Difficulty resuming driving in acute acquired brain injury: Retrospective observational study using discriminant analysis.

OBJECTIVES: We hypothesized that neuropsychological testing and history of falls would be associated with difficulty resume driving after acute acquired brain injury (ABI). This study aimed to analyze ABI facing difficulties in resuming driving in the acute phase. METHODS: We retrospectively analyzed 63 patients receiving assistance in driving-resumption after ABI. Patients were categorized into two groups: driving-resumption-possible and driving-resumption-difficult. Discriminant analysis delineated characteristics of patients experiencing driving-resumption difficulty. Additionally, significant predictors were analyzed using ROC curves. RESULTS: 42 patients were able to resume driving, and 21 experienced difficulties in driving resumption. Factors predicting difficulty returning to driving were age, history of falls, TMT Part B, and ROCF. Furthermore, cut-off values for each were 72 years, 148 seconds for TMT Part B, and 29.5 points for ROCF. CONCLUSIONS: Patients with advanced age, history of falls, delayed TMT Part B, and poor ROCF outcomes may face challenges in resuming driving after ABI. These factors may serve as a valuable metric to assess driving resumption difficulties after ABI.

Predictive Validity of the Scale for the Assessment and Rating of Ataxia for Medium-Term Functional Status in Acute Ataxic Stroke.

OBJECTIVES: This study examines the prognostic validity of the Scale for the Assessment and Rating of Ataxia for patients with acute stroke. MATERIALS AND METHODS: We enrolled 120 patients with posterior circulation stroke having ischemic or hemorrhagic lesions with ataxia who had physical therapy. We recorded the clinical stroke features and obtained the scale for the assessment and rating of ataxia and National Institutes of Health Stroke Scale scores 7 days after admission and at discharge. Predictive factors for a 3-month modified Rankin Scale score of <3 were investigated. RESULTS: During hospitalization, the Scale for the Assessment and Rating of Ataxia score decreased from 7.5 (interquartile range, 4.5-12.5) to 4.0 (interquartile range, 1.5-8.0) points, whereas the National Institutes of Health Stroke Scale score changed from 1 (interquartile range, 0-3) to 1 (interquartile range, 0-2) point. A significant correlation between functional outcome and the Scale for the Assessment and Rating of Ataxia scores 7 days after onset was observed. The cutoff value for the assessment and rating of ataxia for predicting favorable outcome (modified Rankin scale, 0-2) at 3 months post-onset was 14 points (0-40) at 7 days after onset. CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia scores showed good responsiveness to neurological changes in patients with acute ataxic stroke, could predict functional outcomes 3 months after onset on day 7, and could be a useful and reliable marker for patients with ataxic stroke.

Arterial Spin Labeling Magnetic Resonance Imaging for Differentiating Acute Ischemic Stroke from Epileptic Disorders.

BACKGROUND: Differential diagnosis between acute ischemic stroke (AIS) and epilepsy-related stroke mimics is sometimes difficult in the emergency department. We investigated whether a combination of diffusion-weighted imaging (DWI) and arterial spin labeling imaging (ASL) is useful in distinguishing AIS from epileptic disorders. METHODS: The study included suspected AIS patients who underwent emergency MRI including both DWI and ASL, and who exhibited DWI high-intensity lesions corresponding to neurological symptoms. We investigated the relationship between the ASL results from within and/or around DWI lesions and the final clinical diagnosis. RESULTS: Eighty-five cases were included (mean age, 71 ± 13 years; 47 men). The time from onset to the MRI examination was 493 ± 536 minutes. ASL showed hyperintensity in 13 patients, isointensity in 43, and hypointensity in 29. All ASL hyperintensities were observed in the cortex, with 4 patients (31%) presenting with AIS and 9 (69%) with an epileptic disorder. All of the AIS patients with ASL hyperintensity were diagnosed with cardioembolic stroke (4/4, 100%), with magnetic resonance angiography demonstrating recanalization of the occluded artery in all cases (4/4, 100%). In the 9 patients with an epileptic disorder, the area of ASL hyperintensity typically extended beyond the vascular territory (7/9, 78%) and involved the ipsilateral thalamus (7/9, 78%). All patients with ASL isointensity and hypointensity were diagnosed with AIS; none had epileptic disorders. CONCLUSIONS: Although cortical ASL hyperintensity can indicate cardioembolic stroke with recanalization, hyperintensity beyond the vascular territory may alternatively suggest an epileptic disorder in suspected AIS patients with DWI lesions.

