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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.

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Congress of Neurological Surgeons.)

Background: Even mild head trauma can cause severe intracranial hemorrhage in patients with cerebrospinal fluid (CSF) shunts for hydrocephalus. CSF shunts are considered a risk factor for subdural hematoma (SDH). The management of acute SDH (ASDH) in shunted patients with normal pressure hydrocephalus can be challenging. Addressing the hematoma and the draining function of the shunt is important. To preserve the shunt, we set the shunt valve pressure to the highest and perform hematoma evacuation for ASDH. In this study, we report the surgical cases of ASDH in patients with shunts., Methods: Between 2013 and 2019, five patients with ASDH and CSF shunts underwent hematoma evacuation at our hospital. We retrospectively analyzed data regarding their clinical and radiological presentation, hospitalization course, the use of antithrombotic medications, and response to different treatment regimens., Results: The patients presented with scores of 5-14 in the Glasgow coma scale and severe neurological signs, consciousness disturbance, and hemiparesis. Most patients were elderly, taking antithrombotic medications (four of five cases), and had experienced falls (4 of 5 cases). All patients underwent hematoma evacuation following resetting their programmable shunt valves to their maximal pressure setting and shunt preservation. ASDH enlargement was observed in only one patient who underwent burr-hole drainage. Glasgow outcome scale scores at discharge were 1 and 3, respectively., Conclusion: In hematoma evacuation, increasing the valve pressure may reduce the bleeding recurrence. To preserve the shunt, setting the shunt valve pressure to the highest level and performing endoscopic hematoma evacuation with a small craniotomy could be useful., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Surgical Neurology International.)

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 influences 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In patients presenting neck pain and hemiparesis, differentiation between cerebral infarction and cervical spinal epidural hematoma is vital yet challenging, particularly when magnetic resonance imaging (MRI) is not feasible. A 59-year-old woman presented with a sudden onset of left-sided hemiparesis and neck pain. MRI was contraindicated because the patient underwent embolization in childhood. Head computed tomography (CT) revealed no evidence of hemorrhage or early ischemic signs. Cervical CT revealed no evidence of hematoma within the spinal canal. Myelography and CT myelography revealed no significant cervical spine abnormalities. The diagnosis was cerebral infarction. Cervical spine MRI is the gold standard examination for diagnosing cervical spinal epidural hematoma, but cervical spine CT, myelography, and CT myelography may be useful when MRI is contraindicated., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tanaka et al.)

Deep brain stimulation (DBS) has emerged as an important therapeutic option for several movement disorders; however, the management of acute complications, such as acute subdural hematoma (ASDH), remains challenging. This is the case of a 71-year-old woman with Parkinson's disease who developed ASDH 12 years after bilateral DBS placement. On admission with altered consciousness, imaging revealed significant displacement of the DBS electrodes because of the hematoma. Emergent craniotomy with endoscopic evacuation was performed with preservation of the DBS system. Postoperatively, complete evacuation of the hematoma was confirmed, and the patient experienced significant clinical improvement. ASDH causes significant electrode displacement in patients undergoing DBS. After hematoma evacuation, the electrodes were observed to return to their proper position, and the patient exhibited a favorable clinical response to stimulation. To preserve the DBS electrodes, endoscopic hematoma evacuation via a small craniotomy may be useful., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tanaka et al.)

Spinal dural arteriovenous fistula (SDAVF) is among the most common arterial shunt diseases typically found in middle aged or older men. Herein, we aimed to clarify the reasons for misdiagnoses and delayed diagnoses of SDAVF, determine how these affect prognoses, and establish how they can be prevented. We conducted a PubMed/MEDLINE literature search using "spinal dural arteriovenous fistula", "delayed diagnosis", "late diagnosis", and "misdiagnosis" terms. We identified 18 articles, including 965 SDAVF cases. Patients were predominantly males (71.8-100.0%) (mean age: 53.5-71.0 years). Misdiagnoses rates varied (17.5-100.0%) and encompassed many conditions. The mean time between early manifestations and confirmed diagnosis was approximately 10-15 months and from the first radiologic image revealing dural arteriovenous fistula (DAVF) features to diagnosis was 9.2-20.7 months. Posttreatment outcomes showed a significant improvement in motor functions, gait, and micturition, particularly in patients exhibiting preoperative symptoms over a short period. SDAVF is frequently misdiagnosed or subject to delayed diagnosis, causing poor clinical outcomes. SDAVF symptoms including progressive lower-limb weakness, paresthesia, and vesicorectal dysfunction are indications for spinal magnetic resonance imaging with subsequent spinal angiography, wherein DAVF is evidenced by extensive T2 hyperintensity and flow-void abnormalities. We reported a representative case with delayed diagnosis.

