Body temperature in the acute phase and clinical outcomes after acute ischemic stroke.

BACKGROUND: This study aimed to examine whether post-stroke early body temperature is associated with neurological damage in the acute phase and functional outcomes at three months. METHODS: We included 7,177 patients with acute ischemic stroke within 24 h of onset. Axillary temperature was measured daily in the morning for seven days. Mean body temperature was grouped into five quintiles (Q1: 35.1‒36.5°C, Q2: 36.5‒36.7°C, Q3: 36.7‒36.8°C, Q4: 36.8‒37.1°C, and Q5: 37.1‒39.1°C). Clinical outcomes included neurological improvement during hospitalization and poor functional outcome (modified Rankin scale score, 3-6) at three months. A logistic regression analysis was performed to evaluate the association between body temperature and clinical outcomes. RESULTS: The patient's mean (SD) age was 70.6 (12.3) years, and 35.7% of patients were women. Mean body temperature was significantly associated with less neurological improvement from Q2 (odds ratios [95% confidence interval], 0.77 [0.65-0.99] vs. Q1) to Q5 (0.33 [0.28-0.40], P for trend <0.001) even after adjusting for potential confounders, including baseline neurological severity, C-reactive protein levels, and post-stroke acute infections. The multivariable-adjusted risk of poor functional outcome linearly increased from Q2 (1.36 [1.03-1.79]) to Q5 (6.44 [5.19-8.96], P for trend <0.001). These associations were maintained even in the analyses excluding patients with acute infectious diseases. Multivariable-adjusted risk of poor functional outcome was higher in patients with early body temperature elevation on days 1-3 and with longer duration with body temperature >37.0°C. CONCLUSIONS: Post-stroke early high body temperature is independently associated with unfavorable outcomes following acute ischemic stroke.

Altered properties of amyloidogenic prion protein in genetic Creutzfeldt-Jakob disease with PRNP V180I mutation in response to pentosan polysulfate.

Genetic Creutzfeldt-Jakob disease (gCJD) with V180I prion protein gene (PRNP) mutation shows weaker prion protein (PrP) deposition histologically compared with sporadic CJD, and it is more difficult to detect protease-resistant prion protein in immunoblotting. However, we previously reported the autopsy case of a patient with V180I gCJD who was treated with pentosan polysulfate sodium (PPS); this case had increased protease-resistant PrP deposition. It has been suggested that PPS might reduce protease-resistant PrP; however, the detailed pharmacological and histopathological effects of PPS in humans remain unknown. We examined autopsied human brain tissue from four cases with V180I gCJD that were added to our archives between 2011 and 2021: two cases treated with PPS and two cases without PPS. We conducted a neuropathological assessment, including immunohistochemistry for PrP. We also performed immunoblotting for PrP on homogenate samples from each brain to detect protease-resistant PrP using both a conventional procedure and size-exclusion gel chromatography for the purification of oligomeric PrP. Both PPS-treated cases showed long survival time over 5 years from onset and increased PrP deposition with a characteristic pattern of coarse granular depositions and congophilic PrP microspheres, whereas the cases without PPS showed around 1-year survival from onset and relatively mild neuronal loss and synaptic PrP deposition. Although cortical gliosis seemed similar among all cases, aquaporin 4-expression as a hallmark of astrocytic function was increased predominantly in PPS cases. Immunoblotting of non-PPS cases revealed protease-resistant PrP in the oligomeric fraction only, whereas the PPS-treated cases showed clear signals using conventional procedures and in the oligomeric fraction. These unique biochemical and histopathological changes may reflect the progression of V180I gCJD and its modification by PPS, suggesting the possible existence of toxic PrP-oligomer in the pathophysiology of V180I gCJD and beneficial effects of PPS toward the aggregation and detoxication of toxic PrP-oligomer.

Decreased Estimated Glomerular Filtration Rate and Proteinuria and Long-Term Outcomes After Ischemic Stroke: A Longitudinal Observational Cohort Study.

