Genomic Validation in the UK Biobank Cohort Suggests a Role of C8B and MFG-E8 in the Pathogenesis of Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a severe facial pain disease of uncertain pathophysiology and unclear genetic background. Although recent research has reported a more important role of genetic factors in TN pathogenesis, few candidate genes have been proposed to date. The present study aimed to identify independent genetic variants in the protein-coding genes associated with TN. We focused on genes previously linked to TN based on the results of four proteomic studies conducted by our research team. The goal was to validate these findings on the genetic level to enhance our understanding of the role of genetics in TN. The study is based on the participants from UK Biobank cohort. Following quality control, 175 independent single nucleotide polymorphisms (SNPs) in 17 genes were selected. The study sample comprised of diagnosed TN cases (N = 555) and randomly matched controls (N = 6245) based on specific criteria. Two SNPs corresponding to C8B rs706484 [odds ratio (OR) (95% confidence interval (CI)): 1.357 (1.158-1.590); p: 0.00016] and MFG-E8 rs2015495 [OR (95% CI): 1.313 (1.134-1.521); p: 0.00028] showed significant positive association with TN, indicating a positive effect of the SNP alleles on gene expression and disease risk. Interestingly, both SNPs are Expression Quantitative Trait Loci (eQTLs), and are associated with changes in the expression activity of their corresponding gene. Our findings suggest novel genetic associations between C8B, a key component of the complement system, and MFG-E8, which plays a role in regulating neuroinflammation, in relation to TN. The identified genetic variations may help explain why some individuals develop TN while others do not, indicating a potential genetic predisposition to the condition.

Cerebral contusions - Pathomechanism, predictive factors for progression and historical and current management.

Introduction: Cerebral contusions (CCs) are common traumatic brain injuries known for their propensity to progress. Understanding their mechanical pathogenesis and predictive factors for progression is crucial for optimal management. Research question: To provide an overview of current knowledge on CCs, including pathomechanisms, predictive factors of contusion progression, and management strategies. Material and methods: A literature search was conducted using PubMed, Scopus and ISI web of knowledge focused on articles in English with the words "cerebral contusion" together with the words "traumatic brain injury", "pathomechanism", "progression of contusion", "predictive factors" and "management" alone or in combination. Results: The management of CCs has evolved alongside the advances in neurointensive care, yet there is no consensus. Evidence on the effectiveness of early surgery, importantly, for the group which has the potential to expand, is limited. Some predictive factors for contusion progression have been identified, including age, injury mechanism, coagulopathy and initial contusion volume which could help to guide decision-making. Discussion and conclusion: While various theories exist on pathomechanisms and several predictive factors for progression have been proposed, consensus on optimal management remains elusive. Individualized care guided by the predictive factors is essential. Challenges posed by antithrombotic medications highlight the need for early intervention strategies.Decompressive craniectomy could serve as a potential tool in severe traumatic brain injury management including contusions. Conducting large cohort studies to refine predictive models and harmonizing management approaches would help to improve outcomes of patients with CCs.

Organoids and chimeras: the hopeful fusion transforming traumatic brain injury research.

Research in the field of traumatic brain injury has until now heavily relied on the use of animal models to identify potential therapeutic approaches. However, a long series of failed clinical trials has brought many scientists to question the translational reliability of pre-clinical results obtained in animals. The search for an alternative to conventional models that better replicate human pathology in traumatic brain injury is thus of the utmost importance for the field. Recently, orthotopic xenotransplantation of human brain organoids into living animal models has been achieved. This review summarizes the existing literature on this new method, focusing on its potential applications in preclinical research, both in the context of cell replacement therapy and disease modelling. Given the obvious advantages of this approach to study human pathologies in an in vivo context, we here critically review its current limitations while considering its possible applications in traumatic brain injury research.

Advances in development of biomarkers for brain damage and ischemia.

