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Objective: To evaluate the effects of the neurological "wake-up test" (NWT), defined as interruption of continuous propofol sedation and evaluation of the patient's level of consciousness, on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with severe subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI).Methods: A total of 127 NWT procedures in 21 severely brain-injured adult patients with either TBI (n = 12) or SAH (n = 9) were evaluated. ICP and CPP levels prior to, during and after the NWT procedure were recorded.Results: During the NWT, ICP increased from 13.4 +/- 6 mmHg at baseline to 22.7 +/- 12 (P < 0.05) and the CPP increased from 75.6 +/- 11 to 79.1 +/- 21 mmHg (P < 0.05) in TBI patients. Eight patients showed a reduced CPP during the NWT due to increased ICP. In SAH patients, ICP increased from 10.6 +/- 5 to 16.8 +/- 8 mmHg (P < 0.05) and the CPP increased from 76.9 +/- 13 to 84.6 +/- 15 mmHg (P < 0.05).Conclusion: When continuous propofol sedation was interrupted and NWT was performed in severely brain-injured patients, the mean ICP and CPP levels were modestly increased. A subset of patients showed more pronounced changes. To date, the role of the NWT in the neurointensive care of TBI and SAH patients is unclear. Although the NWT is safe in the majority of patients and may provide useful clinical information about the patient's level of consciousness, alternate monitoring methods are suggested in patients showing marked ICP and/or CPP changes during NWT. [ABSTRACT FROM AUTHOR]

Abstract: Approximately 4000 human beings experience a traumatic brain injury each day in the United States ranging in severity from mild to fatal. Improvements in initial management, surgical treatment, and neurointensive care have resulted in a better prognosis for traumatic brain injury patients but, to date, there is no available pharmaceutical treatment with proven efficacy, and prevention is the major protective strategy. Many patients are left with disabling changes in cognition, motor function, and personality. Over the past two decades, a number of experimental laboratories have attempted to develop novel and innovative ways to replicate, in animal models, the different aspects of this heterogenous clinical paradigm to better understand and treat patients after traumatic brain injury. Although several clinically-relevant but different experimental models have been developed to reproduce specific characteristics of human traumatic brain injury, its heterogeneity does not allow one single model to reproduce the entire spectrum of events that may occur. The use of these models has resulted in an increased understanding of the pathophysiology of traumatic brain injury, including changes in molecular and cellular pathways and neurobehavioral outcomes. This review provides an up-to-date and critical analysis of the existing models of traumatic brain injury with a view toward guiding and improving future research endeavors. [Copyright &y& Elsevier]

Adult rats were subjected to a moderate lateral fluid percussion injury (FPI), followed by survival periods of 2 and 12 h. Regional NMDA subtype glutamate, muscarinic acetylcholine and GABA[sub A] receptor binding in various brain regions was analysed by quantitative in vitro autoradiography and short-lived positron emission tomography tracers [[sup 11]C]cyano-dizocilpine, 4-N-[[sup 11]C]methylpiperidylbenzilate (4-N-[[sup 11]C]MPB), and [[sup 11]C]flumazenil, respectively. The binding potential (BP, B[sub max]/K[sub D]) was calculated. The data with [[sup 11]C]cyano-dizocilpine showed a significant decrease in BP bilaterally for the frontoparietal cortex and hippocampus at both time points, in comparison with that of the sham-operated controls. At 12 h the decrease was significantly more prominent for the ipsilateral cortex and hippocampus than for the contralateral side. The BP of 4-N-[[sup 11]C]MPB was significantly decreased after 2 h for the trauma-side hippocampus, and after 12 h it had decreased for the trauma-site cortex and the bilateral hippocampus. The [[sup 11]C]flumazenil exhibited a significant decrease in BP for the trauma-site cortex and the underlying hippocampus by 2 h after the traumatic brain injury. After 12 h a significantly decreased BP was observed only for the trauma-site cortex. The finding of a decreased BP demonstrates the involvement of these receptor systems in the development of cellular dysfunction, which is widespread and not limited to the site of lateral FPI. [ABSTRACT FROM AUTHOR]