[A case of autoimmune hemolytic anemia diagnosed by occurrence of cardioembolic stroke].

A 79-year-old woman came to us because of sudden onset of dysarthria. She had taken apixaban due to her non-valvular atrial fibrillation. A neurological examination revealed mild facial palsy of her right side, and magnetic resonance imaging showed acute brain infarction at the left frontal lobe. There were no stenotic lesions on intracranial or extracranial magnetic resonance angiography, and she was diagnosed with cardioembolic stroke. Intravenous infusion of heparin and edaravone was initiated, and her neurological symptoms improved. However, she gradually developed jaundice and anemia. Gastro-intestinal bleeding was not observed, and her blood test met the diagnostic criteria for hemolytic anemia. Because both the direct Coombs test and cold agglutinin were positive, she was diagnosed with mixed-type autoimmune hemolytic anemia. Although her serum hemoglobin level decreased to 7.0 g/dl on the 12th hospital day, her anemia gradually improved after steroidal therapy with transfusion. It was revealed that she had shown mild anemia (hemoglobin: 9.2-10.9 g/dl) and hyperbilirubinemia (total bilirubin: 1.8-2.6 mg/dl) for 6 months. Therefore, her latent autoimmune hemolytic anemia became activated with the occurrence of cardioembolic stroke. Autoimmune hemolytic anemia might have promoted cardiac thrombus formation despite the administration of an anticoagulant in this case. It should be noted that autoimmune hemolytic anemia can develop as thrombotic disease. In the present case, autoimmune hemolytic anemia was diagnosed based on the development of cardioembolic stroke.

A case of hyperparathyroidism-associated parkinsonism successfully treated with cinacalcet hydrochloride, a calcimimetic.

BACKGROUND: Some metabolic disorders, including abnormal calcium metabolism, can develop and worsen parkinsonism. However, whether hyperparathyroidism can cause parkinsonism remains controversial. CASE PRESENTATION: An 83-year-old woman with a history of right thalamic hemorrhage and drug-induced parkinsonism, was admitted due to worsening of parkinsonian symptoms including mask-like face, bradykinesia, freezing of gait, and rigidity. She had been diagnosed with autoimmune hepatitis and was being treated with prednisolone. Examinations revealed hypercalcemia (14.3 mg/dL) with an increased level of intact parathyroid hormone (iPTH) (361 pg/mL). Her symptoms were resistant to some additional anti-parkinsonian drugs; however, cinacalcet hydrochloride, a calcimimetic for the treatment of secondary hyperparathyroidism, normalized levels of serum calcium and iPTH, and remarkably improved her symptoms. CONCLUSIONS: In the present case, we speculate that hypercalcemia probably due to secondary hyperparathyroidism that had developed during steroid therapy deteriorated the parkinsonism.

Paradoxical Brain Embolism in Elderly Subjects with Small Atrial Septal Defects.

BACKGROUND: Atrial septal defects have a low prevalence in the general population, and are recognized as a rare cause of paradoxical brain embolism. METHODS: We extensively examined stroke causes in patients with acute stroke admitted to a single stroke center within 1 year. RESULTS: Among 186 consecutive patients, transesophageal or transthoracic echocardiography revealed 5 cases of paradoxical brain embolism: 3 (1.6%) were related to atrial septal defects, whereas 2 were patent foramen ovale patients. Although right-to-left shunt may have occurred after the development of acute pulmonary embolism in atrial septal defects case #1, the Valsalva maneuver elicited right-to-left shunt in atrial septal defects cases #2 and #3. The 3 cases were elderly (>60 years old), harbored small defects with normal systemic hemodynamics, and had not experienced any clinical symptoms related to atrial septal defects. CONCLUSIONS: Small atrial septal defect may cause paradoxical embolism as its initial related event, particularly in elderly subjects.

Histopathology of Giant Coronary Artery Aneurysm Associated with Coronary Artery Fistula.

Giant coronary artery aneurysms related to coronary fistula are rare, and the precise mechanisms by which they occur are unknown. We present a case of giant coronary artery aneurysm of the left coronary artery to the pulmonary artery fistula with a lack of internal and (or) external elastic lamina and medial degeneration.

Postural Orthostatic Tachycardia in a Patient with Type 2 Diabetes with Diabetic Neuropathy.

