記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

DOI： 10.1016/j.jns.2023.120772

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. AIMS: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. METHODS: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. RESULTS: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). CONCLUSIONS: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.

DOI： 10.1177/17474930231185468

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 37-year-old man who had a low grade fever for 5 days admitted to our hospital due to disturbance of consciousness and seizure. Brain MRI showed abnormal hyperintensity in the bilateral temporal lobes, cortical and subcortical lesions on fluid-attenuated inversion recovery image. Treponemal and non-treponemal specific antibodies were positive in serum and cerebrospinal fluid, therefore he was diagnosed as having neurosyphilis. Treatment with intravenous penicillin G and metylpredonisolone improved his clinical symptons, imaging abnormalities and CSF findings. Patients of neurosyphilis with mesiotemporal encephalitis show common features such as young age, HIV-negative, subacute cognitive impairment and seizure, as seen in our case. Early diagnosis of neurosyphilis and appropriate treatment make clinical improvement, however the clinical diagnosis of neurosyphilis is sometime difficult because most patients present with disturbance of consciousness or seizure. The possibility of neurosyphilis should be considered when MRI results indicate temporal abnormalities.

DOI： 10.5692/clinicalneurol.cn-001811

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The effectiveness of long-term dual antiplatelet therapy (DAPT) to prevent recurrent strokes in patients with lacunar stroke remains unclarified. Therefore, this study aimed to compare and to elucidate the safety and effectiveness of DAPT and single antiplatelet therapy (SAPT) in preventing recurrence in chronic lacunar stroke. METHODS: CSPS.com (Cilostazol Stroke Prevention Study for Antiplatelet Combination) was a prospective, multicenter, randomized controlled trial. In this prespecified subanalysis, 925 patients (mean age, 69.5 years; 69.4% men) with lacunar stroke were selected from 1884 patients with high-risk noncardioembolic stroke, enrolled in the CSPS.com trial after 8 to 180 days following stroke. Patients were randomly assigned to receive either SAPT or DAPT using cilostazol and were followed for 0.5 to 3.5 years. The primary efficacy outcome was the first recurrence of ischemic stroke. The safety outcomes were severe or life-threatening bleeding. RESULTS: The DAPT group receiving cilostazol and either aspirin or clopidogrel and SAPT group receiving aspirin or clopidogrel alone comprised 464 (50.2%) and 461 (49.8%) patients, respectively. Ischemic stroke occurred in 12 of 464 patients (1.84 per 100 patient-years) in the DAPT group and 31 of 461 patients (4.42 per 100 patient-years) in the SAPT group, during follow-up. After adjusting for multiple potential confounding factors, ischemic stroke risk was significantly lower in the DAPT group than in the SAPT group (hazard ratio, 0.43 [95% CI, 0.22-0.84]). The rate of severe or life-threatening hemorrhage did not differ significantly between the groups (2 patients [0.31 per 100 patient-years] versus 6 patients [0.86 per 100 patient-years] in the DAPT and SAPT groups, respectively; hazard ratio, 0.36 [95% CI, 0.07-1.81]). CONCLUSIONS: In patients with lacunar stroke, DAPT using cilostazol had significant benefits in reducing recurrent ischemic stroke incidence compared with SAPT without increasing the risk of severe or life-threatening bleeding. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr; Unique identifier: UMIN000012180.

DOI： 10.1161/STROKEAHA.122.039900

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective In recent decades, living conditions have changed drastically. However, there are few data regarding the interaction between living conditions and the risk of ischemic stroke (IS) in young adults. The present study explored the association between living conditions or marital status and the risk factors, etiology, and outcome of IS in young adults. Methods We prospectively enrolled patients with incident IS who were 20-49 years old from 37 clinical stroke centers. We collected the demographic data, living conditions, marital status, vascular risk factors, disease etiology, treatment, and outcomes at discharge. A comparison group was established using the official statistics of Japan. We categorized patients into the two groups based on living conditions: solitary group and cohabiting group. Clinical characteristics were then compared between living conditions. Results In total, 303 patients were enrolled (224 men; median age at the onset: 44 years old). Significant factors associated with the incidence of IS were as follows: solitary status, body mass index >30 kg/m2, current smoking, heavy alcohol consumption, hypertension, diabetes mellitus, and dyslipidemia. Furthermore, in the solitary group, the proportions of men, unmarried individuals, and current smokers were significantly higher than in the cohabiting group. In addition, poor outcomes (modified Ranking Scale ≥ 4) of IS were more common in the solitary group than in the cohabiting group. Conclusion Our study showed that not only conventional vascular risk factors but also living conditions, especially living alone while unmarried, were independent risk factors for IS in young adults.

DOI： 10.2169/internalmedicine.0912-22

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Mechanical thrombectomy (MT) has been reported to be effective within 24 h after last known well (LKW) by the DAWN (DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo) trial and within 16 h after LKW by the DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. However, there have been few reports of MT more than 16 h after LKW, and the efficacy and safety of MT more than 24 h after LKW have not yet been demonstrated. We evaluated the efficacy and safety of MT more than 16 h after LKW. METHODS: Using data from the Nippon Medical School Hospital MT registry from April 2011 to August 2022, consecutive patients with anterior circulation large vessel occlusion (LVO) and prehospital modified Rankin scale (mRS) scores of 0-3 were enrolled. Patients were classified into the following three groups: early group (LKW &lt;6 h), middle group (LKW 6-16 h), and late group (LKW &gt;16 h). The clinical characteristics and outcomes were compared among these three groups. RESULTS: Among 778 patients in the MT registry, 624 were enrolled. The early group included 432 patients, the middle group included 123 patients, and the late group included 69 patients. The patients had a median age of 77 years (interquartile range, 68-83), and 359 were male (57.5%). The median prehospital mRS score was 1 (interquartile range, 1-1), median National Institutes of Health Stroke Scale score on admission was 17 (interquartile range, 10-23), and median Alberta Stroke Program Early CT Score was 10 (interquartile range, 8-10). Regarding safety and efficacy, the proportions of cases with successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b-3; 85.4% vs. 92.7% vs. 88.7%; p = 0.47), symptomatic intracranial haemorrhage (6.4% vs. 5.7% vs. 7.2%; p = 0.99), mRS score ≤3 at 90 days (52.0% vs. 60.2% vs. 44.9%; p = 0.11), and mRS score of 6 at 90 days (11.3% vs. 10.6 vs. 8.7%; p = 0.37) were not significantly different between the three groups. CONCLUSION: Patients who received MT more than 16 h after LKW experienced the same safety and efficacy as those who received MT at 0-16 h after LKW. MT more than 16 h after LKW may be safe and effective for stroke patients with LVO.

DOI： 10.1159/000531153

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: There are a few accurate predictors of patient outcomes after mechanical thrombectomy (MT). OBJECTIVE: To investigate whether the National Institutes of Health Stroke Scale (NIHSS) score 24 hours after stroke onset could predict favorable outcomes at 90 days in patients with acute stroke treated with MT. METHODS: Patients from the SKIP study were enrolled in this study. Using receiver operating characteristic curves, the optimal cut-off NIHSS score 24 hours after stroke onset was calculated to distinguish between favorable (modified Rankin Scale score 0-2) and unfavorable (modified Rankin Scale score 3-6) outcomes at 90 days. These receiver operating characteristic curves were compared with those of previously reported predictors of favorable outcomes, such as the ΔNIHSS score (baseline NIHSS score-NIHSS score at 24 h), percent delta (ΔNIHSS score × 100/baseline NIHSS score), and early neurological improvement indices. RESULTS: A total of 177 patients (median age, 72 years; female, 65 [37%]) were enrolled, and 109 (61.9%) had favorable outcomes. The respective sensitivity, specificity, and area under the curve values for an NIHSS of 10 were 92.6%, 80.7%, and .906; a ΔNIHSS score of 7 were 70.6%, 76.1%, and .797; and percent delta of 48.3% were 85.3%, 80.7%, and .890. CONCLUSION: NIHSS score <10 at 24 hours after stroke onset is a strong predictor of favorable outcomes at 90 days in patients treated with MT.

DOI： 10.1227/neu.0000000000002139

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 59-year-old woman presented with right hemiparesis and was transported from outside hospital. MRI revealed acute infarction and the left middle cerebral artery M2 occlusion. Intravenous infusion of recombinant tissue-type plasminogen activator, and mechanical thrombectomy (MT) were performed. The cause of cerebral infarction was diagnosed as Libman-Sacks endocarditis. She discharged without sequelae. After 10 months later, she presented with mild cognitive decline, and MRI showed new white matter lesion in left deep white matter. In magnetic resonance spectroscopy, the lesion showed an increased rate of choline/creatine, and a decreased rate of N-acetylaspartate/creatine, elevated lactate peak. When new higher brain dysfunction presented after recanalization by MT, it might be related to the delayed white matter lesion.

DOI： 10.5692/clinicalneurol.cn-001749

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIMS: Early initiation of enteral nutrition (EN) is recommended for acute stroke patients, but it is time-consuming. Reducing EN administration time without increasing the frequency of complications is a worthwhile goal. We aimed to determine whether this goal was feasible. METHODS: Consecutive acute stroke patients with severe dysphagia within 72 h of hospital admission who received EN were retrospectively enrolled. Patients were classified into two groups (Rapid administration group: 100 mL/5 min on days 1-3 after stroke onset and 200 mL/30 min on days 4-7, Conventional administration group: 100 mL/h on days 1-3 and 200 mL/h on days 4-7). RESULTS: Among 118 consecutive acute stroke patients, 71 patients [median age, 77 (68-82) years; 37 (52%) males] were enrolled. The baseline clinical characteristics of the rapid administration group (45 patients) and the conventional administration group (26 patients) did not differ. The total duration of EN administration in the first week after stroke onset was significantly longer in the conventional vs. rapid administration group [21 (15-21) h vs. 6 (2-8) h, p < 0.01]. There were no significant differences in the frequency of diarrhea (42% vs. 42%, p = 1.00), vomiting (0% vs. 7%, p = 0.29), or pneumonia (15% vs. 7%, p = 0.41). There was also no difference in the percentage of patients with one or more complications (54% vs. 49%, p = 0.81). CONCLUSIONS: Rapid administration of EN is safe and has the potential to decrease the time required for EN feeding.

DOI： 10.1016/j.jns.2022.120270

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Medical Association of Nippon Medical School  

Ischemic stroke is a very rare etiology in cases of isolated trochlear nerve palsy, and no reports of ipsilateral trochlear nerve palsy caused by unilateral stroke have so far been published. However, we now report a case of isolated trochlear nerve palsy due to ipsilateral dorsal small midbrain infarction in a 70-year-old woman who presented with acute onset of diplopia. There were no other clinical manifestations, but brain magnetic resonance imaging revealed a small ischemic lesion in the right dorsal midbrain, showing that isolated trochlear nerve palsy can be caused by stroke.

DOI： 10.1272/jnms.jnms.2021_88-515

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Several studies have investigated the predictors of functional outcome in patients with ischemic stroke after mechanical thrombectomy (MT). However, it is not clear whether pre-stroke cognitive (PSC) impairment is associated with the functional outcome of patients treated with MT. METHODS: We enrolled 113 patients treated with MT from December 2016 to November 2018. PSC was evaluated using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Poor outcome was defined as a modified Rankin Scale score of 3-6. We compared the clinical characteristics between the groups with poor outcome (n = 61) and good outcome (n = 52) to determine if PSC could be a predictor of poor outcome. RESULTS: IQCODE was significantly higher in the group with poor outcome than good outcome (3.34 vs. 3.13, P = 0.017). Moreover, the following metrics differed between those two groups: age (75.9 vs. 71.6 years old, P = 0.010), the percentage of females (39.9% vs. 17.3%, P = 0.009), the percentage with hypertension (72.1% vs. 44.2%, P = 0.003), National Institutes of Health Stroke Scale (NIHSS) score on admission (20 vs. 11, P < 0.001), and no successful recanalization (24.5% vs. 7.7%; P = 0.025). Multivariable logistic regression analysis demonstrated that PSC (OR: 5.59; 95% CI: 1.55-23.47), history of hypertension (OR: 3.33; 95% CI: 1.29-9.11), no successful recanalization (OR: 5.51; 95% CI: 1.49-25.03), and NIHSS score on admission (OR: 1.14; 95% CI: 1.07-1.22) were associated with poor outcome 3 months after stroke onset. CONCLUSIONS: PSC was significantly and independently associated with poor functional outcome in patients treated with MT.