Background: Cortical contusions are common in moderate-severe traumatic brain injury (TBI). Cortical contusions often expand, potentially causing neuro-worsening several hours to days post-trauma. While contusion expansion (CE) may affect outcome, potential clinical and radiological markers that can predict CE have been insufficiently explored. In the present single-center retrospective observational cohort study, we evaluated clinical outcome by the Glasgow Outcome Scale extended (GOSE) scale and evaluated risk factor for CE., Method: Adult TBI patients > 18 years of age, and of all injury severities, were included. Main variables of interest were low platelet count, defined as < 150 × 10 9 /L, presence of bifrontal contusions and CE, defined as absolute contusion volume increase in cm 3 . Factors associated with CE and clinical outcome according to GOSE were analyzed., Results: Between 2012-2022, 272 patients were included. Contusion size on admission correlated positively with CE, as did the Marshall and Rotterdam radiological classification scores. Bifrontal contusions were significantly larger at admission, experienced larger CE, and had a worse outcome than contusions in other locations. Patients with a platelet count < 150 × 10 9 /L experienced a greater volume CE and had a worse outcome when compared to patients with a normal platelet count. In a multivariate analysis, CE remained significantly associated with a poor outcome six months post- injury., Conclusion: Contusion volume at admission, Marshall CT classification and Rotterdam CT score, positively correlated to CE. Bifrontal contusions and a platelet count < 150 × 10 9 /L were associated with CE, and a poor clinical outcome. Large CE volumes were associated with a worse clinical outcome, and CE was per se associated with outcome in a multivariate analysis. Management of these risk factors for CE in the acute post-injury setting may be needed to attenuate contusion expansion and to improve clinical outcome in TBI patients suffering from cortical contusion injuries., (© 2024. The Author(s).)

Introduction: A subgroup of severe Traumatic Brain Injury (TBI) patients, known as ultra-severe (us-TBI), is most commonly defined as a post-resuscitation Glasgow Coma Scale (GCS) of 3-5. There is uncertainty on whether these critically injured patients can benefit from neurosurgical intervention., Research Question: The available evidence regarding the decision-making and outcome following management of us-TBI patients is critically reviewed., Material and Methods: Selected databases (PubMed, Google Scholar, Scopus and Cochrane Library) were searched from 1979 to May 2024 for publications on us-TBI patients, with a focus on treatment strategy, mortality and functional outcomes. Inclusion criteria were adult patients >18 years old with closed head trauma and admission post-resuscitation GCS 3-5. Studies were independently assessed for inclusion by two reviewers, and potential disagreements were solved by consensus., Results: Where such data could be extracted, mortality rate was 27-100%, and favorable outcome was observed in 4-30% of us-TBI patients. While early aggressive neurosurgical management was associated with decreased mortality, a high proportion of patients survived with unfavorable functional status., Discussion and Conclusion: With supportive care only, outcome of patients with us-TBI is almost universally poor. Early and aggressive neurosurgical intervention in addition to best medical management can lead to favorable functional outcome in selected cases particularly in younger patients with an initial GCS>3 and traumatic mass lesions. There is insufficient data regarding the effectiveness of neurosurgical management on the outcome of us-TBI patients. and the decision to initiate treatment should be based on an individual basis., Competing Interests: Not applicable. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Sports-related concussions may cause white matter injuries and persistent post-concussive symptoms (PPCS). We hypothesized that athletes with PPCS would have neurocognitive impairments and white matter abnormalities that could be revealed by advanced neuroimaging using ultra-high field strength diffusion tensor (DTI) and diffusion kurtosis (DKI) imaging metrics and cerebrospinal fluid (CSF) biomarkers. A cohort of athletes with PPCS severity limiting the ability to work/study and participate in sport school and/or social activities for ≥6 months completed 7T magnetic resonance imaging (MRI) (morphological T1-weighed volumetry, DTI and DKI), extensive neuropsychological testing, symptom rating, and CSF biomarker sampling. Twenty-two athletes with PPCS and 22 controls were included. Concussed athletes performed below norms and significantly lower than controls on all but one of the psychometric neuropsychology tests. Supratentorial white and gray matter, as well as hippocampal volumes did not differ between concussed athletes and controls. However, of the 72 examined white matter tracts, 16% of DTI and 35% of DKI metrics (in total 28%) were significantly different between concussed athletes and controls. DKI fractional anisotropy and axial kurtosis were increased, and DKI radial diffusivity and radial kurtosis decreased in concussed athletes when compared with controls. CSF neurofilament light (NfL; an axonal injury marker), although not glial fibrillary acidic protein, correlated with several diffusion metrics. In this first 7T DTI and DKI study investigating PPCS, widespread microstructural alterations were observed in the white matter, correlating with CSF markers of axonal injury. More white matter changes were observed using DKI than using DTI. These white matter alterations may indicate persistent pathophysiological processes following concussion in sport.

Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood-brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [ 18 F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R 2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [ 18 F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.

Introduction: Traumatic brain injury to thalamo-cortical pathways is associated with posttraumatic morbidity. Diffuse mechanical forces to white matter tracts and deep grey matter regions induce an inflammatory response and vascular damage resulting in progressive neurodegeneration. Pro-inflammatory cytokines, including interleukin-1β (IL-1β), may contribute to the link between inflammation and the injured capillary network after TBI. This study investigates whether IL-1β is a key contributor to capillary alterations and changes in pericyte coverage in the thalamus and cortex after TBI., Methods: Animals were subjected to central fluid percussion injury (cFPI), a model of TBI causing widespread axonal and vascular pathology, or sham injury and randomized to receive a neutralizing anti-IL-1β or a control, anti-cyclosporin A antibody, at 30 min post-injury. Capillary length and pericyte coverage of cortex and thalamus were analyzed by immunohistochemistry at 2- and 7-days post-injury., Results and Conclusion: Our results show that early post-injury attenuation of IL-1β dependent inflammatory signaling prevents capillary damage by increasing pericyte coverage in the thalamus., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Özen, Clausen, Flygt, Marklund and Paul.)

Introduction: The American Association of Neurologic Surgeons guidelines on the management of traumatic spinal cord injury (SCI), updated in 2013, focus on spinal cord perfusion, early decompressive surgery, and venous thromboembolism (VTE) prophylaxis to improve neurological outcome., Research Question: How neurocritical care and initial management have changed with the implementation of updated management guidelines, focusing on guidelines adherence and neurological outcome., Material and Methods: Systemic physiological variables, time to neurosurgical treatment and VTE prophylaxis, and neurological outcome, were retrospectively collected from adult patients treated for cervical SCI 2001-2021., Results: Fifty-two patients were included. Mean arterial blood pressure (MAP) was significantly higher after 2013 (86±9.9 mmHg) when compared to before 2013 (79±9.9 mmHg), p = 0.041. Median time to surgery was 41 h before, and 20 h after 2013 (p = 0.029). Time to VTE prophylaxis was six days before and four days after 2013. Most neurocritical care complications were less commonly observed after 2013. Despite improved adherence to treatment goals, 44 % of MAP levels were below target, and 33% of patients were operated beyond 24h post-injury. Neurological outcome was not improved after implementation of the revised guidelines., Discussion and Conclusion: While implementation of the revised 2013 guidelines improved most aspects of the acute SCI management, many guideline targets were not met in a large subset of patients. Strict adherence to the acute neurocritical management goals, and early surgical treatment, is likely crucial when aiming to improve SCI outcome., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Niklas Marklund reports a relationship with Polarcool Inc that includes: consulting or advisory. Niklas Marklund reports a relationship with Teqcool that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Mild traumatic brain injury is common in children and it can be challenging to accurately identify those in need of urgent medical intervention. The Scandinavian guidelines for management of minor and moderate head trauma in children, the Scandinavian Neurotrauma Committee guideline 2016 (SNC16), were developed to aid in risk stratification and decision-making in Scandinavian emergency departments (EDs). This guideline has been validated externally with encouraging results, but internal validation in the intended healthcare system is warranted prior to broad clinical implementation., Objective: We aim to validate the diagnostic accuracy of the SNC16 to predict clinically important intracranial injuries (CIII) in paediatric patients suffering from blunt head trauma, assessed in EDs in Sweden and Norway., Methods and Analysis: This is a prospective, pragmatic, observational cohort study. Children (aged 0-17 years) with blunt head trauma, presenting with a Glasgow Coma Scale of 9-15 within 24 hours postinjury at an ED in 1 of the 16 participating hospitals, are eligible for inclusion. Included patients are assessed and managed according to the clinical management routines of each hospital. Data elements for risk stratification are collected in an electronic case