Asymptomatic brain lesions, such as lacunar infarction, perivascular spaces, cerebral white matter lesions, and cerebral microbleeds, neck ultrasonography, magnetic resonance imaging, atrial fibrillation, dyslipidemia, and diabetes should be examined. Antihypertensive drugs, antiplatelet therapy, and statins and dietary and exercise guidance should be considered as treatments. Antiplatelet therapy may increase the risk of cerebral hemorrhage; therefore, caution should be exercised after considering its suitability in patients. The key is to explain the results of face-to-face examinations.

ObjectiveNeurological deterioration after mild traumatic brain injury (TBI) has been recognized as a poor prognostic factor. Early detection of neurological deterioration would allow appropriate monitoring and timely therapeutic interventions to improve patient outcomes. In this study, we developed a machine learning model to predict the occurrence of neurological deterioration after mild TBI using information obtained on admission.MethodsThis was a retrospective cohort study of data from the Think FAST registry, a multicenter prospective observational study of elderly TBI patients in Japan. Patients with an admission Glasgow Coma Scale (GCS) score of 12 or below or who underwent surgical treatment immediately upon admission were excluded. Neurological deterioration was defined as a decrease of 2 or more points from a GCS score of 13 or more within 24 h of hospital admission. The model predictive accuracy was judged with the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC), and the Youden index was used to determine the cutoff value.ResultsA total of 421 of 721 patients registered in the Think FAST registry between December 2019 and May 2021 were included in our study, among whom 25 demonstrated neurological deterioration. Among several machine learning algorithms, eXtreme Gradient Boosting (XGBoost) demonstrated the highest predictive accuracy in cross-validation, with an AUROC of 0.81 (±0.07) and an AUPRC of 0.33 (±0.08). Through SHapley Additive exPlanations (SHAP) analysis, five important features (D-dimer, fibrinogen, acute subdural hematoma thickness, cerebral contusion size, and systolic blood pressure) were identified and used to construct a better performing model (cross-validation AUROC of 0.84 and AUPRC of 0.34; testing data AUROC of 0.77 and AUPRC of 0.19). At the cutoff value from the Youden index, the model showed a sensitivity, specificity, and positive predictive value of 60, 96, and 38%, respectively. When neurosurgeons attempted to predict neurological deterioration using the same testing data, their values were 20, 94, and 19%, respectively.ConclusionIn this study, our predictive model showed an acceptable performance in detecting neurological deterioration after mild TBI. Further validation through prospective studies is necessary to confirm these results.

OBJECTIVE:This study aimed to assess the effects of focal brain cooling (FBC) on human brain tissue through use of multiple sensing techniques by monitoring cerebrovascular activity and brain temperature. METHODS:Intraoperative brain activity monitoring using a multimodality probe capable of measuring brain temperature, electrocorticography (ECoG) and changes in cerebral hemoglobin concentration was performed in 13 patients with refractory epilepsy. Brain temperature and neurovascular activity were measured beneath and surrounding the FBC device. Data were categorized into three temperature ranges [low-temperature range (LTR, <18 °C), moderate-temperature range (MTR, 18 °C-28 °C), and high-temperature range (HTR, >28 °C)] for analysis. RESULTS:Changes in oxyhemoglobin (ΔO2Hb) and deoxyhemoglobin (ΔHHb) across the temperature ranges showed a U-shape and inverted U-shape pattern, respectively. ΔO2Hb decreased and ΔHHb increased in the MTR, reflecting enhanced neuronal activity and increased oxygen consumption. Conversely, ΔO2Hb increased and ΔHHb decreased in the LTR, indicating suppressed neuronal activity and reduced oxygen consumption. These findings highlight the temperature-dependent modulation of neurovascular activity by FBC, driven by distinct non-linear patterns. CONCLUSIONS:FBC selectively influenced brain electrical activity and hemoglobin concentration, highlighting its subtle effects on neurovascular dynamics. SIGNIFICANCE:These findings provide critical insights into optimizing cooling strategies for neurological disorders using multimodality probes and FBC devices.

