Efficacy and Safety of Elobixibat in Parkinson's Disease with Chronic Constipation: CONST-PD Study.

BACKGROUND: Chronic constipation is a common digestive complication of Parkinson's disease (PD). OBJECTIVES: To verify the usefulness of elobixibat, an ileal bile acid transporter inhibitor, for chronic constipation in PD. METHODS: This double-blind, placebo-controlled study consisted of a 2-week observation/washout period and a 4-week treatment period. All patients received a Bowel Movement Diary at Week -2 and were allocated to elobixibat (10 mg) or placebo at Week 0. Patients visited at Weeks 2 and 4 to report daily spontaneous bowel movements (SBM), stool form, drug use, quality of life (QOL), and safety. Changes in these parameters were assessed. RESULTS: The study included 38 patients in the elobixibat group and 39 in the placebo group, and 37 each completed the study. SBM frequency/week (mean ± standard deviation) increased significantly from 4.2 ± 2.6 at baseline to 5.9 ± 3.2 at Week 4 in the elobixibat group (P = 0.0079), but not in the placebo group (4.5 ± 2.7 to 5.3 ± 3.5; P = 0.0889). On analysis of covariance, the between-group difference in frequency changes at Week 4 (primary endpoint) was not significant after adjustment by baseline and sex (point estimate = 0.8; 95% confidence interval = -0.57 to 2.09, P = 0.2601), although a significant difference (P = 0.0011) was evidenced at Week 1 by a similar analysis. Stool form and scores of satisfaction and stigma were improved by elobixibat. Adverse events were as previously reported. CONCLUSIONS: Elobixibat improved the SBM frequency, though the defined primary endpoint was not evidenced. QOL parameters (stool consistency and treatment satisfaction) were also improved. Elobixibat may have therapeutic benefits in PD patients suffering from chronic constipation. TRIAL REGISTRATION INFORMATION: Trial Registration Number: JPRN-jRCTs031200172 (submitted: October 26, 2020; first patient enrolment: December 23, 2020; https://jrct.niph.go.jp/en-latest-detail/jRCTs031200172).

Microbial lipopolysaccharide-induced inflammation contributes to cognitive impairment and white matter lesion progression in diet-induced obese mice with chronic cerebral hypoperfusion.

AIMS: White matter lesions (WMLs) are involved in the pathological processes leading to cognitive decline and dementia. We examined the mechanisms underlying the exacerbation of ischemia-induced cognitive impairment and WMLs by diet-induced obesity, including lipopolysaccharide (LPS)-triggered neuroinflammation via toll-like receptor (TLR) 4. METHODS: Wild-type (WT) and TLR4-knockout (KO) C57BL/6 mice were fed a high-fat diet (HFD) or low-fat diet (LFD), and subjected to bilateral carotid artery stenosis (BCAS). Diet groups were compared for changes in gut microbiota, intestinal permeability, systemic inflammation, neuroinflammation, WML severity, and cognitive dysfunction. RESULTS: In WT mice, HFD induced obesity and increased cognitive impairment and WML severity compared with LFD-fed mice following BCAS. HFD caused gut dysbiosis and increased intestinal permeability, and plasma LPS and pro-inflammatory cytokine concentrations. Furthermore, HFD-fed mice had higher LPS levels and higher neuroinflammatory status, including increased TLR4 expression, in WMLs. In TLR4-KO mice, HFD also caused obesity and gut dysbiosis but did not increase cognitive impairment or WML severity after BCAS. No difference was found between HFD- and LFD-fed KO mice for LPS levels or inflammatory status in either plasma or WMLs. CONCLUSION: Inflammation triggered by LPS-TLR4 signaling may mediate obesity-associated exacerbation of cognitive impairment and WMLs from brain ischemia.

Impact of D-dimer for pathologic differentiation on transesophageal echocardiography in embolic stroke of undetermined source: a single-center experience.