Acquired brain injury is an urgent situation that requires rapid diagnosis and treatment. Magnetic resonance imaging (MRI) and computed tomography (CT) are required for accurate diagnosis. However, these methods are costly and require substantial infrastructure and specialized staff. Circulatory biomarkers of acute brain injury may help in the management of patients with acute cerebrovascular events and prevent poor outcome and mortality. The purpose of this review is to provide an overview of the development of potential biomarkers of brain damage to increase diagnostic possibilities. For this purpose, we searched the PubMed database of studies on the diagnostic potential of brain injury biomarkers. We also accessed information from Clinicaltrials.gov to identify any clinical trials of biomarker measurements for the diagnosis of brain damage. In total, we present 41 proteins, enzymes and hormones that have been considered as biomarkers for brain injury, of which 20 have been studied in clinical trials. Several microRNAs have also emerged as potential clinical biomarkers for early diagnosis. Combining multiple biomarkers in a panel, along with other parameters, is yielding promising outcomes.

Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients.

Coronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing to CAD by studying a cohort of 60 large Iranian families with at least two members in different generations afflicted with premature CAD (PCAD), defined as established disease at ≤45 years in men and ≤55 years in women. Exome sequencing was performed for a subset of the affected individuals, followed by prioritization and Sanger sequencing of candidate variants in all available family members. Subsequently, apparently healthy carriers of potential risk variants underwent coronary computed tomography angiography (CCTA), followed by co-segregation analysis of the combined data. Putative causal variants were identified in seven genes, ABCG8, CD36, CYP27A1, PIK3C2G, RASSF9, RYR2, and ZFYVE21, co-segregating with familial PCAD in seven unrelated families. Among these, PIK3C2G, RASSF9, and ZFYVE21 are novel candidate CAD susceptibility genes. Our findings indicate that rare variants in genes identified in this study are involved in CAD development.

Medication utilization in traumatic brain injury patients-insights from a population-based matched cohort study.

Introduction: Traumatic brain injury (TBI) is associated with health problems across multiple domains and TBI patients are reported to have high rates of medication use. However, prior evidence is thin due to methodological limitations. Our aim was thus to examine the use of a wide spectrum of medications prescribed to address pain and somatic conditions in a population-based cohort of TBI patients, and to compare this to a sex- and age-matched cohort. We also examined how patient factors such as sex, age, and TBI severity were associated with medication use. Methods: We assessed Swedish nationwide registers to include all individuals treated for TBI in hospitals or specialist outpatient care between 2006 and 2012. We examined dispensed prescriptions for eight different non-psychotropic medication classes for the 12 months before, and 12 months after, the TBI. We applied a fixed-effects model to compare TBI patients with the matched population cohort. We also stratified TBI patients by sex, age, TBI severity and carried out comparisons using a generalized linear model. Results: We identified 239,425 individuals with an incident TBI and 239,425 matched individuals. TBI patients were more likely to use any medication [Odds ratio (OR) = 2.03, 95% Confidence Interval (CI) = 2.00-2.05], to present with polypharmacy (OR = 1.96, 95% CI = 1.90-2.02), and to use each of the eight medication classes before their TBI, as compared to the matched population cohort. Following the TBI, TBI patients were more likely to use any medication (OR = 1.83, 95% CI = 1.80-1.86), to present with polypharmacy (OR = 1.74, 95% CI = 1.67-1.80), and to use all medication classes, although differences were attenuated. However, differences increased for antibiotics/antivirals (OR = 2.02, 95% CI = 1.99-2.05) and NSAIDs/antirheumatics (OR = 1.62, 95% CI = 1.59-1.65) post-TBI. We also found that females and older patients were more likely to use medications after their TBI than males and younger patients, respectively. Patients with more severe TBIs demonstrated increased use of antibiotics/ antivirals and NSAIDs/antirheumatics than those with less severe TBIs. Discussion: Taken together, our results point to poor overall health in TBI patients, suggesting that medical follow-up should be routine, particularly in females with TBI, and include a review of medication use to address potential polypharmacy.