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Eiichi Suehiro reports financial support was provided by 10.13039/100008322CSL Behring K.K. United States. Eiichi Suehiro reports a relationship with Boehringer Ingelheim, Germany that includes: funding grants. 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.)

A 49-year-old woman with a family history of Moyamoya disease presented with sudden onset of right hemiparesis without headache. Magnetic resonance imaging (MRI) of the head revealed a cerebral infarct in the left corona radiata, and magnetic resonance angiography (MRA) revealed severe stenosis of the bilateral internal carotid, middle, anterior, and posterior cerebral arteries. Antithrombotic therapy improved her symptoms. After 2 weeks, MRA revealed changes in cerebral arterial vasodilation, indicating reversible cerebral vasoconstriction syndrome (RCVS). Five months later, she presented with transient dysarthria without headache ; MRA revealed multiple cerebral artery stenosis, and 2 days later, it revealed changes in cerebral arterial vasodilation. RCVS presents with reversible multifocal narrowing of the cerebral arteries with thunderclap headache, commonly observed in middle-aged women. RCVS without headache is rare. RCVS should be a differential diagnosis in patients with multiple cerebral artery stenoses without headache, and serial MRI is important for its diagnosis. J. Med. Invest. 71 : 323-326, August, 2024.

Background: Adjustable shunt valves that have been developed for managing hydrocephalus rely on intrinsically magnetic components ; thus, artifacts with these valves on magnetic resonance imaging (MRI) are inevitable. No studies on valve-induced artifacts in lumboperitoneal shunt (LPS) surgery have been published. Therefore, this study aimed to evaluate valve-induced artifacts in LPS., Methods: We retrospectively reviewed all MRIs obtained between January 2023 and June 2023 in patients with an implanted Codman CERTAS Plus adjustable shunt valve (Integra Life Sciences, Princeton, New Jersey, USA). The valve was placed <1 cm subcutaneously on the paravertebral spinal muscle of the back, with its long axis perpendicular to the body axis. The scans were performed using a Toshiba Medical Systems 1.5 Tesla scanner. The in-plane artifact sizes were assessed as the maximum distance of the artifact from the expected region of the back., Results: All spinal structures or spinal cords can be recognized, even with valve-induced artifacts. The median maximum valve-induced artifact distance on T1-weighted axial imaging was 25.63 mm (mean, 25.98 mm ; range, 22.24-30.94 mm). The median maximum valve-induced artifact distance on T2-weighted axial imaging was 25.56 mm (mean, 26.27 mm ; range, 21.83-29.53 mm)., Conclusion: LPS surgery with adjustable valve implantation on paravertebral muscles did not cause valve-induced artifacts in the spine and spinal cord. We considered that LPS could simplify the postoperative care of these patients. J. Med. Invest. 71 : 154-157, February, 2024.

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., Competing Interests: Dr. Suehiro received research funding from Boehringer Ingelheim., (© Eiichi Suehiro et al., 2023; Published by Mary Ann Liebert, Inc.)

To reduce the number of preventable trauma deaths(PTD), a standardized approach has been established with various training courses and guidelines such as the Japan Advanced Trauma Evaluation and Care and Guidelines for the Diagnosis and Treatment of Traumatic Brain Injury. To prevent PTD, initial treatment, including resuscitation, is crucial in the care of traumatic brain injury(TBI). The Japan Neurotrauma Data Bank recently reported that the number of patients with TBI is increasing. Patients on antithrombotic drugs are also increasing. Although the mortality rate is decreasing, the percentage of patients with favorable outcomes is also decreasing. Therefore, to prevent secondary brain injury, rapid and systematic assessment of physiological abnormalities and resuscitation using the ABCDE approach, diagnosis and treatment of impending D, administration of tranexamic acid(an antifibrinolytic drug), and timely administration of anticoagulant neutralizers are important.