DOI： 10.1007/s10072-021-05158-6

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

【背景と目的】動脈硬化性内頸動脈閉塞例では,閉塞部をガイドワイヤーで通過(lesion cross)することが求められる.頸動脈エコーはlesion cross部位を描出できる可能性がある.【方法】2015年4月から2019年5月までの血栓回収療法例中,内頸動脈起始部の動脈硬化性閉塞例を対象とした.再開通療法後に,術前に施行した頸動脈エコー所見を再評価した.【結果】8例のデータを解析でき,6例でlesion cross部位を頸動脈エコーで描出できていた.Lesion cross部位は,周囲の高輝度から等輝度のプラークと区別でき,低輝度を呈する血管腔として捉えられた.Color Doppler法では3例で血流が入り込む像を描出していた.5例のlesion cross部位は,内頸動脈の前面に位置していた.【結論】頸動脈エコーは,動脈硬化性内頸動脈の急性閉塞部の同定に有用な可能性がある.(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01786&link_issn=&doc_id=20210802450004&doc_link_id=1390007359727753600&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390007359727753600&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Purpose: We investigated whether the signal change on fluid-attenuated inversion recovery (FLAIR) can serve as a tissue clock that predicts the clinical outcome after endovascular thrombectomy (EVT), independently of the onset-to-admission time. Methods: Consecutive patients with acute stroke treated with EVT between September 2014 and December 2018 were enrolled. Based on the parenchymal signal change on FLAIR, patients were classified into FLAIR-negative and FLAIR-positive groups. The clinical characteristics, imaging findings, EVT parameters, and the intracranial hemorrhage defined as Heidelberg Bleeding Classification ≥1c hemorrhage (parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage, and/or subdural hemorrhage) were compared between the 2 groups. A modified Rankin Scale score 0 to 1 at 3 months was considered to represent a good outcome. Results: Of the 227 patients with EVT during the study period, 140 patients (62%) were classified into the FLAIR-negative group and 87 (38%) were classified into the FLAIR-positive group. In the FLAIR-negative group, the patients were older (P=0.011), the onset-to-image time was shorter (P<0.001), the frequency of cardioembolic stroke was higher (P=0.006), and the rate of intravenous thrombolysis was higher (P<0.001) in comparison to the FLAIR-positive group. Although the rate of complete recanalization after EVT did not differ between the 2 groups (P=0.173), the frequency of both any-intracranial hemorrhage and Heidelberg Bleeding Classification ≥1c hemorrhage were higher in the FLAIR-positive group (P=0.004 and 0.011). At 3 months, the percentage of patients with a good outcome (FLAIR-negative, 41%; FLAIR-positive, 27%) was significantly related to the FLAIR signal change (P=0.047), while the onset-to-image time was not significant (P=0.271). A multivariate regression analysis showed that a FLAIR-negative status was independently associated with a good outcome (odds ratio, 2.10 [95% CI, 1.02–4.31], P=0.044). Conclusions: A FLAIR-negative status may predict the clinical outcome more accurately than the onset-to-admission time, which may support the role of FLAIR as a tissue clock.

DOI： 10.1161/STROKEAHA.120.033374

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Informa UK Limited  

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by reactivation of JC virus (JCV). Typical PML shows confluent, bilateral but asymmetric, subcortical lesions in the supratentorial white matter on magnetic resonance imaging (MRI). We report here a 50-year-old woman with systemic lupus erythematosus complicated with lymphoma who developed PML with atypical brain MRI findings limited to the infratentorial area at presentation. She presented with numbness on the right side of the face, including her tongue, clumsiness of the right hand, and gait disturbance, after completion of remission induction therapy for lymphoma, including rituximab. Brain MRI demonstrated a solitary lesion limited to the cerebellum and brainstem, but a definitive diagnosis could not be made from cerebrospinal fluid study or tentative histologic evaluation of brain biopsy specimens. Despite methylprednisolone pulse therapy, her neurological deficits progressively worsened. One month later, in-depth analysis of her cerebrospinal fluid and brain biopsy specimens confirmed the presence of JCV. Eventually, the localised unilateral crescent-shaped cerebellar lesions on MRI expanded to the contralateral cerebellum, middle cerebellar hemisphere, pons, and midbrain and finally developed multifocal invasion into the white matter of the cerebral hemispheres. Our case suggests that PML could first present with a solitary infratentorial lesion in immunocompromised patients.

DOI： 10.1080/24725625.2021.1899763

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 79-year-old woman developed consciousness disturbance, left eye deviation, right hemiplegia and aphasia with hypoxemia. Chest X-ray showed bilateral pulmonary edema. MRI revealed the left internal carotid artery occlusion and entire left middle cerebral artery infarct including insular cortex. We performed mechanical thrombectomy therapy and TICI3 recanalization was obtained. During operation, the respiratory condition deteriorated and the ventilator was started after mechanical thrombectomy therapy. Chest X-ray showed butterfly shadow, which indicated pulmonary edema. Pulmonary edema improved on the 2nd day of onset, and disappeared on the 3rd day. There was no heart diseases such as Takotsubo myocardiopathy, acute cardiac failure and cardiomyopathy on echocardiography and electrocardiography. Therefore, we diagnosed her as having neurogenic pulmonary edema due to cerebral infarction including insular cortex. We consider that left insular cortex infarction was a trigger of neurogenic pulmonary edema. If hypoxemia associated with infarction including the insular cortex, neurogenic pulmonary edema should be considered for medical treatment.

DOI： 10.5692/clinicalneurol.cn-001491

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Importance: Whether intravenous thrombolysis is needed in combination with mechanical thrombectomy in patients with acute large vessel occlusion stroke is unclear. Objective: To examine whether mechanical thrombectomy alone is noninferior to combined intravenous thrombolysis plus mechanical thrombectomy for favorable poststroke outcome. Design, Setting, and Participants: Investigator-initiated, multicenter, randomized, open-label, noninferiority clinical trial in 204 patients with acute ischemic stroke due to large vessel occlusion enrolled at 23 hospital networks in Japan from January 1, 2017, to July 31, 2019, with final follow-up on October 31, 2019. Interventions: Patients were randomly assigned to mechanical thrombectomy alone (n = 101) or combined intravenous thrombolysis (alteplase at a 0.6-mg/kg dose) plus mechanical thrombectomy (n = 103). Main Outcomes and Measures: The primary efficacy end point was a favorable outcome defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 2 at 90 days, with a noninferiority margin odds ratio of 0.74, assessed using a 1-sided significance threshold of .025 (97.5% CI). There were 7 prespecified secondary efficacy end points, including mortality by day 90. There were 4 prespecified safety end points, including any intracerebral hemorrhage and symptomatic intracerebral hemorrhage within 36 hours. Results: Among 204 patients (median age, 74 years; 62.7% men; median National Institutes of Health Stroke Scale score, 18), all patients completed the trial. Favorable outcome occurred in 60 patients (59.4%) in the mechanical thrombectomy alone group and 59 patients (57.3%) in the combined intravenous thrombolysis plus mechanical thrombectomy group, with no significant between-group difference (difference, 2.1% [1-sided 97.5% CI, -11.4% to ∞]; odds ratio, 1.09 [1-sided 97.5% CI, 0.63 to ∞]; P = .18 for noninferiority). Among the 7 secondary efficacy end points and 4 safety end points, 10 were not significantly different, including mortality at 90 days (8 [7.9%] vs 9 [8.7%]; difference, -0.8% [95% CI, -9.5% to 7.8%]; odds ratio, 0.90 [95% CI, 0.33 to 2.43]; P > .99). Any intracerebral hemorrhage was observed less frequently in the mechanical thrombectomy alone group than in the combined group (34 [33.7%] vs 52 [50.5%]; difference, -16.8% [95% CI, -32.1% to -1.6%]; odds ratio, 0.50 [95% CI, 0.28 to 0.88]; P = .02). Symptomatic intracerebral hemorrhage was not significantly different between groups (6 [5.9%] vs 8 [7.7%]; difference, -1.8% [95% CI, -9.7% to 6.1%]; odds ratio, 0.75 [95% CI, 0.25 to 2.24]; P = .78). Conclusions and Relevance: Among patients with acute large vessel occlusion stroke, mechanical thrombectomy alone, compared with combined intravenous thrombolysis plus mechanical thrombectomy, failed to demonstrate noninferiority regarding favorable functional outcome. However, the wide confidence intervals around the effect estimate also did not allow a conclusion of inferiority. Trial Registration: umin.ac.jp/ctr Identifier: UMIN000021488.

DOI： 10.1001/jama.2020.23522

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

症例は、79歳、女性。意識障害、全失語、左共同偏倚、右片麻痺で発症し、胸部X線とCTで肺水腫、低酸素血症を認めた。頭部MRAで左内頸動脈から中大脳動脈は描出されず、MRIでは島皮質を含む左中大脳動脈全域に梗塞を認めた。左内頸動脈閉塞症に対して経皮的血栓回収療法を施行しTICI3の再開通を得た。呼吸状態が悪化し経皮的血栓回収療法直後に気管内挿管行い、人工呼吸器管理を行った。肺水腫は第2病日には著明に改善、第3病日には消失し呼吸状態も改善した。経胸壁心臓超音波、心電図では、心疾患はなく脳梗塞に伴い二次性に生じた神経原性肺水腫と診断した。本症例は左島皮質梗塞が神経原性肺水腫の引き金になったと考えられた。(著者抄録)

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J01550&link_issn=&doc_id=20210120270006&doc_link_id=1390286981379460480&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390286981379460480&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. METHODS: From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. RESULTS: A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59-79] years; National Institutes of Health Stroke Scale score 9 [17][3-17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19-1.84, p < 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19-2.09, p = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44-0.68, p < 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01-1.59, p = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55-0.99, p = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73-1.14, p = 0.395). CONCLUSION: Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

DOI： 10.1159/000515411

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Computed tomography (CT) can be used for visualizing acute intracerebral hemorrhages (ICHs) as distinct hyperdense areas and cerebral edema as perihematomal low-density areas (LDAs). We observed a perihematomal LDA on CT, which appeared to be part of a hemorrhage on magnetic resonance imaging (MRI) in acute ICH. We named this "CT perihematomal rim" and evaluated its characteristics and clinical significance. Methods We stratified patients with acute ICH according to the presence or absence of a CT perihematomal rim and then compared their radiologic findings. Logistic regression analyses were performed to assess whether the CT findings can predict the presence of a CT perihematomal rim. Patients Patients within 24 hours of ICH onset who were admitted between September 1, 2014, and October 31, 2018, were registered. Results Overall, 139 patients (91 men; mean age, 66 years) were investigated. CT perihematomal rims were observed in 40 patients (29%). ICH volumes on CT were 30% smaller than those on MRI in patients with CT perihematomal rims. On a multivariate analysis, the presence of a CT perihematomal rim was independently associated with the maximum diameter of the perihematomal LDA. According to a receiver operating characteristic analysis, the maximum LDA diameter threshold was 7.5 mm (sensitivity, 85%; specificity, 83%). Conclusion CT perihematomal rims were observed in 29% of the patients with acute ICH. A perihematomal LDA (>7.5 mm) in acute ICH cases should be considered a CT perihematomal rim. Clinicians should be aware that the ICH volume on CT may be underestimated by 30%.