report form by the examining doctor. The primary outcome is defined as CIII within 1 week of injury. Secondary outcomes of importance include traumatic CT findings, neurosurgery and 3-month outcome. Diagnostic accuracy of the SNC16 to predict endpoints will be assessed by point estimate and 95% CIs for sensitivity, specificity, likelihood ratio, negative predictive value and positive predictive value., Ethics and Dissemination: The study is approved by the ethical board in both Sweden and Norway. Results from this validation will be published in scientific journals, and a tailored development and implementation process will follow if the SNC16 is found safe and effective., Trial Registration Number: NCT05964764., Competing Interests: Competing interests: JU, NM and OC are members of the SNC committee, a non-profit organisation independent from financial company support, who are responsible for the SNC16 guidelines. None of the authors have any financial competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Senescence is a negative prognostic factor for outcome and recovery following traumatic brain injury (TBI). TBI-induced white matter injury may be partially due to oligodendrocyte demise. We hypothesized that the regenerative capacity of oligodendrocyte precursor cells (OPCs) declines with age. To test this hypothesis, the regenerative capability of OPCs in young [(10 weeks ±2 (SD)] and aged [(62 weeks ±10 (SD)] mice was studied in mice subjected to central fluid percussion injury (cFPI), a TBI model causing widespread white matter injury. Proliferating OPCs were assessed by immunohistochemistry for the proliferating cell nuclear antigen (PCNA) marker and labeled by 5-ethynyl-2'-deoxyuridine (EdU) administered daily through intraperitoneal injections (50 mg/kg) from day 2 to day 6 after cFPI. Proliferating OPCs were quantified in the corpus callosum and external capsule on day 2 and 7 post-injury (dpi). The number of PCNA/Olig2-positive and EdU/Olig2-positive cells were increased at 2dpi (p < .01) and 7dpi (p < .01), respectively, in young mice subjected to cFPI, changes not observed in aged mice. Proliferating Olig2+/Nestin+ cells were less common (p < .05) in the white matter of brain-injured aged mice, without difference in proliferating Olig2+/PDGFRα+ cells, indicating a diminished proliferation of progenitors with different spatial origin. Following TBI, co-staining for EdU/CC1/Olig2 revealed a reduced number of newly generated mature oligodendrocytes in the white matter of aged mice when compared to the young, brain-injured mice (p < .05). We observed an age-related decline of oligodendrogenesis following experimental TBI that may contribute to the worse outcome of elderly patients following TBI., (© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)

Introduction: Sport-related concussions (SRC) have been a concern in all sports, including soccer. The long-term effects of soccer-related head injuries are a public health concern. The Concussion in Sport Group (CISG) released a consensus statement in 2017 and several soccer governing associations have published their own SRC guidelines while referring to it but it is unclear whether this has been universally adopted., Research Question: We aimed to investigate whether guidelines published by soccer associations have any discrepancies; and the extent to which they follow the CISG recommendations., Materials and Methods: A scoping review of available soccer-specific SRC guidelines was performed via databases PubMed, Google Scholar, and official soccer association websites via web browser Google. The inclusion criteria were soccer-specific SRC guidelines. Comparisons between guidelines were made concerning the following index items: initial (on-site) assessment, removal from play, re-evaluation with neuroimaging, return-to-sport protocol, special populations, and education., Results: Nine soccer associations with available guidelines were included in this review. Guidelines obtained were from official associations in the United Kingdom, United States of America, Canada, Australia, and New Zealand. When compared to each other and the CISG recommendations, discrepancies were found within guidelines regarding the index items. Additionally, major soccer associations in some countries famous for soccer were found to have not published any publicly available guidelines., Discussion and Conclusion: SRC guidelines from different soccer associations contain discrepancies which may be detrimental to athletes, both short and long-term. We recommend that all major soccer governing associations publish guidelines that are standardised and accessible to all athletes., Competing Interests: The authors declare no financial conflicts of interest., (© 2024 The Authors.)

