Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial.

BACKGROUND: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. METHODS: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. FINDINGS: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). INTERPRETATION: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. FUNDING: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.

Adult-onset epilepsy and risk of traumatic brain injury: a nationwide cohort study.

BACKGROUND: A knowledge gap exists regarding the risk of traumatic brain injury (TBI) in patients with epilepsy. METHODS: Patients with adult-onset epilepsy during 2005-2018 in Finland were studied using retrospective longitudinal national registry-linkage design. Patients with epilepsy (n=35 686; 51% men; mean age 56.6 years) were 1:1 matched to non-epileptic controls by age, sex, comorbidity burden and cohort entry year. The primary outcome was TBI leading to admission or death, secondary outcomes were TBI admission, fatal TBI, acute neurosurgical operations (ANOs) for TBI and TBI recurrence. RESULTS: The cumulative rate of the primary endpoint was 1.2% at 1 year, 5.6% at 10 years and 7.3% at 14 years in the epilepsy group versus 2.9% at 14 years in the matched controls (HR=3.77; p<0.0001). Epilepsy was associated with increased risk of TBI admission (6.9% vs 2.7%; HR=3.96; p<0.0001), ANOs (1.3% vs 0.4%; HR=7.00; p<0.0001) and fatal TBI (1.3% vs 0.5%; HR=3.82; p<0.0001), during follow-up. Competing risk analyses confirmed the association of epilepsy with all outcomes (p<0.0001). Epilepsy was associated with TBI recurrence during follow-up (HR 1.72; p=0.002). CONCLUSION: Patients with adult-onset epilepsy have a significantly increased risk of severe and fatal TBI. The results underline the importance of TBI prevention in epilepsy.

Plasma neurofilament light admission levels and development of axonal pathology in mild traumatic brain injury.

BACKGROUND: It is known that blood levels of neurofilament light (NF-L) and diffusion-weighted magnetic resonance imaging (DW-MRI) are both associated with outcome of patients with mild traumatic brain injury (mTBI). Here, we sought to examine the association between admission levels of plasma NF-L and white matter (WM) integrity in post-acute stage DW-MRI in patients with mTBI. METHODS: Ninety-three patients with mTBI (GCS ≥ 13), blood sample for NF-L within 24 h of admission, and DW-MRI ≥ 90 days post-injury (median = 229) were included. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized WM tracts of the whole brain. Outcome was assessed using the Extended Glasgow Outcome Scale (GOSE) at the time of imaging. Patients were divided into CT-positive and -negative, and complete (GOSE = 8) and incomplete recovery (GOSE < 8) groups. RESULTS: The levels of NF-L and FA correlated negatively in the whole cohort (p = 0.002), in CT-positive patients (p = 0.016), and in those with incomplete recovery (p = 0.005). The same groups showed a positive correlation with mean MD, AD, and RD (p < 0.001-p = 0.011). In CT-negative patients or in patients with full recovery, significant correlations were not found. CONCLUSION: In patients with mTBI, the significant correlation between NF-L levels at admission and diffusion tensor imaging (DTI) measurements of diffuse axonal injury (DAI) over more than 3 months suggests that the early levels of plasma NF-L may associate with the presence of DAI at a later phase of TBI.

Post-acute blood biomarkers and disease progression in traumatic brain injury.