Extracellular vesicles in plasma and cerebrospinal fluid in patients with COVID-19 and neurological symptoms.

INTRODUCTION: Increased levels of extracellular vesicles (EVs) are associated with haemostatic disturbances in various clinical settings. However, their role in COVID-19 patients is still not fully clear. In the present study we investigated EVs in plasma from patients with COVID-19 and neurological symptoms in relation to the activation of coagulation. METHODS: Nineteen COVID-19 patients with neurological symptoms and twenty-three aged-matched healthy individuals were included. Global coagulation assays were performed and levels of EVs were determined by flow-cytometry in plasma and cerebrospinal fluid (CSF). RESULTS: A procoagulant state characterized by significantly increased overall coagulation- (OCP) and overall haemostatic potential (OHP), diminished overall fibrinolytic potential (OFP) together with a denser fibrin structure was found in patients with COVID-19. Flow cytometry revealed elevated levels of plasma circulating EVs derived from neutrophils (MPO+) and platelets (CD61+), as well as EVs expressing phosphatidylserine (PS+) and complement component C5b-9 (TCC+) in patients with COVID-19 compared with controls. The concentrations of PS+, CD61+ and TCC+ EVs were positively correlated with OCP and OHP in COVID-19 patients. Moreover, we identified CD61+, MPO+ and endothelial cell-derived EVs, as well as EVs exposing PS and TCC in the CSF of patients suffering from neurological symptoms during COVID-19. CONCLUSION: The unique finding in this study was the presence of EVs in the CSF of COVID-19 patients with neurologic manifestations as well as higher expression of complement protein on circulating plasma EVs. EVs may indicate blood-brain barrier damage during SARS-COV-2 infection.

Increased Incidence and Mortality of Civilian Penetrating Traumatic Brain Injury in Sweden: A Single-Center Registry-Based Study.

BACKGROUND: Penetrating trauma to the head and neck has increased during the past decade in Sweden. The aim of this study was to characterize these injuries and evaluate the outcomes for patients treated at a tertiary trauma center. METHODS: Swedish trauma registry data were extracted on patients with head and neck injuries admitted to Karolinska University Hospital (Stockholm, Sweden) between 2011 and 2019. Outcome information was extracted from hospital records, with the primary endpoints focusing on the physiological outcome measures and the secondary endpoints on the surgical and radiological outcomes. RESULTS: Of 1436 patients with penetrating trauma, 329 with penetrating head and neck injuries were identified. Of the 329 patients, 66 (20%) had suffered a gunshot wound (GSW), 240 (73%) a stab wound (SW), and 23 (7%) an injury from other trauma mechanisms (OTMs). The median age for the corresponding 3 groups of patients was 25, 33, and 21 years, respectively. Assault was the primary intent, with 54 patients experiencing GSWs (81.8%) and 158 SWs (65.8%). Patients with GSWs had more severe injuries, worse admission Glasgow coma scale, motor, scores, and a higher intubation rate at the injury site. Most GSW patients underwent major surgery (59.1%) as the initial procedure and were more likely to have intracranial hemorrhage (21.2%). The 30-day mortality was 45.5% (n = 30) for GSWs, 5.4% (n = 13) for SWs, and 0% (n = 0) for OTMs. There was an annual increase in the incidence and mortality for GSWs and SWs. CONCLUSIONS: Between 2011 and 2019, an increasing annual trend was found in the incidence and mortality from penetrating head and neck trauma in Stockholm, Sweden. GSW patients experienced more severe injuries and intracranial hemorrhage and underwent more surgical interventions compared with patients with SWs and OTMs.

Mild Traumatic Brain Injury in the Maturing Brain: An Investigation of Symptoms and Cognitive Performance in Soldiers Returning From Afghanistan and Iraq.