BACKGROUND: Embolic stroke of undetermined source (ESUS) encompasses diverse embologenic mechanisms, which transesophageal echocardiography (TEE) is critical to detect. Specific markers related to each embolic source in ESUS is not fully studied. We focused on D-dimer levels, and explored the association of D-dimer with potential embolic sources (PES) identified on TEE in ESUS. METHODS: Consecutive patients with ESUS were included in this study. Clinical characteristics including D-dimer levels were compared between ESUS patients with and without TEE, and among none of, one, and at least two PES in ESUS patients undergoing TEE. Factors related to elevation of D-dimer were analyzed. RESULTS: A total of 211 patients (age, 69.3 ± 13.2 years; 149 males) with ESUS were enrolled. Of these, 115 received TEE, displaying significantly younger age and lower D-dimer levels than patients without TEE (P < 0.05), and 20 (17%), 61 (53%), and 34 (30%) patients were classified into none of, one, and ≥ two PES, respectively. On multiple logistic regression analysis, D-dimer levels were related to one PES (odds ratio [OR]: 9.01; 95% confidence interval [CI]: 1.00-81.51; P = 0.050) and PES ≥ two (OR: 9.76; 95% CI: 1.07-88.97; P = 0.043). Right-to-left shunt (RLS) with deep venous thrombosis (DVT)(OR: 13.94; 95% CI: 1.77-109.99; P = 0.012) and without DVT (OR: 3.90; 95% CI: 1.20-12.70; P = 0.024) were associated with elevation of D-dimer. CONCLUSIONS: D-dimer levels were higher in patients with PES. Among PES, RLS, with and without DVT, were associated with increase of D-dimer in ESUS.

Post-Treatment Plasma D-Dimer Levels Are Associated With Short-Term Outcomes in Patients With Cancer-Associated Stroke.

Background and Objective: Hypercoagulability is associated with increased risks of ischemic stroke and subsequent mortality in patients with active cancer. This study investigated the relationships between plasma D-dimer levels after stroke treatment and short-term outcomes in patients with cancer-associated stroke. Methods: This retrospective, observational, multicenter study analyzed consecutive patients with cancer-associated ischemic stroke. Hypercoagulability was assessed by plasma D-dimer levels before and after stroke treatment. Short-term outcomes were assessed in terms of poor outcomes (a modified Rankin Scale score >3), cumulative rates of recurrent ischemic stroke, and mortality at 30 days after admission. Results: Of 282 patients, 135 (47.9%) showed poor outcomes. Recurrent ischemic stroke was observed in 28 patients (9.9%), and the cumulative mortality rate was 12.4%. Multivariate analysis showed that post-treatment plasma D-dimer levels ≥10 µg/ml were independently associated with both poor outcomes (adjusted odds ratio [OR], 9.61; 95% confidence interval [CI], 3.60-25.70; P < 0.001) and mortality (adjusted OR, 9.38; 95% CI, 3.32-26.44; P < 0.001). Pre-treatment plasma D-dimer levels ≥10 µg/ml were not associated with these outcomes. Patients who received heparin had higher pre-treatment plasma D-dimer levels than those treated with other anticoagulants. Heparin produced a significant reduction in D-dimer levels from pre- to post-treatment without increasing the incidence of hemorrhagic events. Conclusion: A high plasma D-dimer level after stroke treatment was associated with poor short-term outcomes in patients with cancer-associated stroke. Using anticoagulants to reduce D-dimer levels may improve short-term outcomes in these patients.

Investigating the efficacy and safety of elobixibat, an ileal bile acid transporter inhibitor, in patients with Parkinson's disease with chronic constipation: a multicentre, placebo-controlled, randomised, double-blind, parallel-group stud (CONST-PD).

INTRODUCTION: Chronic constipation worsens the quality of life (QOL) of patients with Parkinson's disease (PD). Elobixibat, an ileal bile acid transporter inhibitor, is a useful laxative, but its effect on chronic constipation in patients with PD remains unclear. Therefore, we designed a placebo-controlled, randomised, double-blind study to investigate the efficacy and safety of elobixibat in patients with PD with chronic constipation. METHODS AND ANALYSIS: The study will consist of 2-week observation and 4-week treatment periods. Patients with clinically established PD will record the status of spontaneous bowel movements and use of rescue medications/concomitant medications in a Bowel Movement Diary from the start of the observation period at visit 1 (week -2). At visit 2 (week 0), patients will be assessed for final registration based on the diary records and physical examinations, and allocated to either the elobixibat or placebo group. Daily intake of the investigational drug will be recorded in the diary. Patients will undergo laboratory tests and answer constipation-related, PD-related and QOL-related questionnaires at visits 2 and 4 (week 4). Subjective symptoms and objective findings will be collected at visits 2, 3 (week 2) and 4. Since patients' motor function might be improved by treatment of constipation, the use of dopamine preparations will also be monitored. Bowel movement data and other parameters will be compared between groups.Safety information will be collected as adverse events, specifically focusing on those occurring in association with study conduct. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Helsinki Declaration, the Clinical Trials Act of the Japan Ministry of Health, Labour and Welfare, and related laws and regulations. The study was approved by the Juntendo University Certified Review Board. The results will be disseminated through an online study registry (Japan Registry of Clinical Trials), presented at scientific conferences, and published in medical journals. TRIAL REGISTRATION NUMBER: JPRN-jRCTs031200172; Pre-results.