A 24-year-old Japanese man with type 2 diabetes mellitus and diabetic neuropathy was admitted to our ward to evaluate the cause of orthostatic intolerance. During a head-up tilt test, his heart rate increased from 105 to 155 beats/minute within 3 minutes, and chest discomfort began. He was diagnosed with postural orthostatic tachycardia syndrome (POTS), and orthostatic intolerance disappeared after ß-blocker treatment. Scintigraphy using 123I-metaiodobenzylguanidine showed decreased cardiac uptake. Power spectral analysis of heart rate variability for 24 hours in Holter electrocardiography demonstrated decreases in both sympathetic and parasympathetic nervous system activities, with a greater decrease in parasympathetic activity than sympathetic activity. The relative sympathetic hyperactivity in the present patient with diabetic neuropathy seemed to be related to POTS.

Causes of Ischemic Stroke in Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: Oral anticoagulants (OACs) reduce the incidence of embolic events associated with non-valvular atrial fibrillation (NVAF); however, ischemic stroke can still occur in such patients. Although there are various causes of ischemic stroke in patients with NVAF, their medication status at onset has scarcely been studied. This retrospective study aimed to determine the underlying causes of ischemic stroke in patients with NVAF in relation to pre-stroke anticoagulation. METHODS: Among Japanese patients with acute ischemic stroke enrolled in the Fukuoka Stroke Registry from June 2007 to May 2013, 1,302 patients with NVAF who had been hospitalized within 24 h of onset were included in this study, and their backgrounds, pre-stroke use of OACs and prothrombin time-international normalized ratio (PT-INR) on admission were investigated. Strokes were regarded as being non-cardioembolic (CE) type when causes other than NVAF had been identified. The sub-therapeutic range (TR) for warfarin was defined according to Japanese guidelines for pharmacotherapy of atrial fibrillation. RESULTS: Atrial fibrillation had been diagnosed prior to onset of stroke in 704 of 1,302 patients (54%). However, it had not been detected before or on admission, but identified later during hospitalization in 270 patients (21%). Of the patients who had atrial fibrillation on admission but had not been diagnosed as having it, 108 (8%) had not received any medication before onset of stroke and 220 (17%) had received medications other than OACs. OACs had been administered to 415 (59%) of the patients with known atrial fibrillation. The proportion of pre-stroke CHADS2 or CHA2DS2-VASc scores ≥1 ranged from 93 to 99% depending on whether atrial fibrillation had been diagnosed or anticoagulation therapy administered before stroke onset. The PT-INR was in the sub-TR on admission in 283 of 399 patients (71%) receiving warfarin. Male sex, smoking and previous stroke were more prevalent in patients with values within or over the TR of PT-INR than in those in the sub-TR. Non-CE stroke was more prevalent in patients with values above the lower therapeutic limit of the recommended PT-INR than in those in the sub-TR (p < 0.001). The number of CE strokes was much smaller in patients with high admission PT-INR values; this was not observed for non-CE ischemic strokes (p < 0.001). CONCLUSIONS: In the clinical setting, under-diagnosis, underuse and sub-therapeutic doses of OACs are major causes of ischemic stroke in patients with NVAF. However, non-CE ischemic strokes may develop in patients receiving therapeutic doses of warfarin.

Epileptic Ictal Hyperperfusion on Arterial Spin Labeling Perfusion and Diffusion-Weighted Magnetic Resonance Images in Posterior Reversible Encephalopathy Syndrome.

BACKGROUND: The hemodynamic state of the posterior dominant vasogenic edema in posterior reversible encephalopathy syndrome (PRES) is controversial. The aim of this retrospective study was to examine the contribution of epileptic ictal hyperperfusion in patients with PRES using combined magnetic resonance perfusion imaging with arterial spin labeling (ASL) and diffusion-weighted magnetic resonance imaging (MRI). METHODS: A detailed review of chronological MRI findings in 2 patients, including diffusion-weighted imaging (DWI) and ASL, with special reference to clinical and electroencephalographic findings, was performed. At the onset of PRES, both patients developed secondary generalized seizures. RESULTS: At the first PRES episode in Case 1, ASL and DWI clearly depicted "ictal hyperperfusion" and prolonged epilepsy-induced cytotoxic edema in the left parieto-occipital lobe cortex, located around the vasogenic edema of the PRES lesion in the left occipital lobe (hypoperfused area). At the second and third episodes (2 and 7 months after the first episode, respectively), although recurrent PRES was ruled out, ASL and DWI clearly demonstrated ictal hyperperfusion in the left posterior temporal and parieto-occipital lobes associated with partial nonconvulsive status epilepticus, which developed around the PRES-related old hematoma lesion. In Case 2, peri-ictal MRI findings of ictal ASL hyperperfusion and cortical hyperintensity on DWI were also noted in the left parieto-occipital lobe, but were mild compared with Case 1. CONCLUSIONS: Combined use of DWI and ASL can provide information on hemodynamic state associated with epileptic ictal hyperperfusion in the various phases of PRES.