There is substantial interest in the potential for traumatic brain injury to result in progressive neurological deterioration. While blood biomarkers such as glial fibrillary acid protein (GFAP) and neurofilament light have been widely explored in characterizing acute traumatic brain injury (TBI), their use in the chronic phase is limited. Given increasing evidence that these proteins may be markers of ongoing neurodegeneration in a range of diseases, we examined their relationship to imaging changes and functional outcome in the months to years following TBI. Two-hundred and three patients were recruited in two separate cohorts; 6 months post-injury (n = 165); and >5 years post-injury (n = 38; 12 of whom also provided data ∼8 months post-TBI). Subjects underwent blood biomarker sampling (n = 199) and MRI (n = 172; including diffusion tensor imaging). Data from patient cohorts were compared to 59 healthy volunteers and 21 non-brain injury trauma controls. Mean diffusivity and fractional anisotropy were calculated in cortical grey matter, deep grey matter and whole brain white matter. Accelerated brain ageing was calculated at a whole brain level as the predicted age difference defined using T1-weighted images, and at a voxel-based level as the annualized Jacobian determinants in white matter and grey matter, referenced to a population of 652 healthy control subjects. Serum neurofilament light concentrations were elevated in the early chronic phase. While GFAP values were within the normal range at ∼8 months, many patients showed a secondary and temporally distinct elevations up to >5 years after injury. Biomarker elevation at 6 months was significantly related to metrics of microstructural injury on diffusion tensor imaging. Biomarker levels at ∼8 months predicted white matter volume loss at >5 years, and annualized brain volume loss between ∼8 months and 5 years. Patients who worsened functionally between ∼8 months and >5 years showed higher than predicted brain age and elevated neurofilament light levels. GFAP and neurofilament light levels can remain elevated months to years after TBI, and show distinct temporal profiles. These elevations correlate closely with microstructural injury in both grey and white matter on contemporaneous quantitative diffusion tensor imaging. Neurofilament light elevations at ∼8 months may predict ongoing white matter and brain volume loss over >5 years of follow-up. If confirmed, these findings suggest that blood biomarker levels at late time points could be used to identify TBI survivors who are at high risk of progressive neurological damage.

Blood-based biomarkers and traumatic brain injury-A clinical perspective.

Blood-based biomarkers are promising tools to complement clinical variables and imaging findings in the diagnosis, monitoring and outcome prediction of traumatic brain injury (TBI). Several promising biomarker candidates have been found for various clinical questions, but the translation of TBI biomarkers into clinical applications has been negligible. Measured biomarker levels are influenced by patient-related variables such as age, blood-brain barrier integrity and renal and liver function. It is not yet fully understood how biomarkers enter the bloodstream from the interstitial fluid of the brain. In addition, the diagnostic performance of TBI biomarkers is affected by sampling timing and analytical methods. In this focused review, the clinical aspects of glial fibrillary acidic protein, neurofilament light, S100 calcium-binding protein B, tau and ubiquitin C-terminal hydrolase-L1 are examined. Current findings and clinical caveats are addressed.

Changing epidemiology of traumatic brain injury among the working-aged in Finland: Admissions and neurosurgical operations.

BACKGROUND: Recent studies from Finland have highlighted an increase in the incidence of traumatic brain injuries (TBI) in older age groups and high overall mortality. We performed a comprehensive study on the changing epidemiology of TBI focusing on the acute events in the Finnish working-age population. METHODS: Nationwide databases were searched for all emergency ward admissions with a TBI diagnosis for persons of 16-69 years of age during 2004-2018. RESULTS: In the Finnish working-age population, there were 52,487,099 person-years, 38,810 TBI-related hospital admissions, 4664 acute neurosurgical operations (ANO), and 2247 cases of in-hospital mortality (IHM). The TBI-related hospital admission incidence was 94/100,000 person-years in men, 44/100,000 in women, and 69/100,000 overall. The incidence rate of admissions increased in women, while in men and overall, the rate decreased. The incidence rate increased in the group of 60-69 years in both genders. Lowest incidence rates were observed in the age group of 30-39 years. Occurrence risk for TBI admission was higher in men in all age groups. Trends of ANOs decreased overall, while decompressive craniectomy was the only operation type in which a rise in incidence was found. Evacuation of acute subdural hematoma was the most common ANO. Mean length of stay and IHM rate halved during the study years. CONCLUSIONS: In Finland, the epidemiology of acute working-aged TBI has significantly changed. The rates of admission incidences, ANOs, and IHM nowadays represent the lower end of the range of these acute events reported in the western world.