Background: All available recommendations about the management of antithrombotic therapies (ATs) in patients who experienced traumatic brain injury (TBI) are mainly based on expert opinion because of the lack of strength in the available evidence-based medicine. Currently, the withdrawal and the resumption of AT in these patients is empirical, widely variable, and based on the individual assessment of the attending physician. The main difficulty is to balance the thrombotic and hemorrhagic risks to improve patient outcome., Methods: Under the endorsement of the Neurotraumatology Section of Italian Society of Neurosurgery, the Italian Society for the Study about Haemostasis and Thrombosis, the Italian Society of Anaesthesia, Analgesia, Resuscitation, and Intensive Care, and the European Association of Neurosurgical Societies, a working group (WG) of clinicians completed two rounds of questionnaires, using the Delphi method, in a multidisciplinary setting. A table for thrombotic and bleeding risk, with a dichotomization in high risk and low risk, was established before questionnaire administration. In this table, the risk is calculated by matching different isolated TBI (iTBI) scenarios such as acute and chronic subdural hematomas, extradural hematoma, brain contusion (intracerebral hemorrhage), and traumatic subarachnoid hemorrhage with patients under active AT treatment. The registered indication could include AT primary prevention, cardiac valve prosthesis, vascular stents, venous thromboembolism, and atrial fibrillation., Results: The WG proposed a total of 28 statements encompassing the most common clinical scenarios about the withdrawal of antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients who experienced blunt iTBI. The WG voted on the grade of appropriateness of seven recommended interventions. Overall, the panel reached an agreement for 20 of 28 (71%) questions, deeming 11 of 28 (39%) as appropriate and 9 of 28 (32%) as inappropriate interventions. The appropriateness of intervention was rated as uncertain for 8 of 28 (28%) questions., Conclusions: The initial establishment of a thrombotic and/or bleeding risk scoring system can provide a vital theoretical basis for the evaluation of effective management in individuals under AT who sustained an iTBI. The listed recommendations can be implemented into local protocols for a more homogeneous strategy. Validation using large cohorts of patients needs to be developed. This is the first part of a project to update the management of AT in patients with iTBI., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Introduction: Planning cranioplasty (CPL) in patients with suspected or proven post-traumatic hydrocephalus (PTH) poses a significant management challenge due to a lack of clear guidance., Research Question: This project aims to create a European document to improve adherence and adapt to local protocols based on available resources and national health systems., Methods: After a thorough non-systematic review, a steering committee (SC) formed a European expert panel (EP) for a two-round questionnaire using the Delphi method. The questionnaire employed a 9-point Likert scale to assess the appropriateness of statements inherent to two sections: "Diagnostic criteria for PTH" and "Surgical strategies for PTH and cranial reconstruction.", Results: The panel reached a consensus on 29 statements. In the "Diagnostic criteria for PTH" section, five statements were deemed "appropriate" (consensus 74.2-90.3 %), two were labeled "inappropriate," and seven were marked as "uncertain."In the "Surgical strategies for PTH and cranial reconstruction" section, four statements were considered "appropriate" (consensus 74.2-90.4 %), six were "inappropriate," and five were "uncertain.", Discussion and Conclusion: Planning a cranioplasty alongside hydrocephalus remains a significant challenge in neurosurgery. Our consensus conference suggests that, in patients with cranial decompression and suspected hydrocephalus, the most suitable diagnostic approach involves a combination of evolving clinical conditions and neuroradiological imaging. The recommended management sequence prioritizes cranial reconstruction, with the option of a ventriculoperitoneal shunt when needed, preferably with a programmable valve. We strongly recommend to adopt local protocols based on expert consensus, such as this, to guide patient care., Competing Interests: No conflict of interest is to be disclosed by Salvatore Chibbaro, Thomas Sauvigny, Ivan Timofeev, Harry Mee, and Ismail Zaed. Corrado Iaccarino received educational grants from 10.13039/100009006Integra Lifescience. Franco Servadei received consultancy and speaker fees from Finceramica, Integra Life Sciences, and Upsurgeon. Silvio Franchetti received education grants producing HA., (© 2024 The Authors.)