BACKGROUND: It remains unclear how chronic kidney disease and its underlying pathological conditions, kidney dysfunction, and kidney damage, are associated with cardiovascular outcomes. This study aimed to determine whether kidney dysfunction (ie, decreased estimated glomerular filtration rate), kidney damage (ie, proteinuria), or both are associated with the long-term outcomes after ischemic stroke. METHODS: A total of 12 576 patients (mean age, 73.0±12.6 years; 41.3% women) with ischemic stroke who were registered in a hospital-based multicenter registry, Fukuoka Stroke Registry, between June 2007 and September 2019, were prospectively followed up after stroke onset. Kidney function was assessed by estimated glomerular filtration rate and categorized into G1: ≥60 mL/(min·1.73 m2), G2: 45-59 mL/(min·1.73 m2), and G3: <45 mL/(min·1.73 m2). Kidney damage was evaluated by proteinuria using a urine dipstick test and classified into P1: -, P2: ±/1+, and P3: ≥2+. Hazard ratios and 95% CI for events of interest were estimated by a Cox proportional hazards model. Long-term outcomes included recurrence of stroke and all-cause death. RESULTS: During the median follow-up of 4.3 years (interquartile range, 2.1-7.3 years), 2481 patients had recurrent stroke (48.0/1000 patient-years) and 4032 patients died (67.3/1000 patient-years). Chronic kidney disease was independently associated with increased risks of stroke recurrence and all-cause death even after adjustment for multiple confounding factors, including traditional cardiovascular risk factors. Both estimated glomerular filtration rate and proteinuria were independently associated with increased risks of stroke recurrence (multivariable-adjusted hazard ratio [95% CI], G3: 1.22 [1.09-1.37] versus G1, P3: 1.25 [1.07-1.46] versus P1) and death (G3: 1.45 [1.33-1.57] versus G1, P3: 1.62 [1.45-1.81] versus P1). In subgroup analyses, effect modifications were found in the association of proteinuria with death by age and stroke subtype. CONCLUSIONS: Kidney dysfunction and kidney damage were independently, but differently, associated with increased risks of recurrent stroke and all-cause death.

Usefulness of combining CISS and digital subtraction angiography in diagnosis of isolated posterior inferior cerebellar artery dissection.

A 63-year-old man was admitted to our stroke center with brain infarction in the left posterior inferior cerebellar artery (PICA) territory. The initial MRI showed no findings suggestive of arterial dissection, and post-discharge MRI showed no temporal changes. Digital subtraction angiography (DSA) revealed vasodilation of the proximal portion of the PICA but it was uncertain whether dissection was present. Discrepancy between the outer contour seen on constructive interference in steady state (CISS) MRI and the inner contour seen on DSA suggested the presence of intramural hematoma. The patient was diagnosed with brain infarction caused by isolated PICA dissection (iPICAD). Imaging evaluation of combined CISS and DSA may be particularly useful for identification of small iPICAD lesions.

Different hemodynamics of basal ganglia between moyamoya and non-moyamoya diseases using intravoxel incoherent motion imaging and single-photon emission computed tomography.

BACKGROUND: Moyamoya disease (MMD) and non-MMD have different pathogenesis, clinical presentation, and treatment policy. PURPOSE: To identify differences in hemodynamics between MMD and non-MMD using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT). MATERIAL AND METHODS: Patients who had undergone 99mTc-ECD or 123I-IMP SPECT, and IVIM imaging were retrospectively studied. IVIM imaging was acquired using six different b-values. Cerebral blood flow ratio (CBFR) in the basal ganglia was calculated using a standardized volume-of-interest template. The cerebellum was used as a reference region. IVIM perfusion fraction (f) was obtained using a two-step fitting algorithm. Elliptical regions of interest were placed in bilateral basal ganglia on the IVIM f map. Patients were classified into MMD and non-MMD groups. The correlation between CBFR and mean IVIM f (fmean) in the basal ganglia was evaluated using Spearman's rank correlation coefficient. RESULTS: In total, 20 patients with MMD and 28 non-MMD patients were analyzed. No significant differences in fmean were observed among MMD, affected hemisphere with non-MMD (non-MMDaff), and unaffected hemispheres with non-MMD (non-MMDunaff). A negative correlation was seen between fmean and CBFR in the MMD group (r = -0.40, P = 0.0108), but not in the non-MMD group (non-MMDaff, r = 0.07, P = 0.69; non-MMDunaff, r = -0.22, P = 0.29). No significant differences were found among MMD and non-MMD patients, irrespective of SPECT tracers. CONCLUSION: The combination of IVIM MRI and SPECT appears to allow non-invasive identification of differences in hemodynamics between MMD and non-MMD.