Arterial Spin Labeling Perfusion Magnetic Resonance Image with Dual Postlabeling Delay: A Correlative Study with Acetazolamide Loading (123)I-Iodoamphetamine Single-Photon Emission Computed Tomography.

BACKGROUND: Perfusion magnetic resonance image with arterial spin labeling (ASL) provides a completely noninvasive measurement of cerebral blood flow (CBF). However, arterial transient times can have a marked effect on the ASL signal. For example, a single postlabeling delay (PLD) of 1.5 seconds underestimates the slowly streaming collateral pathways that maintain the cerebrovascular reserve (CVR). To overcome this limitation, we developed a dual PLD method. SUBJECTS AND METHODS: A dual PLD method of 1.5 and 2.5 seconds was compared with (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading to assess CVR in 10 patients with steno-occlusive cerebrovascular disease. RESULTS: In 5 cases (Group A), dual PLD-ASL demonstrated low CBF with 1.5-second PLD in the target area, whereas CBF was improved with 2.5-second PLD. In the other 5 cases (Group B), dual PLD-ASL depicted low CBF with 1.5-second PLD, and no improvement in CBF with 2.5-second PLD in the target area was observed. On single-photon emission computed tomography, CVR was maintained in Group A but decreased in Group B. CONCLUSIONS: Although dual PLD methods may not be a completely alternative test for (123)I-iodoamphetamine single-photon emission computed tomography with acetazolamide loading, it is a feasible, simple, noninvasive, and repeatable technique for assessing CVR, even when employed in a routine clinical setting.

Arterial Spin-Labeling Magnetic Resonance Perfusion Imaging with Dual Postlabeling Delay in Internal Carotid Artery Steno-occlusion: Validation with Digital Subtraction Angiography.

BACKGROUND: Arterial spin-labeling magnetic resonance perfusion imaging (ASL-MRI) allows noninvasive measurement of cerebral blood flow (CBF) but depends on the arterial transit time (ATT). With the commonly used single postlabeling delay (PLD) of 1.5 seconds, slow flow through collateral vessels may be underestimated. We used both 1.5 and 2.5 seconds to overcome this problem. We validated these PLD settings by measuring the ATT and identifying the angiographic circulation using digital subtraction angiography (DSA). METHODS: We retrospectively selected 5 patients with unilateral occlusion or stenosis of the internal carotid artery (ICA) in whom ASL-MRI showed low CBF with 1.5-second PLD in the target area and improved CBF with 2.5-second PLD. We then compared the ASL-MRI findings visually with DSA findings at 1.5 and 2.5 seconds after injection of the contrast. When arterial transit artifacts (ATAs), attributed to stagnant intravascular spin-labeled blood, were observed, DSA findings were analyzed visually at 4.5 seconds. RESULTS: DSA revealed that the hypovascular area seen at 1.5 seconds was improved via the primary and secondary collaterals and delayed anterograde flow at 2.5 seconds. Serpiginous or round-shaped ATAs, which appeared in nearly the same configuration on dual PLD ASL-MRI, were attributed to stagnant collaterals and flow in the M2 portion of the middle cerebral artery and ICA during the late venous phase. CONCLUSIONS: Use of dual PLD times was validated by the DSA findings. ATA detection using the dual PLDs also differentiated well-developed and stagnant collateral vessels from focal hyperperfusion.

Nonconvulsive partial status epilepticus mimicking recurrent infarction revealed by diffusion-weighted and arterial spin labeling perfusion magnetic resonance images.