Cross-national examination of adolescent suicidal behavior: a pooled and multi-level analysis of 193,484 students from 53 LMIC countries.

INTRODUCTION: Suicide is a leading cause of adolescent mortality worldwide. We aimed to estimate the prevalence and identify individual-level and country-level factors which might explain the variability in suicidal behavior among students in 53 low to middle income countries. METHODS: We used data on adolescents aged 12-16 years from the Global School-based Student Health Surveys from 2009-2016. The suicidal behaviors investigated included suicide ideation, suicidal planning and suicide attempt. The prevalence was estimated for 53 countries, while a multilevel logistic regression analysis (33 countries) was used to investigate the associations of these behaviors with individual and country-level contextual risk factors. The contextual variables included the Gini Coefficient, Gross Domestic Product per capita, pupil-to-teacher ratios, population density, homicide rates, law criminalizing suicide and the night light index. RESULTS: The overall prevalence of suicide ideation, making a plan and suicide attempt were 10.4%, 10.3% and 11.0%, respectively. The highest prevalence rates reported were from the Americas. The strongest risk factors associated with suicidal behavior included anxiety, loneliness, no close friends and the substance abuse. Among the country level variables, the night light index was associated with making a suicide plan and attempting suicide. CONCLUSION: The non-significant country level findings were not entirely surprising given the mixed results from prior studies. Additional knowledge is thus achieved with regard to country level factors associated with suicidal behavior across adolescent populations.

Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury.

BACKGROUND: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting. METHODS: Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011-2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13-15 was classified as mild (mTBI); GCS 9-12 as moderate (moTBI) and GCS 3-8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed. RESULTS: Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls. CONCLUSIONS: S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting.

Cerebral Venous Thrombosis: Finnish Nationwide Trends.

BACKGROUND AND PURPOSE: Epidemiology of cerebral venous thrombosis (CVT) has been reported to be changing. Because long-term nationwide data are needed to confirm this, we studied CVT occurrence between 2005 and 2014 in Finland. METHODS: All acute CVT admissions were retrieved from a mandatory registry covering mainland Finland. Patients aged ≥18 years were included. One admission per patient was allowed. RESULTS: We identified 563 patients with CVT (56.5% women). Overall incidence was 1.32/100 000 (95% CI, 1.21-1.43) per year with a 5.0% annual increase. In people <55 years of age, incidence was 0.92/100 000 (0.76-1.10) for men and 1.65/100 000 (1.43-1.89) for women, whereas for those 55 years or older incidence was 1.61 (1.34-1.91) for men and 1.17 (0.96-1.41) for women. In-hospital mortality was 2.1% with no sex difference. One-year mortality was 7.9%. Long-term mortality was higher in men (adjusted hazard ratio, 1.61 [1.09-2.38]) and in older patients (1.95 [1.69-2.24]; per 10-year increment). CONCLUSIONS: Overall incidence of CVT in Finland was similar to that reported in the Netherlands and in Australia. There was a 5.0% yearly increase in the rate of admissions while in-hospital mortality was low. Sex-specific incidence rates differed markedly between younger and older people. Long-term mortality increased with age and was higher in men.

High-Risk Periods for Adult Traumatic Brain Injuries: A Nationwide Population-Based Study.