Usefulness of Ultrasonography in the Diagnosis and Follow-up of Extracranial Vertebral Artery Dissection.

Extracranial vertebral artery dissection is a cerebrovascular disease that occurs most commonly in young people. A 32-year-old man experienced sudden cervical pain and was diagnosed with left vertebral artery dissection after arterial changes were identified by ultrasonography. The reduction in the size of an intramural hematoma in the left vertebral artery and in the peak systolic velocity were evaluated over time. Computed tomography, magnetic resonance imaging, and cerebral angiography are generally performed to diagnose and follow-up extracranial vertebral artery dissection; however, carotid ultrasonography has an advantage over these modalities by enabling the simultaneous observation of vascular morphology and hemodynamics.

Ankle-Brachial Index and Cardio-Ankle Vascular Index as Predictors of Cognitive Decline Over Time After Carotid Endarterectomy.

OBJECTIVE: Patients with carotid stenosis risk cognitive impairment even after carotid endarterectomy (CEA) because of the long-term presence of vascular risk factors. Early prediction of cognitive decline is useful because early appropriate training for impaired cognitive domains can improve their functions. Ankle-brachial index (ABI) and cardio-ankle vascular index (CAVI) are frequently used as general indicators of systemic atherosclerosis and are associated with cognitive function in the general population. This study aimed to evaluate the utility of those vascular biomarkers for predicting cognitive decline in patients after CEA. METHODS: Patients who had undergone both CEA at our institute and cognitive evaluations between March 2016 and January 2022 were invited to participate in this study. Associations between ABI or CAVI three years before baseline and cognitive function at baseline were assessed retrospectively in 94 patients, and associations between ABI or CAVI at baseline and three-year changes in cognitive functions were assessed prospectively in 24 patients. Cognitive functions were assessed using the Frontal Assessment Battery (FAB) and Neurobehavioral Cognitive Status Examination (Cognistat). RESULTS: Low ABI three years before baseline was associated with poor performances on Cognistat and FAB at baseline. ABI, as a continuous measure, three years before baseline, showed positive linear associations with total Cognistat score and subscores for naming, construction, and judgment at baseline. The Wilcoxon signed-rank test showed that the total Cognistat score, total FAB score, and subscores for attention and inhibitory control declined after three years. CAVI at baseline was negatively associated with three-year changes in total Cognistat score and subscores for naming, construction, and memory. CONCLUSION: Cognitive function can decline over time in patients with carotid stenosis even after CEA. ABI and CAVI might be useful to predict cognitive function and its decline among patients who have undergone CEA.

Five-Year Changes in Cognitive Function and Their Predictor in Adult Moyamoya Disease.

OBJECTIVE: The long-term outcomes of cognitive function in moyamoya disease remain unknown. We aimed to assess 5-year changes in cognitive function in adult moyamoya disease patients and to evaluate the value of the magnetic resonance angiography (MRA) steno-occlusive score to predict cognitive changes. METHODS: Participants comprised 20 consecutive patients whose cognitive functions had been evaluated using the Frontal Assessment Battery (FAB) and Neurobehavioral Cognitive Status Examination (Cognistat) at baseline and reassessed 5 years later. RESULTS: The total FAB score and total Cognistat score were lower after 5 years in 9 patients each. The Wilcoxon signed-rank test showed that subscores for conceptualization and comprehension increased, while subscores for mental flexibility, programming, and inhibitory control significantly decreased after 5 years. The right MRA total score and right posterior cerebral artery score were negatively associated with 5-year changes in the total FAB score and total Cognistat score. The right posterior cerebral artery score was significantly associated with changes in subscores for mental flexibility, programming, sensitivity to interference, and construction. CONCLUSIONS: Specific cognitive domains can decline over time in patients with adult moyamoya disease. MRA findings might be useful for predicting future declines in cognitive function.