The development of novel anti-seizure drugs targeting novel mechanisms is crucial, especially for patients with intractable epilepsy. Previous studies using focal onset seizure rodent models have demonstrated that Icilin and WS-3, agonists of the transient receptor potential melastatin 8 (TRPM8) channel, suppress drug-induce epileptiform discharges (EDs) and seizures (ESs). In contrast, TRPM8 deficiency exacerbates EDs and ESs. This study investigated the mechanism underlying the anti-seizure effects of the TRPM8 agonist, WS-3, using a focal onset seizure mouse model. Mice were injected with WS-3 either before or after administering the seizure inducer, penicillin G potassium. EDs, ESs, and glutamate levels were subsequently evaluated. In wild-type (WT) mice, WS-3 injected after the seizure inducer reduced glutamate levels and ED power by 44% and 60%, respectively, with a positive correlation between WS-3 efficacy and these parameters. WS-3 injection before seizure induction suppressed the increase in glutamate levels and the development of ED and ES, with positive correlations observed among the three parameters. Conversely, TRPM8-knockout mice showed no anti-seizure effects from WS-3. TRPM8 deficiency led to a further increase in the glutamate levels, ED power, and ES severity after the seizure inducer injection. Additionally, TRPM8-deficient mice experienced EDs with fewer glutamate exposures and shortened latency to ED development following seizure induction. These findings suggest that TRPM8 agonists suppress the development of EDs and ESs by reduction of extracellular glutamate levels, indicating that TRPM8 channels may represent a promising treatment option for epilepsy.

This study aimed to investigate the patterns of anticoagulation therapy and coagulation parameters and to develop a prediction model to predict the type of anticoagulation therapy in geriatric patients with traumatic brain injury. A retrospective analysis was performed using the nationwide neurotrauma database of Japan. Elderly patients (65 years) with traumatic brain injury. Patients were divided into 3 groups based on their daily anticoagulant medication (none, direct oral anticoagulant [DOAC], and vitamin K antagonist [VKA]), and coagulation parameters were compared in each group. We then developed a machine-learning model to predict the anticoagulant using coagulation parameters and visualized the pattern using a heat map. A total of 495 patients were enrolled and divided into 3 groups: none (n = 439), DOACs (n = 37), and VKA (n = 19). Comparing none to DOAC and DOAC to VKA for prothrombin time-international normalized ratio (PT-INR), the mean difference and 95% confidence intervals (CIs) were 0.38 (95% CI: 0.59-0.17) and 1.56 (95% CI: 1.21-1.90), and for activated partial thromboplastin time (APTT), the mean difference between none to DOAC and DOAC to VKA was 3.46 (95% CI: 0.98-5.94) and 95% CI was 7.39 (95% CI: 3.29-11.48). A prediction model for the type of anticoagulant used by PT-INR and APTT was developed using machine-learning methods, and a heat map visually revealed their relationship with acceptable predictive ability. This study revealed the characteristic patterns of coagulation parameters in anticoagulants and a pilot model to predict anticoagulant use.

Brain cooling is an effective method for suppressing abnormal brain activity and reducing brain inflammation, particularly in conditions such as epileptic seizures and cerebral infarction. Traditional focal brain cooling techniques, that use devices like Peltier elements are effective, but can cover only a limited area. To overcome this limitation, we introduced a thin, flexible thermally conductive sheet that can extend the cooling range without an increase in the size of the cooling source. This study employed a severe cerebral infarction model in cats to evaluate the efficacy of this approach, and aimed to prevent ischemic damage and explore potential therapeutic applications. The middle cerebral artery (MCA) was occluded for 3 h, followed by reperfusion. Cooling was then initiated using the thermally conductive sheet, which was placed over the perfusion area with the cooling source positioned on the ectosylvian gyrus. Cooling was continued for 24 h, during which ECoG (electrocorticographic activity) and brain temperature were simultaneously monitored to assess both immediate and long-term effects. Results demonstrated that the thermally conductive sheet effectively reduced brain temperatures of a broad area below 20 ℃. This significantly limited the expansion of the infarct size compared to focal cooling. However, significant cerebral edema persisted despite these benefits, indicating that broad cooling alone may not be sufficient to mitigate brain swelling. These findings indicate that though extensive cooling can effectively reduce infarct size, additional strategies, such as anti-inflammatory therapies, are needed to optimize outcomes in patients with severe cerebral infarction.