DOI： 10.2169/internalmedicine.6653-20

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The feasibility of performing MRI first for patients with suspected hyperacute stroke in real-world practice has not been fully examined. Moreover, most past studies of reducing door-to-reperfusion time (DRT) in endovascular treatment (EVT) were conducted using CT. The aim of this study was to evaluate the feasibility of an MRI-first policy and to examine the effects of a quality improvement (QI) process for reducing DRT using MRI. METHODS: From January 2013 to December 2018, consecutive patients with acute stroke who came to hospital directly and were treated with emergent EVT were prospectively enrolled into the present study. In principle, MRI was performed first for patients with suspected acute stroke. A step-by-step QI process for decreasing DRT was adopted during this period. Time metrics for EVT were compared between specific time periods. RESULTS: A total of 180 patients (71 women; median age 76 years (range 69-64); National Institutes of Health Stroke Scale score 17 (range 10-23)) were included in the present study. More patients in the late phase were managed with the MRI-first policy (p<0.001). DRT (199 min in Phase 1, 135 min in Phase 2, 129 min in Phase 3, and 121 min in Phase 4, p<0.001) was significantly reduced across the phases. The percentage of patients with DRT <120 min increased significantly across time periods (p<0.001). Symptomatic intracerebral hemorrhage did not increase across phases (p=0.575). CONCLUSION: An MRI-first policy was feasible, and DRT decreased considerably with a step-by-step QI process. This process may be applicable to other hospitals.

DOI： 10.1136/neurintsurg-2019-015625

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study aimed to evaluate the risk factors, etiology, and outcomes of ischemic stroke (IS) in Japanese young adults. METHODS: This was a prospective multicenter study. We enrolled patients aged 16 to 55 years with IS within seven days of the onset of symptoms. We assessed the demographic data, risk factors, stroke etiology, and outcome at discharge. The clinical characteristics were compared between sexes and among age groups. RESULTS: We prospectively enrolled 519 patients (median age, 48 years: 139 females). The mean National Institute of Health Stroke Scale score was 3.6 ± 0.2. The most common risk factors were hypertension (HT) (55%), dyslipidemia (DL) (47%), and current smoking (42%). Body mass index, incidence of current smoking, and heavy alcohol consumption were higher in males. The prevalence of current smoking, HT, DL, and diabetes mellitus increased with aging. The most common etiologic subgroup of IS was small vessel disease (145/510, 28%). Intracranial arterial dissection (IAD) was the most common among the other determined causes (56/115, 49%). The outcome at discharge was relatively good (mRS 0-1, 71.7%); however, poor outcome (mRS ≥ 4) was observed at an incidence of 9.5%. CONCLUSIONS: Most young adults with IS had modifiable risk factors, of which prevalence increased with age. This emphasizes lifestyle improvement to prevent IS in the young population. Furthermore, we indicated that the incidence rate of IAD was high among the other determined causes.

DOI： 10.1016/j.jns.2020.117068

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記述言語：英語  

Aortogenic embolic stroke (AES) is an important stroke mechanism. However, as many stroke patients have aortic atheromatous lesions, it is unclear whether these lesions are the cause of these strokes. Cholesterol crystals are the solid, crystalline form of cholesterol that is found in atherosclerosis, but not in cardiac diseases such as atrial fibrillation, valvular diseases, and cardiomyopathy. Therefore, if a cholesterol crystal is found in a thrombus removed by mechanical thrombectomy (MT), this makes it possible to diagnose a patient as having an atheromatous lesion. Here, we report an AES case with a cholesterol crystal found in a thrombus removed by MT. A 67-year-old man was admitted due to consciousness disturbance, aphasia, and right hemiplegia. Diffusion-weighted imaging (DWI) showed a hyperintense area in the left frontal lobe, and magnetic resonance angiography demonstrated a branch occlusion of the left middle cerebral artery (MCA). MT was performed 1.5 h after stroke onset, with the thrombus removed and a left occluded MCA completely recanalized. Carotid duplex ultrasonography did not reveal any plaque in the carotid artery. Echocardiography did not show any abnormal function or findings, including thrombus. Transesophageal echocardiography showed a 4.9 mm atheromatous lesion at the aortic arch. Therefore, we suspected this patient as having an AES due to the embolic source of atheromatous lesion at the aortic arch. Pathological examination of the embolus revealed a cholesterol crystal cleft in the thrombus. Therefore, we diagnosed this patient as having AES caused by an atheromatous lesion at the aortic arch.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.105178

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: We investigated the impact of complete recanalization beyond partial recanalization in distal (M2) middle cerebral artery (MCA) occlusion. METHODS: Data regarding M2 occlusion patients treated with endovascular thrombectomy (EVT) and/or intravenous thrombolysis (tPA) were reviewed from our prospective EVT registry and multicenter tPA (YAMATO study) data bank. Complete recanalization was modified thrombolysis with cerebral infarction score (TICI) of 3 at the end of EVT or similar appearances of both MCAs on magnetic resonance angiography (MRA) within 1.5 h after tPA. Partial recanalization was defined as TICI ≥2b or > 50% recanalization on MRA. At 3 months, favorable outcome was defined as a modified Rankin Scale score ≤ 2. RESULT: Data on 121 patients were analyzed. EVT-alone was in 38 patients; combined EVT and tPA in 28; and tPA-alone in 55. Complete recanalization was achieved in 27 (22%), partial recanalization in 48 (40%), and no-to-limited recanalization in 46 (38%). At 3 months, 51% of patients had favorable outcomes, and this rate was significantly higher in the complete recanalization group than in the partial and no-to-limited recanalization groups (75% vs. 41% vs. 49%, p = .043). Multivariate regression analysis showed that complete recanalization was an independent parameter related to favorable outcomes (odds ratio 4.78, 95% CI: 1.16-19.73, p = .030). However, combined complete and partial recanalization was not associated with favorable outcomes (odds ratio 1.49, 95% CI 0.53-4.22, p = .449). CONCLUSION: Complete recanalization, but not partial recanalization, at the end of EVT and tPA therapy is associated with favorable outcomes in patients with M2 occlusion.

DOI： 10.1016/j.jns.2020.116873

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

© 2020 Elsevier B.V. Background: The cardio-ankle vascular index (CAVI) has been proposed as a useful parameter for arteriosclerotic diseases. However, whether it is associated with stroke risk in Japanese subjects remains unclear. Methods: In total, 280 Japanese subjects (92 females, 52.6 ± 5 years old) underwent a medical check-up. CAVI value and risk factors for arterial dysfunction were evaluated; the predicted 10-year stroke risk was measured by the Japan Public Health Center study. Results: Age, sex, body mass index, and systolic blood pressure were significant independent predictors of CAVI. CAVI values were significantly elevated in the high, compared with the medium-low and low predicted risk groups. A significant odds ratio (OR) for the high-risk group was noted in the highest quartile of CAVI values (OR, 14.67; 95% confidence interval [CI], 3.17–68.0), compared with the lowest quartile, after adjusting for potential confounders. A significant OR for very high predicted stroke risk was also found for each quartile increase (OR, 3.04; 95% CI, 1.87–4.94) and 1-standard deviation increase (OR, 2.24; 95% CI, 1.52–3.30) in CAVI value. Conclusion: Elevated CAVI values were related to an elevated predicted stroke risk, suggesting that CAVI could be a suitable surrogate marker for finding subjects at an increased risk of first-ever stroke.

DOI： 10.1016/j.jns.2020.116862

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Urinary liver-type fatty-acid binding protein (L-FABP), which is a biomarker of kidney tubule injury, has been studied extensively and established as a risk marker of acute kidney injury (AKI). However, no evidence has indicated whether kidney tubule injury is associated with the development of AKI and mortality in patients with acute ischemic stroke. METHODS: Acute ischemic stroke patients hospitalized in the stroke care unit (SCU) within 24 hours after symptom onset were prospectively investigated. AKI was defined on the basis of Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Baseline urinary L-FABP was measured upon admission. We evaluated the association among urinary L-FABP, the incidence of AKI, and 90-day mortality adjusted for renal function, albuminuria, and other potentially predictive variables using the multivariable analysis. RESULTS: In total, 527 acute ischemic stroke patients (342 males; median age 74 years) were enrolled to the study. Twenty-seven patients (5.1%) occurred AKI within 7 days after admission. In the univariate analysis, high urinary L-FABP level had positive associations with AKI (53.8 μg/g Cr vs. 3.9 μg/g Cr, P<0.001) and 90-day mortality (15.5 μg/g Cr vs. 4.0 μg/g Cr, P<0.001). In the multivariate analysis, elevated urinary L-FABP level (per 10 μg/g Cr increase) was independently associated with AKI (Odds ratio 1.225; 95% confidence interval (CI), 1.083-1.454, P=0.003) and 90-day mortality (Hazard ratio 1.091; 95% CI, 1.045-1.138, P<0.001). CONCLUSION: Urinary biomarker of kidney tubule injury is independently associated with the development of AKI and 90-day mortality in patients with acute ischemic stroke treated at the SCU.

DOI： 10.1111/ene.14448

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Some hyperacute stroke patients have unfavorable outcomes after endovascular thrombectomy (EVT) despite successful recanalization. We hypothesized that a cardiac parameter, moderate-to-severe mitral regurgitation (MR), might decrease the rate of favorable clinical outcome after EVT in patients with atrial fibrillation (AF). METHOD: From our prospective EVT registry, AF patients who underwent transthoracic echocardiography (TTE) were retrospectively analyzed. Based on the presence of moderate-to-severe MR, patients were assigned to either significant MR or nonsignificant MR group. The severity of MR was determined by the ratio of the color Doppler jet area to the left atrial area in mid-systole. Moderate-to-severe MR was estimated to be at a ratio of >20%. Favorable outcome was defined as having a modified Rankin Scale score of 0-1 at 3 months. RESULT: 127 patients with AF who underwent TTE were included in the study. TTE results found that 25 (20%) patients had significant MR. Patients with significant MR were older (p = 0.051) and had enlarged left (p = 0.015) and right (p = 0.002) atria. Tricuspid and aortic regurgitation (p = 0.007 and 0.043, respectively) were more severe in significant MR group. At 3 months, favorable outcomes were 11% in the significant MR group and 26% in the non-significant MR group (p = 0.031). Multivariate regression analysis reported that moderate-to-severe MR was a negative predictor of favorable outcome (odds ratio = 0.14; 95% confidence interval = 0.02, 0.84; p = 0.031). CONCLUSIONS: Significant MR might prevent the clinical recovery of AF patients.

DOI： 10.1080/01616412.2020.1773611

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

A 30-year-old woman presented with paresthesia in her left lower limb and blurred vision. She had bilateral horizontal gaze palsy with the absence of cranial nerve symptoms such as horizontal saccades, pursuit, and facial nerve palsy. Considering her convalescence, we speculated that her pure bilateral horizontal gaze palsy was mainly caused by disturbance in paramedian pontine reticular formation (PPRF). Pure horizontal gaze palsy may also be a characteristic feature of multiple sclerosis.

DOI： 10.1111/ncn3.12395

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Myeloproliferative neoplasms (MPNs) including polycythemia vera (PV) and essential thrombocythemia (ET) have an increased risk of ischemic stroke. However, little is known about brain morphological changes and the cerebral vasculature in MPNs. The aim of the present study is to clarify the prevalence rates of brain infarcts (BIs) on magnetic resonance imaging (MRI) and to assess the detailed clinical and MRI characteristics in those patients. METHODS: We prospectively enrolled patients with MPNs who underwent brain MRI between September 2017 and June 2019. BI patterns were characterized by the numbers and locations of BIs on MRI. RESULTS: A total of 101 patients were included in the present study. BIs were observed in 23 patients (23%). Multiple logistic regression analysis showed that age > 60 years (odds ratio (OR) 7.34, 95% confidence interval (CI) 1.08-49.7, p = .041) and history of thrombosis (OR 40.6, 95% CI 7.97-207, p < .0001) were independently associated with BIs, but not the JAK2V617F mutation. Of the 23 patients with BIs, eight patients (35%) had multiple territorial infarcts, and large vessel involvement was identified in five patients (22%). Two patients had thrombus formation in large vessels. CONCLUSIONS: Among patients with MPNs who underwent MRI, BIs were observed in 23% of patients followed up in our center. Older age and thrombosis history were independently associated with BIs. Some patients with MPNs may present with distinctive MRI findings including multiple territorial infarcts and thrombus formation in large vessels.