Background: The purpose of this study was to examine whether the temperature difference between the jugular bulb and pulmonary artery (ΔTjb-pa) is associated with the neurological outcome of patients with severe traumatic brain injury (TBI)., Methods: We conducted a post hoc analysis of a multicenter randomized controlled trial of mild therapeutic hypothermia (TH, 32.0-34.0°C) or fever control (FC, 35.5-37.0°C) for the patients with severe TBI. ΔTjb-pa averaged every 12 h and the variation in ΔTjb-pa were compared between patients with favorable (n = 39) and unfavorable (n = 37) neurological outcomes. These values were also compared in the TH and FC subgroups., Results: The average ΔTjb-pa values in patients with favorable and unfavorable outcomes were 0.24 ± 0.23 and 0.06 ± 0.36°C, respectively (P < 0.001). ΔTjb-pa trended significantly higher in the favorable outcome patients than in the unfavorable outcome patients throughout the 120 h after onset of severe TBI (P < 0.001). The variation in ΔTjb-pa from 0 to 72 h was significantly lower in the favorable outcome patients than in the unfavorable outcome patients (0.8 ± 0.8 vs 1.8 ± 2.5°C, respectively, P = 0.013). From 72 to 120 h, there was no significant difference in the variation in ΔTjb-pa. Significant differences between patients with favorable and unfavorable outcomes in ΔTjb-pa and the variation in ΔTjb-pa were similar in the TH subgroup, but not evident in the FC subgroup., Conclusions: A reduction in ΔTjb-pa and greater variation in ΔTjb-pa were associated with an unfavorable outcome in patients with severe TBI, especially those treated with TH. When treating severe TBI patients, it is important to understand that there will be differences in temperature reflecting the brain environment and the systemic temperature, depending on the severity and outcome of TBI during TH., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Fujita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Japan Neurotrauma Data Bank is a source of epidemiological data for patients with severe traumatic brain injury (TBI) and is sponsored by the Japan Society of Neurotraumatology. In this report, we examined the changes in the treatment of severe TBI in Japan based on data of the Japan Neurotrauma Data Bank. Controlling and decreasing intracranial pressure (ICP) are the primary objective of severe TBI treatment. Brain-oriented whole-body control or neurocritical care, including control of cerebral perfusion pressure, respiration, and infusion, are also increasingly considered important because cerebral tissues require oxygenation to improve the outcomes of patients with severe TBI. The introduction of neurocritical care in Japan was delayed compared with that in Western countries. However, the rate of ICP monitoring increased from 28.0% in 2009 to 36.7% in 2015 and is currently likely to be higher. Neurocritical care has also become more common, but the functional prognosis of patients has not significantly improved in Japan. Changes in the background of patients with severe TBI suggest the need for improvement of acute-phase treatment for elderly patients. Appropriate social rehabilitation from the subacute to chronic phases and introduction of cellular therapeutics are also needed for patients with TBI.

Background: Standardization of seamless treatment from prehospital injury care to initial injury and specialized care through collaboration among departments have been promoted in Japan since 2000. This survey was conducted to examine the current status of the system for treatment of traumatic brain injury (TBI) in Japan., Methods: In February 2022, questionnaires on the treatment system and TBI care were sent to 869 facilities that participated in a training program held by the Japan Neurosurgical Society. Responses were received from 480 facilities (55.2%). These responses were compared with those in a similar survey performed in 2008., Results: Among the responding facilities, 39.4% had neurosurgeons in emergency departments. Initial care for TBI was the responsibility of the neurosurgery department in 42.3% of the facilities, the emergency department in 26.0%, and jointly between these departments in 29.6%; and neurocritical care was managed by the neurosurgery department in 81.9%, the emergency department in 5.2%, and jointly in 12.1%. For patients with acute-phase TBI, intracranial pressure monitoring was performed in 72.1%. Active normothermia was performed in 86.0%, and decompressive craniectomy in 99.4%, as required. There was compliance with guidelines for treatment and management of TBI in 93.3%., Conclusions: Comparison with the 2008 results suggested role-sharing between 2 departments in TBI treatment is increasing. TBI treatment compliance with the guidelines was high. In-hospital mortality of Japanese patients with TBI has decreased since 2000. This may be due to the progress with standardization of TBI treatment and collaboration among departments in compliance with guidelines., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Thrombotic aneurysms at the nonbranching segment of the distal anterior cerebral artery (ACA) are extremely rare and difficult to differentiate from cavernous malformations by radiographic features alone., Observations: Computed tomography and magnetic resonance imaging of a 30-year-old female patient with a chronic headache complaint revealed a 22-mm frontal lobe mass. The mass showed heterogeneous mixed intensity and hemosiderin deposits on magnetic resonance images. It was not visualized by conventional angiography, indicating that the mass and ACA/other vessels were not connected. The patient was preoperatively diagnosed with a cavernous malformation. However, during resection, the mass surface was white and smooth, different from a cavernous malformation. Although the mass was adherent to the pericallosal artery branch, no luminal continuity was observed. After detachment, the mass was completely resected. Pathological and immunohistochemical findings indicated a vessel wall and interior thrombus. The patient was rediagnosed with a thrombotic aneurysm at the distal ACA nonbranching segment and discharged 10 days postsurgery without neurological deficits., Lessons: Because radiographic findings of thrombotic aneurysm and cavernous malformation are similar, mass lesions in contact with major arteries should be differentiated as thrombotic aneurysms, even when the artery lumen appears disconnected from the mass.

