The current status of reversal therapy in Japan for elderly patients with head injury treated with antithrombotic agents: A prospective multicenter observational study.

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.

Cerebral infarction following administration of andexanet alfa for anticoagulant reversal in a patient with traumatic acute subdural hematoma.

Background: Anticoagulants prevent thrombosis in patients with atrial fibrillation (AF) and venous thromboembolism but increase the risk of hemorrhagic complications. If severe bleeding occurs with anticoagulant use, discontinuation and rapid reversal are essential. However, the optimal timing for resuming anticoagulants after using reversal agents remains unclear. Here, we report early cerebral infarction following the use of andexanet alfa (AA), a specific reversal agent for factor Xa inhibitors, in a patient with traumatic acute subdural hematoma (ASDH). The possible causes of thromboembolic complication and the optimal timing for anticoagulant resumption are discussed. Case Description: An 84-year-old woman receiving rivaroxaban for AF presented with impaired consciousness after a head injury. Computed tomography (CT) revealed right ASDH. The patient was administered AA and underwent craniotomy. Although the hematoma was entirely removed, she developed multiple cerebral infarctions 10 h after the surgery. These infarctions were considered cardiogenic cerebral embolisms and rivaroxaban was therefore resumed on the same day. This case indicates the possibility of early cerebral infarction after using a specific reversal agent for factor Xa inhibitors. Conclusion: Most studies suggest that the safest time for resuming anticoagulants after using reversal agents is between 7 and 12 days. The present case showed that embolic complications may develop much earlier than expected. Early readministration of anticoagulant may allow for adequate prevention of the acute thrombotic syndromes.

Incidence of Chronic Subdural Hematoma after Mild Head Trauma in Elderly Patients with or without Pre-traumatic Conditioning of Anti-thrombotic Drugs.

Anti-thrombotic drugs may increase the risk for chronic subdural hematoma (CSDH). However, whether to continue or discontinue/counteract these drugs has not been investigated in patients with mild head trauma. CSDH incidence after mild head trauma, as well as the risk for CSDH in patients with anti-thrombotic drugs, were investigated in this study. The study included 765 consecutive elderly (>65 y.o.) patients with mild head trauma and an initial Glasgow Coma Scale (GCS) score of 14 or 15. All patients received initial CT within 24 hours after trauma and were re-examined 30 days after trauma to detect CSDH formation, repeating for every 30 days to examine symptomatic CSDH progression. Patients were divided into two groups, with anti-thrombotic drugs (n = 195) or without them (n = 263), to investigate the influence of pre-traumatic conditioning with anti-thrombotic drugs on CSDH. The whole sample was 458 out of 765 cases. The incidence of CSDH formation was 91 out of 458 cases (19.9%) after mild head trauma, with no significant difference between with and without anti-thrombotic drugs. CSDH progressed as symptomatic in 21 out of 458 cases (4.6%), with no significant difference between with and without anti-thrombotic drugs. Pre-traumatic conditioning with anti-thrombotic drugs and its continuation after trauma did not affect the incidence of formation or symptomatic progression of CSDH. This finding suggests that discontinuing and/or counteracting anti-thrombotic drugs may be unnecessary in patients with mild head trauma.

Organized Chronic Subdural Hematoma: A Condition Presenting Mixed-Density Hematoma without Gradation Density on Brain CT.

Organized chronic subdural hematoma is a neurological condition characterized by organized clot formation inside the hematoma. Unlike nonorganized chronic subdural hematoma with persistent bleeding inside, organized subdural hematoma is often a nonurgent condition that does not require emergency drainage, unless progressive cerebral compression with neurological disturbances is present. However, as the CT values in organized clot formation and active bleeding fall in similar ranges, distinguishing these 2 conditions with different emergency levels based on brain CT alone is sometimes difficult. Here, we describe the case of a 78-year-old man with persistent nocturia who was referred to our hospital. He had a history of head trauma on the left side about 1 year ago, followed by neurosurgery at another hospital. Brain CT revealed a multiseptated subdural space and a mixed-density hematoma without gradation density on the contralateral side of the past head trauma region. Based on the lack of progressive neurological disturbances and the absence of gradation density in CT values inside the hematomas, his condition was judged as nonurgent, and emergency drainage was spared. One year after his first visit to our hospital, the patient experienced a normal life without any neurological disturbances, except for nocturia. The absence of gradation density in CT values along the gravity direction inside the organized hematoma may be a clue to estimate nonurgency without persistent active bleeding inside.