Right entorhinal cortical thickness is associated with Mini-Mental State Examination scores from multi-country datasets using MRI.

PURPOSE: To discover common biomarkers correlating with the Mini-Mental State Examination (MMSE) scores from multi-country MRI datasets. METHODS: The first dataset comprised 112 subjects (49 men, 63 women; range, 46-94 years) at the National Hospital Organization Kyushu Medical Center. A second dataset comprised 300 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (177 men, 123 women; range, 57-91 years). Three-dimensional T1-weighted MR images were collected from both datasets. In total, 14 deep gray matter volumes and 70 cortical thicknesses were obtained from MR images using FreeSurfer software. Total hippocampal volume and the ratio of hippocampus to cerebral volume were also calculated. Correlations between each variable and MMSE scores were assessed using Pearson's correlation coefficient. Parameters with moderate correlation coefficients (r > 0.3) from each dataset were determined as independent variables and evaluated using general linear model (GLM) analyses. RESULTS: In Pearson's correlation coefficient, total and bilateral hippocampal volumes, right amygdala volume, and right entorhinal cortex (ERC) thickness showed moderate correlation coefficients (r > 0.3) with MMSE scores from the first dataset. The ADNI dataset showed moderate correlations with MMSE scores in more variables, including bilateral ERC thickness and hippocampal volume. GLM analysis revealed that right ERC thickness correlated significantly with MMSE score in both datasets. Cortical thicknesses of the left parahippocampal gyrus, left inferior parietal lobe, and right fusiform gyrus also significantly correlated with MMSE score in the ADNI dataset (p < 0.05). CONCLUSION: A positive correlation between right ERC thickness and MMSE score was identified from multi-country datasets.

Oxidized Albumin and Cartilage Acidic Protein-1 as Blood Biomarkers to Predict Ischemic Stroke Outcomes.

Background: There is high demand for blood biomarkers that reflect the therapeutic response or predict the outcomes of patients with acute ischemic stroke (AIS); however, few biomarkers have been evidentially verified to date. This study evaluated two proteins, oxidized albumin (OxHSA) and cartilage acidic protein-1 (CRTAC1), as potential prognostic markers of AIS. Methods: The ratio of OxHSA to normal albumin (%OxHSA) and the level of CRTAC1 in the sera of 74 AIS patients were analyzed on admission (day 0), and at 1 and 7 days after admission. AIS patients were divided into two groups according to their modified Rankin Scale (mRS) at 3 months after discharge: the low-mRS (mRS < 2) group included 48 patients and the high-mRS (mRS ≥ 2) group included 26 patients. The differences in %OxHSA and CRTAC1 between the two groups on days 0, 1, and 7 were evaluated. Results: The mean %OxHSA values of the high-mRS group on days 0, 1, and 7 were significantly higher than those of the low-mRS group (p < 0.05). The CRTAC1 levels continuously increased from day 0 to day 7, and those of the high-mRS group were significantly higher than those of the low-mRS group on day 7 (p < 0.05). Conclusions: These results suggest that higher %OxHSA and CRTAC1 are associated with poor outcomes in AIS patients. An index that combines %OxHSA and CRTAC1 can accurately predict the outcomes of AIS patients.

Identification of predictors for mini-mental state examination and revised Hasegawa's Dementia Scale scores using MR-based brain morphometry.

PURPOSE: The early detection of cognitive function decline is crucial to help manage or slow the progression of symptoms. The Mini-Mental State Examination (MMSE) and revised Hasegawa's Dementia Scale (HDS-R) are widely used in screening for cognitive impairment. The purpose of this study was to explore common predictors of the two different cognitive testing systems using MR-based brain morphometry. MATERIALS AND METHODS: This retrospective study included 200 subjects with clinical suspicion of cognitive impairment who underwent 3D T1-weighted MRI at our institution between February 2019 and August 2020. Variables related to the volume of deep gray matter and 70 cortical thicknesses were obtained from the MR images using voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) and FreeSurfer software. The correlation between each variable including age and MMSE/HDS-R scores was evaluated using uni- and multi-variate logistic regression analyses. RESULTS: In univariate analysis, parameters include hippocampal volume and bilateral entorhinal cortex (ERC) thickness showed moderate correlation coefficients with both MMSE and HDS-R scores. Multivariate analysis demonstrated the right ERC thickness was the common parameter which significantly correlates with both MMSE and HDS-R scores (p < 0.05). CONCLUSION: Right ERC thickness appears to offer a useful predictive biomarker for both MMSE and HDS-R scores.