This study was aiming at investigating the extent of neuronal damage in cases of traumatic brain injury (TBI) with diffuse axonal injury (DAI) using 123 I-iomazenil(IMZ) SPECT and MRI. We compared the findings in 31 patients with TBI without any major focal brain lesions and 25 age-matched normal controls. Subjects underwent 123 I-IMZ SPECT and MRI, and also assessment by cognitive function tests. The partial volume effect of 123 I-IMZ SPECT was corrected using MRI. In the patients with TBI, decreased spatial concentration of 123 I-IMZ binding was detected in the medial frontal/orbitofrontal cortex, posterior cingulate gyrus, cuneus, precuneus, and superior region of the cerebellum. ROC analysis of 123 I-IMZ SPECT for the detection of neuronal injury showed a high diagnostic ability of 123 I-IMZ binding density for TBI in these areas. The decreased 123 I-IMZ uptake density in the cuneus and precuneus was associated with cognitive decline after the injury. In the patients with TBI, brain atrophy was detected in the frontal lobe, anterior temporal and parietal cortex, corpus callosum, and posterior part of the cerebellum. Evaluation of the neuronal integrity by 123 I-IMZ SPECT and MRI provides important information for the diagnosis and pathological interpretation in cases of TBI with DAI.

Purpose: Abusive head trauma (AHT) is a serious cause of morbidity and mortality in the pediatric population, especially in young infants. This review of the literature aimed to understand the characteristics of AHT in Japan., Methods: PubMed and the Japanese database Ichuushi were searched to understand the differences in AHT between Japan and other countries., Results: Shaking was identified as an uncommon cause of injury, while mothers were the most common perpetrator of pediatric AHT in Japan. Although uncommon in other countries, infantile subdural hematoma caused by an accidental slight head injury was reported in Japan., Conclusion: As in other countries, AHT is a major condition which pediatric neurosurgeons face in Japan. The mechanisms of injury and perpetrators of AHT seemed to differ slightly between western countries and Japan. Additionally, non-accidental infantile acute subdural hematoma was reported mainly in Japan. Therefore, further care and fair judgment is necessary when investigating child abuse in Japan., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: A neuroendoscope is a technical advance that allows surgeons to visualize certain regions of the brain that was previously inaccessible through the use of a surgical microscope. Several neuroendoscope designs have been implemented by other neurosurgeons over the past 5 years. The advantage of a neuroendoscope is the addition of a flexible and narrow tip that allows for safe entry into intracranial structures for clinical observation. However, there are some limitations to this approach. Here, we report the use of a modified angioscope as a newly developed neuroendoscope to be employed in observing intracranial structures., Methods: We report the use of an angioscope that is 1.8 mm in diameter and has both a thin and flexible tip. In this study, the angioscope was inserted into the lumen of an aspirator tube, and the tip of the device was placed at the intracranial area of intended observation area. Image findings were evaluated using an established in vivo goat brain model., Results: The angioscope was light in weight and maneuverable and could be reached and observed in the blind spot using a surgical microscope. From the cerebellopontine angle, the lower cranial nerves and trigeminal nerve could be observed, and from the cisterna magna, the floor of the fourth ventricle and the aqueduct could be seen., Conclusion: The angioscope is a useful instrument to observe intracranial locations safely and effectively even within a limited surgical field. Further modifications will be required to use the angioscope in various craniotomy procedures., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Patients with traumatic brain injury(TBI)have various pathological conditions, such as direct cell destruction by external force, compression by hematoma, vascular injury, ischemia, complicated hypoxia, and hypotension. These pathological conditions occur simultaneously at the time of injury. In some cases, contaminated wounds may be treated, and infection patterns different from the scheduled neurosurgical cases should be managed. In cases of severe TBI, immunocompromised patients are considered to be at high risk of infection. Infection control during the initial stage of treatment affects patient prognosis. In addition, large craniotomy, including decompressive craniectomy, is required to manage intracranial pressure(ICP), which causes skin infection due to delayed wound healing. Furthermore, placement of drainage tubes and transducers for a long period of time might be necessary to manage ICP, and the patient is likely to develop surgical site infection(SSI). In this paper, we describe the characteristic surgical procedure and discuss ways to control SSI in TBI cases.