OBJECTIVE: The majority of traumatic brain injuries (TBIs) are classified as mild and occur in young individuals. The course of recovery varies but can result in chronic or troubling outcomes. The impact of age on TBI outcomes in young adults before complete brain maturation is not well studied. METHODS: In this study, we compared the effects of mild TBI on cognitive performance and self-reported TBI symptoms and posttraumatic stress disorder (PTSD) in 903 soldiers in 3 different age groups: 24 years or younger, 25 to 27 years, and 28 to 40 years. The soldiers had returned from war zones in Iraq and were screened for TBI within a few days of return. Cognitive performance was measured with the Automated Neuropsychological Assessment Metrics of Military TBI Version 4 (ANAM4). Symptoms associated with mild TBI were self-reported on the Neurobehavioral Symptom Inventory, and the PTSD Checklist-Civilian Version (PCL-C). RESULTS: Soldiers with TBI in every age group had significantly higher prevalence of most symptoms than those with no TBI. Soldiers with TBI also reported more chronic pain sites, regardless of age. Soldiers aged 28 to 40 years with TBI had the lowest cognitive performance scores (ANAM) across several subtests, both unadjusted and adjusted. The Global Deficit Score was significantly higher for soldiers aged 28 to 40 years and 25 to 27 years with TBI than for soldiers younger than 24 years with no TBI. After adjusting for PTSD symptoms, education, and number of lifetime TBIs, the overall test battery mean for soldiers aged 28 to 40 years with TBI was significantly lower than for soldiers younger than 24 years with no TBI. CONCLUSION: Soldiers with mild TBI in the younger age group show more symptoms associated to frontal lobe function while soldiers in the older group suffer more cognitive impairment. This may warrant further study as it may indicate a propensity to later cognitive decline among soldiers who were older at the time of injury.

Clinical and laboratory characteristics of children with severe and nonsevere COVID-19 in Kermanshah, west of Iran: A retrospective study.

Background and Aims: The study aimed to collect and compare clinical and laboratory findings of children with severe and nonsevere COVID-19 in Kermanshah City, located in the west of Iran. Methods: The study was conducted on 500 children with COVID-19 hospitalized in Mohammad-Kermanshahi Hospital in Kermanshah City. Pediatric COVID-19 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) test using respiratory secretion samples. Medical records were reviewed and information related to demographic characteristics, underlying diseases, clinical manifestations, laboratory findings, and chest computed tomography (CT) scans were all extracted from electronic and paper records. Patients were divided into three groups according to the severity of the disease: mild, moderate, and severe. Clinical and laboratory findings were compared between the groups and the collected data were analyzed by statistical methods. Results: Out of 500 patients, 286 were boys and 214 were girls. Of the patients, 321 cases were only COVID-19, while 179 patients were diagnosed as Multisystem Inflammatory Syndrome in Children (MIS-C) positive. The average age of COVID-19 patients was 3.85 ± 4.48 and of MIS-C patients was 3.1 ± 3.5. In order, fever, cough, and heart disorders were the most common symptoms in patients with COVID-19 and MIS-C, respectively. In terms of disease severity, 246 patients had mild disease, 19 patients had moderate disease, and 56 patients had severe disease. In severe patients, the average number of white blood cells (WBC) was higher, while the average number of lymphocytes was lower. Also, in these patients, the average age was lower, and most of them had respiratory distress. In mild patients, often cough, diarrhea, and vomiting were observed. Conclusion: The results of our study showed that laboratory factors such as WBC count, lymphocyte count, CT findings, Respiratory distress, cough, diarrhea, and vomiting can be used to evaluate the severity of COVID-19 in children.

Prehospital and emergency department airway management of severe penetrating trauma in Sweden during the past decade.