BACKGROUND AND OBJECTIVES:The impact of preinjury anticoagulation on coagulation parameters over time after traumatic brain injury (TBI) has remained unclear. Based on the hypothesis that preinjury anticoagulation significantly influences the progression and persistence of TBI-induced coagulopathy, we retrospectively examined the association of preinjury anticoagulation with various coagulation parameters during the first 24 hours postinjury in 5 periods. METHODS:Data from the Japanese registry of patients with TBI aged ≥65 years admitted between 2019 and 2021 were used. Time since injury was classified into 5 categories through a graphical analysis of coagulation parameters. We examined the association between preinjury anticoagulation and the platelet count, prothrombin time-international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), D-dimer level, and fibrinogen level during each period by analysis of covariance using 10 clinical factors as confounding factors. RESULTS:Data from 545 patients and 795 blood tests were analyzed. The patients' mean age was 78.9 years, and 87 (16%) received anticoagulation therapy. The preinjury anticoagulation group had significantly greater Rotterdam computed tomography scores and poorer outcomes at discharge than the control group, with significantly lower D-dimer levels and higher fibrinogen levels. Analysis of covariance revealed significant associations between the D-dimer level and preinjury anticoagulation within 2 to 24 hours postinjury, APTT and preinjury anticoagulation within 1 to 24 hours, and PT-INR and preinjury anticoagulation throughout all periods up to 24 hours postinjury. CONCLUSION:Despite more severe TBI signs and poorer outcomes, the preinjury anticoagulation group had significantly lower D-dimer levels, especially within 2 to 24 hours postinjury. Thus, D-dimer levels during this period may not reliably represent TBI severity in patients receiving anticoagulation therapy before injury. Preinjury anticoagulation was also associated with an elevated PT-INR and prolonged APTT from early to 24 hours postinjury, highlighting the importance of aggressive anticoagulant reversal early after injury.

The incidence of subarachnoid hemorrhages (SAHs) in Japan has recently decreased. However, trends in the annual rates of unruptured cerebral aneurysms (UCAs) are unclear because calculations based on follow-up periods are limited to patients with ruptured cerebral aneurysms. We aimed to clarify current trends in the estimated annual rupture rates of UCAs in Japan and to identify the most relevant contributing factors. We analyzed data from the Japanese Ministry of Health, Labour and Welfare and records of the Japan Neurosurgical Society. The estimated annual rupture rates of UCAs between 2003 and 2018 were calculated according to age-adjusted mortality rates of SAH and number of treated ruptured cerebral aneurysms (RCAs). We estimated trends in annual rupture rates using sensitivity analysis and assessed associations between estimated annual rupture rates and the prevalences of hypertension and current smoking. The estimated annual rupture rate of UCAs significantly decreased from 1.44 to 0.87

Spreading depolarization (SD) develops after stroke and traumatic brain injury and may contribute to secondary brain damage. These diseases are often accompanied by intracranial hypertension, but little is known about the effects of intracranial pressure (ICP) on SD. Here, we study the effect of increased ICP on hemodynamic and metabolic response to SD in rats. SDs were triggered at different ICPs and cerebral perfusion pressures (CPP). The regional cerebral blood flow (rCBF), partial pressure of brain tissue oxygen (PbtO2), cerebral extracellular glucose and lactate concentrations were recorded. Fluoro-Jade staining was used to quantify neuronal injury in cortex. At high ICP (50 mmHg) with low CPP (30 mmHg), rCBF and PbtO2 were monophasically decreased in contrast to a monophasically increased pattern under normal conditions. Neuronal death increased in both hemispheres but much more on the side where SDs were triggered. At high ICP (50 mmHg) with normal CPP (70 mmHg), CBF and metabolism during SD did not differ from baseline, and neuronal death did not increase even on the side of SD induction. These data suggest that maintaining CPP at 70 mmHg, even when the ICP is as high as 50 mmHg, preserves normal blood flow and metabolism during SD events and prevents neuronal degeneration.