An 88-year-old woman with acute disseminated encephalomyelitis following messenger ribonucleic acid-based COVID-19 vaccination.

A global pandemic has resulted from the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). To control the spread of SARS-CoV-2 infection, several SARS-CoV-2 vaccines have been developed and administered in a wide range of age groups. Messenger ribonucleic acid (mRNA)-based COVID-19 vaccines are the most widely used. We present the case of an 88-year-old woman who was diagnosed with acute disseminated encephalomyelitis (ADEM) following her second mRNA COVID-19 vaccination. She was admitted to hospital with disturbed consciousness (Glasgow Coma Scale E1V1M4) and gaze-evoked nystagmus. Brain magnetic resonance imaging revealed bilateral presence of middle cerebellar peduncle sign. Following steroid pulse therapy, clinical symptoms improved. The occurrence of ADEM following COVID-19 vaccination does not question the importance of vaccination programs during the COVID-19 pandemic. COVID-19 vaccines have been administered to individuals of a wide range of ages, from children to older adults. Thus, ADEM could occur following COVID-19 vaccination at any age, although ADEM is rare in older adults.

Hashimoto's encephalopathy with gait disturbance caused by sensory ganglionopathy: A case report and review of the literature.

Hashimoto's encephalopathy (HE) is a steroid-responsive encephalopathy characterized by several neurological symptoms. HE mainly involves the central nervous system; the peripheral nervous system is rarely involved. We treated a previously healthy elderly man showing mild cognitive decline and subacute progressive gait disturbance due to severe sensory deficits, including sensation of touch and deep sensation with elevated anti-NH2 terminal of α-enolase and anti-thyroid antibodies. His sensory disturbance symptoms improved after steroid therapy, suggesting that the neuropathy was related to HE. His disease was characteristic of HE in that his sensory deficits responded well and rapidly to steroid therapy. A nerve conduction study showed reduced sensory nerve action potentials in all limbs, indicating that his neuropathy was not "axonopathy", but "sensory ganglionopathy", which can occur concurrently with autoimmune disorders. Dysautonomia may be the responsible pathomechanism because of the vulnerability of the blood-nerve barrier at the ganglia. Although the pathophysiology of HE has not been clearly elucidated, autoimmune inflammation has been reported in a number of autopsy cases, indicating that sensory ganglionopathy can develop with HE. Therefore, HE should be recognized as one type of "treatable neuropathy".

Role of the Gut Microbiota in Stroke Pathogenesis and Potential Therapeutic Implications.

BACKGROUND: Major advances have been made in stroke treatment and prevention in the past decades. However, the burden of stroke remains high. Identification of novel targets and establishment of effective interventions to improve stroke outcomes are, therefore, needed. Recent research highlights the contribution of the gut microbiota to stroke pathogenesis. SUMMARY: Compositional and functional alterations of the gut microbiota, termed dysbiosis, are linked to stroke risk factors, such as obesity, metabolic diseases, and atherosclerosis. In acute cerebral ischemia, the gut microbiota plays a key role in bidirectional interactions between the gut and brain, referred to as the microbiota-gut-brain axis. Gut dysbiosis prior to ischemic stroke affects outcomes. Additionally, the brain affects the gut microbiota during acute ischemic brain injury, which in turn impacts outcomes. Interactions between the gut microbiota and stroke pathogenesis are mediated by several factors including bacterial components (e.g., lipopolysaccharide), gut microbiota-related metabolites (e.g., short-chain fatty acids and trimethylamine N-oxide), and the immune and nervous systems. Clinical studies have reported that patients with acute ischemic stroke exhibit gut dysbiosis, which is associated with host metabolism and inflammation, as well as functional outcomes. Modulation of the gut microbiota or its metabolites improves conditions related to stroke pathogenesis, including inflammation, cardiometabolic disease, atherosclerosis, and thrombosis. Key Messages: Accumulating evidence indicates that the gut microbiota plays a possible role in stroke pathogenesis. Modulation of the gut microbiota may provide a novel therapeutic strategy for the treatment and prevention of stroke.