BACKGROUND: Prehospital tracheal intubation (TI) is associated with increased mortality in patients with penetrating trauma, and the utility of prehospital advanced airway management is debated. The increased incidence of deadly violence in Sweden warrants a comprehensive evaluation of current airway management for patients with penetrating trauma in the Swedish prehospital environment and on arrival in the emergency department (ED). METHODS: This was an observational, multicenter study of all patients with penetrating trauma and injury severity scores (ISSs) ≥ 15 included in the Swedish national trauma register (SweTrau) between 2011 and 2019. We investigated the frequency and characteristics of prehospital and ED TI, including 30-day mortality and patient characteristics associated with TI. RESULT: Of 816 included patients, 118 (14.5%) were intubated prehospitally, and 248 (30.4%) were intubated in the ED. Patients who were intubated prehospitally had a higher ISS, 33 (interquartile range [IQR] 25, 75), than those intubated in the ED, 25 (IQR 18, 34). Prehospital TI was associated with a higher associated mortality, OR 4.26 (CI 2.57, 7.27, p < 0.001) than TI in the ED, even when adjusted for ISS (OR 2.88 [CI 1.64, 5.14, p < 0.001]). Hemodynamic collapse (≤ 40 mmHg) and low GCS score (≤ 8) were the characteristics most associated with prehospital TI. Traumatic cardiac arrests (TCAs) occurred in 154 (18.9%) patients, of whom 77 (50%) were intubated prehospitally and 56 (36.4%) were intubated in the ED. A subgroup analysis excluding TCA showed that patients with prehospital TI did not have a higher mortality rate than those with ED TI, OR 2.07 (CI 0.93, 4.51, p = 0.068), with OR 1.39 (0.56, 3.26, p = 0.5) when adjusted for ISS. CONCLUSION: Prehospital TI was associated with a higher mortality rate than those with ED TI, which was specifically related to TCA; intubation did not affect mortality in patients without cardiac arrest. Mortality was high when airway management was needed, regardless of cardiac arrest, thereby emphasizing the challenges posed when anesthesia is needed. Several interventions, including whole blood transfusions, the implementation of second-tier EMS units and measures to shorten scene times, have been initiated in Sweden to counteract these challenges.

Access to Rehabilitation After Hospitalization for Traumatic Brain Injury: A National Longitudinal Cohort Study in Sweden.

BACKGROUND: Rehabilitation is suggested to improve outcomes following traumatic brain injury (TBI), however, the extent of access to rehabilitation among TBI patients remains unclear. OBJECTIVE: To examine the level of access to rehabilitation after TBI, and its association with health and sociodemographic factors. METHOD: We conducted a longitudinal cohort study using Swedish nationwide healthcare and sociodemographic registers. We identified 15 880 TBI patients ≥18 years hospitalized ≥3 days from 2008 to 2012 who were stratified into 3 severity groups; grade I (n = 1366; most severe), grade II (n = 5228), and grade III (n = 9268; least severe). We examined registered contacts with specialized rehabilitation or geriatric care (for patients ≥65 years) during the hospital stay, and/or within 1 year post-discharge. We performed a generalized linear model analysis to estimate the risk ratio (RR) for receiving specialized rehabilitation or geriatric care after a TBI based on sociodemographic and health factors. RESULTS: Among TBI patients, 46/35% (grade I), 14/40% (grade II), and 5/18% (grade III) received specialized rehabilitation or geriatric care, respectively. Being currently employed or studying was positively associated (RR 1.7, 2.3), while living outside of a city area was negatively associated (RR 0.36, 0.79) with receiving specialized rehabilitation or geriatric care. Older age and a prior substance use disorder were negatively associated with receiving specialized rehabilitation (RR 0.51 and 0.81). CONCLUSION: Our results suggest insufficient and unequal access to rehabilitation for TBI patients, highlighting the importance of organizing and standardizing post-TBI rehabilitation to meet the needs of patients, regardless of their age, socioeconomic status, or living area.

The management of severe traumatic brain injury in the initial postinjury hours - current evidence and controversies.