DOI： 10.1016/j.jns.2020.116990

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

A 88-year-old man suddenly presented with aphasia and right hemiparesis. The diffusion-weighted image of MRI showed ischemic lesions on the left middle cerebral artery area, and MRA showed the left intracranial artery (ICA) occlusion. Therefore, we diagnosed him as having acute ischemic stroke and treated with mechanical thrombectomy (MT). The DWI of MRI showed ischemic lesions on the left middle cerebral artery area, and MRA showed the left ICA occlusion. Therefore, we performed MT and continued best medical treatment, but ICA was reoccluded. Six day later, aspergillus was found in the thrombus from ICA. Then, we considered that ICA occlusion was caused by aspergillus. We experienced a patient specified the cause by thrombus pathology. The pathological diagnosis of the thrombus getting by MT is usefulness for stroke etiology.

DOI： 10.5692/clinicalneurol.cn-001400

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Evaluation of cognitive status is not performed routinely in the acute stroke setting. This study aimed to evaluate the frequency of early cognitive impairment in patients with minor ischemic stroke, analyze the factors associated with early cognitive impairment, and assess functional outcomes. METHODS: In this prospective study, 112 consecutive patients with acute minor ischemic stroke were enrolled. Neuroimages were assessed for semiquantitative evaluation of brain atrophy and small vessel disease (SVD) markers. Cognitive performance was measured within 5 days of onset using Montreal Cognitive Assessment (MoCA) scores. Functional outcome analyses were adjusted for demographic variables, premorbid cognitive status, education level, vascular risk factors, neuroimaging characteristics, stroke severity, and MoCA scores. RESULTS: The median MoCA score was 22, and 63% of patients had cognitive impairment. Factors independently associated with cognitive impairment were education (odds ratios [OR], .79; confidence intervals [CI], .63-.99), smoking (OR, .26; 95%CI, .073-.89), and temporal horn atrophy (OR, 4.73; 95% CI, 1.66-13.49). Factors independently associated with poor functional outcome were total MoCA score (OR, .78; 95%CI, .62-.95) and the sum of 4 MoCA subscores (visuospatial/executive, attention, language, and orientation; OR, .72; 95%CI, .53-.92). The cutoff value of the sum of 4 MoCA subscores for predicting poor outcome was 13 points with 76.5% sensitivity and 81.1% specificity. CONCLUSIONS: Early cognitive impairment was common after minor ischemic stroke and was associated with preexisting temporal horn atrophy but not SVD markers. The sum of 4 MoCA subscores was useful in predicting the functional outcome.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104749

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

症例は88歳の男性である。右麻痺、失語を認め救急搬送された。来院時の頭部MRI/Aにて左中大脳動脈領域に新規梗塞巣と左内頸動脈の閉塞を認めたため、機械的脳血栓回収療法を施行した。その後内科的治療を行うも、左内頸動脈は再閉塞した。血栓病理でアスペルギルス真菌塊を認めた。副鼻腔炎と骨破壊を認めており、アスペルギルスが内頸動脈に直接浸潤し、血栓を形成し、閉塞したことが考えられた。血栓病理によって原因の特定に至った症例を経験した。原因不明の脳梗塞は、機械的血栓回収療法によって回収された血栓を確認することで、原因が判明する可能性がある。(著者抄録)

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記述言語：英語  

Myotonic dystrophy type 1 (DM1) is an autosomal dominant inherited muscular dystrophy caused by an expanded CTG repeat in the dystrophia myotonica protein kinase (DMPK) gene. Cardiac involvements in DM1 are characterized by cardiac conduction delays and atrial or ventricular tachycardia, which increase the risk of sudden cardiac death when compared with general population. Only a few reports have investigated the association between DM1 and inherited arrhythmias, including Brugada syndrome and a splicing abnormality of the SCN5A gene, encodes the α-subunit of cardiac voltage-gated Na+ channels. Here we report a 24-year-old male patient with progressive grip myotonia and dysphagia, who was genetically diagnosed with idiopathic ventricular fibrillation (IVF) caused by a novel V1764fsX1786 frameshift mutation in the SCN5A gene at the age of 18 years. Family history was negative for arrhythmia, cardiac sudden death, and neuromuscular disorders. Genetic analysis using the Southern blot technique revealed 350 CTG repeats in the DMPK gene. This is the first case of DM1 with genetically confirmed overlapping CTG repeat expansion and a V1764fsX1786 frameshift mutation in the SCN5A gene. Our case suggests that a loss-of-function in the cardiac sodium channel may contribute to the cardiac complications in DM1 patients.

DOI： 10.1016/j.jocn.2020.02.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Cognitive assessment is not performed routinely in the acute stroke setting. We investigated factors associated with cognitive impairment and the differences between the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores in patients with acute stroke. METHODS: In this prospective study, 881 consecutive patients (median age, 73 years) with acute stroke were enrolled. Clinical characteristics, such as education, vascular risk factors, premorbid cognitive status using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), and stroke severity, were assessed. Cognitive performance was measured using MMSE and MoCA within 5 days of stroke onset. RESULTS: Both MMSE and MoCA were feasible in 621 (70.5%) patients. Factors independently associated with nonfeasibility were age (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.02-1.08), IQCODE score (OR: 1.02; 95%CI: 1.00-1.04), and National Institutes of Health Stroke Scale (NIHSS) score (OR, 1.16; 95%CI, 1.12-1.20). Impaired MoCA (with a cut-off <26/30) performance was observed in 544 of 621 (87.6%) patients. Factors independently associated with cognitive impairment were age (OR: 1.06; 95%CI: 1.03-1.10) and NIHSS score (OR: 1.34; 95%CI: 1.14-1.57). Eighty percent of patients with normal MMSE scores had an impaired MoCA score (MMSE-MoCA mismatch). The differences were highest in the visuospatial (94.8% versus 65.3%; P < .0001), recall (76.6% versus 35.6%; P < .0001), abstraction (82.5% versus 49.8%; P < .0001), and language (72.3% versus 65.9%; P < .0001) domains between the normal MMSE and MoCA group and MMSE-MoCA mismatch group. CONCLUSIONS: The MoCA can be particularly useful in patients with cognitive deficits undetectable on the MMSE in the acute stroke phase.

DOI： 10.1016/j.jstrokecerebrovasdis.2020.104688

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Catheter ablation (CA) has been reported to reduce risk of stroke in patients with nonvalvular atrial fibrillation (NVAF) in retrospective studies. However, the risks and benefits of CA have not been well elucidated in patients with NVAF and who have suffered a recent ischemic stroke in prospective randomized trials. Thus, the aim of the STABLED clinical trial is to investigate the efficacy and safety of CA with anticoagulant therapy using edoxaban in patients with NVAF and a history of recent ischemic stroke. METHODS AND DESIGN: The STABLED trial is a multicenter, prospective, randomized, open-label, standard medication-controlled study in Japan. The target patient number is 250, comprising 125 patients receiving standard medication and 125 receiving CA. For patients allocated to the CA group, ablation is to be performed between 1 to 6 months from the onset of index stroke. The observation period will be 3 years from the day of random allocation of the final patient to any of the groups. The primary outcome measure is the composite of recurrence of ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure. CONCLUSION: This study will investigate the effectiveness and safety of CA and basic anticoagulation treatment with edoxaban for patients with NVAF who have suffered a recent ischemic stroke. The aim is to determine the best evidence for an optimal treatment strategy for patients with NVAF and recent stroke. TRIAL REGISTRATION: UMIN000031424/NCT03777631.

DOI： 10.1016/j.jjcc.2019.06.002

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: National institutes of Health Stroke Scale (NIHSS) score and the presence of successful recanalization are crucial determinants of clinical outcome in patients with major artery occlusion. However, it is unknown whether successful recanalization rate after endovascular therapy (EVT) depends on NIHSS score. METHODS: From our prospective EVT registry, data on patients with an occlusion at the internal carotid artery or middle cerebral artery were analyzed. Successful recanalization was judged as positive when reperfusion of the thrombolysis in cerebral infarction (TICI) scale ≥2b was observed. Successful recanalization rate was also evaluated based on the NIHSS score subgroups: 0-8, 9-16, 17-24, and >24. Multivariate regression analysis was used to evaluate the impact of NIHSS score on successful recanalization. RESULTS: We studied 183 patients (age 76 [68-83], male 110 [60%], NIHSS score 19 [14-24]). One hundred and forty-six (80%) patients had the successful recanalization. Patients achieved the recanalization had lower NIHSS score as 18 (12-23), contrary those failed it had higher NIHSS score as 24 (20-27) (p < .001). Successful recanalization rate was correlated to the NIHSS score grade; 100% in the NIHSS 0-8 group, 88% in 9-16, 81% in 17-24, and only 60% in >24 (p < .001). Multivariate regression analysis showed NIHSS score was an independent parameter of recanalization (odds ratio 0.905 [95%CI 0.837-0.979], p = .013). CONCLUSION: NIHSS score may serve as a predictor of successful recanalization. Recanalization is relatively easier in mild stroke than in those with severe stroke.

DOI： 10.1016/j.jns.2019.06.033

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掲載種別：研究論文（学術雑誌）  

Background: National institutes of Health Stroke Scale (NIHSS) score and the presence of successful recanalization are crucial determinants of clinical outcome in patients with major artery occlusion. However, it is unknown whether successful recanalization rate after endovascular therapy (EVT) depends on NIHSS score. Methods: From our prospective EVT registry, data on patients with an occlusion at the internal carotid artery or middle cerebral artery were analyzed. Successful recanalization was judged as positive when reperfusion of the thrombolysis in cerebral infarction (TICI) scale ≥2b was observed. Successful recanalization rate was also evaluated based on the NIHSS score subgroups: 0–8, 9–16, 17–24, and >24. Multivariate regression analysis was used to evaluate the impact of NIHSS score on successful recanalization. Results: We studied 183 patients (age 76 [68–83], male 110 [60%], NIHSS score 19 [14–24]). One hundred and forty-six (80%) patients had the successful recanalization. Patients achieved the recanalization had lower NIHSS score as 18 (12−23), contrary those failed it had higher NIHSS score as 24 (20–27) (p < .001). Successful recanalization rate was correlated to the NIHSS score grade; 100% in the NIHSS 0–8 group, 88% in 9–16, 81% in 17–24, and only 60% in >24 (p < .001). Multivariate regression analysis showed NIHSS score was an independent parameter of recanalization (odds ratio 0.905 [95%CI 0.837–0.979], p = .013). Conclusion: NIHSS score may serve as a predictor of successful recanalization. Recanalization is relatively easier in mild stroke than in those with severe stroke.

DOI： 10.1016/j.jns.2019.06.033

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記述言語：英語  

Here, we report the case of a 27-year-old woman with tuberous sclerosis complex who underwent successful endovascular intervention for cerebral venous thrombosis at the superior sagittal sinus. She had protein S deficiency and a long-term history of anemia caused by menorrhagia from uterine fibroids, possibly leading to a hypercoagulable state. Cerebral venous sinus thrombosis accounts for ~0.5-1% of all strokes. Several cases of venous thrombosis in patients with tuberous sclerosis complex and protein S or protein C deficiency have been reported, but further studies are needed to identify whether an association of this rare combination may be explained.