Left Atrial Appendage Flow Velocity and Multiple Infarcts in Cryptogenic Stroke.

BACKGROUND: To validate the hypothesis that cryptogenic stroke with multiple infarcts included embolic stroke due to left atrial appendage (LAA) dysfunction, the present retrospective observational study was aimed to clarify the association between LAA flow velocity (LAA-FV) and multiple infarcts in patients with cryptogenic stroke. METHODS: From consecutive patients with cryptogenic stroke admitted to our hospital within 7 days after onset, patients without brain magnetic resonance imaging (MRI) on admission or without transesophageal echocardiography (TEE) during acute hospitalization were excluded, and the remaining patients were enrolled. Multiplicity of fresh infarcts was assessed using diffusion-weighted images from brain MRI. LAA-FV was defined as LAA peak emptying flow velocity on TEE. RESULTS: Of 786 enrolled patients, 522 patients (66%) had a single infarct, and the remaining 264 patients (34%) had multiple infarcts. The percentage of multiple infarcts decreased with increasing quartiles of LAA-FV (p for trend <0.001). The adjusted odds ratio for multiple infarcts decreased with increasing quartiles of LAA-FV (adjusted odds ratio in the fourth quartile, 0.39; 95% confidence interval, 0.25-0.60; compared with the first quartile). LAA-FV as a continuous variable was negatively associated with multiple infarcts (adjusted odds ratio per 10 cm/s, 0.87; 95% confidence interval, 0.81-0.92). CONCLUSIONS: Reduced LAA-FV on TEE was associated with multiple infarcts in patients with cryptogenic stroke. The present findings indicate that cryptogenic stroke with multiple infarcts includes embolic stroke due to LAA dysfunction.

Dabigatran vs. Aspirin for Secondary Prevention After Embolic Stroke of Undetermined Source　- Japanese Subanalysis of the RE-SPECT ESUS Randomized Controlled Trial.

BACKGROUND: The international Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the EfficaCy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate versus Acetylsalicylic Acid in Patients with Embolic Stroke of Undetermined Source (RE-SPECT ESUS) trial did not demonstrate superiority of dabigatran over aspirin for reduction of recurrent strokes in patients with embolic strokes of undetermined source (ESUS). Based on pre-defined subanalyses, the safety and efficacy of dabigatran vs. aspirin in Japanese patients was assessed.Methods and Results:ESUS patients were randomized to receive either dabigatran (150 or 110 mg twice daily) or aspirin (100 mg once daily). Of 5,390 patients randomized, 594 were Japanese. Most Japanese patients (99.8%) underwent brain magnetic resonance imaging for trial screening, compared to 76.8% of non-Japanese (P<0.0001). In the Japanese cohort, over a 19.4-month median follow-up period, recurrent stroke as the primary outcome occurred in 20/294 patients (4.3%/year) in the dabigatran group and 38/300 (8.3%/year) in the aspirin group (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.32-0.94). Major bleeding occurred in 12 patients (2.5%/year) and 17 patients (3.5%/year), respectively (HR, 0.72; 95% CI, 0.34-1.52). In contrast, in the non-Japanese cohort, recurrent stroke occurred in 4.1%/year and 4.3%/year, respectively, showing no apparent difference in recurrent stroke for dabigatran vs. aspirin (HR, 0.91; 95% CI, 0.74-1.14). The P-interaction for treatment and region did not reach statistical significance (P=0.09). CONCLUSIONS: Dabigatran was putatively associated with a lower relative risk of recurrent stroke compared with aspirin in Japanese ESUS patients.