[Clinical Characteristics of Talk and Deteriorate in Traumatic Brain Injury in the Elderly].

Recently, the incidence of traumatic brain injury(TBI)has been increased in elderly people. This study addresses the clinical characteristics of TBI in elderly people. The most frequent cause of TBI in elderly people is either falls on the ground or from heights since both motor and physiological functions are degraded such people. Acute subdural hematoma(ASDH)is the most frequent among acute traumatic intracranial lesions. Its high frequency could be possibly associated with increased volume of the subdural space resulting from atrophy of the brain in elderly people. Delayed aggravation of other intracranial hematomas have also been explained by such anatomical and physiological changes in elderly people. A recent study demonstrated that the survival rate of 2-6 days after TBI was significantly lower in the elderly people than younger adults, suggesting that "talk and deteriorate" may play an important role for the poor outcome in elderly people with TBI, although its mechanisms are not fully understood. Coagulopathy after TBI and pre-injury antithrombotic agents may be associated with such a delayed aggravation, making the management of TBI in elderly people in difficult. Establishing preventions and treatments for TBI in elderly people is urgent.

Preoperative Risks of Cerebral Infarction in Pediatric Moyamoya Disease.

Background and Purpose: In pediatric moyamoya disease, there have been few reports of the risk factors for preoperative cerebral infarction, especially during the waiting period before surgery. The clinical and radiological findings of surgically treated pediatric moyamoya patients were evaluated to analyze the risk factors for cerebral infarction seen from onset to surgery. Methods: Between August 2003 and September 2019, 120 hemispheres of 71 patients under 18 years of age with moyamoya disease were surgically treated by direct and indirect bypass procedures. The mean age of all surgical hemispheres at diagnosis was 6.7±3.9 years (6 months­17 years). The potential risk factors for preoperative infarction were examined statistically. Results: Multivariate logistic regression analysis showed that risk factors for infarction at the time of diagnosis were age at diagnosis (odds ratio [OR], 0.68 [95% CI, 0.57­0.82]; P<0.0001) and the magnetic resonance angiography (MRA) score (OR, 2.29 [95% CI, 1.40­3.75]; P=0.001). Univariate analysis showed that risk factors for infarction while waiting for surgery were age at diagnosis (OR, 0.61 [95% CI, 0.46­0.80]; P<0.0001), the MRA score (OR, 1.75 [95% CI, 1.26­2.41]; P=0.0003), and onset of infarction (OR, 40.4 [95% CI, 5.08­322.3]; P<0.0001). Multiple comparisons showed that patients under 4 years of age were at a significantly high risk of infarction at the time of diagnosis and while waiting for surgery. Time from diagnosis to surgery of >2 months was a significant risk factor for infarction while waiting for surgery in patients under 6 years of age. Conclusions: Young age at diagnosis and a high MRA score may be associated with rapid disease progression and result in preoperative infarction. We recommend that surgery be performed within 2 months of diagnosis for the patients under 4 years of age with a high MRA score (>5) and cerebral infarction. Further study is needed to define the optimal timing of surgery.

Mutism resulting from heterochronic bilateral cerebellar hemorrhages - A case report.

BACKGROUND: Cerebellar mutism (CM) is a neurological condition characterized by lack of speech due to cerebellar lesions. Interruption of the bilateral dentatothalamocortical (DTC) pathways at midline structure seems the principal cause of CM but not fully understood. We described a rare case of CM due to heterochronic bilateral cerebellar hemorrhages. CASE DESCRIPTION: An 87-year-old woman presented with depression of alertness after sudden vomiting. Neurologically, mild dysmetria and mutism were observed. The head computed tomography (CT) showed both a fresh right cerebellar hemorrhage and an obsolete left one. The patient was diagnosed as CM since both the thalamus and the supplementary motor area were bilaterally intact on both CT and magnetic resonance imaging. Medical treatment and rehabilitation improved her ataxia and ambulation. She became cognitively alert and could communicate by nodding, shaking her head, or facial expression. However, her mutism did not change at 4 months after the stroke. CONCLUSION: There are few reports on CM due to direct injuries to the bilateral dentate nuclei. Since our case did not show any injury other than bilateral dentate nuclei, this report can support the hypothesis that the interruptions of the bilateral DTC are the cause of CM.