Mucosal-Associated Invariant T Cells Are Involved in Acute Ischemic Stroke by Regulating Neuroinflammation.

Background Mucosal-associated invariant T (MAIT) cells have been associated with inflammation in several autoimmune diseases. However, their relation to ischemic stroke remains unclear. This study attempted to elucidate the role of MAIT cells in acute ischemic stroke in mice. Methods and Results We used MR1 knockout C57BL/6 (MR1-/-) mice and wild-type littermates (MR1+/+). After performing a transient middle cerebral artery occlusion (tMCAO), we evaluated the association with inflammation and prognosis in the acute cerebral ischemia. Furthermore, we analyzed the tMCAO C57BL/6 mice administered with the suppressive MR1 ligand and the vehicle control. We also evaluated the infiltration of MAIT cells into the ischemic brain by flow cytometry. Results showed a reduction of infarct volume and an improvement of neurological impairment in MR1-/- mice (n=8). There was a reduction in the number of infiltrating microglia/macrophages (n=3-5) and in their activation (n=5) in the peri-infarct area of MR1-/- mice. The cytokine levels of interleukin-6 and interleukin-17 at 24 hours after tMCAO (n=3-5), and for interleukin-17 at 72 hours after tMCAO (n=5), were lower in the MR1-/- mice. The administration of the suppressive MR1 ligand reduced the infarct volume and improved functional impairment (n=5). Flow cytometric analysis demonstrated there was a reduction of MAIT cells infiltrating into the ischemic brain at 24 hours after tMCAO (n=17). Conclusions Our results showed that MAIT cells play an important role in neuroinflammation after focal cerebral ischemia and the use of MAIT cell regulation has a potential role as a novel neuroprotectant for the treatment of acute ischemic stroke.

Cerebral Microbleeds and Chronic Kidney Disease in Acute Ischemic Stroke Patients with Atrial Fibrillation.

BACKGROUND: Cerebral microbleeds (CMBs) are associated with the risk of intracerebral hemorrhage in stroke patients with atrial fibrillation (AF). We investigated the association between CMBs and chronic kidney disease (CKD) in patients with acute ischemic stroke and AF. METHODS: We retrospectively examined consecutive patients with acute ischemic stroke and AF who underwent brain gradient-echo T2*-weighted magnetic resonance imaging. The number and distribution (lobar, deep or infratentorial, and mixed) of CMBs were assessed. Kidney function was assessed according to the estimated glomerular filtration rate (eGFR), which was calculated using a modified version of the Modification of Diet in Renal Disease equation. RESULTS: Of the 357 included patients, 105 (29.4%) had CMBs. CKD (eGFR < 60 mL/min/1.73 m2) was found in 131 (36.7%) patients. Patients with CKD showed a higher prevalence of any form of CMB (41.2% versus 22.6%, P < .001), deep or infratentorial CMBs (19.9% versus 9.3%, P < .01), and mixed CMBs (14.5% versus 5.3%, P < .01) than those without CKD. After adjusting for age and other confounding factors, CKD was found to be independently associated with the presence of any form of CMB (odds ratio 1.89, P = .02) and mixed CMBs (odds ratio 3.10, P < .01). Moreover, moderate to severe CKD (eGFR < 45 mL/min/1.73 m2) was independently associated with the presence of multiple CMBs (odds ratio 2.31, P = .04). CONCLUSIONS: CMBs and CKD are common in acute ischemic stroke patients with AF, and CKD may be a risk factor for CMBs. Further longitudinal studies are needed to evaluate whether maintaining kidney function can prevent the development of CMBs.

Metabolic endotoxemia promotes neuroinflammation after focal cerebral ischemia.