This study aimed to investigate the effects of focal brain cooling (FBC) on spreading depolarization (SD), which is associated with several neurological disorders. Although it has been studied from various aspects, no medication has been developed that can effectively control SD. As FBC can reduce neuronal damage and promote functional recovery in pathological conditions such as epilepsy, cerebral ischemia, and traumatic brain injury, it may also potentially suppress the onset and progression of SD.We created an experimental rat model of SD by administering 1M potassium chloride (KCl) to the cortical surface. Changes in neuronal and vascular modalities were evaluated using multimodal recording, which simultaneously recorded brain temperature (BrT), wide range electrocorticogram, and two-dimensional cerebral blood flow. The rats were divided into two groups (cooling [CL] and non-cooling [NC]). Warm or cold saline was perfused on the surface of one hemisphere to maintain BrT at 37°C or 15°C in the NC and CL groups, respectively. Western blot analysis was performed to determine the effects of FBC on endothelial nitric oxide synthase (eNOS) expression.In the NC group, KCl administration triggered repetitive SDs (mean frequency = 11.57/h). In the CL group, FBC increased the duration of all KCl-induced events and gradually reduced their frequency. Additionally, eNOS expression decreased in the cooled brain regions compared to the non-cooled contralateral hemisphere.The results obtained by multimodal recording suggest that FBC suppresses SD and decreases eNOS expression. This study may contribute to developing new treatments for SD and related neurological disorders.

Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally and within Japan. We executed a prospective, observational post-marketing surveillance study of patients receiving 4F-PCC for the first time between September 19, 2017 and August 15, 2018 in Japan. Patients were subjected to a comprehensive follow-up for a duration of 4 weeks. Of 1381 eligible patients, 1271 (92

Japan is one of the world's most aging societies and the number of elderly patients taking antithrombotic drugs is increasing. In recent years, dual antiplatelet therapy (DAPT), in which two antiplatelet drugs are administered, has become common in anticipation of its high therapeutic efficacy. However, there are concerns about increased bleeding complications in use of DAPT. Therefore, the goal of this study was to investigate the effects of DAPT in patients with traumatic brain injury (TBI). A prospective, multicenter, observational study was conducted from December 2019 to May 2021 to examine the effects of antithrombotic drugs and reversal drugs in 721 elderly patients with TBI. In the current study, the effect of DAPT on TBI was examined in a secondary analysis. Among the registered patients, 132 patients taking antiplatelet drugs only were divided into those treated with single antiplatelet therapy (SAPT) (n=106) and those treated with DAPT (n=26) prior to TBI. Glasgow Coma Scale (GCS) on admission, pupillary findings, course during hospitalization, and outcome were compared in the two groups. A similar analysis was performed in patients with a mild GCS of 13-15 (n=95) and a moderate to severe GCS of 3-12 (n=37) on admission. The DAPT group had significantly more males (67.0 % vs. 96.2 %), a higher severity of illness on admission, and a higher frequency of brain herniation findings on head CT (21.7 % vs. 46.2 %), resulting in significantly higher mortality (12.3 % vs. 30.8 %). The only significant factor for mortality was severity on admission. The rate of DAPT was significantly higher in patients with a moderate to severe GCS on admission, and DAPT was the only significant factor related to severity on admission. These findings suggest that the severity of injury on admission infiuences the outcome six months after injury, and that patients with more severe TBI on admission are more likely to have been treated with DAPT compared to SAPT.