Background: Novice neurosurgeons require neurosurgical technique training, but the current method is demanding and time consuming. Therefore, it is crucial to perform training using an appropriate and informative method. In this report, we describe our attempts to provide training in neurosurgical techniques using goat in vivo brain model and to demonstrate the effectiveness of this model., Methods: Under general anesthesia, the surgery was performed on a male goat in the prone position. A midline liner skin incision was made in the scalp, six burr holes were drilled, a craniectomy was performed, and the dura was incised in an arcuate fashion. We attempted the interhemispheric approach and a retrosigmoid approach., Results: It was confirmed that common neurosurgical approaches are achievable in this model. Furthermore, anatomical structures such as nerves and blood vessels were similar to those of humans. Moreover, the goat brain was similar in color and texture to that of humans., Conclusion: Unlike a cadaver brain, in vivo brain requires hemostasis and careful dissection, which provides the surgeons a realistic experience of actual neurosurgery., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Surgical Neurology International.)

Therapeutic hypothermia for severe traumatic brain injury (TBI) has been repeatedly studied, but no past studies have assessed the detailed head computed tomography (CT) findings. We sought to investigate individual CT findings of severe TBI patients treated with targeted temperature management utilizing the head CT database obtained from the Brain Hypothermia study. Enrolled patients underwent either mild therapeutic hypothermia (32.0°C-34.0°C) or fever control (35.5°C-37.0°C). We assessed individual head CT images on arrival and after rewarming and investigated the correlations with outcomes. The initial CT data were available for 125 patients (hypothermia group = 80, fever control group = 45). Baseline characteristics and CT findings, such as hematoma thickness and midline shift, were similar in all aspects between the two groups. The favorable outcomes in the hypothermia and fever control groups were 38 (47.5%) and 24 (53.3%; p  = 0.53) for all 125 patients, respectively; 21 (46.7%) vs. 10 (38.5%; p  = 0.50) for 71 patients with acute subdural hematoma (SDH), respectively; and 12 (75.0%) vs. 4 (36.4%; p  = 0.045) in 27 young adults (≤50 years) with acute SDH, respectively. There was a trend toward favorable outcomes for earlier time to reach 35.5°C (190 vs. 377 min, p  = 0.052) and surgery (155 vs. 180 min, p  = 0.096) in young patients with acute SDH. The second CT image revealed progression of the brain injury. This study demonstrated the potential benefits of early hypothermia in young patients with acute SDH, despite no difference in CT findings between the two groups. However, the small number of cases involved hindered the drawing of definitive conclusions. Future studies are warranted to validate the results., Competing Interests: No competing financial interests exist., (© Hitoshi Kobata et al., 2022; Published by Mary Ann Liebert, Inc.)

Background: Vaccines against coronavirus disease 2019 have a high level of efficacy and safety across all populations. However, numerous case series have been published on neurological disorders, including Bell's palsy, Guillain-Barre syndrome, transverse myelitis, and multiple sclerosis. The authors presented a case of trigeminal neuropathy after coronavirus vaccination in a patient who had undergone microvascular decompression (MVD) for trigeminal neuralgia (TN)., Observations: A 77-year-old woman presented with acute trigeminal neuropathy after receiving a Pfizer-BioNtech vaccination (tozinameran) against severe acute respiratory syndrome coronavirus 2. The patient had undergone MVD for TN and the facial pain completely disappeared. One month later, she received the first injection of the tozinameran vaccine. Twelve hours after vaccination, she presented with numbness and pain induced by touching any place on the entire right face. No eruption was observed on her face. The serum herpes zoster virus antibodies were confirmed within the normal range. Magnetic resonance imaging revealed no abnormalities. The authors suspected a right trigeminal neuropathy after vaccination. Administration of carbamazepine and pregabalin improved TN but facial numbness persisted, especially in the mandibular division., Lessons: The coronavirus is a possible etiology of secondary trigeminal neuropathy in the case of MVD for TN.

Background: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome., Methods: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels., Results: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups., Conclusions: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups., (© 2021. The Author(s).)

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.

More than half of the patients with severe head injuries are elderly people in Japan due to the impact of entering a super-aging society. Elderly people take antithrombotic drugs at a high rate. According to the Japan Neurotrauma Data Bank, many patients with head injuries taking antithrombotic drugs sustain falls, indicating an increased risk of deterioration due to low-energy trauma. It has also been pointed out that many hemorrhagic lesions occur due to the effects of antithrombotic drugs, and there is a risk that hematoma will increase later. As an appropriate response in such patients, if bleeding findings are noted on head CT, discontinuation/reversal of antithrombotic drugs should be considered even if the severity is mild. Reversal therapy should be performed in an appropriate manner as quickly and reliably as possible. Some effects of reversal therapy have been reported in small-scale observational studies. Discontinued antithrombotic drugs should be resumed in the neurotrauma subacute phase. Resuming antithrombotic drugs reduces the risk of ischemic complications, but increases the risk of bleeding complications. To summarize, the benefits of resuming antithrombotic drugs have been reported, and it is recommended that antithrombotic drugs be resumed 3-10 days after injury.