Endoscopic Hematoma Evacuation for Intracerebral Hemorrhage Under Local Anesthesia: Factors That Affect the Hematoma Removal Rate.

OBJECTIVE: Recent advances in endoscopic surgery have led to more patients being able to undergo endoscopic removal of hypertensive intracerebral hemorrhage (HICH). However, because of the minimal invasiveness, endoscopic HICH removal through a narrow surgical window can result in a low removal rate. The goal of the present study was to investigate the factors that affect the removal rate of HICH evacuation. METHODS: The data from 28 patients with supratentorial HICH who had undergone endoscopic hematoma evacuation were retrospectively analyzed. The inclusion criteria were spontaneous supratentorial HICH with a hematoma volume >30 mL, admission to the hospital within 24 hours of ictus, and a Glasgow coma scale score of ≥4. RESULTS: Of the 28 patients, 9 were women and 19 were men, ranging in age from 41 to 86 years (mean, 60.7 ± 12.7). The hematoma location was the basal ganglia in 25 patients and subcortical in 3 patients. The mean preoperative hematoma volume was 62.4 ± 22.5 mL. The hematoma removal rate was <60% for 11 patients (poor evacuation group) and ≥60% for in 17 patients (good evacuation group). Comparing the 2 groups, chronic renal failure treated with hemodialysis (P = 0.0072, χ2 test), liver cirrhosis (P = 0.023, χ2 test), and surgeon experience with ≥10 cases of endoscopic HICH removal (P = 0.016, χ2 test) were significant factors related to the HICH removal rate. CONCLUSION: To achieve a good removal rate, surgeons should have experience performing the endoscopic procedure. Also, patients with end-stage chronic renal failure or liver cirrhosis should be excluded.

Bilateral Upper Cerebellar Hemorrhage Due to Pial Arteriovenous Fistula and Its Pathophysiological Insight.

OBJECTIVES: Bilateral upper cerebellar hemorrhage is extremely rare clinical entity but relatively known as postoperative neurosurgical complication with as-yet unknown etiology. Here, we report a case of bilateral upper cerebellar hemorrhage due to pial arteriovenous fistula (pAVF) and discuss the possible pathophysiology of this bleeding pattern. CASE DESCRIPTION: A 4-year-old boy who was previously healthy presented with a sudden onset of headache, vomiting, and gait instability. Computed tomography revealed atypical bleeding in the sulci of bilateral cerebellar hemispheres facing the tentorium. Despite the symmetric distribution of bleeding, T2-weighted magnetic resonance imaging showed flow void adjacent to the lateral margin of bleeding. Diffusion-weighted magnetic resonance imaging showed increased apparent diffusion coefficient value in the hemorrhagic lesion, suggesting vasogenic edema. Vertebral angiogram revealed a pAVF, which was fed by the hemispheric branch of superior cerebellar artery. It drained via the venous varix, inferiorly into the tortuous and engorged inferior hemispheric vein, indicating venous congestion. On the venous phase of vertebral angiogram, the superior vermian vein, which is one of the main drainers of the superior part of the cerebellum, was not opacified. Transarterial n-butyl-2-cyanoacrylate embolization was performed to prevent rebleeding, and the pAVF was treated successfully. The patient's follow-up has been uneventful for 3 years. CONCLUSIONS: We reported an extremely rare case of cerebellar pAVF presenting as bilateral upper cerebellar hemorrhage. Severe congestion of upper cerebellar veins seemed to be a possible pathophysiology of this specific bleeding pattern.

Newly Diagnosed Acquired Hemophilia A Manifesting as Massive Intracranial Hemorrhage Following a Neurosurgical Procedure.

OBJECTIVE: Increased attention has been paid to limiting preoperative hemostatic screening because assessment of patient history can be used as an alternative. However, there may be some clinical pitfalls in overlooking acquired coagulopathies. Here, we present a case of newly diagnosed acquired hemophilia A (AHA) that manifested as a massive intracranial hemorrhage without unexplained bleeding history or abnormal hemostatic results. CASE DESCRIPTION: A 58-year-old man, who had a history of surgical clipping of an anterior communicating artery aneurysm 30 years ago, experienced subarachnoid hemorrhage because of a ruptured middle cerebral artery aneurysm. He underwent surgical clipping and external decompressive craniectomy; 30 days later, cranioplasty was performed without preoperative hemostatic screening because of his normal coagulation status at the time of a previous surgery. Persistent wound bleeding and epistaxis suddenly began 6 hours after surgery. Computed tomography (CT) revealed a massive intracranial hematoma in the damaged parenchyma, although the patient was asymptomatic. At that time, laboratory tests showed isolated prolonged activated partial thromboplastin time and the presence of factor VIII inhibitor, which confirmed AHA. To manage the bleeding, fresh frozen plasma was transfused for 4 consecutive days, and hemostasis was finally achieved. Thereafter, the laboratory test results were normalized in 5 weeks. The patient's clinical course has been uneventful for 7 months without recurrence of AHA. CONCLUSIONS: Acquired coagulopathies are relatively rare but life-threatening. Because clinical history is insufficient to predict an acquired coagulopathy, preoperative hemostatic screening should be performed before each neurosurgical procedure.