Background: Acute exacerbation of head injury in elderly patients due to use of antithrombotic agents has become a concern in countries with aging populations. Reversal agents are recommended for treatment, but its usage is unclear. Therefore, we conducted a prospective observational study in this patient population to monitor usage of reversal therapy. Methods: The subjects were 721 elderly patients aged ≥65 years old who were hospitalized in 15 centers from December 2019 to May 2021. Patients were divided into groups who did not receive antithrombotic agents (Group A), who received antithrombotic agents, but did not receive reversal therapy (Group B), and were treated with antithrombotic agents and reversal therapy (Group C). Age, gender, mechanism of injury, neurologic and imaging findings on admission, clinical course after admission and surgery, outcomes and complications were compared among these groups. Time from injury to reversal therapy was examined based on outcomes to investigate trends in the timing of administration of the reversal agent. Results: Acute exacerbation during the clinical course occurred in 9.8 %, 15.8 % and 31.0 % of cases in Groups A, B and C, respectively, and differed significantly among the groups. On head CT, the incidences of hematoma were 35.7 %, 36.5 % and 60.4 %, respectively, with this incidence being significantly higher in Group C; and the respective rates of craniotomy were 18.8 %, 14.0 % and 50.9 %, again with this rate being significantly higher in Group C. The good outcome and mortality rates were 57.1 %, 52.5 % and 35.8 %, and 14.5 %, 18.0 % and 24.5 %, respectively, and both were poorest in Group C. Times from injury to treatment with a reversal agent were significantly shorter in patients without compared to those with acute exacerbation (405.9 vs. 880.8 min) and in patients with favorable outcomes compared to those with unfavorable outcomes (261.9 vs. 543.4 min). Conclusion: Similarly to previous studies, the incidence of acute exacerbation was increased by use of antithrombotic agents. These results suggest that patients in Japan who require hematoma evacuation due to symptom exacerbation tend to be treated with reversal agents. Although it is difficult to assess the efficacy of reversal therapy from this study, earlier treatment with reversal agents before the occurrence of acute exacerbation may be useful to improve outcomes.

OBJECTIVE:Cerebral infarction due to cerebral vasospasm (IVS) after aneurysmal subarachnoid hemorrhage is associated with poor outcomes and symptomatic cerebral vasospasm (SVS). However, the difference of risk factors between SVS and IVS was unclear to date. In this study, we aimed to elucidate the risk factors for SVS and IVS based on the registry study. METHODS:The modified World Federation of Neurosurgical Societies scale study comprises 1863 cases. Patients with aneurysmal subarachnoid hemorrhage who underwent radical treatment within 72 hours with a premorbid modified Rankin Scale score 0-2 as the inclusion criteria were retrospectively examined. The risk factors for SVS and IVS were analyzed using multivariable logistic regression analysis. RESULTS:Among them, 1090 patients who met the inclusion criteria were divided into 2 groups according to SVS and IVS; 273 (25%) patients with SVS and 92 (8.4%) with IVS. Age was not a risk factor for SVS, but for IVS, and Fisher scale was a risk factor for SVS, but not for IVS. CONCLUSIONS:The prevalence of IVS was not associated with the Fisher scale but with older age, suggesting possible factors other than SVS. Different associated factors between SVS and IVS were confirmed in this study.

Background: Febrile seizures (FSs) are the most frequent type of seizures in infancy and childhood. Epileptiform discharges (EDs) on electroencephalogram at the time of first FS recurrence can increase the risk of epilepsy development. Therefore, inhibition of EDs is important. Recently, WS-3, a transient receptor potential melastatin 8 (TRPM8) agonist, reportedly suppressed penicillin G-induced cortical-focal EDs. However, the effects of TRPM8 agonists on FSs remain unknown. In this study, we aimed to clarify the effects of the TRPM8 agonist, and the absence of TRPM8 channels, on hyperthermia-induced FS by analyzing the fast ripple band. Methods: Hyperthermia (43°C for 30 min) induced by a heating pad caused FSs in postnatal day 7 wild-type (WT) and TRPM8 knockout (TRPM8KO) mice. FSs were defined as EDs occurring during behavioral seizures involving hindlimb clonus and loss of the righting reflex. Mice were injected with 1% dimethyl sulfoxide or 1 mM WS-3 20 min before the onset of hyperthermia, and electroencephalograms; movies; and rectal, brain and heating pad temperatures were recorded. Results: In wild-type mice, WS-3 reduced the fast ripple amplitude in the first FS without changing rectal and brain temperature thresholds. In contrast, the anti-FS effect induced by the TRPM8 agonist was not observed in TRPM8KO mice and, compared with wild-type mice, TRPM8 deficiency lowered the rectal and brain temperature thresholds for FSs, exacerbated the fast ripple amplitude, and prolonged the duration of the initial FS induced by hyperthermia. Conclusion: Our findings suggest that TRPM8 agonists can be used to treat hyperthermia-induced FSs.