PURPOSE OF REVIEW: To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the initial postinjury hours. RECENT FINDINGS: Prehospital management of sTBI should adhere to Advanced Trauma Life Support (ATLS) principles. Maintaining oxygen saturation and blood pressure within target ranges on-scene by anesthetist, emergency physician or trained paramedics has resulted in improved outcomes. Emergency department (ED) management prioritizes airway control, stable blood pressure, spinal immobilization, and correction of impaired coagulation. Noninvasive techniques such as optic nerve sheath diameter measurement, pupillometry, and transcranial Doppler may aid in detecting intracranial hypertension. Osmotherapy and hyperventilation are effective as temporary measures to reduce intracranial pressure (ICP). Emergent computed tomography (CT) findings guide surgical interventions such as decompressive craniectomy, or evacuation of mass lesions. There are no neuroprotective drugs with proven clinical benefit, and steroids and hypothermia cannot be recommended due to adverse effects in randomized controlled trials. SUMMARY: Advancement of the prehospital and ED care that include stabilization of physiological parameters, rapid correction of impaired coagulation, noninvasive techniques to identify raised ICP, emergent surgical evacuation of mass lesions and/or decompressive craniectomy, and temporary measures to counteract increased ICP play pivotal roles in the initial management of sTBI. Individualized approaches considering the underlying pathology are crucial for accurate outcome prediction.

Prehospital transportation of severe penetrating trauma victims in Sweden during the past decade: a police business?

INTRODUCTION: Sweden is facing a surge of gun violence that mandates optimized prehospital transport approaches, and a survey of current practice is fundamental for such optimization. Management of severe, penetrating trauma is time sensitive, and there may be a survival benefit in limiting prehospital interventions. An important aspect is unregulated transportation by police or private vehicles to the hospital, which may decrease time but may also be associated with adverse outcomes. It is not known whether transport of patients with penetrating trauma occurs outside the emergency medical services (EMS) in Sweden and whether it affects outcome. METHOD: This was a retrospective, descriptive nationwide study of all patients with penetrating trauma and injury severity scores (ISSs) ≥ 15 registered in the Swedish national trauma registry (SweTrau) between June 13, 2011, and December 31, 2019. We hypothesized that transport by police and private vehicles occurred and that it affected mortality. RESULT: A total of 657 patients were included. EMS transported 612 patients (93.2%), police 10 patients (1.5%), and private vehicles 27 patients (4.1%). Gunshot wounds (GSWs) were more common in police transport, 80% (n = 8), compared with private vehicles, 59% (n = 16), and EMS, 32% (n = 198). The Glasgow coma scale score (GCS) in the emergency department (ED) was lower for patients transported by police, 11.5 (interquartile range [IQR] 3, 15), in relation to EMS, 15 (IQR 14, 15) and private vehicles 15 (IQR 12.5, 15). The 30-day mortality for EMS was 30% (n = 184), 50% (n = 5) for police transport, and 22% (n = 6) for private vehicles. Transport by private vehicle, odds ratio (OR) 0.65, (confidence interval [CI] 0.24, 1.55, p = 0.4) and police OR 2.28 (CI 0.63, 8.3, p = 0.2) were not associated with increased mortality in relation to EMS. CONCLUSION: Non-EMS transports did occur, however with a low incidence and did not affect mortality. GSWs were more common in police transport, and victims had lower GCS scorescores when arriving at the ED, which warrants further investigations of the operational management of shooting victims in Sweden.

Preparation of pH-sensitive composite polyethersulfone membranes embedded by Ag(I) coordination polymer for the removal of cationic and anionic dyes.