DOI： 10.1093/omcr/omz060

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Atrial fibrillation (AF) is the leading cause of cardioembolic stroke (CES), and patients with stroke and AF are frequently assumed to have CES. However, strokes presumably due to atherosclerotic pathophysiologies in large or small vessels can also occur in patients with AF. The aims of the present study were to clarify the prevalence of and factors related to a non-cardioembolic etiology in acute stroke patients with AF. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF were retrospectively recruited. The concomitant presence of non-cardioembolic features (small vessel occlusion [SVO] or large artery atherosclerosis [LAA]) on imaging was evaluated. The frequency of and factors associated with co-existing SVO/LAA features were assessed. RESULTS: A total of 560 consecutive patients with AF and acute stroke (237 women; median age 78 [IQR 71-85] years; NIHSS score 9 [3-20]) were enrolled. Of these, 42 (7.5%) had co-existing SVO/LAA features. Multivariable logistic regression analysis showed that the brain natriuretic peptide level (BNP, OR 0.78, p = .030 per 100 pg/mL increase) was independently and negatively associated with co-existing SVO/LAA features and receiver operating characteristic curve analysis revealed the practical cut-off BNP value was 130 pg/mL (sensitivity 54% and specificity 68%). CONCLUSION: SVO/LAA features were found in 7.5% of acute stroke patients with AF. A relatively low BNP level on admission was independently associated with co-existing SVO/LAA features. Thorough examination for a more appropriate etiology may be particularly necessary in acute stroke patients with AF and a relatively low BNP level.

DOI： 10.1016/j.jns.2019.03.031

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Anticoagulant therapy often requires temporary interruption. Nevertheless, the frequency and clinical characteristics of stroke patients who develop stroke during anticoagulant interruption are not fully known. METHODS: From March 2011 through May 2017, consecutive acute ischemic stroke patients with AF who were admitted to our stroke unit were retrospectively recruited. Patients who developed ischemic stroke during anticoagulant interruption were defined as those who developed ischemic stroke within 30 days from anticoagulant interruption. The frequency and clinical characteristics of patients during anticoagulant interruption were analyzed. RESULTS: A total of 561 patients with AF and acute ischemic stroke (237 women; median age 78 [IQR 71-85] years) were admitted during the study period. Of these, 21 (3.7%, 12 patients discontinued vitamin K antagonist [VKA] and 9 discontinued direct oral anticoagulants [DOACs]) patients were admitted during the period of anticoagulant interruption. Severity and functional outcomes in stroke patients during anticoagulant interruption were not different from those without anticoagulant treatment. The number of days between anticoagulant interruption and stroke onset was shorter in patients who discontinued DOACs (3 [3-5] days) than in those who discontinuedVKAs (10 [7-20] days, p = .004). The major reason for interruption was planning of invasive procedures (52%). Guideline deviations were suspected in 82% of such cases. CONCLUSION: Patients developing stroke during anticoagulant interruption accounted for 3.7% of stroke patients with AF. Strokes occurred relatively early after interruption, especially in patients who discontinued DOACs. Guideline deviations was frequent.

DOI： 10.1016/j.jns.2019.03.018

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We investigated the precise clinical and radiologic characteristics of intracerebral hemorrhage associated with direct oral anticoagulant use. METHODS: Patients with acute spontaneous intracerebral hemorrhage admitted to our department from September 2014 to November 2017 were retrospectively analyzed. Clinical and neuroradiological characteristics of patients with direct oral anticoagulant-related intracerebral hemorrhage, and effects of prior treatment on the severity at admission and on outcome at discharge were assessed. RESULTS: Of the 301 enrolled patients (103 women; median age 68 years), 261 received no oral anticoagulants (86.8%), 20 received warfarin (6.6%), and 20 received direct oral anticoagulants (DOACs) (6.6%). Median initial National Institutes of Health Stroke Scale scores differed significantly among the groups (P = .0283). Systolic blood pressure (P = .0031) and estimated glomerular filtration rate (P = .0019) were significantly lower in the oral anticoagulant-related intracerebral hemorrhage group than in other groups. Total small vessel disease scores were significantly higher in the oral anticoagulant-related intracerebral hemorrhage group than in the warfarin group (P = .0413). Multivariate analysis revealed that prior oral anticoagulant treatment (odds ratio: 0.21, 95% confidence interval: 0.05-0.96, P = .0445) was independently negatively associated with moderate-to-severe neurological severity (stroke scale score ≥10) after adjusting for intracerebral hemorrhage location and various risk factors. There were significant differences in hematoma volume in the basal ganglia (P = .0366). CONCLUSIONS: DOAC-related intracerebral hemorrhage may occur particularly in patients with a high risk of bleeding; however, they had a milder initial neurological severity than those with warfarin-related intracerebral hemorrhage, possibly due to relatively smaller hematoma volume, especially in the basal ganglia.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.12.013

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Because the efficacy and safety of anticoagulant therapy in patients with acute intracerebral hemorrhage (ICH) are not fully known, present study aimed to elucidate the current status and the safety of anticoagulant therapy, mainly direct oral anticoagulants (DOACs), for acute ICH and anticoagulant-indicated patients. Methods and Results: From September 2014 through March 2017, consecutive patients with acute (<7 days from onset), spontaneous ICH were retrospectively enrolled from a prospective registry. Whether to start anticoagulation was at the attending physicians' discretion, and thromboembolic or hemorrhagic events during hospitalization were analyzed. A total of 236 patients (80 women [34%]; median age 69 [interquartile range 61-79] years; National Institutes of Health stroke scale score 7 [3-16]) were enrolled. Of them, 47 patients (20%) had an indication for anticoagulant therapy (33 had atrial fibrillation, 14 developed deep vein thrombosis), and 41 of 47 patients (87%) were actually treated with anticoagulant therapy (DOACs were used in 34 patients) after a median of 7 days from ICH onset. There was neither hematoma expansion nor excessive hemorrhagic complications during hospitalization after starting anticoagulant therapy. CONCLUSIONS: Anticoagulant therapy was conducted for approximately 90% of anticoagulation-indicated patients after a median of 7 days from ICH onset. The predominant anticoagulant medications were DOACs. Anticoagulant therapy started from the acute phase of ICH should be safe.

DOI： 10.1253/circj.CJ-18-0938

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.biopha.2018.09.084

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その他リンク： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26293328/

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND PURPOSE: The association between thyroid hormone levels and long-term clinical outcome in patients with acute stroke has not yet been thoroughly studied. The purpose of the present study was to test the hypothesis that thyroid hormone levels are associated with 3-month functional outcome and mortality after acute stroke. METHODS: We retrospectively analyzed 702 consecutive patients with acute stroke (251 women; median age, 73 years) who were admitted to our department. General blood tests, including thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were performed on admission. Neurological severity was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores on admission and modified Rankin Scale (mRS) scores at 3 months after stroke onset. Poor outcome was defined as an mRS score of 3-5 or death. The impact of thyroid function on 3-month outcome was evaluated using multiple logistic regression analysis. RESULTS: Poor functional outcome was observed in 295 patients (42.0%). Age (P < .0001), female sex (P < .0001), admission NIHSS score (P < .0001), smoking (P = .0026), arterial fibrillation (P = .0002), preadmission mRS (P < .0001), estimated glomerular filtration rate (P = .0307), and ischemic heart disease (P = .0285) were significantly associated with poor functional outcome, but no relationship between FT4, TSH, and poor functional outcome was found. A multivariate logistic regression analysis showed that low FT3 values (<2.00 pg/mL) were independently associated with poor functional outcome (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.60-6.24) and mortality (OR, 2.55; 95% CI, 1.33-4.91) at 3 months after stroke onset. CONCLUSIONS: Our data suggest that a low FT3 value upon admission is associated with a poor 3-month functional outcome and mortality in patients with acute stroke.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.06.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study investigated changes in anticoagulant use, treatment, and functional outcomes in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF) over a 6-year period. Methods and Results: Patients with AIS and NVAF admitted to our department from April 2011 to March 2017 were analyzed retrospectively. Patients were divided into 3 groups based on the time of the initial visit (Periods 1-3, corresponding to April 2011-March 2013, April 2013-March 2015, and April 2015-March 2017, respectively). Associations between prescribed medication prior to event and stroke severity, reperfusion therapy, and outcomes were assessed. There was no significant change in the rate of insufficient warfarin and inappropriately lowered doses of direct oral anticoagulant (DOAC) treatment over time. The number of patients receiving prior DOAC treatment increased, but neurological severity on admission was milder than in the other 2 groups. The rate of reperfusion therapy increased from 19.9% (Period 1) to 42.7% (Period 3) for moderate-to-severe stroke patients. Multivariate logistic regression analysis revealed that reperfusion therapy was independently positively associated with good functional outcomes, but negatively associated with mortality (odds ratios [95% confidence intervals] 7.14 [3.34-15.29] and 0.13 [0.008-0.69], respectively). CONCLUSIONS: Inappropriate anticoagulant use for stroke patients with NVAF did not decrease over time. An increase in reperfusion therapy was a strong factor in improved functional outcomes and mortality.

DOI： 10.1253/circj.CJ-18-0561

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.omtm.2018.07.009

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その他リンク： https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-26293328/

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background The aims of the present study were to investigate the relationships between prior direct oral anticoagulant ( DOAC ) therapy and infarct volume and the site of arterial occlusion in patients with acute ischemic stroke and non-valvular atrial fibrillation. Methods and Results From March 2011 through November 2016, consecutive patients with acute ischemic stroke in the middle cerebral artery territory and non-valvular atrial fibrillation were recruited. The infarct volume was assessed semi-automatically using initial diffusion-weighted imaging, and the arterial occlusion site was evaluated on magnetic resonance angiography. The effect of prior DOAC treatment on the site of arterial occlusion was assessed by multivariate ordinal logistic regression analysis. A total of 330 patients (149 women; median age 79 [quartiles 71-86] years; median National Institutes of Health Stroke Scale score 11 [4-21]) were enrolled. Of these, 239 were on no anticoagulant, 40 were undertreated with a vitamin K antagonist ( VKA ), 22 were sufficiently treated with VKA ( PT - INR ≥1.6), and 29 were on a DOAC before the acute ischemic stroke. The infarct volume on admission differed among the groups (median 14.5 [2.0-59.8] cm3 in patients with no anticoagulation, 24.8 [2.1-63.0] in undertreated VKA , 1.3 [0.3-13.5] in sufficient VKA , and 2.3 [0.5-21.0] in DOAC , P=0.001). Multivariate analysis showed that prior DOAC treatment was independently and negatively associated with more proximal artery occlusion (odds ratio [OR] 0.34, P=0.015), compared with no anticoagulant. Conclusions DOAC treatment before the event was associated with smaller infarct volume and decreased risk of greater proximal artery occlusion in acute ischemic stroke patients with non-valvular atrial fibrillation, compared with no anticoagulation.

DOI： 10.1161/JAHA.118.009507

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background and Purpose- The strong evidence of endovascular therapy in acute ischemic stroke patients with large vessel occlusion (LVO) is revealed. Such patients are required to direct transport to the hospital capable of endovascular therapy. There are several prehospital scales available for paramedics to predict LVO. However, they are time consuming, and several of them include factors caused by other types than LVO. Therefore, we need a fast, simple, and reliable prehospital scale for LVO. Methods- We developed a new prehospital stroke scale, emergent large vessel occlusion (ELVO) screen, for paramedics to predict LVO. The study was prospectively performed by multistroke centers. When paramedics referred to stroke center to accept suspected stroke patients, we obtain the following information over the telephone. ELVO screen was designed focusing on cortical symptoms: 1 observation; presence of eye deviation and 2 questions; paramedics show glasses, what is this? and paramedics show 4 fingers, how many fingers are there? If the presence of eye deviation or ≥1 of the 2 items were incorrect, ELVO screen was identified as positive. We evaluated between results of ELVO screen and presence of LVO on magnetic resonance angiography at hospital arrival. Results- A total of 413 patients (age, 74±13 years; men, 234 [57%]) were enrolled. Diagnosis was ischemic stroke, 271 (66%); brain hemorrhage 73 (18%); subarachnoid hemorrhage, 7 (2%); and not stroke, 62 (15%). One hundred fourteen patients had LVO (internal carotid artery, 33 [29%]; M1, 52 [46%]; M2, 21 [18%]; basilar artery, 5 [4%]; P1, 3 [3%]). Sensitively, specificity, positive predictive value, negative predictive value, and accuracy for ELVO screen to predict LVO were 85%, 72%, 54%, 93% and 76%, respectively. Among 233 patients with negative ELVO screen, only 17 (7%) had LVO, which indicated to be an ideal scale to avoid missing endovascular therapy. Conclusions- The ELVO screen is a simple, fast, and reliable prehospital scale for paramedics to identify stroke patients with LVO for whom endovascular therapy is an effective treatment.