Background: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies., Methods: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted., Results: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak)., Conclusions: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients., (© 2024. The Author(s).)

Introduction: A blood-based biomarker (BBBM) test could help to better stratify patients with traumatic brain injury (TBI), reduce unnecessary imaging, to detect and treat secondary insults, predict outcomes, and monitor treatment effects and quality of care., Research Question: What evidence is available for clinical applications of BBBMs in TBI and how to advance this field?, Material and Methods: This narrative review discusses the potential clinical applications of core BBBMs in TBI. A literature search in PubMed, Scopus, and ISI Web of Knowledge focused on articles in English with the words "traumatic brain injury" together with the words "blood biomarkers", "diagnostics", "outcome prediction", "extracranial injury" and "assay method" alone-, or in combination., Results: Glial fibrillary acidic protein (GFAP) combined with Ubiquitin C-terminal hydrolase-L1(UCH-L1) has received FDA clearance to aid computed tomography (CT)-detection of brain lesions in mild (m) TBI. Application of S100B led to reduction of head CT scans. GFAP may also predict magnetic resonance imaging (MRI) abnormalities in CT-negative cases of TBI. Further, UCH-L1, S100B, Neurofilament light (NF-L), and total tau showed value for predicting mortality or unfavourable outcome. Nevertheless, biomarkers have less role in outcome prediction in mTBI. S100B could serve as a tool in the multimodality monitoring of patients in the neurointensive care unit., Discussion and Conclusion: Largescale systematic studies are required to explore the kinetics of BBBMs and their use in multiple clinical groups. Assay development/cross validation should advance the generalizability of those results which implicated GFAP, S100B and NF-L as most promising biomarkers in the diagnostics of TBI., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Iftakher Hossain reports financial support was provided by The Finnish medical Foundation. Peter Hutchinson reports financial support was provided by 10.13039/501100000297Royal College of Surgeons of England. Iftakher Hossain reports financial support was provided by The 10.13039/501100007417Paulo Foundation. Iftakher Hossain reports financial support was provided by The 10.13039/501100003125Finnish Cultural Foundation. Niklas Marklund reports financial support was provided by 10.13039/501100011077Skåne University Hospital ALF funds. Niklas Marklund reports financial support was provided by 10.13039/501100017237Hans-Gabriel af Trolle Wachtmeister Foundation. Niklas Marklund reports financial support was provided by Swedish 10.13039/501100003792Brain Foundation. Peter Hutchinson reports a relationship with NIHR Cambridge Clinical Research Facility, Addenbrookes Hospital that includes: funding grants., (© 2023 The Authors.)

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., Competing Interests: Data AvailabilityData may be obtained from a third party and are not publicly available. The Public Access to Information and Secrecy Act in Sweden prohibits us from making individual level data publicly available due to ethical concerns about identification. Researchers who are interested in replicating our work can apply for individual level data from: Statistics Sweden (mikrodata@scb.se) for data from the Total Population Register and the Longitudinal Integrated database for Health Insurance and Labour Market Studies; The National Board of Health and Welfare (registerservice@socialstyrelsen.se) for data from The Patient Register and Cause of Death Register. Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N.M. is scientific advisor for PolarCool Inc, outside the submitted work. HL reports receiving grants from Shire Pharmaceuticals; personal fees from and serving as a speaker for Medice, Shire/Takeda Pharmaceuticals, and Evolan Pharma AB; and sponsorship for a conference on attention-deficit/hyperactivity disorder from Shire/Takeda Pharmaceuticals and Evolan Pharma AB, all outside the submitted work. The other authors have no competing/conflict of interests to declare.