In this review, traumatic brain injury (TBI) is found to be a frequent cause of contact in primary and secondary healthcare services. Intracranial haemorrhage associated with TBI occurs when direct or indirect forces to the head damage intracranial vessels. Patients with mild TBI, defined as a GCS of 14-15, seldom require CT imaging unless they were unconscious or had a seizure at the time of injury, are receiving anticoagulant therapy, have coagulopathies, present with focal neurological deficits, have shunt-treated hydrocephalus, or show clinical signs of a skull fracture.

Symptomatic chronic subdural hematoma is treated by surgical evacuation followed by drain insertion for post-operative drainage. There is no international consensus on the location of the drain (subdural or subperiosteal), the type of drainage (passive or active suction), or the duration of drainage (hours or days). However, a growing body of literature highlights the risk of iatrogenic brain injury during subdural drain insertion, causing increased interest in the subperiosteal drainage technique, which has been suggested to be equally effective. There is no consensus on the optimal subperiosteal drain insertion technique, resulting in numerous technical variations in the published literature. Additionally, drain anchoring is crucial to prevent the drain from displacing away from the burr hole. To address both issues, this article presents a standardized method for subperiosteal drain insertion and a novel anchorage technique for drains. All necessary drain entry-, exit-, and anchorage points are clearly defined and marked prior to placement of local anesthesia and skin incision. The stepwise insertion and anchorage of the drain are thoroughly described and illustrated, as well as the removal of the drain after post-operative drainage is complete.

BACKGROUND:In Denmark, the current treatment of patients with symptomatic chronic subdural hematoma (CSDH) is single burr hole hematoma evacuation followed by 24-h passive subdural drainage. However, recent studies indicate that 24-h active subperiosteal drainage may be safer and have fewer recurrences. The upcoming SUPERDURA trial will investigate 24-h active subperiosteal drainage versus 24-h passive subdural drainage following single burr-hole evacuation of symptomatic CSDH. This study presents the statistical analysis plan for the SUPERDURA trial. METHODS:SUPERDURA is a national multi-center non-inferiority randomized clinical trial. The primary outcome is a composite of 90-day mortality and ipsilateral recurrent CSDH requiring reoperation within the 90-day observation period. Secondary outcomes are 90-day simplified modified Rankin Scale questionnaire (smRSq) score, complications related to surgery, postoperative serious adverse events during the admission and at 90 days, and length of hospitalization. Exploratory outcomes are smRSq score as an ordinal outcome, each component of the primary outcome, and discharge destination. A total of 354 participants must be included (177 in each intervention group) in the study to achieve a stable power > 90% with an alpha of 5% for non-inferiority testing of the primary composite outcome with a margin at 7% absolute risk increase. The allocation sequence and block sizes are blinded to the investigators. Interim analyses for safety and efficacy/futility will be performed after follow-up is completed for 120 and 240 participants, respectively. A Data Safety Monitoring Committee charter has been created following published recommendations. Final analysis will be done by two statisticians blinded to the intervention, creating two abstracts that are unblinded once approved by the study steering committee. DISCUSSION:The proposed analysis plan is designed in accordance with current guidelines, has clinically important primary and secondary outcomes, and was submitted before the inclusion of the first participant in the SUPERDURA trial to limit bias and increase study transparency and reproducibility. TRIAL REGISTRATION:ClinicalTrials.gov identifier NCT06621407.

Although there has been a considerable increase in the understanding of glioblastoma and investigations into the therapeutic utility of several novel putative active compounds, the prognosis of glioblastoma patients remains dismal. This paradox makes glioblastoma a unique disease, in which the availability of key molecular and biological insight does not translate into therapeutic discovery or improved outcomes. Much of the challenge in glioblastoma treatment is attributable to a dearth of tools capable of accurately selecting patients who might benefit from current standard-of-care or targeted therapies. Moreover, the lack of reliable circulating biomarkers also delays treatment initiation and hampers evaluation of the therapeutic response. However, the emergence of a personalized medicine paradigm using extracellular vesicles has the potential to revolutionize cancer treatment, bringing renewed hope for patients with glioblastoma. In this review, we provide a brief overview of the current standard-of-care therapies, immunotherapeutic approaches and their clinical limitations. We then introduce the need for a personalized model and discuss the conceptual underpinnings of how extracellular vesicle cargo as a superior liquid biopsy tool can be used for a new personalized therapeutic approach in glioblastoma.