Background: The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group., Methods: We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0 °C-34.0 °C] or fever control [35.5 °C-37.0 °C]). We calculated Hb levels during early phase by the formula: (admission Hb + Hb on day 1) / 2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery)., Results: We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1 day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P = 0.018)., Conclusions: High early phase Hb levels are associated with favorable neurological outcomes after severe TBI., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Burr hole surgery in the emergency room can be lifesaving for patients with acute subdural hematoma (ASDH). In the first part of this study, a strategy of combined burr hole surgery, a period of intracranial pressure (ICP) monitoring, and then craniotomy was examined for safe and effective treatment of ASDH. Since 2012, 16 patients with severe ASDH with indications for burr hole surgery were admitted to Kenwakai Otemachi Hospital. From 2012 to 2016, craniotomy was performed immediately after burr hole surgery (emergency [EM] group, n = 10). From 2017, an ICP sensor was placed before burr hole surgery. After a period for correction of traumatic coagulopathy, craniotomy was performed when ICP increased (elective [EL] group, n = 6). Patient background, bleeding tendency, intraoperative blood transfusion, and outcomes were compared between the groups. In the second part of the study, ICP was measured before and after burr hole surgery in seven patients (including two of the six in the EL group) to assess the effect of this surgery. Activated partial thromboplastin time (APTT) and prothrombin time-international normalized ratio (PT-INR) were significantly prolonged after craniotomy in the EM group, but not in the EL group, and the EM group tended to require a higher intraoperative transfusion volume. The rate of good outcomes was significantly higher in the EL group, and ICP was significantly decreased after burr hole surgery. These results suggest the value of burr hole surgery followed by ICP monitoring in patients with severe ASDH. Craniotomy can be performed safely using this method, and this may contribute to improved outcomes.

Mass gatherings are events characterized by "the concentration of people at a specific location for a specific purpose over a set period of time that have the potential to strain the planning and response resources of the host country or community." Previous reports showed that, as a result of the concentration of people in the limited area, injury and illness occurred due to several factors. The response plan should aim to provide timely medical care to the patients and to reduce the burden on emergency hospitals, and to maintain a daily emergency medical services system for residents of the local area. Although a mass gathering event will place a significant burden on the local health-care system, it can provide the opportunity for long-term benefits of public health-care and improvement of daily medical service systems after the end of the event. The next Olympic and Paralympic Games will be held in Tokyo, during which mass gatherings will occur on a daily basis in the context of the coronavirus disease (COVID-19) epidemic. The Academic Consortium on Emergency Medical Services and Disaster Medical Response Plan during the Tokyo Olympic and Paralympic Games in 2020 (AC2020) was launched 2016, consisting of 28 academic societies in Japan, it has released statements based on assessments of medical risk and publishing guidelines and manuals on its website. This paper outlines the issues and countermeasures for emergency and disaster medical care related to the holding of this big event, focusing on the activities of the academic consortium., Competing Interests: Approval of the research protocol: N/A. Informed consent: N/A. Registry and the registration no. of the study/trial: N/A. Animal studies: N/A. Conflict of interest: None declared., (© 2021 The Authors. Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background: As the aging rate in the traumatic brain injury population increases, the number of patients taking antithrombotic drugs is also expected to increase among the population with traumatic brain injury; however, the utility or risk of reversal of such drugs is unclear. Therefore, we performed a retrospective cohort study of the effect of reversal of antithrombotic drugs on geriatric traumatic brain injury at our hospital., Methods: The study subjects included 83 patients(65 years or older)with intracranial traumatic lesions or skull fractures who were admitted to our hospital during 2013-2018. According to the hospital's protocol, we performed platelet transfusion in patients taking antiplatelet drugs, prothrombin complex concentrate(PCC)administration in patients taking warfarin and direct oral anticoagulants except dabigatran: factor IX complex before January 2018 and four-factor PCC after February 2018. We administered idarucizumab in the case of dabigatran. Fresh frozen plasma transfusion was additionally performed in operative cases., Results: Twenty-six patients took antithrombotic drugs. There was no significant difference in the ratio of talk and deteriorate, favorable outcome(Glasgow Outcome Scale: good recovery+moderate disability), and hospitalization period between the non-antithrombotic and antithrombotic administration groups involving reversal. The timing of antithrombotic drug resumption varied, but no major embolic event occurred during the follow-up period., Conclusion: This study suggests that reversal of antithrombotic drugs in geriatric traumatic brain injury may contribute to suppression of talk and deteriorate and lead to more favorable outcomes. As there are also contradictory reports about the utility of reversal, additional studies should be performed for confirmation.