Idarucizumab, a monoclonal antibody fragment that rapidly reverses the anticoagulant effects of dabigatran, was approved in Japan in September 2016, at which time an all-case, postmarketing surveillance (PMS) study was initiated to collect data on idarucizumab in Japanese patients. Interim results were published previously, and the final results are reported herein. This multicenter, open-label, uncontrolled, non-interventional PMS study was conducted in Japanese patients who received idarucizumab at the approved dose (2 × 2.5 g/50 ml) and had uncontrolled bleeding (group A) or required an emergency procedure (group B). The primary endpoint was the frequency of adverse drug reactions (ADRs). The secondary endpoint was the maximum extent of reversal of the anticoagulant effects of dabigatran, within 4 h of idarucizumab administration, based on activated partial thromboplastin time (aPTT). The final analysis included 804 patients. ADRs during the idarucizumab treatment and post-treatment periods were reported in 17 of 542 patients (3.1 Atrial fibrillation is an irregular heart rhythm (arrhythmia), and the type of atrial fibrillation not caused by a heart valve problem is known as “non-valvular atrial fibrillation” or NVAF. People with NVAF have an increased risk of ischemic stroke, in which a blood clot (thrombus) blocks an artery in the brain. Drugs that inhibit blood clots, known as anticoagulants, are prescribed to people with NVAF to prevent ischemic stroke. Historically, warfarin has been one of the most prescribed anticoagulant drugs. However, a novel anticoagulant drug, known as dabigatran, has clinical advantages over warfarin and is approved in many countries for people with NVAF. People who take anticoagulants may experience life-threatening bleeding or need urgent surgery, and thus rapid and effective reversal of the anticoagulant effects is critical. The drug idarucizumab specifically binds to dabigatran to reverse its anticoagulant effects in people with uncontrolled bleeding or who require an urgent procedure. Idarucizumab was approved for use in Japan in September 2016. In Japan, drug companies are obligated to collect data after a new drug is launched as an approval condition, which is done through a postmarketing surveillance study. Here, we report the final results of a postmarketing surveillance study conducted between September 2016 and November 2020 to evaluate the safety and effectiveness of idarucizumab in Japanese patients receiving dabigatran. The results of our study show that idarucizumab can safely and effectively reverse the anticoagulant effects of dabigatran in Japanese patients, and support the continued use of idarucizumab in Japan in clinical practice.

Use of anticoagulants is increasing with the aging of societies. The safe first-line drug is likely to be a direct oral anticoagulant (DOAC), but outcomes of treatment of traumatic brain injury (TBI) with anticoagulants are uncertain. Therefore, we examined the clinical effect of idarucizumab as reversal therapy in elderly patients with TBI who were treated with dabigatran. A retrospective multi-center observational study was performed in patients >= 65 years of age who developed acute traumatic subdural hematoma during treatment with dabigatran and underwent reversal therapy with idarucizumab. The items examined included patient background, neurological and imaging findings at arrival, course after admission, complications, and outcomes. A total of 23 patients were enrolled in the study. The patients had a mean age of 78.9 years. Cause of TBI was fall in 60.9% of the subjects. Mean Glasgow Coma Scale score at arrival was 8.7; anisocoria was present in 31.8% of cases. Exacerbation of consciousness was found in 30.4%, but only in 13.3% of subjects treated with idarucizumab before consciousness and imaging findings worsened. Dabigatran was discontinued in 81.8% of cases after hematoma development, with a mean withdrawal period of 12.1 days. The favorable outcome rate was 21.7%, and mortality was 39.1%. In multi-variate analysis, timing of idarucizumab administration was associated with a favorable outcome. There were ischemic complications in 3 cases (13.1%), and all three events occurred >= 7 days after administration of idarucizumab. These findings suggest that in cases that develop hematoma during treatment with dabigatran, it is important to administer idarucizumab early and restart dabigatran after conditions stabilize.