Ganciclovir is often used compassionately for encephalitis due to cytomegalovirus (CMV) and human herpes virus 6b (HHV-6b). Ganciclovir pharmacokinetic studies in the central nervous system (CNS) generally rely on single measurements in the cerebrospinal fluid (CSF) or homogenized brain tissue. Therefore the objective was to compare brain extracellular fluid (ECF) concentrations of ganciclovir with plasma and CSF concentrations in a porcine model, using microdialysis during a 24 h period. Six Danish landrace pigs (female, age 4 months, 31-37 kg) received two weight-adjusted intravenous doses of ganciclovir. Unbound ganciclovir concentrations were determined by microdialysis over 24 h in five compartments: CSF (lateral ventricle, cisterna magna, and lumbar) and brain ECF (cortical and subcortical). Data were compared with paired plasma samples. Ganciclovir concentrations >IC50 for CMV (1.6 µg/mL) were achieved in all compartments. Concentrations >IC90 for CMV (8.3 µg/mL) were only achieved in plasma and the lumbar CSF compartment. The concentration time curves indicated higher lumbar and cisternal CSF concentrations than ECF concentrations. The ECF compartments achieved greater maximum concentration (Cmax), area under the concentration time curve (AUC), and time >IC50 after the second dose, and an accumulation ratio (Rac) >1. The greater Cmax, AUC, time >IC50, and Rac >1 in the ECF compartments with repeated dosages suggest that therapeutic concentrations may be achieved during long-term treatment. A higher loading dose might be warranted to improve early viral inhibition.

Introduction : Cervical disc herniation (CDH) in working-age adults may cause substantial functional impairment. However, little is known about how patients transition from primary care to specialist evaluation, and whether regional differences in referral pathways influence management and outcome. Aim: To examine regional variation in referral pathways, surgical rates, and work capacity outcomes in Denmark’s five healthcare regions. Methods : Using national registry data, we identified 4,322 citizens aged 18–65 diagnosed with incident CDH in 2017. Patients were stratified by region and the type of department first referred to e.g. medical, surgical, or emergency. Work capacity one year prior to diagnosis was categorized as low (<20%), intermediate (20–80%), or high (≥80%) of a standard 37-hour work week and followed for two years after initial specialized health care sector admission the. Results : Admission rates were consistent across regions, ranging from 12 to 13 per 10,000 citizens. Nationally, the surgical rate was 1,296 per 10,000 admitted patients. However, surgical rates varied markedly between regions, from 793 per 10,000 in the Capitol Region to 2,320 per 10,000 in the Region of Northern Denmark. Nationally, 60.5 percent of patients were admitted through medical departments, 30.7 percent through surgical departments, and 8.8 percent through emergency departments, but the pathways differed substantially across the regions of Denmark. The highest surgical rate was observed among those referred through emergency departments, where 95 of 379 admitted patients underwent surgery (2,507 per 10,000 admitted patients). In contrast, medical departments admitted 2,615 patients, of whom 182 received surgery (696 per 10,000 admitted patients), while surgical departments admitted 1,328 patients, with 283 undergoing surgery (2,132 per 10,000 admitted patients). A total of 87 percent of patients with high and 83 percent with intermediate baseline work capacity regained pre-diagnosis work capacity within six months, whereas only 5% of those with low capacity achieved a work capacity of 20% or above within two years. Conclusion : Despite similar national admission rates for CDH, substantial regional disparities were observed in referral practices and surgical intervention rates. The findings suggest a need for more research into the optimal specialized clinical pathway for CDH patients who are refractory to initial conservative treatment in the primary health sector.

This study investigates outcomes in patients undergoing surgery for chronic subdural hematoma comparing those receiving vs not receiving antithrombotic therapy.