DOI： 10.1161/STROKEAHA.118.022107

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Rapid adaption of endovascular thrombectomy (EVT) is essential for patients with large arterial occlusion (LAO). Although patients transferred need longer transportation, they have an advantage of preadmission diagnosis regarding arterial occlusion. The aim of the present study is to evaluate whether optimizing the assessment at comprehensive center for patients transferred may improve the clinical outcome after EVT. Data on consecutive patients treated with EVT between September 2014 and May 2017 were studied. Generally, we have two distinct protocols for EVT candidates: 1) the transfer group, patients are directly taken to the CT and escorted to the angiography room; and 2) the direct group, patients receive the routine emergent evaluation and examined with MRI/MRA. Good outcome was defined as modified Rankin Scale score ≤1 at 3 months. Thirty-one (29%) patients were classified into the transfer group and the 77 (71%) were into the direct group. Although the onset to door time was longer in the transfer group (175 [137-275] min. vs. 76 [51-260] min, P = 0.001), the rate of good outcome was similar between the 2 groups (41% vs. 25%, P = 0.205). By multivariate regression analysis, the onset to reperfusion time was the independent factor (odds ratio 0.982, 95%CI: 0.967-0.998, P = 0.026) associated with good outcome, while transfer itself was not the independent parameter (odds ratio 0.732, 95%CI: 0.125-4.291, P = 0.730). Regarding time parameters, door to picture time (11 [7-24] min vs. 27 [21-39] min., P < 0.001) and picture to puncture time (27 [18-60] min. vs. 54 [39-78] min, P < 0.001) were shorter in the transfer group. Thus, the onset to puncture time (234 [177-299] min. vs. 170 [125-367] min, P = 0.063) and the onset to reperfusion time (271 [208-352] min. vs. 237 [159-382] min., P = 0.183) were similar between the 2 groups. Shortening the initial evaluation at comprehensive stroke center can provide a good outcome for patients transferred.

DOI： 10.5692/clinicalneurol.cn-001181

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist, clinically used for seizure control, has been reported to exert neuroprotective effects in experimental models of neurodegenerative diseases. However, few studies have investigated the therapeutic effects of PER in brain injury including stroke. Our aim was to investigate the neuroprotective potential of PER using a rat transient middle cerebral artery occlusion (MCAO) model. Sprague-Dawley rats underwent 90-min MCAO followed by intraperitoneal PER administration at a dose of 1.5 mg/kg. Infarct volumes, neurological deficits, and immunological analyses were performed at 7 days after MCAO. PER significantly reduced infarct volumes (p < 0.05) and improved motor function (p < 0.05) compared with vehicle. Immunological analysis showed that PER significantly inhibited microglial activation, pro-inflammatory cytokine expression, and oxidative stress compared with vehicle. Moreover, PER suppressed neurodegeneration in the cortical ischemic boundary zone, via downregulation of Bcl-2-associated x and upregulation of Bcl-extra-large with Akt activation. In addition, post-stroke secondary neuronal damage and cognitive impairments, using the Y-maze test, were assessed 30 days after MCAO. PER significantly improved spatial working memory, which was accompanied by hippocampal CA1 neuronal loss and cortical thinning, compared with vehicle. These results indicate that PER attenuates infarct volumes and motor function deficits possibly through its anti-inflammatory, antioxidant, and anti-apoptotic activities, mediated via activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the acute ischemic phase, and further ameliorates post-stroke cognitive impairments via the suppression of secondary neuronal damage in the chronic ischemic phase.

DOI： 10.1016/j.neuroscience.2018.06.043

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

血栓回収療法例の転院受け入れをCT室とし、初療室を経ずに脳血管造影検査室へ移動する体制を検討した。転帰良好は転院群で11例(41%)、直接搬送群で15例(25%)と差はなかった(P=0.205)。発症から来院は転院群で長かったが(P=0.001)、来院から画像や、画像から穿刺までの時間は転院群で短く(共にP&lt;0.001)、発症から再灌流までの時間は両群で同等であった(P=0.183)。発症から再灌流は転帰良好に関連(オッズ比0.982、95% CI:0.967〜0.998、P=0.026)したが、発症から来院までの時間や転院の因子自体は関連していなかった(P=0.064、0.730)。院内プロトコールの迅速化は転帰を改善させるかもしれない。(著者抄録)

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders  

Background and Purpose: Anemia upon hospital admission is a known predictor of poor functional outcomes in patients with acute cerebral infarction. However, it remains unclear whether reductions in hemoglobin levels during hospitalization influence stroke outcomes. We investigated the association between in-hospital decline in hemoglobin and poor outcomes. Materials and Methods: We retrospectively analyzed data from 480 consecutive patients who had experienced acute cerebral infarction and presented without anemia between January 2012 and March 2015. Decline in hemoglobin was taken as the difference between hemoglobin levels upon admission and nadir hemoglobin. Poor outcome was defined as a modified Rankin Scale score 3-6. A multivariate analysis of the relationship between decline in hemoglobin and poor outcome at discharge was conducted for various patient characteristics. Results: The mean hemoglobin level at admission was 14.3 ± 1.3 g/dL, whereas the mean nadir hemoglobin value was 13.1 ± 1.9 g/dL, with a mean decline in hemoglobin of 1.3 ± 1.5 g/dL. In patients with poor outcomes, mean decline in hemoglobin was significantly reduced to 3.1 g/dL (P &lt
.001). The optimal cutoff decline in hemoglobin required to distinguish a poor outcome was 1.5 g/dL whereas the sensitivity and specificity were 62% and 82.3%, respectively, with an area under the curve of .77 (P &lt
.0001). A decline in hemoglobin below 1.5 g/dL was found to be an independent predictor of poor outcome (odds ratio: 2.10
confidence interval: 1.10-3.99
P = .023). Conclusion: Decline in hemoglobin in patients hospitalized with acute stroke may be associated with poor outcome.

DOI： 10.1016/j.jstrokecerebrovasdis.2018.01.026

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記述言語：日本語   出版者・発行元：(一社)日本脳神経超音波学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Introduction Endovascular treatment for acute ischemic stroke with acute large-vessel occlusion (ALVO) has established benefits, and rapid treatment is vital for mechanical thrombectomy in ALVO. Time from onset of stroke to groin puncture (OTP) is a practical and useful clinical marker, and OTP should be shortened to obtain the maximum benefit of thrombectomy. Objective The aim of the present study was to assess the impact of early treatment of anterior circulation stroke within three hours after symptom onset and to evaluate the role of OTP in determining outcomes after endovascular therapy. Methods Consecutive patients with acute stroke due to major artery (internal carotid or middle cerebral arteries) occlusion who underwent endovascular recanalization between March 2014 and January 2017 were retrospectively evaluated. Patients were stratified by OTP into three categories: 0-≤3 h, >3-≤6 h, and >6 h. The primary outcome measure was a 90-day modified Rankin scale score of 0-2 (good outcome). Results Data were analyzed from 100 patients (mean age, 76.6 years; mean National Institutes of Health Stroke Scale score, 17). Groin puncture occurred within 0-≤3 h in 51 patients, >3-≤6 h in 28, and >6 h in 21. Median OTP in each group was 126 min (range, 57-168 min), 238 min (range, 186-360 min) and 728 min (range, 365-1492 min), respectively. On multivariable logistic regression analysis, category of OTP represented an independent predictor of patient outcome (adjusted odds ratio, 0.48; 95% confidence interval, 0.25-0.93; p = 0.029). Conclusions OTP is a prehospital and in-hospital workflow-based indicator. In this single-center study, OTP was found to independently affect functional outcomes after endovascular stroke treatment.

DOI： 10.1177/1591019917747247

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W.B. Saunders  

Background: Poststroke infection (PSI) is common and is usually associated with a severe prognosis. We investigated the association between PSI and thyroid hormones, which are critical to immune regulation, in patients with acute stroke. Methods: We retrospectively enrolled 520 consecutive patients with acute ischemic stroke (326 men
age, 71.9 ± 13.2 years) admitted to our department between September 2014 and June 2016. The impact of serum thyroid hormone levels measured at admission (thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]) on the PSI was evaluated using multivariate logistic regression analysis. Results: We diagnosed 107 patients (20.6%
pneumonia, 65
urinary tract infection, 19
others, 23) with PSIs. While age (P &lt
.001), body mass index (P =.0012), preadmission modified Rankin scale score (P =.0001), National Institutes of Health Stroke Scale score on admission (P &lt
.001), admission FT3 level (P &lt
.001), atrial fibrillation (P &lt
.001), and ischemic heart disease (P =.0451) were significantly associated with PSI, we found no relationship among TSH levels, FT4 levels, and PSI occurrence. After multivariate adjustment, patients with PSIs were more frequently in the Q1 quartile (≤2.25 pg/mL) than in the Q2 (2.26-2.55 pg/mL
P =.0251), Q3 (2.56-2.89 pg/mL
P =.0007), or Q4 (≥2.90 pg/mL
P =.0010) quartiles of FT3 levels. Moreover, low FT3 levels (&lt
2.29 pg/mL) were independently associated with PSI occurrence (P =.0013). Conclusions: Low FT3 levels at admission are independently associated with PSI occurrence.

DOI： 10.1016/j.jstrokecerebrovasdis.2017.09.012

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dr. Dietrich Steinkopff Verlag GmbH and Co. KG  

Stroke-associated infection (SAI) is a common and serious complication of stroke. This study aimed to assess the effects of SAI on patient mortality and functional outcome at 3 months after stroke onset. We retrospectively analyzed 809 consecutive patients with acute stroke (517 men and 292 women
median age, 72 years) who were admitted to our department between September 2014 and June 2016. SAI was defined as an infection diagnosed during the hospitalization period. Poor outcome was defined as a modified Rankin Scale (mRS) score of 3–5 or death (mRS score of 6). The effect of SAI on functional outcome was evaluated using a multivariate logistic regression analysis. SAI occurred in 169 patients (20.9%)
of these, 106 (62.7%) had pneumonia, 23 (13.6%) had a urinary-tract infection, and 40 (23.7%) had other types of infection. Patients with SAI were older, more likely to be female, had lower body mass indices, had higher stroke severity, and were more likely to have atrial fibrillation and a history of ischemic heart disease than patients without SAI. Poor functional outcome and mortality were more common in patients with SAI than in patients without SAI (poor functional outcome 41.8 vs. 4.8%, mortality 24.3 vs. 3.9%, respectively). After adjusting for age, sex, stroke severity, and various comorbidities, SAI was independently associated with poor functional outcome [odds ratio (OR) 6.88
95% confidence interval (CI) 3.72–12.73] and mortality (OR 4.45, 95% CI 2.27–8.72) at 3 months after stroke onset. Our results suggest that SAI during the hospitalization period is independently associated with 3-month poor functional outcome and mortality.