Objective: The harmful effects of hyperoxemia have been reported in critically ill patients with various disorders, including those with brain injuries. However, the effect of hyperoxemia on aneurysmal subarachnoid hemorrhage (aSAH) patients is unclear. In this study the authors aimed to determine whether hyperoxemia during the hyperacute or acute phase in patients with aSAH is associated with delayed cerebral ischemia (DCI) and poor neurological outcome., Methods: In this single-center retrospective study, data from patients with aSAH treated between January 2011 and June 2017 were reviewed. The patients were classified into groups according to whether they experienced DCI (DCI group and non-DCI group) and whether they had a poor outcome at discharge (poor outcome group and favorable outcome group). The background characteristics and time-weighted average (TWA) PaO2 during the first 24 hours after arrival at the treatment facility (TWA24h-PaO2) and between the first 24 hours after arrival and day 6 (TWA6d-PaO2), the hyperacute and acute phases, respectively, were compared between the groups. Factors related to DCI and poor outcome were evaluated with logistic regression analyses., Results: Of 197 patients with aSAH, 42 patients experienced DCI and 82 patients had a poor outcome at discharge. TWA24h-PaO2 was significantly higher in the DCI group than in the non-DCI group (186 [141-213] vs 161 [138-192] mm Hg, p = 0.029) and in the poor outcome group than in the favorable outcome group (176 [154-205] vs 156 [136-188] mm Hg, p = 0.004). TWA6d-PaO2 did not differ significantly between the groups. Logistic regression analyses revealed that higher TWA24h-PaO2 was an independent risk factor for DCI (OR 1.09, 95% CI 1.01-1.17, p = 0.037) and poor outcome (OR 1.17, 95% CI 1.06-1.29, p = 0.002)., Conclusions: Hyperoxemia during the first 24 hours was associated with DCI and a poor outcome in patients with aSAH. Excessive oxygen therapy might have an adverse effect in the hyperacute phase of aSAH.

Introduction: Elevated intracranial pressure(ICP)can cause secondary brain injury after severe traumatic brain injury(TBI), and ICP is the key factor that determines the outcome. Therefore, prediction of elevation of ICP during the course of the injury would allow for more effective care of patients with severe TBI. In this study, we investigated predictive factors for elevation of ICP in patients with severe acute subdural hematoma(ASDH)., Methods: Twenty patients with severe isolated ASDH were admitted to our hospital between January 2009 and April 2016. The patients were divided into two groups with a maximum ICP of ≥20mmHg(elevated ICP group)and <20mmHg(normal ICP group). Age, mechanism of injury, Glasgow Coma Scale score on admission, initial head computed tomography findings, vital signs, serological and blood gas examinations, initial ICP, and clinical outcome were evaluated., Results: The elevated ICP group had significantly higher initial ICP(5.0±3.1 vs. 30±22.4mmHg, p<0.01), arterial oxygen pressure(151.2±68.3 vs. 314.2±197.1mmHg, p<0.05), and activated partial thromboplastin time(APTT;28.17±3.1 vs. 35.96±8.0, p<0.05)at admission, and significantly lower fibrinogen level(273.3±65.1 vs. 188.1±82.4mg/dL, p<0.05)and favorable outcome rate(p<0.01)., Conclusions: Our results show that high initial ICP, APTT, and arterial oxygen and low fibrinogen levels are associated with ICP elevation in patients with severe ASDH. These factors might be useful for the indication of therapeutic methods such as decompressive craniectomy.

Objective: Developed countries have rapidly aging populations and the use of antithrombotic drugs is increasing. We investigated the effects of antithrombotic drugs and reversal of these drugs in patients with geriatric traumatic brain injury (TBI)., Methods: Age, sex, mechanism of injury, Glasgow Coma Scale on admission, head computed tomography findings, antithrombotic therapy, acute exacerbation, and outcomes at discharge were examined in 711 patients with geriatric TBI, complicated with traumatic intracranial hemorrhage using data from the Japan Neurotrauma Data Bank Project 2015 (JNTDB P2015). These items were compared between patients who did and did not receive antithrombotic therapy. We also conducted a questionnaire survey of reversal of antithrombotic therapy at hospitals participating in the JNTDB P2015. Acute exacerbation was compared in hospitals that did and did not regularly use reversal of this therapy., Results: The major cause of injury was a fall. In head computed tomography, acute subdural hematoma was found in 65.7% of the subjects. Antithrombotic therapy was performed in 30.4% of subjects, and these subjects were significantly older than those who did not receive this therapy; many had a fall as the mechanism of injury, and the level of consciousness was significantly exacerbated with this therapy. In hospitals that performed regular reversal, late exacerbation of the level of consciousness was suppressed., Conclusions: Patients with geriatric TBI who are given antithrombotic drugs have a risk for late exacerbation, even if initially diagnosed with mild TBI. Therefore, there is a possibility that reversal of antithrombotic drugs is important to suppress the risk of deterioration of patients with TBI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