BACKGROUND:Multimodal neuromonitoring (MMM) aids early detection of secondary brain injury in neurointensive care and facilitates research in pathophysiologic mechanisms of the injured brain. Invasive ICP monitoring has been the gold standard for decades, however additional methods exist (aMMM). It was hypothesized that local practices regarding aMMM vary considerably and that inter-and intracenter consensus is low. The survey aimed to investigate this hypothesis including the knowledge, attitudes towards, and use of aMMM in the neurointensive care setting in the Nordic countries. METHOD:The survey was distributed amongst 54 neurosurgical trainees at a Nordic neurosurgery training course and supplemented with 16 center-appointed neuromonitoring experts representing 16 of the 19 neurosurgical centers in the Nordic countries (Norway, Sweden, Denmark, and Finland). RESULTS:The response rate was 100% amongst the training course attendents, as well as the center-appointed experts with a total of 70 respondents. The experts covered 16/19 Nordic centers. In-center disagreement was high concerning the use of aMMM methods. In patients with traumatic brain injury, subarachnoid hemorrhage, or other acute brain injuries 50% of the appointed experts stated transcranial Doppler ultrasound (TCD) to be used in most cases in their ICU, and an additional 25% for selected cases. Most appointed experts agreed on electroencephalography (EEG) for selected cases 63%, but only 19% for most cases. Routine use of Invasive brain tissue oxygenation (PbtO2) was stated by 25-63% and cerebral microdialysis (CMD) by 19-38%. The main perceived concerns with aMMM methods were the usefulness for outcome-changing interventions (43%) and financial issues (19%). Most respondents (67%) believed automated combined analysis of aMMM to be a likely future scenario. CONCLUSION:There was a remarkable variation in the reported use of aMMM among Nordic neurosurgical centers, indicating an extensive lack of consensus on need and utility. Surprisingly routine use of TCD was stated by 75%, presumably for routine monitoring of SAH patients, whereas CMD was mostly considered a research tool. Interestingly, junior staff and appointed experts disagreed on intended local routines, indicating that application of aMMM was more governed organically and by case than on explicit guidelines or that uniform management was not prioritized.

OBJECTIVE: Chronic subdural hematoma (CSDH) poses a significant recurrence risk, yet predicting recurrence and its impact remains a challenge. This study investigates whether patient competence-defined as the ability to understand and make informed medical decisions-affects recurrence risk, and examines how recurrence impacts patients' quality of life (QoL) at a 90-day postsurgical follow-up. METHODS: In this subanalysis of the Drain Time 2 trial, we analyzed data from 330 patients undergoing primary surgery for CSDH. Patients were categorized as competent (n = 281) or incompetent (n = 49) based on clinician evaluations. We explored associations among patient competence, recurrence, mortality, and QoL using the Short Form Health Survey (SF-36) questionnaire. Statistical analyses included logistic regression for recurrence and mortality, and independent t-tests and multiple linear regression for SF-36 scores. RESULTS: Of 330 patients, no significant correlation was found between patient incompetence and CSDH recurrence. Recurrence rates were 20% in competent patients and 14% in incompetent patients (P = 0.382). However, incompetence was significantly associated with increased mortality (unadjusted odds ratio [OR]: 24.3, P < 0.001; fully adjusted OR: 41, P < 0.001) and the composite outcome of recurrence or death (unadjusted OR: 2.2, P = 0.019; fully adjusted OR: 2.3, P = 0.021). Preoperative SF-36 scores improved significantly postoperatively (107.2 to 113.9, P < 0.001); yet no significant difference in QoL was observed between competent patients with and without recurrence CONCLUSIONS: Patient incompetence was not significantly associated with CSDH recurrence within 90 days. However, it was strongly associated with increased mortality. Additionally, recurrence did not significantly impact the QoL in competent patients at follow-up. Further research is needed to investigate long-term QoL outcomes, particularly among incompetent patients, to better understand potential lasting effects.

Pigs are increasingly used as a large animal model for pharmacologic CNS research due to the anatomical and physiological similarities between the porcine and human central nervous systems (CNS). However, accessing the cerebrospinal fluid (CSF) in larger pig breeds by conventional lumbar puncture techniques can be challenging due to an oblique orientation of the spinal spinous processes and a limited interlaminar space. Accordingly, an open surgical procedure for inserting a lumbar spinal catheter for continuous CSF sampling at the L4/L5 level in pigs is thoroughly described in this work. After positioning the pig and identifying the anatomical landmarks, a dorsal midline surgical incision is made to expose the spinous processes. By advancing the introducer needle, the spinal catheter is inserted inside the thecal sac of the spinal canal while leaving the bone structures of the spine intact. This method allows continuous infusion into or sampling from the porcine thecal sac with minimal bleeding or CSF leakage. The procedure is simple, time-efficient, and reproducible across different experimental setups, offering significant potential for various pre-clinical studies, including pharmacokinetic research, surgical training, and spinal cord injury models.