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria and a potent inflammatory stimulus for the innate immune response via toll-like receptor (TLR) 4 activation. Type 2 diabetes is associated with changes in gut microbiota and impaired intestinal barrier functions, leading to translocation of microbiota-derived LPS into the circulatory system, a condition referred to as metabolic endotoxemia. We investigated the effects of metabolic endotoxemia after experimental stroke with transient middle cerebral artery occlusion (MCAO) in a murine model of type 2 diabetes (db/db) and phenotypically normal littermates (db/+). Compared to db/+ mice, db/db mice exhibited an altered gut microbial composition, increased intestinal permeability, and higher plasma LPS levels. In addition, db/db mice presented increased infarct volumes and higher expression levels of LPS, TLR4, and inflammatory cytokines in the ischemic brain, as well as more severe neurological impairments and reduced survival rates after MCAO. Oral administration of a non-absorbable antibiotic modulated the gut microbiota and improved metabolic endotoxemia and stroke outcomes in db/db mice; these effects were associated with reduction of LPS levels and neuroinflammation in the ischemic brain. These data suggest that targeting metabolic endotoxemia may be a novel potential therapeutic strategy to improve stroke outcomes.

Eicosapentaenoic-to-Arachidonic Acid Ratio Predicts Mortality and Recurrent Vascular Events in Ischemic Stroke Patients.

AIMS: The ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) is related to major adverse events and death in cardiovascular diseases. The association between long-term prognosis of ischemic stroke and EPA/AA ratio has not been clarified. METHODS: Acute ischemic stroke patients who had undergone blood examinations for polyunsaturated fatty acids were enrolled. Major cardiovascular events, including recurrence of ischemic stroke, occurrence of cardiovascular and peripheral artery diseases and hemorrhagic stroke, and death, were analyzed, retrospectively. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, laboratory data including EPA/AA ratio, and treatments associated with major cardiovascular events and death. RESULTS: A total of 269 patients (mean age, 70±13 years; 179 men) were enrolled. During follow-up (mean, 2.3 ±1.0 years), 64 patients exhibited major cardiovascular events and death (annualized rate, 10.5% per person-year). Multivariate Cox analysis revealed that EPA/AA ratio (hazard ratio, 0.26; 95% confidence interval, 0.07- 0.99; p=0.048) and statin therapy (hazard ratio, 0.43; 95% confidence interval, 0.25-0.73; p=0.002) correlated inversely with major cardiovascular events and death. In the Kaplan-Meier analysis, cumulative event-free rates were significantly lower among patients with EPA/AA ratio ＜0.33 and patients without statin therapy (p=0.006). CONCLUSIONS: Low EPA/AA ratio at baseline and treatment without statins could predict mortality, recurrent ischemic stroke, cardiovascular and peripheral artery diseases, and hemorrhagic stroke among patients with acute ischemic stroke. The combination of baseline EPA/AA ratio and statin therapy could be critical in predicting the long-term prognosis of ischemic stroke patients.

Adequate Adherence to Direct Oral Anticoagulant is Associated with Reduced Ischemic Stroke Severity in Patients with Atrial Fibrillation.

BACKGROUND: The impact of adherence to direct oral anticoagulants (DOACs) is unknown. We aimed to assess the effects of preceding anticoagulation treatment on neurologic severity at admission and functional outcomes at discharge in patients with atrial fibrillation (AF) who developed acute ischemic stroke. METHODS: We retrospectively assessed consecutive patients with acute ischemic stroke and AF. Adherence to DOACs was assessed using the 4-item Morisky Medication Adherence Scale. Associations between preceding DOAC treatment and stroke severity at admission and functional outcomes at hospital discharge were examined. RESULTS: Of 387 patients with AF and acute ischemic stroke, 248 (64.1%) were not administered an anticoagulant before stroke onset, 95 (24.5%) had subtherapeutic warfarin with an international normalized ratio less than 2 at the time of stroke, 16 (4.1%) had therapeutic warfarin, 6 (1.6%) had DOACs with nonadherence, and 22 (5.7%) had DOACs with adequate adherence. Multivariate analysis showed that DOAC treatment with adequate adherence was associated with lower odds of severe stroke (National Institute of Health Stroke Scale ≥10 at admission) (odds ratio, .24; 95% confidence interval, .03-.98; P = .04) and higher odds of excellent recovery (modified Rankin Scale score, 0-1 at discharge) (odds ratio, 4.89; 95% confidence interval, 1.51-20.6; P < .01) compared with no anticoagulation therapy. CONCLUSIONS: Preceding DOAC treatment with adequate adherence has beneficial effects on stroke severity at admission and functional outcome at discharge in patients with AF. Hence, our results encourage an increased effort to bolster adherence to DOACs in patients with AF.