INTRODUCTION: There is minimal existing available information on nationwide seasonal peaks in traumatic brain injuries (TBIs). This lack of information is an impediment to the effective development of prevention programs, societal policies, and hinders the resourcing of medical emergency services. Our current aim is to study nationwide population-based high-risk periods TBI over a 15-year study period in Finland. METHODS: Nationwide databases were searched for all admissions with a TBI diagnosis and later for deaths of persons ≥16 years of age during 2004-2018. The search included all hospitals that provide acute TBI care in Finland. RESULTS: The study period included 69,231 TBI-related hospital admissions (men = 62%). We found that for men, the highest rate of TBIs occurred on Saturdays, whereas women experience the highest rate of TBIs on Mondays. The highest rate of TBIs in men occurred in July, while women experienced the highest rate of TBIs in January. TBI-related hospital admissions (incidence risk ratio [IRR] 1.090, 95% CI 1.07-1.11, p < 0.0001) and mortality within 30 days after TBI (hazard ratio [HR] 1.057, 95% CI 1.001-1.116, p = 0.0455) were more common on public holidays and weekends than on weekdays. There was an increasing trend in the proportion of TBI-related hospital admissions occurring on public holidays and weekends from 2004 (31.5%) to 2018 (33.4%) (p = 0.0007). In summer months, TBI-related hospital admissions (IRR 1.10, 95% CI 1.08-1.12, p < 0.0001) and 30-day mortality (HR 1.069, 95% CI 1.010-1.131, p = 0.0211) were more common than in other months. TBIs occurred more often in younger and healthier individuals on these index days and times. In terms of specific public holidays, the TBI risk was overall higher on New Year's Eves and Days (IRR 1.40, 95% CI 1.25-1.58, p < 0.0001) and Midsummer's Eves and Days (IRR 1.36, 95% CI 1.20-1.54, p < 0.0001), compared to nonworking days. This finding was significant in both genders. CONCLUSIONS: TBI-related hospital admissions and mortality were more common on public holidays, weekends, and in summer months in Finland. People who sustained TBIs on these days were on average younger and healthier. The occurrence of TBIs on public holidays and weekends is increasing at an alarming rate.

How do we identify the crashing traumatic brain injury patient - the neurosurgeon's view.

PURPOSE OF REVIEW: To provide an overview on recent advances in the field of assessment and monitoring of patients with severe traumatic brain injury (sTBI) in neurocritical care from a neurosurgical point of view. RECENT FINDINGS: In high-income countries, monitoring of patients with sTBI heavily relies on multimodal neurocritical parameters, nonetheless clinical assessment still has a solid role in decision-making. There are guidelines and consensus-based treatment algorithms that can be employed in both absence and presence of multimodal monitoring in the management of patients with sTBI. Additionally, novel dynamic monitoring options and machine learning-based prognostic models are introduced. Currently, the acute management and treatment of secondary injury/insults is focused on dealing with the objective evident pathology. An ongoing paradigm shift is emerging towards more proactive treatment of neuroworsening as soon as premonitory signs of deterioration are detected. SUMMARY: Based on the current evidence, serial clinical assessment, neuroimaging, intracranial and cerebral perfusion pressure and brain tissue oxygen monitoring are key components of sTBI care. Clinical assessment has a crucial role in identifying the crashing patient with sTBI, especially from a neurosurgical standpoint. Multimodal monitoring and clinical assessment should be seen as complementary evaluation methods that support one another.

Multiple formin proteins participate in glioblastoma migration.

BACKGROUND: The prognosis of glioblastoma remains poor, related to its diffuse spread within the brain. There is an ongoing search for molecular regulators of this particularly invasive behavior. One approach is to look for actin regulating proteins that might be targeted by future anti-cancer therapy. The formin family of proteins orchestrates rearrangement of the actin cytoskeleton in multiple cellular processes. Recently, the formin proteins mDia1 and mDia2 were shown to be expressed in glioblastoma in vitro, and their function could be modified by small molecule agonists. This finding implies that the formins could be future therapeutic targets in glioblastoma. METHODS: In cell studies, we investigated the changes in expression of the 15 human formins in primary glioblastoma cells and commercially available glioblastoma cell lines during differentiation from spheroids to migrating cells using transcriptomic analysis and qRT-PCR. siRNA mediated knockdown of selected formins was performed to investigate whether their expression affects glioblastoma migration. Using immunohistochemistry, we studied the expression of two formins, FHOD1 and INF2, in tissue samples from 93 IDH-wildtype glioblastomas. Associated clinicopathological parameters and follow-up data were utilized to test whether formin expression correlates with survival or has prognostic value. RESULTS: We found that multiple formins were upregulated during migration. Knockdown of individual formins mDia1, mDia2, FHOD1 and INF2 significantly reduced migration in most studied cell lines. Among the studied formins, knockdown of INF2 generated the greatest reduction in motility in vitro. Using immunohistochemistry, we demonstrated expression of formin proteins FHOD1 and INF2 in glioblastoma tissues. Importantly, we found that moderate/high expression of INF2 was associated with significantly impaired prognosis. CONCLUSIONS: Formins FHOD1 and INF2 participate in glioblastoma cell migration. Moderate/high expression of INF2 in glioblastoma tissue is associated with worse outcome. Taken together, our in vitro and tissue studies suggest a pivotal role for INF2 in glioblastoma. When specific inhibiting compounds become available, INF2 could be a target in the search for novel glioblastoma therapies.