DOI： 10.1007/s00415-017-8714-6

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記述言語：英語  

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DOI： 10.1016/j.jns.2016.06.063

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

Background: Insufficient anticoagulant intensity on admission is common in stroke patients with atrial fibrillation (AF) on vitamin K antagonist (VKA) therapy. Nevertheless, the effects of VKA under-treatment on stroke severity or arterial occlusion are not well known. The aim of the present study was to investigate the relationship between insufficient VKA therapy and stroke severity, or the site of arterial occlusion in patients with acute ischemic stroke (AIS) and AF. Methods and Results: From March 2011 through July 2016, 446 consecutive patients with AF and AIS were recruited. Of the 446 patients, 364 (167 women
median age, 79 years
IQR, 71–86 years) with anterior-circulation stroke were assessed to investigate the effects of insufficient VKA. Of these, 281 were on no anticoagulant, 53 were undertreated with a VKA, and 30 were sufficiently treated with VKA on admission (PT-INR ≥2.0 for patients &lt
70 years and PT-INR ≥1.6 for ≥70 years old). On multivariate analysis, insufficient VKA was independently associated with severe stroke (i.e., initial NIHSS score ≥10
OR, 2.70, P=0.022) and higher prevalence of proximal artery occlusion (OR, 1.91
P=0.039) compared with no anticoagulant therapy. Conclusions: Insufficient VKA therapy on admission was associated with higher severity of stroke and higher prevalence of proximal artery occlusion in patients with AF and acute anterior-circulation stroke compared with no anticoagulant medication.

DOI： 10.1253/circj.CJ-17-1110

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DOI： 10.1159/000490461

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER HEIDELBERG  

Cortical superficial siderosis (cSS) is a pathologic and radiologic diagnosis of hemosiderin deposition in subpial brain layers. However, cSS has not been fully studied in patients with acute stroke. Here, we investigated the prevalence of cSS in patients with acute stroke and analyzed the relationship between cSS and different clinical and neuroimaging characteristics. From September 2014 through June 2016, consecutive patients with acute stroke who were admitted to our department were retrospectively investigated. We analyzed the prevalence of cSS and the associations between cSS and risk factors, the topographic distribution of cerebral microbleeds (CMBs), and the severity of white matter lesions (WMLs). In total, 739 patients (589 patients with ischemic stroke/transient ischemic stroke [IS/TIA] and 150 with intracerebral hemorrhage [ICH]; mean age, 71.4 years) were enrolled. We identified cSS in six (1.0%) patients with IS/TIA and seven (4.7%) patients with ICH. The presence of cSS was associated with ICH (P &lt; 0.0001), WMLs (P = 0.0105), and lobar and non-lobar CMBs (both P &lt; 0.0001); no associations between cSS and age, sex, cardiovascular risk factors, IS subtype classification, or antiplatelet and anticoagulant therapy were found. In a multivariable logistic regression analysis, high numbers of lobar CMBs (ae&lt;yen&gt; 2; odds ratio, 11.03; 95% confidence interval, 2.03-205.40; P = 0.0029) were independently associated with cSS. Furthermore, cSS was often located near lobar CMBs. Our results suggest that cSS is prevalent in ICH and is independently associated with lobar CMBs; however, no associations between cSS and other risk factors or comorbidities were observed.

DOI： 10.1007/s00415-017-8646-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.omtm.2017.06.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Objective: Isolated deep subcortical infarcts develop as a result of occlusion of the penetrating arteries from the internal carotid artery (ICA) and the proximal (M1) and distal middle cerebral artery (MCA). However, the clinical and neuroimaging characteristics of infarcts due to the occlusion of the distal MCA penetrating artery are unclear.
Methods: Consecutive patients with ischemic stroke or transient ischemic attack with magnetic resonance imaging (MRI) performed within 2 days of onset were studied retrospectively. Using coronal MRI data, isolated deep subcortical infarcts were classified into two groups: 1) proximal group, described as being longer than they are wide, which were expected to be related to the occlusion of the ICA or M1 penetrating artery; and 2) distal group, described as oblong, which were expected to be associated with the occlusion of penetrating arteries from the distal MCA (M2/M3/M4).
Results: A total of 653 consecutive acute ischemic stroke patients (proximal group, 50 [7.7%]; distal group, 14 [2.1%]) were enrolled. Baseline clinical characteristics were not different between the 2 groups. Modified Rankin Scale scores were lower in the distal group than in the proximal group 3 months after stroke onset (1.43 +/- 0.36 vs. 226 +/- 1.35, p = 0.023). We measured the lengths of the infarcts in the X and Y directions using axial MRI. The X/Y ratio was larger in tile distal group than in the proximal group (1.3 +/- 0.6 vs. 0.7 +/- 02, p &lt; 0.01), which indicated that distal MCA penetrating artery infarcts appear more oblong on axial MRI.
Conclusions: One cause for deep subcortical infarction is the occlusion of the distal MCA penetrating arteries, which occurs in 22% of patients with deep subcortical infarctions. These patients had better clinical outcomes than those with ICA and M1 penetrating artery infarctions. Distal MCA penetrating artery infarctions appear oblong on axial MRI. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2016.07.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

BACKGROUND: Hypertension is one of the main comorbidities associated with dyslipidemia. This study aimed to examine the extent to which dyslipidemia increases the risk of developing hypertension in a Japanese working-age male population. METHODS AND RESULTS: We analyzed data from 14 215 nonhypertensive male workers (age 38±9 years) who underwent annual medical checkups. Subjects were followed up for a median of 4 years to determine new-onset hypertension, defined as blood pressure (BP) ≥140/90 mm Hg or use of antihypertensive medication. The associations between serum lipid levels and development of hypertension were examined. During the follow-up period, 1483 subjects developed hypertension. After adjusting for age, body mass index, impaired fasting glucose/diabetes, baseline BP category, alcohol intake, smoking, exercise, and parental history of hypertension, subjects with a total cholesterol (TC) level ≥222 mg/dL were at a significantly increased risk of developing hypertension (hazard ratio: 1.28; 95% CI: 1.06-1.56) compared to subjects with a TC level ≤167 mg/dL. Similar results were observed for subjects with high low-density lipoprotein cholesterol (LDLC) and non-high-density lipoprotein cholesterol (HDLC) levels. A U-shaped relationship was found between HDLC level and risk of hypertension; compared to the third quintile, the multiadjusted hazard ratio was 1.22 (95% CI: 1.03-1.43) in the lowest quintile and 1.34 (95% CI: 1.12-1.60) in the highest quintile. CONCLUSIONS: Elevated serum levels of TC, LDLC, and non-HDLC were associated with an increased risk of hypertension in working-age Japanese men. For HDLC, risk of hypertension was increased at both low and high levels.

DOI： 10.1161/JAHA.115.003053

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer Japan  

The neuroendocrine system is composed of the hypothalamus and pituitary gland
the nervous system controls the release of hormones from the pituitary gland. The secretory activity of the endocrine glands was formerly thought to be outside the direct control of the nervous system. Since the 1950s, the brain has been recognized as the center of the system controlling and regulating the physiological processes of the human body, and, currently, the neuroendocrine-immune network is proposed to mediate a bidirectional interaction between the neuroendocrine and immune systems. This network is responsible for maintaining homeostasis and orchestrating the essential responses to inflammation or injury through a tightly regulated network of neuropeptides, hormones, cytokines, and chemokines. Further investigation into neuroendocrine-immune crosstalk could shed light on the pathogenesis of diverse diseases, such as inflammatory and central nervous system diseases.

DOI： 10.1007/978-4-431-54490-6_3

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記述言語：日本語   掲載種別：研究論文（学術雑誌）   出版者・発行元：日本脳循環代謝学会  

イブジラストは脳梗塞後遺症に伴う慢性脳循環障害に使用されている.今回,我々は中大脳動脈永久閉塞モデルを用いて,イブジラスト投与による脳保護効果について検討を行った.雄性SDラットに,イブジラスト30mg/kg/日を虚血7日前から経口胃管投与後,永久閉塞を行った.虚血後30分と24時間にMRIを撮像した.虚血後24時間後にMRIを用いて脳血流低下領域を測定し,神経徴候,梗塞体積,浮腫index(%)を評価すると共に,免疫組織化学的検討を行った.イブジラスト投与群はコントロール群と比較して脳血流低下領域が縮小し,神経徴候は改善し,梗塞体積および脳浮腫も縮小した.また,イブジラスト投与により,虚血周辺部の酸化ストレスマーカーや炎症マーカー発現の抑制を認めた.今回の結果から,イブジラストは脳虚血後の血流障害の改善や酸化ストレス軽減,虚血後炎症の抑制を介して脳保護作用を発揮することが示唆された.(著者抄録)

DOI： 10.16977/cbfm.26.2_19

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Valproic acid (VPA) is widely used for the clinical treatment of epilepsy. Previous studies have demonstrated that VPA ameliorates brain injury following experimental stroke. However, the effect of VPA in stroke models featuring comorbid conditions has not been fully explored. In this study, we investigate the effects of VPA on permanent ischemic stroke with hyperglycemia. Hyperglycemia Was induced by streptozotocin (STZ) injection 3 days before. Test animals received a single injection of VPA immediately after induction of ischemia. Control animals received occlusion and physiological saline injection, or STZ, occlusion, and saline. Magnetic resonance imaging of cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) was performed 60 min after ischemia. Infarct volume, neurological deficits, rotarod test performance, and immunohistological markers were assessed 3 days after ischemia. Hyperglycemia significantly expanded the area of decreased of CBF and ADC, and increased the number of myeloperoxidase-positive cells, ionized calcium binding adapter molecule 1-positive cells, inducible nitric oxide synthase-positive cells, von Willebrand factor-positive cells, and Fluoro-Jade C-positive cells in the ischemic boundary zone, which was accompanied by increased infarct volume and deteriorated neurological deficit and rotarod test compared with normoglycemia (P &lt;0.05). VPA significantly alleviated the aggravation of functional outcome accompanied by suppressing these inflammation, endothelial injury, and neuronal degeneration compared with saline-treated group (P&lt;0.05). A single injection of VPA following permanent ischemia in STZ-induced hyperglycemic rats ameliorates neurological deficits and reduces neuronal degeneration by inhibiting inflammation and endovascular injury. VPA may be promising as a candidate therapy for human stroke. (C) 2015 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2015.02.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Objective The significance of early mild clinical improvement after intravenous tissue plasminogen activator (IVtPA) treatment is unclear. Therefore, we examined whether the timing of clinical improvement after IVtPA predicted the clinical outcome at 3 months.
Methods Consecutive patients with acute cerebral infarction in the anterior circulation who received IVtPA treatment within 3 hours of the onset of symptoms were enrolled in the study. Patients were classified according to the timing of clinical improvement [early responder (ER), National Institutes of Health Stroke Scale (NIHSS) score improved &gt;= 4 points or who had a score of 0 within 2 hours after IVtPA; late responder (LR), a similar improvement between 2 and 24 hours; and non-responder (NR)] and according to the arterial occlusion site (P group, internal carotid artery and proximal middle cerebral artery M1 region; and D group, distal M1 and M2).
Results Ninety-three patients [median age, 74 (67-79) years; 54 men (58%); median NIHSS score, 11 (7-16)] were enrolled in the study. The P group consisted of 48 (52%) patients and the D group consisted of 45 (48%) patients. Thirty-eight patients (41%) were classified as ERs, 20 (22%) as LRs, and 35 (38%) as NRs. On a multivariate regression analysis, the P group [odds ratio (OR), 3.24; 95% confidence interval (CI), 1.08-10.45; p=0.036] and NR (OR, 4.04; 95% CI, 1.29-14.27; p=0.016) were independent predictors of a poor outcome. ER (47%, p=0.01) and LR (45%, p=0.01) patients showed fewer poor outcomes than NR (77%) patients, but the rate did not differ significantly between the ER and LR patients.
Conclusion Early mild clinical recovery did not predict a good outcome. The occlusion site was a stronger predictor of clinical improvement after IVtPA administration.

DOI： 10.2169/internalmedicine.54.4990

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：S. Karger AG  

Introduction: Levodopa (LD) is important in the clinical treatment of Parkinson's disease (PD), and the changes of its pharmacokinetics may affect the clinical outcome. LD is mainly absorbed in the upper intestine
thus, the pharmacokinetics of LD may change after gastrointestinal operation. Here, we present the case of a patient who underwent resection of the intestine and compared his LD pharmacokinetics before and after resection. Case Presentation: A 72-year-old Japanese male PD patient developed jaundice and was diagnosed with cholangiocarcinoma. Pancreaticoduodenectomy was performed and part of the stomach, total duodenum, and part of the jejunum were resected. The patient had been treated with LD, and his pharmacokinetics was checked twice at the age of 68 years. Because LD is absorbed in the duodenum and jejunum, we checked his pharmacokinetics again after the operation. The results before the operation were almost similar
however, in comparison, the area under the curve and peak drug concentration was reduced, and the time-to-peak drug concentration and elimination halftime were elongated after the operation. Conclusion: Physicians must pay attention to the change of LD pharmacokinetics after gastrointestinal operation.