BACKGROUND:Postoperative drainage after surgical evacuation of chronic subdural haematoma reduces the risk of recurrence, but the optimum drainage time is uncertain. We aimed to investigate the shortest possible drainage time without increasing the haematoma recurrence rate. METHODS:We conducted a randomised, multi-arm and multistage non-inferiority trial at four neurosurgical centres in Denmark. We enrolled adult patients (aged ≥18 years) with symptomatic chronic subdural haematoma. All patients were treated according to the national standard practice with a burr hole above the maximum width of the haematoma. Patients were randomly assigned in a 1:1:1 ratio via a centralised web server to receive 6 h, 12 h, or 24 h of postoperative passive subdural drainage. Randomisation was done by an independent on-call neurosurgeon and was masked until 6 h after surgery. The primary outcome was symptomatic haematoma recurrence at 3 months after surgery; the rate of recurrence was assessed in a regression model for non-inferiority testing, with no missing data. Personnel assessing the primary outcome were masked to group allocation. Non-inferiority was assessed with a prespecified margin of 7%, in a modified intention-to-treat population-defined as patients with randomly assigned treatment excluding those withdrawing from study participation after randomisation, or experiencing acute rebleedings or accidental drain removal. This trial is registered with ISRCTN (number 15186366); the trial was stopped after the first interim analysis on the advice of an independent safety advisory committee. FINDINGS:Between March 1, 2021, and June 30, 2022, 347 patients were enrolled and 331 were followed up to 3 months, 105 were assigned to 6 h of drainage, 111 to 12 h of drainage, and 115 to 24 h of drainage. At admission, 83 (25%) participants were women and 248 (75%) were men, mean age was 75·7 years (SD 10·5), median modified Rankin Scale score was 4 (IQR 3-5), and median Glasgow Coma Scale score was 15 (IQR 14-15). At 3 months after surgery, haematoma recurrence was reported in 28 (27%) of 105 patients who were assigned to 6 h drainage (predicted haematoma recurrence rate 27·0%, 95% CI 18·5 to 35·4), 22 (20%) of 111 assigned to 12 h drainage (19·5%, 12·0 to 27·0), and 12 (10%) of 115 assigned to 24 h drainage (10·4%, 4·8 to 16·0). The risk of haematoma recurrence was increased by 16·5 percentage points (95% CI 6·5 to 26·6) in patients drained for 6 h compared with 24 h, and by 9·1 percentage points (-0·4 to 18·5) in patients drained for 12 h compared with 24 h. Therefore, non-inferiority of 6 h and 12 h of drainage to 24 h of drainage was not established. 20 patients had died by 3 months, seven in the 6 h group, eight in the 12 h group, and five in the 24 h group. The most frequent known causes of death were haematoma recurrence (three in 12 h group), comorbidity (three in 12 h group), and pneumonia (one each in 6 h and 12 h groups, two in 24 h group). The most frequent complication was postoperative infection, reported in 20 (20%) patients in the 6 h group, 25 (23%) in the 12 h group, and 19 (17%) in the 24 h group. The most common infection source was the urinary tract. INTERPRETATION:Patients surgically treated for symptomatic chronic subdural haematoma and postoperatively drained for 6 h or 12 h had higher rates of haematoma recurrence than did patients drained for 24 h. The findings from this non-inferiority trial provide evidence to support 24 h of postoperative drainage as the standard drain time when a fixed drain time approach is used. To provide solid evidence of generalisability of the results to countries other than Denmark, a multinational randomised controlled trial will be needed. FUNDING:None.