The Importance of Combined Antithrombotic Treatment for Capsular Warning Syndrome.

INTRODUCTION: Capsular warning syndrome (CWS) is characterized by recurrent conventional episodes of motor and/or sensory deficits without cortical symptoms. The purpose of this case series study was to evaluate the safety and appropriate treatment for CWS to prevent the development of complete stroke. METHODS: We reviewed our hospital records and previous reports to find patients with neurologically fluctuating profiles, and excluded those with unknown details of initial treatment/final treatment of antiplatelet therapy or radiological findings. RESULTS: We retrieved two cases of CWS from our hospital, which presented motor and/or sensory symptoms followed by complete resolution without complete ischemia. The recurring episodes in both were unable to be stabilized by single antiplatelet therapy but were successfully managed using two or more antiplatelet drugs. In 11 previously reported cases of CWS, the recurring episode was frequency stabilized with plural antiplatelet therapy. CONCLUSION: Multiplicate antiplatelet therapy is important for treatment of CWS, and caution is needed regarding hemorrhagic complications.

Age Stratification and Impact of Eicosapentaenoic Acid and Docosahexaenoic Acid to Arachidonic Acid Ratios in Ischemic Stroke Patients.

AIM: We focused on the ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) to arachidonic acid (AA) and explored the significance of these ratios relative to clinical characteristics by age in ischemic stroke patients. METHODS: We enrolled patients with acute ischemic stroke who underwent radiological investigations and laboratory examinations, including measurement of serum EPA, DHA, and AA levels, and controls. Patients were classified according to age (＜65, 65-74, and ≥ 75 years) and the tertile of EPA/AA and DHA/AA ratios, and clinical aspects were compared with these factors. RESULTS: We analyzed 373 patients (age 70.2±13.4 years; 245 males) and 105 controls. Among stroke patients, patients aged ＜65 years had the lowest EPA/AA (0.35±0.23, p=0.006) and DHA/AA (0.73±0.27, p＜0.001) ratios. Compared with controls, patients aged ＜65 years showed lower EPA/AA (vs. 0.49±0.25, p＜0.001) and DHA/AA (vs. 0.82±0.26, p=0.009) ratios. From logistic regression analysis, the EPA/AA (odds ratio 0.18, 95% confidence interval 0.04-0.81, p=0.026) and DHA/AA (odds ratio 0.09, 95% confidence interval 0.02-0.33, p＜0.001) ratios were inversely related to patients aged ＜65 years. According to age-stratified analyses, we found an association of aortic arch calcification with a lower EPA/AA ratio for patients aged ≥ 75 years and an association of multiple infarctions and cerebral white matter lesions with a lower EPA/AA ratio for patients aged 65-74 years (p＜0.05). CONCLUSIONS: The ratios of EPA/AA and DHA/AA could be specific markers for younger stroke patients. The EPA/AA ratio may be related to aortic arch calcification for elderly stroke patients and to multiple infarctions and cerebral white matter disease for middle-aged stroke patients.

Analysis of the Usefulness of the WORSEN Score for Predicting the Deterioration of Acute Ischemic Stroke.

BACKGROUND: Early neurological worsening is associated with increased mortality and long-term functional disability. We developed the WORSEN score for predicting whether patients with stroke will deteriorate during the week after stroke onset and investigated its usefulness. PATIENTS AND METHODS: We retrospectively investigated the cases of 478 patients who were admitted to Juntendo University Hospital between April 2007 and March 2009. Neurological deterioration was defined as a worsening of 4 points or higher on the National Institute of Health Stroke Scale score within 1 week of admission. Based on a previous study, we developed the WORSEN score, which was derived from the following factors: wrong (poor) blood sugar control (W), old myocardial infarction (O), radiological findings (R), infarct size (S), elevated low-density lipoprotein cholesterol (E), and neurological findings (N). Next, we investigated the utility of this scoring system in 456 other patients who were admitted to Juntendo University Hospital and Juntendo Urayasu Hospital between October 2013 and December 2014. RESULTS: First, we checked the utility of the WORSEN score for detecting worsening in cases of stroke. In the first patient group, deterioration was noted in 32.5% of the patients with scores higher than 3 points (sensitivity: .704 and specificity: .744). For checking reproductivity on using the second group, deterioration was detected in 36.1% of the patients with WORSEN scores higher than 3 points (sensitivity: .740 and specificity: .835). CONCLUSIONS: Careful attention should be paid to patients with acute stroke with high WORSEN scores. The WORSEN score might become a valuable tool for detecting the neurological deterioration of ischemic stroke.

