% vs. 81%, respectively). In the LMICs both the evacuation of the contusion and decompressive craniectomy were performed earlier than in UHICs (30% vs. 17% with P<0.001 and 44% vs. 28% with P=0.006, respectively). In the LMICs, the head CT control was performed mostly between 12 and 24 hours from the first imaging (38% vs. 23%, P<0.001). CONCLUSIONS: The current Guidelines on TBI do not always fit to both the resources and circumstances in different countries. Future research and clinical practice guidelines should reflect the greater relevance of TBI in low resource settings.

Desmoid-type fibromatosis of paranasal sinuses with intracranial extension in a child-acase-based review.

PURPOSE: Desmoid-type fibromatosis (DF) is clonal fibroblastic proliferation that arises in the deep soft tissues, tends to reoccur, and is locally invasive. Desmoid-type fibromatosis of paranasal sinuses with intracranial extension is a rare condition that is even rarer in a small child. We aim to share with the reader our literature review, decision-making, and endoscopic endonasal operation procedure that combined gained us favorable results against this benign tumor with unpredictable natural history and disease course. CASE REPORT: We describe the decision-making process in the management of a 3-year-old boy with a history of sudden vision loss and vomiting. MR showed an expansive well-delineated homogeneous tumor in the sphenoid sinus with intracranial extension and optic nerves compression. The diagnosis of a sporadic form of desmoid-type fibromatosis was made using genetic testing of tumor tissue. A total gross removal was carried out with endoscopic endonasal microsurgical approach. At a 3-month follow-up, the patient is without any signs of recurrance. CONCLUSION: The treatment of children with desmoid-type fibromatosis requires a multidisciplinary approach by clinicians experienced with the management of pediatric cancer. While the desmoid-type fibromatosis is a benign, locally invasive tumor, observation should be the first step in the management. In case of life-threatening or symptomatic cases, operations that preserve function and structure should be the first choice for this benign tumor with unpredictable natural history and disease course.

Clinical and Radiological Characteristics of Non-Benign Pineal Cyst Lesions in Children.

Background: With the increasing availability and advances in brain imaging, pineal cyst lesions (PCL) are becoming a common finding in the pediatric population. In the absence of evidence-based guidelines, optimal diagnostic and therapeutic approaches have not been established, and there is a risk of under- or overtreatment of these patients. Objectives: The aim of our study was to evaluate the clinical presentation and radiological features of PCL in a cohort of pediatric patients and to identify clinical parameters more commonly associated with neoplasms in the pineal region. In addition, the prevalence of PCL in the pediatric population of Slovenia was estimated. Methods: In this observational, cohort study, children treated at University Children's Hospital, Ljubljana, Slovenia in the period 1997-2016 were included if PCL was found on brain imaging. We analyzed indications for referral to a neurologist, clinical signs and symptoms, radiological features, treatment and outcome. Results: The cohort consisted of 143 children with PCL. Pineocytoma was suspected in 31 children (21.7%). Six children underwent surgery - pineocytoma was confirmed in two cases and germinoma in one (2/3 of these children had signs of increased intracranial pressure (ICP), while PCL was benign in the remaining 4 cases. Only 2 PCL enlarged during the study period, both <2mm, none of these children developed neoplasm. Two children had PCL >20mm in diameter; both showed signs of increased ICP, one patient was found to have a germinoma of the pineal region, while the other had no neoplasm. Conclusions: Most PCL do not change their features during radiological follow-up and even atypical PCL are very rarely associated with a malignant neoplasm of the pineal region. A PCL larger than 20 mm and signs of increased ICP were identified as potential markers for selecting patients at risk.

Advanced Bio-Based Polymers for Astrocyte Cell Models.

The development of in vitro neural tissue analogs is of great interest for many biomedical engineering applications, including the tissue engineering of neural interfaces, treatment of neurodegenerative diseases, and in vitro evaluation of cell-material interactions. Since astrocytes play a crucial role in the regenerative processes of the central nervous system, the development of biomaterials that interact favorably with astrocytes is of great research interest. The sources of human astrocytes, suitable natural biomaterials, guidance scaffolds, and ligand patterned surfaces are discussed in the article. New findings in this field are essential for the future treatment of spinal cord and brain injuries.

Long-term effect of bilateral STN-DBS on non-motor symptoms in Parkinson's disease: A four-year observational, prospective study.