"Non-convulsive" partial status epilepticus (SE) is an important pathologic condition that should be differentiated from cerebral infarction. Herein, we reported 2 patients who had partial SE associated with old infarction in the right parietal lobe. Each patient had 2 episodes of left hemiparesis and hemisensory disturbance without convulsion. On diffusion-weighted magnetic resonance images (DW-MRI), a hyperintense lesion was noted in the cortex around the old infarction lesion, and recurrent infarction was suspected. Although electroencephalography (EEG) failed to reveal ictal discharges or interictal paroxysmal activities in 3 of 4 episodes, perfusion images with arterial spin labeling (ASL) clearly demonstrated ictal hyperperfusion in the area corresponding to the cortical hyperintense lesion on DW-MRI. After appropriate anticonvulsant treatment based on the diagnosis of partial SE, clinical symptoms were completely improved. These data stress the importance of cortical hyperintensity on DW-MRI and ictal ASL hyperperfusion, even when SE cannot be determined from EEG.

[Infection Control Effect of Dietary Fluid with Whey Peptide in the Management of Patients with Severe Intracranial Hemorrhage During the Acute Stage].

UNLABELLED: Abstract BACKGROUND AND PURPOSE: Patients with severe intracranial hemorrhage (ICH) often develop infectious complications during the acute stage. Animal experiments have demonstrated that enteral immunonutrition with a dietary fluid containing whey peptide (WP) enhances immunoactivity and prevents infection. The aim of the current study was to investigate the infection control effect of WP in the clinical management of patients with severe ICH. METHODS: Fourteen patients with ICH were given enteral nutrition from January 2012 to December 2012. Nine patients were given WP (WP group) and the other five were given control dietary fluid (Non-WP group) for two weeks. We retrospectively analyzed the incidence of infectious complications and chronological changes in white blood cell (WBC) count, C-reactive protein (CRP), and total lymphocyte count. RESULTS: All patients in the Non-WP Group experienced infectious complications, whereas 5 out of 9 patients in the WP Group did not experience them. There was a tendency for a decrease in WBC count and CRP value in the WP group. In contrast, WBC and CRP increased in 3 patients in the Non-WP Group. Total lymphocyte count tended to increase earlier in the WP Group; however this tendency was not noted in the Non-WP Group. CONCLUSION: Although the number of cases was small, our study suggests that WP might have an infection control effect, capable of preventing infectious complications associated with severe ICH in the acute stage.

Factors influencing the reduction in quadriceps muscle thickness in the paretic limbs of patients with acute stroke.

BACKGROUND & AIMS: Muscle atrophy is an early event that occurs after stroke, but there are few reports on the changes in skeletal muscle thickness in acute stroke. This study investigated the factors contributing to reduced muscle thickness in patients with acute stroke. METHODS: In total, 51 patients with stroke and the National Institute of the Health Stroke Scale (NIHSS) > 3 were included in our study. They were admitted to our hospital between July 2017 and May 2020. The quadriceps muscle thickness was measured with an ultrasound device within 2 days after admission and 14 days later. The collected data included age, sex, body mass index, stroke type, neuromuscular electrical stimulation, NIHSS, serum albumin at admission, start of enteral nutrition, Functional Oral Intake Scale (FOIS), start of mobilization and ambulation, number of physical and occupational therapy units, C-reactive protein at admission and whether surgery had been performed. These data were retrospectively retrieved from medical documents. A dietician calculated energy intake, protein intake, and energy adequacy. Multiple regression analysis was used to identify the factors associated with reduced quadriceps muscle thickness. The independent variables were NIHSS, date of start of enteral feeding, protein intake, FOIS, date of mobilization, and date of start of ambulation training. RESULTS: The rate of change in quadriceps muscle thickness of the paretic limb was -15.3 % (interquartile range, -46.1-14.8 %). Multiple regression analysis showed that the factors responsible for the decrease in muscle thickness on the paretic side were FOIS (ß: 0.376; 95 % Cl, 0.999 to 4.541) and the start date of ambulation (ß: -0.378; 95 % Cl, -2.575 to -0.543), with a multiple correlation coefficient of 0.456. CONCLUSION: The FOIS and the start date of ambulation after acute stroke were related to the rate of reduction in muscle thickness on the paretic side.

Amyloid Deposition Mainly Localized in the Basal Area of the Left Ventricle in a Patient with Amyloid Transthyretin Cardiac Amyloidosis.

A 74-year-old Japanese man was admitted to our hospital for catheter ablation of paroxysmal atrial fibrillation. Transthoracic echocardiography revealed basal interventricular septal hypertrophy without apical sparing. Cardiac magnetic resonance imaging revealed late gadolinium enhancement in the hypertrophic lesions. The Kumamoto criteria was one point, and the patient had no carpal tunnel syndrome. However, technetium-99m pyrophosphate scintigraphy revealed an accumulation in the basal region of the left ventricle. A skin biopsy revealed transthyretin (TTR) amyloid deposition. A TTR gene examination revealed no variants. This case suggests that amyloid deposition in TTR may occur in the basal area of the interventricular septum.