d-dimer is a potential biomarker for the detection of traumatic brain injury (TBI). However, the mechanisms that trigger elevation of d-dimer in TBI remain unclear. The purpose of this study was to evaluate the reliability of d-dimer in blood as a biomarker for TBI and to determine the mechanisms involved in regulating its blood levels. Nine patients with moderate to severe isolated TBI (Glasgow Coma Scale [GCS] score 7-13) were admitted to our hospital from May 2013 to June 2014. Blood samples were collected from systemic arteries on arrival and at 1, 3, 5, and 7 days after injury. Blood levels of neuron specific enolase (NSE), d-dimer, and soluble tissue factor (sTF) were measured. NSE (33.4 ng/ml: normal <12.0 ng/ml) and d-dimer (56.1 μg/ml: normal <1.0 μg/ml) were elevated at admission and declined on day 1 after injury. At admission, there were significant correlations of d-dimer levels with NSE (R = 0.727, P = 0.026) and sTF (R = 0.803, P = 0.009) levels. The blood level of d-dimer accurately reflects the degree of brain tissue damage indicated by NSE levels. Our data suggest that release of sTF induced by brain tissue damage may activate the coagulation cascade, leading to elevation of d-dimer.

Background: The association between isolated admission heart rate (HR) and prognosis has been discussed, but not that between gross HR change and neurological outcome in patients with severe traumatic brain injury (TBI). In the acute phase of severe TBI, HR is influenced by several factors (e.g., pain, sympathetic activation, hypovolemia, fever, body temperature). Therefore, admission HR and gross HR change should be examined in patients with TBI treated with a well-designed protocol, such as was done in the Brain Hypothermia (B-HYPO) Study., Methods: This was a post hoc analysis of the B-HYPO Study, which was conducted as a prospective, multicenter, randomized controlled trial in patients with severe TBI receiving mild therapeutic hypothermia (MTH; 32.0 °C-34.0 °C) or fever control (35.5 °C-37.0 °C) in Japan. Patients with MTH were examined, and HR change (%HR) in the early MTH phase was calculated as follows: [admission HR - HR at day 1]/admission HR × 100. Patients were divided into six groups, using admission HR (< 80, 80-99, ≤ 100) and median of %HR; i.e., group (Admission HR < 80 and %HR ≥ 18.6); group (Admission HR < 80 and %HR < 18.6); group (Admission HR 80-99 and %HR ≥ 18.6); group (Admission HR 80-99 and %HR < 18.6); group (Admission HR ≥100 and %HR ≥ 18.6); and group (Admission HR ≥100 and %HR < 18.6). The primary outcome was an adjusted predicted probability of unfavorable neurological outcome at 6 months after TBI according to Glasgow Outcome Scale score, which is a measure of functional recovery and defined as severe disability, persistent vegetative state, and death., Results: Overall, 79 patients with MTH (52.7% of the original trial) were examined; among these, unfavorable neurological outcomes were observed in 53.2%. Among all the groups, group (Admission HR ≥100 and %HR < 18.6) exhibited the highest proportion of unfavorable outcomes, and 82.3% of patients had an adjusted predicted probability of unfavorable outcomes, whereas those in group (Admission HR < 80 and %HR ≥ 18.6) developed only 22.8% (p = 0.04)., Conclusions: Mild HR decrease during the early phase of targeted temperature management following tachycardia at admission can be associated with unfavorable neurological outcomes after severe TBI.

Objective: Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs., Methods: Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD-induced perfusion deficits (spreading ischemia) was assessed in an aSAH-mimicking model., Results: There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059-1.192, p = 0.084). However, the total SD-induced depression duration per recording day (22.2 vs 30.2 minutes, β = -251.905, 95% CI = -488.458 to -15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, β = -0.916, 95% CI = -1.746 to -0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD-induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3-55.1, p = 0.020)., Interpretation: Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH-mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873-885., (© 2018 American Neurological Association.)