BACKGROUND: Several studies have shown beneficial effects of bilateral stimulation of the subthalamic nucleus (STN-DBS) on motor as well as on non-motor symptoms (NMS) up to 36 months post-surgery in advanced Parkinson's disease (PD) patients. We set to explore the long-term effect of STN-DBS on NMS in a four-year follow-up, prospective, observational study. METHODS: Forty patients were enrolled and assessed at baseline. Twenty-eight were followed-up at 6, 12, 24, 36 and 48 months after the operation. The effect of post-operative time on NMS was analyzed by six-level repeated measures ANOVA. In a post-hoc analysis the follow-up scores were compared to baseline using a paired t-test. RESULTS: The following scores stayed improved up to 24 months after surgery, presented as baseline/24 months, p-value (t-test): total Non-Motor Symptoms Scale score (54.0 ± 5.6/44.9 ± 5.0, p = 0.029), Hamilton Anxiety Scale (14.3 ± 1.3/11.3 ± 1.2, p = 0.019) and PDQ39 (53.4 ± 4.5/40.2 ± 2.9, p = 0.012). PD Sleep Scale 2 remained improved throughout the study (17.4 ± 2.0/12.8 ± 1.3 at 48 months, p = 0.032), while Beck Depression Inventory only at six months post-surgery (9.5 ± 1.2/6.7 ± 0.7 at 6 months, p = 0.006). Montreal Cognitive Assessment remained stable up to 24 months and then declined at 36 months (26.3 ± 0.5/25.4 ± 0.5 at 36 months, p = 0.003), Starkstein Apathy Scale deteriorated throughout the study (7.6 ± 0.7/12.7 ± 0.9 at 48 months, p = 0.006). CONCLUSIONS: We observed beneficial effect of STN-DBS in several but not all domains of NMS at least up to 24 months post-op in advanced PD. Further long-term studies on larger cohorts of PD patients and longer follow-up need to be conducted to better understand the long-term effect of STN-DBS on NMS.

Chiari malformations in children: An overview.

Chiari malformations encompass various radiological and clinical entities, sharing the herniation of the rhombencephalic structures through the foramen magnum as a common characteristic. They can be symptomatic or asymptomatic. The therapeutic strategies for these malformations differ on the basis of the diverse pathophysiologic processes that cause them. As Chiari malformations are caused by various pathophysiologic processes, they must be recognized promptly to select the best treatment for each single case.

Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma.

Glioblastoma is the most aggressive cancer among primary brain tumours. As with other cancers, the incidence of glioblastoma is increasing; despite modern therapies, the overall mean survival of patients post-diagnosis averages around 16 months, a figure that has not changed in many years. Cannabigerol (CBG) has only recently been reported to prevent the progression of certain carcinomas and has not yet been studied in glioblastoma. Here, we have compared the cytotoxic, apoptotic, and anti-invasive effects of the purified natural cannabinoid CBG together with CBD and THC on established differentiated glioblastoma tumour cells and glioblastoma stem cells. CBG and THC reduced the viability of both types of cells to a similar extent, whereas combining CBD with CBG was more efficient than with THC. CBD and CBG, both alone and in combination, induced caspase-dependent cell apoptosis, and there was no additive THC effect. Of note, CBG inhibited glioblastoma invasion in a similar manner to CBD and the chemotherapeutic temozolomide. We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy.

Endoscopic supracerebellar infratentorial approach to pineal and posterior third ventricle lesions in prone position with head extension: a technical note.

OBJECTIVE: The supracerebellar infratentorial (SCIT) approach is frequently used for the treatment of lesions in the pineal and posterior third ventricle region and can be performed in a sitting or prone position. We describe our experience with the purely endoscopic SCIT approach, using a prone position, with neck extension and head rotation. METHODS: We analysed all paediatric and adult patients operated on between July 2013 and January 2018 using the purely endoscopic SCIT approach. The surgical procedure was conducted through a paramedian subtorcular key-hole suboccipital craniotomy. The assistant held the endoscope and the surgeon used fine, long shaft instruments for bimanual tumour dissection. The prone position with head retroflexion allowed a gravity-aided enlargement of the anatomical surgical corridor between tentorium and cerebellum and enhanced venous blood drainage, similarly to the sitting or semi-sitting position, but with a decreased risk of air embolism. RESULTS: The approach allowed a complete removal of lesions located in the pineal region and in the posterior part of the third ventricle. Seven patients have been operated with this approach. All of them had the tumour completely removed. No permanent neurological deficits have been observed. CONCLUSIONS: The endoscopic SCIT approach enables effective and safe removal of pineal and posterior third ventricle lesions, even of moderate dimensions (up to 3 cm). The endoscope guarantees a detailed view and illumination of the deep-seated structures. The tumour resection can be performed with bimanual use of microsurgical instruments.