Clinical Characteristics and Outcome in Elderly Patients with Traumatic Brain Injury: For Establishment of Management Strategy.

In recent years, instances of neurotrauma in the elderly have been increasing. This article addresses the clinical characteristics, management strategy, and outcome in elderly patients with traumatic brain injury (TBI). Falls to the ground either from standing or from heights are the most common causes of TBI in the elderly, since both motor and physiological functions are degraded in the elderly. Subdural, contusional and intracerebral hematomas are more common in the elderly than the young as the acute traumatic intracranial lesion. High frequency of those lesions has been proposed to be associated with increased volume of the subdural space resulting from the atrophy of the brain in the elderly. The delayed aggravation of intracranial hematomas has been also explained by such anatomical and physiological changes present in the elderly. Delayed hyperemia/hyperperfusion may also be a characteristic of the elderly TBI, although its mechanisms are not fully understood. In addition, widely used pre-injury anticoagulant and antiplatelet therapies may be associated with delayed aggravation, making the management difficult for elderly TBI. It is an urgent issue to establish preventions and treatments for elderly TBI, since its outcome has been remained poor for more than 40 years.

Acute Subdural Hematoma in Infants with Abusive Head Trauma: A Literature Review.

The number of cases with child abuse is increasing in Japan, and abusive head trauma (AHT) is a major cause of death in abused children. Child abuse has been recognized by the late 19th century, and widely accepted as battered child syndrome in the middle of the 20th century. As terms, there had been considerable mechanistic controversies between shaken-baby and -impact syndrome until the beginning of the 21st century. In recent years, AHT has been utilized as a less mechanistic term. Most of the characteristics of AHT in Japan have been similar to those in the United States as follows: infant is the most common victim, acute subdural hematoma (SDH) is the most common intracranial lesion, and retinal hemorrhage is often complicated. On the other hand, several characteristics have been different as follows: mother is the most common perpetrators, impact is a more common mechanism of trauma than shaking, and external trauma is more common reflecting the existence of impact. Since AHT as well as child abuse is a social pathological phenomenon influenced by victims, perpetrators, socioeconomic circumstances, and so on, various aspects of AHT as well as child abuse can be changed with times. Actually, a recent paper suggests such changes in infants with acute SDH due to AHT. In this review article, AHT, abusive infantile acute SDH in particular, are reviewed from the aspect of neurosurgical perspectives, including its mechanisms of trauma, biomechanics, clinical features, management, and prognosis, to update the trend in Japan.

Delayed Deterioration in Isolated Traumatic Subarachnoid Hemorrhage.

BACKGROUND: Isolated traumatic subarachnoid hemorrhage (SAH) in association with mild traumatic brain injury is considered to be a less severe finding that is not likely to require surgical intervention. No previous reports have described cases warranting craniotomy for isolated traumatic SAH by itself. CASE DESCRIPTION: We report 2 cases of minor head trauma with isolated traumatic SAH that showed delayed clinical deterioration requiring immediate surgical intervention. Initial computed tomography showed isolated traumatic SAH in the basal cistern and Sylvian fissure in both cases. Angiography showed no aneurysmal source. Within 24 hours of each accident, both disturbance of consciousness and hemiparesis deteriorated. Follow-up computed tomography showed formation of intracerebral hematoma adjacent to the Sylvian fissure. Intraoperative findings showed abruption injury of a perforating branch arising from the middle cerebral artery (MCA) as the cause of bleeding. Impact at the time of injury could have caused traction on the MCA in the Sylvian fissure, resulting in abruption of the perforator. CONCLUSIONS: Isolated traumatic SAH seen in the basal cistern and Sylvian fissure carries a risk of late deterioration. A possible cause of hematoma expansion is abruption of a perforating branch arising from the MCA at the time of head injury. When hematoma expansion is identified, surgical evacuation of the hematoma is indicated. Surgical evacuation should be safely performed with the knowledge of the point of bleeding in such patients.