Ischemic Stroke Caused by Carotid Stump at the Common Carotid Artery.

An 84-year-old man developed motor aphasia and right hemiparesis on postoperative day 1 after orchiectomy for suspected malignant lymphoma. He had a history of thoracic endovascular aortic repair for aortic aneurysm using a bypass graft from the right subclavian artery to the left common carotid artery (CCA); however, the graft had become occluded six months later. Brain magnetic resonance imaging revealed acute cerebral infarctions in the left frontal lobe. Carotid ultrasonography revealed a stump at the left CCA, just below the bifurcation, formed by the occluded graft with an oscillating thrombus. This case was rare in that a CCA stump was identified as the embolic source of ischemic stroke.

Neurological Disorders Identified during Treatment of a SARS-CoV-2 Infection.

A 69-year-old man was admitted to our hospital under diagnosis of pneumonia due to severe acute respiratory syndrome-corona virus 2 (SARS-CoV-2) (Day 0). He underwent endotracheal intubation from Day 3. Although his respiratory condition improved and anesthetic drugs were discontinued, no cough reflex was observed despite intubation having been performed until Day 17. His tendon reflexes were also diminished. We suspected that he had developed Guillain-Barré syndrome (GBS), and administered intravenous immunoglobulin from Day 18. The absence of cough reflex improved and extubation was successfully performed on Day 23. Neurological disorders including GBS should be considered when intubated SARS-CoV-2 patients present with a loss of cough reflex during the treatment period.

Recurrent Guillain-Barré and Fisher Syndromes in Two Patients Who Were Subsequently Diagnosed with Aplastic Anemia.

Guillain-Barré (GBS) and Fisher (FS) syndromes rarely recur and the characteristics of recurrence have not been fully elucidated. We describe the cases of 2 patients with GBS or FS that recurred more than twice and who were subsequently diagnosed with aplastic anemia. Case 1 was a 66-year-old man who was diagnosed with aplastic anemia 10 months before admission with limb ataxia and a sensory disturbance of the distal limbs that developed 3 days after an upper respiratory tract infection. He had a history of double vision with ataxia at the ages of 38 and 56 years. Case 2 was a 66-year-old woman who had been treated for aplastic anemia 1 year previously. She had a history of upper limb weakness after upper respiratory tract infections at the ages of 39 and 60 years. Tendon reflexes were absent in both patients at the time of onset and they were respectively diagnosed with FS and GBS and treated with intravenous immunoglobulin. No neurological deficits persisted. Blood findings showed that both were positive for IgG type ganglioside antibodies and HLA-DR15. The positive HLA-DR15 might have been associated with the recurrent GBS or FS and the development of aplastic anemia.

Common carotid flow velocity is associated with cognitive function after carotid endarterectomy.

The relationship between ultrasonographic flow parameters and cognitive function has not been well studied. This study aimed to clarify associations between carotid flow velocity (FV) and cognitive function in patients with a history of carotid endarterectomy (CEA). Ninety-four patients who previously underwent CEA participated in this study. The Neurobehavioral Cognitive Status Examination (Cognistat) and Frontal Assessment Battery (FAB) were adopted to assess cognitive functions at a mean of 6.5 ± 3.2 years after CEA. End-diastolic flow velocity (EDV) of the left and right common carotid artery (CCA) was significantly associated with total Cognistat score (p < 0.001) and total FAB score (p < 0.05). Pulsatility index (PI) of the left CCA was significantly associated with total Cognistat score and total FAB score (p < 0.01). A cut-off right CCA EDV of 14.5 cm/s offered the most reliable predictor of the bottom 25th percentile of total Cognistat score (sensitivity 83.3%, specificity 61.0%, area under the curve (AUC) 0.731, p = 0.0060), while a cut-off left CCA PI of 1.83 was the most reliable predictor of the bottom 25th percentile of total FAB score (sensitivity 73.3%, specificity 60.0%, AUC 0.679, p = 0.0179). Left and right CCA EDV correlated with sub-components of comprehension, construction, judgment, programming (p < 0.01), and conceptualization (p < 0.05). Right CCA EDV correlated with similarity (p < 0.01), repetition, naming, and memory (p < 0.05). Left CCA PI correlated with attention, conceptualization (p < 0.01), repetition, construction, similarity, and mental flexibility (p < 0.05), while right CCA PI correlated with construction (p < 0.05). CCA FV may offer useful markers of cognitive functions in patients with a history of CEA.