A pH-sensitive polyethersulfone (PES) membrane was prepared with the aid of newly synthesized Ag(I) coordination polymer (Ag(I)-CP) particles. Indicating obvious adsorptive property toward dyes, the Ag(I)-based metalorganic framework (MOF) was selected to be used as an additive to improve the dye selectivity of PES membranes for both cationic and anionic dyes. The performance examination and characterization of prepared membranes indicated the influence of Ag(I)-CP in PES membrane improvement. The effect of feed pH approved the membrane response to pH changes in dye removal results. By adjusting feed pH based on pHpzc of Ag(I)-CP, it is possible to remove both anionic and cationic dyes (97% of acid orange 7 (AO) & and 100% of methylene blue (MB)) from the effluent along with an enhanced permeated flux. The results offered a synergism in embedding Ag(I)-CP in PES membrane in dye removal efficiency. The additive particles can be applied with their natural size (200-300 nm) without severe influence on the uniformity of the membrane morphology if the optimum Ag(I)-CP content is considered.

Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19.

A high proportion of patients with coronavirus disease 2019 (COVID-19) experience post-acute COVID-19, including neuropsychiatric symptoms. Objective signs of central nervous system (CNS) damage can be investigated using CNS biomarkers such as glial fibrillary acidic protein (GFAp), neurofilament light chain (NfL) and total tau (t-tau). We have examined whether CNS biomarkers can predict fatigue and cognitive impairment 3-6 months after discharge from the intensive care unit (ICU) in critically ill COVID-19 patients. Fifty-seven COVID-19 patients admitted to the ICU were included with analysis of CNS biomarkers in blood at the ICU and at follow up. Cognitive dysfunction and fatigue were assessed with the Montreal Cognitive Assessment (MoCA) and the Multidimensional Fatigue inventory (MFI-20). Elevated GFAp at follow-up 3-6 months after ICU discharge was associated to the development of mild cognitive dysfunction (p = 0.01), especially in women (p = 0.005). Patients who experienced different dimensions of fatigue at follow-up had significantly lower GFAp in both the ICU and at follow-up, specifically in general fatigue (p = 0.009), physical fatigue (p = 0.004), mental fatigue (p = 0.001), and reduced motivation (p = 0.001). Women showed a more pronounced decrease in GFAp compared to men, except for in mental fatigue where men showed a more pronounced GFAp decrease compared to women. NfL concentration at follow-up was lower in patients who experienced reduced motivation (p = 0.004). Our findings suggest that GFAp and NfL are associated with neuropsychiatric outcome after critical COVID-19.Trial registration The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29).

Interleukin-1 Receptor Antagonist as Therapy for Traumatic Brain Injury.

Traumatic brain injury is a common type of acquired brain injury of varying severity carrying potentially deleterious consequences for the afflicted individuals, families, and society. Following the initial, traumatically induced insult, cellular injury processes ensue. These are believed to be amenable to treatment. Among such injuries, neuroinflammation has gained interest and has become a specific focus for both experimental and clinical researchers. Neuroinflammation is elicited almost immediately following trauma, and extend for a long time, possibly for years, after the primary injury. In the acute phase, the inflammatory response is characterized by innate mechanisms such as the activation of microglia which among else mediates cytokine production. Among the earliest cytokines to emerge are the interleukin- (IL-) 1 family members, comprising, for example, the agonist IL-1ß and its competitive antagonist, IL-1 receptor antagonist (IL-1ra). Because of its early emergence following trauma and its increased concentrations also after human TBI, IL-1 has been hypothesized to be a tractable treatment target following TBI. Ample experimental data supports this, and demonstrates restored neurological behavior, diminished lesion zones, and an attenuated inflammatory response following IL-1 modulation either through IL-1 knock-out experiments, IL-1ß inhibition, or IL-1ra treatment. Of these, IL-1ra treatment is likely the most physiological. In addition, recombinant human IL-1ra (anakinra) is already approved for utilization across a few rheumatologic disorders. As of today, one randomized clinical controlled trial has utilized IL-1ra inhibition as an intervention and demonstrated its safety. Further clinical trials powered for patient outcome are needed in order to demonstrate efficacy. In this review, we summarize IL-1 biology in relation to acute neuroinflammatory processes following TBI with a particular focus on current evidence for IL-1ra treatment both in the experimental and clinical context.