Objective: In elderly populations, the enlargement of the perivascular space is related to small vessel disease and the glymphatic system. Enlarged perivascular spaces (EPVS) in the basal ganglia (EPVS-BG) and EPVS in the centrum semiovale (EPVS-CSO) are associated with different pathophysiological processes. However, the prevalence of EPVS and the factors associated with EPVS location in healthy middle-aged individuals are still unclear. We aimed to determine the prevalence of EPVS and the factors associated with EPVS location among healthy individuals in their 40 s Methods: This study included 5000 consecutive healthy individuals who underwent screening for brain diseases in Japan from August to December 2018. Of them, the data of individuals in their 40 s were extracted and analyzed. The associations of age, sex, body mass index, smoking and drinking history, and medical history with EPVS location were investigated. Similar analyses were performed for the other age groups. A literature review on the factors associated with EPVS location was also performed. Results: A total of 1720 individuals in their 40 s were finally included. The prevalence of EPVS-BG and EPVS-CSO was 7.7% and 9.2%, respectively. Age (years), smoking history, and hypertension were associated with EPVS-BG; none of the studied factors were found to be associated with EPVS-CSO. In the elderly, the factors previously reported to be associated with EPVS-BG included atherosclerosis change, while the factors associated with EPVS-CSO were cerebral amyloid angiopathy-related formation. Conclusion: Both EPVS-BG and EPVS-CSO occurred among healthy individuals in their 40 s, but they did so rarely, and less prevalently than in older age groups. EPVS-BG and EPVS-CSO may represent early imaging signs of the atherosclerotic and cerebral amyloid angiopathy processes, respectively. Data Availability: The anonymized data for this study will be shared upon any qualified investigator's request to the corresponding author. Primary data from this study will be made available upon reasonable request in accordance with the review board of the research institute.

BACKGROUND: As the global population ages, the incidence of traumatic brain injury (TBI) is increasing. Whereas mild TBI can impair the cognitive function of older adults, the cause and background of mild TBI-induced cognitive impairment remain unclear, and the evaluation of risk factors for cognitive impairment after mild TBI remains open for consideration, especially in the aging population. This study aimed to evaluate the risks associated with cognitive impairment following mild TBI. METHODS: Between January 2006 and December 2018, a total of 2209 patients with TBI required hospitalization in Shimane Prefectural Central Hospital. Mild TBI was defined as a Japan Coma Scale <= 10 at admission. Patients' cognitive function was measured with the Hasegawa Dementia Rating Scale-Revised or Mini-Mental State Examination at least twice during the patients' hospital stays. The odds ratio (OR) and 95% confidence interval (CI) of each considered risk factor was calculated with multivariable logistic regression analysis after univariate analysis. RESULTS: Among 1674 patients with mild TBI, 172 patients underwent cognitive function examinations, of whom 145 (84.3%) were found to have cognitive impairment at discharge. Significant risk factors for cognitive impairment included age (P = 0.008) and hypertension (P = 0.013) in univariate analysis; and age (OR, 1.04: 95% CI, 1.01-1.07) and hypertension (OR, 5.81: 95% CI, 1.22-27.68) by multivariable analysis. CONCLUSIONS: Older patients with hypertension displayed a significantly higher risk for cognitive impairment after even mild TBI. These patients warrant careful management after even mild TBI.

Neurological improvement occurs from the subacute to chronic phases in severe traumatic brain injury. We analyzed factors associated with improved neurological findings in the subacute phase, using data from the Japan Neurotrauma Data Bank (JNTDB). The subjects were 1345 patients registered in the JNTDB (Project 2015). Clinical improvement was evaluated by comparing the Glasgow Outcome Scale (GOS) at discharge and 6 months after injury. Of these patients, 157 with severe disability (SD) on the discharge GOS were examined to evaluate factors associated with neurological improvement in the subacute phase. Cases were defined as those with (group I) and without (group N) improvement: a change from SD at discharge to good recovery (GR) or moderate disability (MD) at 6 months after injury. Patient background, admission findings, treatment, and discharge destination were examined. In all patients, the favorable outcome (GR, MD) rate improved from 30.2% at discharge to 35.7% at 6 months after injury. Of SD cases at discharge, 44.6% had a favorable outcome at 6 months (group I). Patients in group I were significantly younger, and had a significantly lower D-dimer level in initial blood tests and a lower incidence of convulsions. In multivariate analysis, discharge to home was a significant factor associated with an improved outcome. Many SD cases at discharge ultimately showed neurological improvement, and the initial D-dimer level may be a predictor of such improvement. The environment after discharge from an acute care hospital may also contribute to an improved long-term prognosis.