Management of Antithrombotic Agents During Surgery or Other Kinds of Medical Procedures With Bleeding: The MARK Study.

Background Optimal management of antithrombotic agents during surgery has yet to be established. We performed a prospective multicenter observational study to determine the current status of the management of antithrombotic agents during surgery or other medical procedures with bleeding (MARK [Management of Antithrombotic Agents During Surgery or Other Kinds of Medical Procedures With Bleeding] study) in Japan. Methods and Results The participants were 9700 patients who received oral antithrombotic agents and underwent scheduled medical procedures with bleeding at 59 National Hospital Organization institutions in Japan. Primary outcomes were thromboembolic events, bleeding events, and death within 2 weeks before and 4 weeks after the procedures. We investigated the relationships between each outcome and patient demographics, comorbidities, type of procedure, and management of antithrombotic therapy. With respect to the periprocedural management of antithrombotic agents, 3551 patients continued oral antithrombotic agents (36.6%, continuation group) and 6149 patients discontinued them (63.4%, discontinuation group). The incidence of any thromboembolic event (1.7% versus 0.6%, P<0.001), major bleeding (7.6% versus 0.4%, P<0.001), and death (0.8% versus 0.4%, P<0.001) was all greater in the discontinuation group than the continuation group. In multivariate analysis, even after adjusting for confounding factors, discontinuation of anticoagulant agents was significantly associated with higher risk for both thromboembolic events (odds ratio: 4.55; 95% CI, 1.67-12.4; P=0.003) and major bleeding (odds ratio: 11.1; 95% CI, 2.03-60.3; P=0.006) in procedures with low bleeding risk. In contrast, heparin bridging therapy was significantly associated with higher risk for both thromboembolic events (odds ratio: 2.03; 95% CI, 1.28-3.22; P=0.003) and major bleeding (odds ratio: 1.36; 95% CI, 1.10-1.68; P=0.005) in procedures with high bleeding risk. Conclusions Discontinuation of oral antithrombotic agents and addition of low-dose heparin bridging therapy appear to be significantly associated with adverse events in the periprocedural period.

[Case report: transient ischemic stroke caused by internal carotid artery occlusion due to compression by pituitary apoplexy and hemodynamic mechanism].

An 87-year-old blind man was admitted due to repeatedly disturbed consciousness and fever. Brain CT showed a pituitary tumor with a hematoma and an occlusive lesion of the right internal carotid artery. He experienced consciousness disturbance and left limb weakness with hypotension for a few minutes on the day of admission. We considered pituitary apoplexy caused adrenal failure with hypotension and transient ischemic attack (TIA) induced by a hemodynamic mechanism. An increased dose of hydrocortisone improved the fever and hypotension, and resolved consciousness disturbance. This is a unique example of TIA caused by the occlusive lesion of the internal carotid artery compressed as a result of pituitary apoplexy and a hemodynamic mechanism.

Ischemic Stroke with Protein S Deficiency Treated by Apixaban.

A 57-year-old man with atherosclerosis obliterans was admitted with sudden-onset sensory aphasia and right hemiparesis. Brain MRI revealed acute cerebral infarctions in the left temporal lobe and magnetic resonance angiography showed occlusion of the posterior branch of the left middle cerebral artery. Transesophageal echocardiography and ultrasonography respectively confirmed a patent foramen ovale and deep vein thrombosis in the bilateral femoral veins. Blood findings showed low protein S antigen, low protein S activity, and a missense mutation of the PROS 1 gene. The administration of apixaban 10 mg BID prevented ischemic stroke recurrence and decreased the deep vein thrombosis. These outcomes indicated that apixaban may be alternative to warfarin for the secondary prevention of ischemic stroke in a patient with a protein S deficiency.