Introduction: Previously, only 40 cases with extradural hemangioblastoma at the spinal nerve (none at the T1 nerve root) have been described in the medical literature. In toto, resection of this hypervascular tumor is essential to avoid bleeding complications. Surgery for hemangioblastoma at the cervicothoracic junction is complex and nerve resection of the T1 results in specific neurodeficits of the hand muscles which are not well known. Case Report: A 34-year-old woman was diagnosed with a slowly growing tumor located at the left foramen T1/T2. Pressure from the tumor resulted in Horner’s syndrome and pain and paresthesia in the upper extremity. The tumor was resected in toto through a posterior midline approach and rib resection and transection of the left T1 and T2 spinal nerves. T2 hemicorporectomy and spinal stabilization were performed to gain access to and mobilize the tumor ventrally. Ptosis decreased after surgery and no neurodeficit was observed except the expected deficit (no deficit was present preoperatively) caused by the T1 resection specifically a small decrease in strength of the abductor and flexor pollicis brevis and opponens pollicis and the lateral two lumbricals. Histological examination of the tumor demonstrated a hemangioblastoma. von Hippel-Lindau disease was ruled out by genetic testing of the patient’s blood. Eight-month postoperatively, all pre-operative symptoms had decreased considerably and the radiographic examination shoved unchanged pedicle screw/rod stabilization of the cervicothoracic junction. Conclusion: Hemangioblastoma is a rare hypervascular tumor very rarely located at the spinal nerve. The tumor should be resected in toto to avoid recurrence and bleeding. In the current case, the location was at the T1 root necessitating complex surgery with laminectomies and hemicorporectomy of T2 and a posterior rib resection/thoracotomy. Spinal stabilization is mandatory. Preferably embolization should be performed preoperatively. T1 transection results in a specific neurodeficit which should be explained to the patient preoperatively. The patients should undergo genetic testing for Hippel-Lindau disease. Keywords: Hemangioblastoma, von Hippel-Lindau disease, in toto resection, hemicorporectomy, spinal nerve root T1 nerve lesion.

BackgroundBrain abscess (BA) is a rare, but severe infection and experimental BA animal models may prove crucial for advances in treatment. This review describes the development of experimental BA models and the clinical advances obtained from these, in a historical perspective.Material and methodsExperimental BA studies from inception until June 15, 2022, were included by searching the PubMed and Embase databases. Inclusion required the use of an experimental BA animal model. Non-bacterial BA models, in vitro studies, veterinarian case-reports, and articles written in non-English language were excluded. Bias was not systematically assessed, and the review was not registered at the PROSPERO.Results79 studies were included. The majority of animal BA models have been based on small rodents using Staphylococcus aureus. The models have delineated the natural development of BA and provided detailed descriptions of the histopathological characteristics consisting of a necrotic centre surrounded by layers of inflammatory cells and fibroblasts encapsulated by a dense collagenous layer. Radiological studies of animal BA have been shown to correlate with the corresponding stages of human BA in both computed tomography and magnetic resonance imaging and may guide diagnosis as well as the timing of neurosurgical intervention. Moreover, pharmacokinetic studies of the intracavitary penetration of various antimicrobials have helped inform medical treatment of BA. Other studies have examined the diverse effects of corticosteroids including decreased cerebral oedema, intracranial pressure, and intracavitary drug concentration, whereas concerns on decreased or weakened capsule formation could not be confirmed. Finally, studies on the immunological response to BA have highlighted potential future immunomodulatory targets.ConclusionsAnimal models have been vital for improvements in the management of BA. Experimental BA models resembling human disease including polymicrobial infection by oral cavity flora in large animals are needed.

Background The subgenual gyrus is a promising target for deep brain stimulation (DBS) against depression. However, to optimize this treatment modality, we need translational animal models. Aim To describe the anatomy and connectivity of the Göttingen minipig subgenual area (sgC). Materials and methods The frontal pole of 5 minipigs was cryosectioned into 40 µm coronal and horizontal sections and stained with Nissl and NeuN-immunohistochemistry to visualize cytoarchitecture and cortical lamination. Eight animals were unilaterally stereotaxically injected in the sgC with anterograde (BDA) and retrograde (FluroGold) tracers to reveal the sgC connectivity. Results In homology with human nomenclature (Brodmann 1909), it can be subdivided into three distinct areas named area 25 (BA25), area 33 (BA33), and indusium griseum (IG). BA25 is a narrow agranular cortex, approximately 1 mm thick. It has a poor laminar differentiation in the deeper layers due to a similar appearance of layer III and V neurons. Perpendicular to the surface cell, poor columns of white matter stretch deep into layers II and III, thereby segregating small groups of closely arranged neurons in the superficial layers. BA33 is less differentiated than BA25. Accordingly, the cortex is narrower and displays a complete lack of laminar differentiation due to diffusely arranged small, lightly stained neurons. It abuts the indusium griseum, which is a neuron-dense band of heavily stained small neurons separating BA33 directly from the corpus callosum and the posteriorly located septum. Conclusion The minipig sgC displays a cytoarchitectonic pattern and connectivity like the human and may be well suited for further translational studies on BA25-DBS against depression.