Polymorphic Ventricular Tachycardia Associated with Coronary Vasospasm in a Patient with Coronavirus Disease 2019 Infection.

A 70-year-old man was admitted to our hospital for restoration of sinus rhythm from atrial fibrillation by direct current counter shocks. On admission, he had a coronavirus disease 2019 (COVID-19) infection and syncope during bed rest. Electrocardiography revealed polymorphic ventricular tachycardia after ST-segment elevation with a normal QT interval. Coronary angiography revealed coronary vasospasm. Coronary vasospasm may be a cause of polymorphic ventricular tachycardia in COVID-19 patients.

Narrowing of the Parent Artery Angle Is Associated With Intracranial Aneurysm Growth.

OBJECTIVE: Although risk factors for intracranial aneurysm growth have been reported, studies investigating the influence of the parent artery angle are limited. In this study, we examined the relationship between intracranial aneurysm growth and parent artery angle narrowing by analyzing long-term follow-up magnetic resonance angiography data. METHODS: We retrospectively reviewed data of patients with untreated aneurysms and those treated by simple coil embolization, who were followed up by magnetic resonance angiography for over 24 months at the Steel Memorial Yawata Hospital between August 2007 and March 2023. We investigated the relationship of aneurysm growth with parent artery angle narrowing, age, sex, follow-up duration, previous subarachnoid hemorrhage, hypertension, smoking, aneurysm location, aneurysm type, maximum size, and neck size. RESULTS: A total of 180 aneurysms of 162 patients (women, n=113; untreated, n=136) were included. The median age at aneurysm diagnosis was 71 (63.8-76) years and the median follow-up duration was 69 (45-120) months. Among the 180 aneurysms, 41 (untreated, n=30; treated by simple coil embolization, n=11) showed growth during the follow-up period, with a risk of 4.4%/patient-year. In the univariable analysis, the parent artery angles on the initial and last follow-up images and angle change were significantly associated with aneurysm growth. However, in the multivariable analysis, the association remained significant only for angle change (odds ratio, 2.21; 95% confidence interval, 1.42-3.45). The cutoff value of parent artery angle change for intracranial aneurysm growth was -3.4°. CONCLUSION: Parent artery angle narrowing was significantly associated with intracranial aneurysm growth. This parameter may be useful for the monitoring of patients with unruptured intracranial aneurysms and may contribute to discerning the mechanism of intracranial aneurysm growth.

Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity: Prespecified Subgroup Analysis of the ANNEXA-4 Study in Japan.

AIMS: Andexanet alfa, a specific antidote to factor Xa (FXa) inhibitors, has been approved for clinical use in several countries, including Japan, based on the results from the phase 3 trial ANNEXA-4. We aimed to assess the efficacy and safety of andexanet alfa treatment in FXa inhibitor-related acute major bleeding in patients enrolled for ANNEXA-4 in Japan. METHODS: This prespecified analysis included patients enrolled at Japanese sites in the prospective, open-label, single-arm ANNEXA-4 trial. Eligible patients had major bleeding within 18 hours of oral FXa inhibitor administration. The coprimary efficacy endpoints were percent change in anti-FXa activity and proportion of patients achieving excellent or good hemostatic efficacy 12 hours post-treatment. RESULTS: A total of 19 patients were enrolled, all of whom had intracranial hemorrhage; 16 patients were evaluable for efficacy. Median percent reduction in anti-FXa activity from baseline to nadir was 95.4% in patients taking apixaban, 96.1% in patients taking rivaroxaban, and 82.2% in patients taking edoxaban. Overall, 14/16 patients (88%) achieved excellent or good hemostasis (apixaban, 5/5; rivaroxaban, 6/7; edoxaban, 3/4). Within 30 days, treatment-related adverse events (AEs) and serious AEs occurred in 2 and 5 patients, respectively. One patient died during follow-up, and 2 patients experienced thrombotic events. CONCLUSION: Treatment with andexanet alfa rapidly reduced anti-FXa activity with favorable hemostatic efficacy in Japanese patients with acute major bleeding. Serious AEs of thrombotic events during rapid reversal of anti-FXa activity arose as particular safety concerns in this population as with previous studies.