Emerging Risk Factors for Recurrent Vascular Events in Patients With Embolic Stroke of Undetermined Source.

BACKGROUND AND PURPOSE: Underlying embolic causes diagnosed by transesophageal echocardiography could be implicated in mechanisms of embolic stroke of undetermined source. We aimed to explore factors, including underlying embolic causes, related to recurrent vascular events in embolic stroke of undetermined source. METHODS: Patients who fulfilled the diagnostic criteria for embolic stroke of undetermined source and whose potential embolic sources were examined by transesophageal echocardiography were included. Recurrent vascular events, including ischemic stroke, cardiovascular and peripheral artery diseases, and vascular death, were retrospectively analyzed. Cox proportional hazards regression analysis was used to explore factors, including clinical characteristics, embolic causes on transesophageal echocardiography, and the Calcification in the Aortic Arch, Age, Multiple Infarction score (CAM), based on the degree of aortic arch calcification on chest radiograph (0-3 points), age (≥70 years; 1 point), and multiple infarctions on magnetic resonance imaging (multiple infarcts in 1, 2, or ≥3 territories of large intracranial arteries, 1, 2, or 3 points) associated with recurrent vascular events. RESULTS: A total of 177 patients (age, 64.1±14.2 years; 127 men) were enrolled. Thirty-one patients had recurrent vascular events (follow-up, 3.5±2.7 years; annualized rate, 5.0% per person-year). Among embolic causes on transesophageal echocardiography, incidence of recurrent vascular events was high in patients with large aortic arch plaques (7.5% per person-year). Diabetes mellitus (hazard ratio, 2.56; 95% confidence interval, 1.23-5.32; P=0.012) and CAM score grade (hazard ratio, 2.29; 95% confidence interval, 1.11-4.72; P=0.026) predicted recurrent vascular events. CONCLUSIONS: History of diabetes mellitus and the CAM score could be novel risk factors for recurrent vascular events in embolic stroke of undetermined source.

Diagnostic Utility of Splenial Lesions in a Case of Legionnaires' Disease due to Legionella pneumophila Serogroup 2.

We herein report the case of a 49-year-old man with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) associated with Legionnaires' disease due to Legionella pneumophila serogroup 2. Past reports suggest that Legionella infection is frequent in cases of MERS-associated pneumonia. Obtaining an early diagnosis of legionella infection is a challenge, especially if a Legionella pneumophila serogroup other than serogroup 1 contains the causative agent. In this case, the splenial lesion played an important role in recognizing the legionella infection. We suggest that legionella infection should be considered as a differential diagnosis in cases of splenial lesions associated with pneumonia.

Three cases of cervicocephalic artery dissection in an amusement park.

About 20 cases of cerebrovascular accidents in amusement parks have been documented. However, only a few cases of amusement park stroke (APS) after roller coaster rides have been reported. Here, we present triggers of stroke, clinical characteristics, and the angiographic appearance of 3 consecutive patients of APS. Their clinical characteristics included young age, absence of atherosclerotic risk factors, and severe injuries. Serial changes in angiographic appearance led to the diagnosis of cervicocephalic artery dissection (CAD). Patients A and B were diagnosed with isolated middle cerebral artery (MCA) dissection, and patient C was diagnosed with internal carotid artery dissection involving MCA dissection. Running excitedly toward an attraction in patient A, a go-kart ride in patient B, and riding in an enhanced motion vehicle in patient C were considered as the likely triggers for APS. We had specific cases with APS associated with CAD, which can occur under diverse contexts other than roller coaster rides at amusement parks. Our findings suggest that the variable directions of the high gravitational forces induced by vehicle riding or running excitedly might injure the MCA or internal carotid artery, and thereby cause CAD in the amusement park.