Surgical management of traumatic acute subdural hematoma in adults: a review.

Traumatic acute subdural hematoma (ASDH) is a major clinical entity in traumatic brain injury (TBI). It acts as a space occupying lesion to increase intracranial pressure, and is often complicated by co-existing lesions, and is modified by cerebral blood flow (CBF) changes, coagulopathy, and delayed hematomas. Because of its complicated pathophysiology, the mortality of ASDH is still remaining high. In this review article, its epidemiology, pathophyiology, surgical treatment, and salvage ability are described. With regard to epidemiology, as the population ages, growing number of elderly patients with ASDH, especially patients with prehospital anticoagulant and antiplatelets, increase. Concerning pathophysiology, in addition to well-known initial intracranial hypertension and subsequent ischemia, delayed hyperemia/hyperperfusion, or delayed hematoma is being recognized frequently in recent years. However, optimal treatments for these delayed phenomenons have not been established yet. With regard to surgical procedures, all of craniotomy, decompressive craniectomy, and initial trephination strategies seem to be effective, but superiority of each procedure have not been established yet. Since Glasgow Coma Scale (GCS) scores, age, papillary reaction, and computed tomographic findings are strongly correlated to outcome, each factor has been investigated as an indicator of salvage ability. None of them, however, has been defined as such one. In future studies, epidemiological changes as population ages, management of delayed pathophysiology, superiority of each surgical procedures, and salvage ability should be addressed.

[Epidemiology of chronic subdural hematomas].

BACKGROUND AND PURPOSE: The Japanese population is aging faster than any other population in the world, affecting the epidemiology of which frequently occurs in the elderly. In this study, the epidemiological aspect of chronic subdural hematoma (CSDH) is investigated, using data of the Miyagi Traumatic Head Injury Registry Project. PATIENTS AND METHODS: From January 2005 to December 2007, 1,445 patients with CSDH were registered in the project (M:F=1,021:424, mean age 71.2±12.8 y.o.). Using these patient's records, the incidence of CSDH was investigated, as well as causes of head injury, severity, and outcome. RESULTS: The overall incidence of CSDH was 20.6/100,000/year, with 76.5 in the age group of 70-79 y.o. and 127.1 in the over 80 y.o. group. Ground level fall was the most frequent cause of trauma in the elderly, in contrast to traffic accident, which was the most frequent cause in the younger generation. Compared to the younger generation, neurological condition was severer in the elderly at the time of admission, and the outcome was poorer at the time of discharge. CONCLUSION: Compared to previous reports, this study demonstrates a marked increase in the incidence of CSDH. Not only population aging but also current medical trends (such as increases of the elderly patients who receive hemodialysis, anticoagulant, and/or antiplatelet therapy) may influence the increase of CSDH incidence.

[Hemorrhagic infarction complicated by obliteration of the superior sagittal sinus by depressed skull fracture after a hammer injury: a case report].

The authors have encountered a case of compound depressed skull fracture in a 59 year-old-man complicated by occlusion of the anterior 1/3 part of the superior sagittal sinus (SSS). He was hit by a hammer at the midline of the frontal region, and transferred to our emergency care unit. On admission, there was laceration of skin at the midline of the forehead, but the patient had no neurological deficit. Skull radiograph showed a depressed skull fracture over the SSS. Computed tomography (CT) scan showed a small brain contusion adjacent to the depressed fracture. Digital subtraction angiography (DSA) showed occlusion of the anterior 1/3 part of SSS, and extravasations of contrast medium from cortical arterioles and capillaries. CT taken at 4 hours after injury showed enlargement of the lesion with extravasations of contrast medium and the patient manifested consciousness disturbance at this point. Distribution of extravasations suggested the occurrence of hemorrhagic infarction. Elevation of the depressed skull was thus performed under general anesthesia. There was laceration of the dura 5 mm away from the SSS and lacerations of cortical vessels, but there was no apparent damage to SSS itself. The depressed bone was replaced with artificial bone. The patient was discharged without any neurological deficit. Preoperative angiography was helpful to understand the hemodynamics and risk of massive bleeding during the operation.