Evaluation of Miethke M.scio Device Implantation for Intracranial Pressure Monitoring in Patients with Cerebrospinal Fluid Disorders.

BACKGROUND: Patients with complex shunt-related problems and varying diagnoses of cerebrospinal fluid (CSF) disturbance can present with headache and clinical symptoms that may be difficult to relate to underdrainage or overdrainage. Telemetric intracranial pressure (ICP) monitoring may assist in evaluating individual patients and assessing shunt function and adjustment. We report a case series of patients receiving a Miethke M.scio sensor. METHODS: Between June 2016 and August 2021, 14 patients older than 18 years with different diagnoses underwent ventriculoperitoneal shunt surgery and received a Miethke M.scio sensor. RESULTS: Patients had idiopathic intracranial hypertension (n = 3), obstructive hydrocephalus caused by tumors (n = 4), and malformations (n = 5). Headaches (71%) and visual impairment (50%) were the most common symptoms before surgery and 65% of the symptoms were improved after surgery. In total, 25 measurements were made and 11 of these led to changes in the shunt settings. Postoperative measurements were taken in 8 patients and the most common indication of ICP measurement was headache and/or control of the shunt settings. CONCLUSIONS: The Miethke M.scio is a safe and valuable device to use in shunt-treated patients, in particular those expected to need assessment of ICP monitoring postoperatively. Repeated ICP measurements can also assist in personalized adjustment of the shunt setting to optimize CSF flow in this diverse patient group. Future studies should include a standardized protocol with ICP measurements correlated to the symptoms and cause of CSF disturbances to provide better understanding of the dynamics of the ICP in each patient.

Myoclonus in patients with COVID-19: Findings of autoantibodies against brain structures in cerebrospinal fluid.

BACKGROUND AND PURPOSE: COVID-19 is associated with multiple neurological manifestations. The clinical presentation, trajectory, and treatment response for three cases of myoclonus during COVID-19 infection, with no previous neurological disease, are decsribed. METODS: Analysis of cerebrospinal fluid from the cases using indirect immunohistochemistry. RESULTS: Antibodies against rodent brain tissue, and similarities in staining patterns were observed, indicating the presence of antineuronal immunoglobulin G autoantibodies targeting astrocytes in the hippocampus. CONCLUSION: Our results demontrate cerebrospinal fluid antineuronal antibodies indicating an an autoimmune involvment in the pathogenesis in COVID-19 associated myoclonus.

Huge variability in restrictions of mobilization for patients with aneurysmal subarachnoid hemorrhage - A European survey of practice.

Introduction: One of the major goals of neurointensive care is to prevent secondary injuries following aSAH. Bed rest and patient immobilization are practiced in order to decrease the risk of DCI. Research question: To explore the current practices in place concerning the management of patients with aSAH, specifically, protocols and habits regarding restrictions of mobilization and HOB positioning. Material and methods: A survey was designed, modified, and approved by the panel of the Trauma & Critical Care section of the EANS to cover the practice of restrictions of patient mobilization and HOB positioning in patients with aSAH. Results: Twenty-nine physicians from 17 countries completed the questionnaire. The majority (79.3%) stated that non-secured aneurysm and the presence of an EVD were the factors related to the establishment of restriction of mobilization. The average duration of the restriction varied widely ranging between 1 and 21 days. The presence of an EVD (13.8%) was found to be the main reason to recommend restriction of HOB elevation. The average duration of restriction of HOB positioning ranged between 3 and 14 days. Rebleeding or complications related to CSF over-drainage were found to be related to these restrictions. Discussion and conclusion: Restriction of patient mobilization regimens vary widely in Europe. Current limited evidence does not support an increased risk of DCI rather the early mobilization might be beneficial. Large prospective studies and/or the initiative of a RCT are needed to understand the significance of early mobilization on the outcome of patients with aSAH.