A decade of geriatric traumatic brain injuries in Finland: population-based trends.

BACKGROUND: we investigated trends of traumatic brain injury (TBI)-related hospitalisations, deaths, acute neurosurgical operations (ANO), and lengths of hospital stay (LOS) in patients aged ≥70 years in Finland using a population-based cohort. METHODS: nationwide databases were searched for all admissions with a TBI diagnosis as well as later deaths for persons ≥70 years of age during 2004-2014. RESULTS: the study period included 20,259 TBI-related hospitalisations (mean age = 80.7 years, men = 48.9%). The incidence of TBI-related hospitalisations was 283/100,000 person-years with an estimated overall annual increase of 2.9% (95% CI: 0.4-5.9%). There was an annual decrease of 2.2% in in-hospital mortality (IHM) in men (95% CI: 0.1-4.3%), with no change in women or overall. There was an annual decrease of 1.1% in odds for ANOs among hospitalised overall (95% CI: 0.1-2.1%) and of 1.4% in men (95% CI: 0.0-2.7%), while no change was observed in women. LOS decreased annually by 2.5% (95% CI: 2.1-2.9%). The incidence of TBI-related deaths was 70/100,000 person-years with an estimated annual increase of 1.6% in women (95% CI: 0.2-2.9%), but no change in men or overall. Mean ages of TBI-related admissions and deaths increased (P < 0.001). INTERPRETATION: the incidence rate of geriatric TBI-related hospitalisations increased, especially in women, but LOS and the rate of ANOs among hospitalised decreased. The overall TBI-related mortality remained stable, and IHM decreased in men, while in women, the overall mortality increased and IHM remained stable. However, the overall incidence rates of TBI-related hospitalisations and deaths and the number of cases of IHM were still higher in men.

Cerebral autoregulation after aneurysmal subarachnoid haemorrhage. A preliminary study comparing dexmedetomidine to propofol and/or midazolam.

BACKGROUND: Cerebral autoregulation is often impaired after aneurysmal subarachnoid haemorrhage (aSAH). Dexmedetomidine is being increasingly used, but its effects on cerebral autoregulation in patients with aSAH have not been studied before. Dexmedetomidine could be a useful sedative in patients with aSAH as it enables neurological assessment during the infusion. The aim of this preliminary study was to compare the effects of dexmedetomidine on dynamic and static cerebral autoregulation with propofol and/or midazolam in patients with aSAH. METHODS: Ten patients were recruited. Dynamic and static cerebral autoregulation were assessed using transcranial Doppler ultrasound during propofol and/or midazolam infusion and then during three increasing doses of dexmedetomidine infusion (0.7, 1.0 and 1.4 µg/kg/h). Transient hyperaemic response ratio (THRR) and strength of autoregulation (SA) were calculated to assess dynamic cerebral autoregulation. Static rate of autoregulation (sRoR)% was calculated by using noradrenaline infusion to increase the mean arterial pressure 20 mm Hg above the baseline. RESULTS: Data from nine patients were analysed. Compared to baseline, we found no statistically significant changes in THRR or sROR%. THRR was (mean ± SD) 1.20 ± 0.14, 1.17 ± 0.13 (P = .93), 1.14 ± 0.09 (P = .72) and 1.19 ± 0.18 (P = 1.0) and sROR% was 150.89 ± 84.37, 75.22 ± 27.75 (P = .08), 128.25 ± 58.35 (P = .84) and 104.82 ± 36.92 (P = .42) at baseline and during 0.7, 1.0 and 1.4 µg/kg/h dexmedetomidine infusion, respectively. Dynamic SA was significantly reduced after 1.0 µg/kg/h dexmedetomidine (P = .02). CONCLUSIONS: Compared to propofol and/or midazolam, dexmedetomidine did not alter static cerebral autoregulation in aSAH patients, whereas a significant change was observed in dynamic SA. Further and larger studies with dexmedetomidine in aSAH patients are warranted.