Background: Knowledge regarding CNS pharmacokinetics of moxifloxacin is limited, with unknown consequences for patients with meningitis caused by bacteria resistant to beta-lactams or caused by TB. Objective: (i) To develop a novel porcine model for continuous investigation of moxifloxacin concentrations within brain extracellular fluid (ECF), CSF and plasma using microdialysis, and (ii) to compare these findings to the pharmacokinetic/pharmacodynamic (PK/PD) target against TB. Methods Six female pigs received an intravenous single dose of moxifloxacin (6 mg/kg) similar to the current oral treatment against TB. Subsequently, moxifloxacin concentrations were determined by microdialysis within five compartments: brain ECF (cortical and subcortical) and CSF (ventricular, cisternal and lumbar) for the following 8 hours. Data were compared to simultaneously obtained plasma samples. Chemical analysis was performed by high pressure liquid chromatography with mass spectrometry. The applied PK/PD target was defined as a maximum drug concentration (C-max):MIC ratio >8. Results: We present a novel porcine model for continuous in vivo CNS pharmacokinetics for moxifloxacin. C-max and AUC0-8h within brain ECF were significantly lower compared to plasma and lumbar CSF, but insignificantly different compared to ventricular and cisternal CSF. Unbound C-max:MIC ratio across all investigated compartments ranged from 1.9 to 4.3. Conclusion: A single dose of weight-adjusted moxifloxacin administered intravenously did not achieve adequate target site concentrations within the uninflamed porcine brain ECF and CSF to reach the applied TB CNS target.

Purpose To evaluate patient demographics, surgery characteristics, and patient-reported clinical outcomes related to the implementation of lumbar PTED in Denmark by surgeons novice to the PTED technique. Methods All adult patients treated with a lumbar PTED from our first surgery in October 2020 to December 2021 were included. Data was generated by journal audit and telephone interview. Results A total of 172 adult patients underwent lumbar PTED. Surgery duration was a median of 45.0 (35.0–60.0) minutes and patients were discharged a median of 0 (0–1.0) days after. Per operatively one procedure was converted to open microdiscectomy due to profuse bleeding. Post operatively one patient complained of persistent headache (suggestive of a dural tear), two patients developed new L5 paresthesia, and three patients had a newly developed dorsal flexion paresis (suggestive of a root lesion). Sixteen patients did not complete follow-up and 24 (14.0%) underwent reoperation of which 54.2% were due to residual disk material. Among the remaining 132 patients, lower back and leg pain decreased from 7.0 (5.0–8.5) to 2.5 (1.0–4.5) and from 8.0 (6.0–9.1) to 2.0 (0–3.6) at follow-up, respectively ( p < 0.001). Additionally, 93.4% returned to work and 78.8% used less analgesics. Post hoc analysis comparing the early half of cases with the latter half did not find any significant change in surgery time, complication and reoperation rates, nor in pain relief, return to work, or analgesia use. Conclusion Clinical improvements after lumbar PTED performed by surgeons novel to the technique are satisfactory, although the reoperation rate is high, severe complications may occur, and the learning curve can be longer than expected.

Chronic malignant pain is a common and feared condition. Especially, since many patients do not achieve proper pain relief from conventional peroral medication regimes and possible unacceptable side effects of high dosing. As argued in this review, in these patients, continuous intrathecal infusion of pain medicine by a programmable subcutaneously placed pump enables good pain relief, less systemic side effects, and better life quality. Intrathecal pain treatment should therefore be considered in patients with a proper performance score and suitable estimated life expectancy.