Influence of Concomitant Extracranial Injury on Functional and Cognitive Recovery From Mild Versus Moderateto Severe Traumatic Brain Injury.

OBJECTIVE: To determine the effect of extracranial injury (ECI) on 6-month outcome in patients with mild traumatic brain injury (TBI) versus moderate-to-severe TBI. PARTICIPANTS/SETTING: Patients with TBI (n = 135) or isolated orthopedic injury (n = 25) admitted to a UK major trauma center and healthy volunteers (n = 99). DESIGN: Case-control observational study. MAIN MEASURES: Primary outcomes: (a) Glasgow Outcome Scale Extended (GOSE), (b) depression, (c) quality of life (QOL), and (d) cognitive impairment including verbal fluency, episodic memory, short-term recognition memory, working memory, sustained attention, and attentional flexibility. RESULTS: Outcome was influenced by both TBI severity and concomitant ECI. The influence of ECI was restricted to mild TBI; GOSE, QOL, and depression outcomes were significantly poorer following moderate-to-severe TBI than after isolated mild TBI (but not relative to mild TBI plus ECI). Cognitive impairment was driven solely by TBI severity. General health, bodily pain, semantic verbal fluency, spatial recognition memory, working memory span, and attentional flexibility were unaffected by TBI severity and additional ECI. CONCLUSION: The presence of concomitant ECI ought to be considered alongside brain injury severity when characterizing the functional and neurocognitive effects of TBI, with each presenting challenges to recovery.

Reliability of serum S100B measurement following mild traumatic brain injury: a comparison of assay measurements from two laboratories.

OBJECTIVE: There is enormous research and clinical interest in blood-based biomarkers of mild traumatic brain injury (MTBI) sustained in sports, daily life, or military service. We examined the reliability of a commercially available assay for S100B used on the same samples by two different laboratories separated by 2 years in time. METHODS AND PROCEDURES: A cohort of 163 adult patients (head CT-scanned, n = 110) with mild head injury were enrolled from the emergency department (ED). All had Glasgow Coma Scale scores of 14 or 15 in the ED (94.4% = 15). The mean time between injury and venous blood sampling was 2.9 h (SD = 1.4; Range = 0.5-6.0 h). Serum S100B was measured at two independent centers using the same high throughput clinical assay (Elecsys S100B®; Roche Diagnostics). RESULTS: The Spearman correlation between the two assays in the total sample (N = 163) was r = 0.93. A Wilcoxson Signed Ranks test indicated that the median scores for the values differed (Z = 2,082, p < .001, Cohen's d = 0.151, small effect size). The values obtained from the two laboratories were very similar for identifying traumatic intracranial abnormalities (sensitivity = 80.1% versus 85.7%). CONCLUSIONS: The serum S100B results measured using the same assay in different laboratories yielded highly correlated and clinically similar, but clearly not identical, results.

Integrative Analysis of Circulating Metabolite Profiles and Magnetic Resonance Imaging Metrics in Patients with Traumatic Brain Injury.

Recent evidence suggests that patients with traumatic brain injuries (TBIs) have a distinct circulating metabolic profile. However, it is unclear if this metabolomic profile corresponds to changes in brain morphology as observed by magnetic resonance imaging (MRI). The aim of this study was to explore how circulating serum metabolites, following TBI, relate to structural MRI (sMRI) findings. Serum samples were collected upon admission to the emergency department from patients suffering from acute TBI and metabolites were measured using mass spectrometry-based metabolomics. Most of these patients sustained a mild TBI. In the same patients, sMRIs were taken and volumetric data were extracted (138 metrics). From a pool of 203 eligible screened patients, 96 met the inclusion criteria for this study. Metabolites were summarized as eight clusters and sMRI data were reduced to 15 independent components (ICs). Partial correlation analysis showed that four metabolite clusters had significant associations with specific ICs, reflecting both the grey and white matter brain injury. Multiple machine learning approaches were then applied in order to investigate if circulating metabolites could distinguish between positive and negative sMRI findings. A logistic regression model was developed, comprised of two metabolic predictors (erythronic acid and myo-inositol), which, together with neurofilament light polypeptide (NF-L), discriminated positive and negative sMRI findings with an area under the curve of the receiver-operating characteristic of 0.85 (specificity = 0.89, sensitivity = 0.65). The results of this study show that metabolomic analysis of blood samples upon admission, either alone or in combination with protein biomarkers, can provide valuable information about the impact of TBI on brain structural changes.

Chronic subdural hematomas in Finnish patients with Huntington's disease.

BACKGROUND: Many features of Huntington's disease (HD) make these patients susceptible to subdural hematomas (SDH), but there are no previous reports on the epidemiology of SDH in this population. We investigated the incidence and risk factors of chronic SDH. METHODS: A national cohort of 192 Finnish patients with HD was investigated. Information was gathered from medical records and administrative registries. RESULTS: The incidence rate of SDH was 68.3/100,000 person-years among the 192 patients. Seven patients were identified with a chronic SDH at or after the diagnosis of HD. Their age was 58.5 ± 15.0 years (mean ± SD) at the time of diagnosis of HD and 60.9 ± 14.1 years at the time of diagnosis of SDH. The incidence rate of chronic SDH after the diagnosis of HD was 4.7/1000 person-years and by 8.3 years of follow-up the cumulative risk was 5.4 %. Review of the patient charts revealed only a few of the common risk factors for chronic SDH, but the rate of reoperations was high. CONCLUSIONS: The incidence of chronic SDH was higher in patients with HD than that in the general population. Incidence of chronic SDH began to increase at the time of expected motor onset of HD. Common risk factors of SDH were scarce aside from fall-related head injuries.

Injury profiles, demography and representativeness of patients with TBI attending a regional emergency department.

OBJECTIVES: The aim of this study was to describe the demography and epidemiology of Finnish patients with TBI and to analyse the representativeness of a study sample. MATERIALS AND METHODS: This prospective multi-centre study was conducted as part of an international collaboration within the EU-funded TBIcare project. The study group was recruited from patients attending the regional emergency department (ED) of the Turku University Hospital, Finland. Pre-defined exclusion criteria included age < 18 years, more than 2 weeks from the injury and uncertain diagnosis of TBI. To be included, a need for an acute head CT (NICE-criteria) was required. RESULTS: Of the 620 patients with TBI or suspected TBI, 203 patients were recruited to the study. Falls were the most common injury mechanism. The study group included more males than the total eligible population (p = 0.011), but no other statistical differences were found. The most common cause for being excluded was lack of information available to the research group before discharge (34%). CONCLUSION: This study supports previous findings that falls are the most common injury mechanism in the Western countries. Uncertainty about the diagnosis of TBI, lack of representativeness without continuous recruitment and poor information transfer about the ED attendees are major challenges for prospective TBI studies.