DOI： 10.1159/000381181

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掲載種別：研究論文（学術雑誌）  

© 2014. Background: We aimed to examine whether serum levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and C-reactive protein (CRP) are associated with the risk of developing metabolic syndrome in middle-aged men. Methods: In this longitudinal study, serum ADMA and CRP levels were measured in Japanese men without metabolic syndrome, which was diagnosed according to the currently accepted unified criteria. The subjects were followed-up for a maximum of four years to determine new-onset metabolic syndrome. A Cox proportional hazards model with adjusting for potential confounders was applied to determine the hazard ratio (HR) for developing metabolic syndrome according to serum levels of ADMA and CRP, considered either alone or in combination. Results: Of the 848 subjects (mean age, 43. ±. 6. years), 100 subjects developed metabolic syndrome. High ADMA levels (≥. 0.45. μmol/L) alone did not show a significant HR for developing metabolic syndrome, while high CRP levels (≥. 0.3. mg/L) did (HR 1.75, 95% CI 1.12-2.74). The combination of high levels of both CRP and ADMA had a high HR (2.09, 95% CI 1.12-3.76) as compared to low levels of both markers. In contrast, the HR was not significant in the combination of high CRP and low ADMA levels, as well as low CRP and high ADMA levels. Conclusions: Serum CRP, but not ADMA, levels were associated with the risk of metabolic syndrome. Nevertheless, the risk of metabolic syndrome could be predicted more reliably by considering these two markers together rather than CRP alone.

DOI： 10.1016/j.ijcme.2014.10.001

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Objectives: Levodopa (LD) is the most effective antiparkinsonian drug used in the treatment of Parkinson disease (PD). Sex differences in the bioavailability of LD have been shown previously. In addition, epidemiological sex differences in PD have been reported, suggesting an involvement of estrogen. In this study, we evaluated the pharmacokinetics of LD in elderly patients with PD to examine the influence of estrogen.
Methods: After the oral administration of a tablet of LD 100 mg/carbidopa 10 mg in 128 PD patients (including 91 elderly patients; age at examination, 75 years or older), plasma LD concentrations were measured at 6 points until 180 minutes, and pharmacological parameters were calculated. Then, differences in these parameters between sex were compared.
Results: The area under the curve (AUC) and the AUC adjusted for body weight were found to be significantly greater in the female subjects compared with the male subjects (P&lt;0.0001 and P&lt;0.0001, respectively). Furthermore, in the elderly patients, the AUC and the AUC adjusted for body weight were significantly greater among the female subjects (P &lt; 0.0001 and P &lt; 0.0001, respectively).
Conclusions: Even in the elderly cohort, the women had a significantly greater bioavailability of LD. In conclusion, to avoid the development of motor complications during LD treatment, it is important to consider the sex differences in the bioavailability of LD.

DOI： 10.1097/WNF.0000000000000051

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio- and cerebrovascular diseases. However, whether ADMA levels are related to the risk of stroke in the Japanese general population remains unclear. Methods We examined 769 Japanese men (mean age, 47 ± 5 years) undergoing health examinations. Each subject's ADMA level and various vascular risk factors were assessed; the predicted 10-year stroke risk was calculated using the point-based prediction model from the Japan Public Health Center Study. Results In a multiple linear regression analysis, age, body mass index, estimated glomerular filtration rate, and current smoking status were significant independent determinants of ADMA levels. A significant odds ratio (OR) for high predicted stroke risk (10-year risk ≥ 5%)was noted in the highest quartile of ADMA levels (OR, 2.47; 95% CI, 1.002-6.07), compared with the lowest quartile, after adjusting for potential confounding factors. A significant OR for high predicted stroke risk was also found for each standard deviation increment in ADMA level (adjusted OR, 1.46; 95% CI, 1.10-1.92). Conclusion Elevated ADMA levels were significantly associated with an increased predicted stroke risk, suggesting that measuring ADMA levels may be useful for identifying middle-aged Japanese men with a high risk of stroke. © 2013 Elsevier B.V.

DOI： 10.1016/j.jns.2013.12.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cerebral infarction of unknown origin at admission accounts for half of all cerebral infarction cases in some institutions. However, the factors associated with cerebral infarction prognosis have not been sufficiently examined. Here, we investigated whether aortic arch plaques (AAPs) on transoesophageal echocardiography (TOE) were associated with the prognosis of cerebral infarction of unknown origin at admission. METHODS: Of 571 patients who were hospitalised between June 2009 and September 2011, 149 (age: 67 ± 14 years; 95 men) with cerebral infarctions of unknown origin at admission underwent TOE and were enrolled in this study. We examined their clinical characteristics, the incidence of intermittent atrial fibrillation detected on 24-hour electrocardiography, and the echographic findings of the carotid artery in the hospital. A poor prognostic outcome was defined as a modified Rankin Scale score of ≥3 after 90 days. RESULTS: In all, 110 patients (74%) showed good prognoses and 39 patients (26%) showed poor outcomes. A National Institutes of Health Stroke Scale score of >6 on admission [odds ratio (OR) = 6.77; 95% confidence interval (CI): 2.59-18.8; p < 0.001] and AAPs of ≥4 mm (OR = 2.75; 95% CI: 1.19-6.91; p = 0.024) showed significant associations with a poor prognosis of cerebral infarction of unknown origin at admission. CONCLUSIONS: Thick AAPs could be a factor in the prediction of a poor prognosis of cerebral infarction of unknown origin at admission. The establishment of international standards for aortogenic brain embolisms is required. Future prospective studies should examine cerebral infarctions of unknown origin.

DOI： 10.1159/000362434

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: Asymmetric dimethylarginine (ADMA) has recently been investigated as a risk marker for cardio-and cerebrovascular diseases. However, it is not currently known whether the ADMA levels are related to the risk of stroke in Japanese women. Methods: We examined 192 Japanese women (mean age, 55±9 years, range, 40-80 years) who underwent health examinations. The ADMA level and various vascular risk factors of each subject were assessed, and the predicted 10-year stroke risk was calculated using the point-based prediction model provided by the Japan Public Health Center study. Results: In a correlation coefficient analysis, age was found to be the only factor significantly correlated with the ADMA level. A significant odds ratio (OR) for a high predicted stroke risk (10-year risk, ≥5%) was noted in the highest ADMA level tertile (6.24; 95% CI, 1.13-34.5; p=0.036) compared with the lowest tertile, after adjusting for potential confounding factors. A significant OR for a high predicted stroke risk was also found for each increment in the ADMA tertile and standard deviation (adjusted OR, 2.42; 95% CI, 1.09-5.34; p=0.029; and 2.51; 95% CI, 1.24-5.11; p=0.011, respectively). Conclusions: An elevated ADMA level is significantly associated with an increased predicted stroke risk, suggesting that measuring the ADMA level is useful for identifying Japanese women with an elevated stroke risk.

DOI： 10.5551/jat.22582

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担当区分：筆頭著者   掲載種別：研究論文（大学，研究機関等紀要）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ PUBLISHING GROUP  

Objective: Brain white matter hyperintensities can be divided into periventricular hyperintensity (PVH) and deep-and-subcortical white matter hyperintensity (DSWMH); the former contributes more to cognitive dysfunction and infarction risk. We conducted the present investigation to define the relationship between PVH and DSWMH.
Design: Cross-sectional study.
Setting: University hospital.
Participants: We prospectively enrolled 228 healthy Japanese volunteers with relative risk values (RRVs) &gt;0.5.
Primary outcome measures: We investigated whether it is possible to use the RRV to predict PVH and DSWMH.
Results: Among 228 volunteers, 103 (45.1%) and 157 (68.8%) exhibited PVH and DSWMH, respectively. Age, body mass index and PVH were significant independent determinants of RRV. A significant OR for PVH was noted in the highest RRV tertile compared with the lowest, after adjusting for potential confounding factors. A significant OR for high predicted PVH risk was found for RRV levels as well.
Conclusions: Elevated RRV levels were significantly associated with increased predicted PVH, suggesting that measuring the plasma protein-conjugated acrolein, interleukin 6 and C reactive protein levels may be useful for identifying Japanese at high risk for PVH.

DOI： 10.1136/bmjopen-2014-005598

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：3  

A 39-year-old man with a history of rupture of a sinus of Valsalva aneurysm experienced an ischemic stroke. Although the patient presented left-sided hemiparesis for a week, no abnormal signals were indicated on diffusion-weighted imaging with repeated magnetic resonance scans. Carotid ultrasound and cerebral angiography were conducted, and they revealed hypoplasty of the left internal carotid artery with a low-lying carotid bifurcation at the level of the C6 vertebra. In addition, he was diagnosed with intellectual disabilities, evaluated by the Wechsler Adult Intelligence Scale-III, and congenital velopharyngeal insufficiency. We herein present the first report of a patient with cardio-cerebrovascular abnormalities, intellectual disabilities, and an otorhinolaryngological abnormality. © 2013 S. Karger AG, Basel.

DOI： 10.1159/000356292

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: Intra-arterial transplantation of bone marrow mononuclear cells (BMMCs) effectively improves neuronal function and limits the infarct size. We monitored the fate of BMMCs labeled with super paramagnetic iron oxide (SPIO) until 7 days after the transplantation using high-field magnetic resonance imaging (MRI). METHODS: Male Sprague-Dawley rats were subjected to 90-minute focal ischemia using the intraluminal suture technique followed by transplantation of 1 × 10(7) BMMCs or vehicle only via the ipsilateral carotid artery immediately after reperfusion. Autologous BMMCs were labeled with SPIO by electroporation prior to ischemia. MRI studies were performed at 1 hour, 24 hours, 3 days, and 7 days after reperfusion on each rat. The total infarct volume and the volume of negative dots were measured on T2-weighted images and T2*-weighted images, respectively. RESULTS: One hour after BMMC transplantation, we confirmed wide spread distribution of BMMCs in the ischemic hemisphere as a negative dot. The volume of negative dot normalized by hemispheric volume decreased rapidly and was seldom seen at the seventh day after transplantation. The infarct volume was significantly smaller in the transplanted group than the vehicle group at 24 hours and 7 days after reperfusion. DISCUSSION: The present study established In vivo monitoring of intra-arterial transplanted SPIO-labeled BMMCs immediately after reperfusion using MRI of a rat transient focal ischemia model. The accumulation of BMMCs in ischemic lesion at the acute stage of ischemia can be part of the conditions to limit the infarct size.

DOI： 10.1179/1743132813Y.0000000171

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND OBJECTIVE: It has been reported that medical treatment with cilostazol (cilo) as an antiplatelet may increase a substance P level in the striatum to shorten the latent time of swallowing reflex (LTSR). We undertook a pilot study to confirm whether cilo administration to patients with cerebral infarction is effective in increasing their plasma substance P level and then in ameliorating the status of LTSR. METHODS AND SUBJECTS: Eligible subjects were recruited, after informed consents, from 20 hospitalized patients with acute-phase cerebral infarction within 72 hours from the onset. At the start of treatment, the subjects were assigned at random to those given aspirin alone (non-cilo group) and those given aspirin plus cilo (cilo group). Plasma substance P levels and LTSR values were measured at the starting point (baseline), 28 days after, and 180 days after. RESULTS AND DISCUSSION: No significant time-dependent change in plasma substance P level was found probably because of large individual differences but, 28 days after the start of treatment, this value tended to become higher in cilo group than in non-cilo group (P<0.10). Whereas, in terms of fold changes of LTSR in cilo group, there was a significant between-term difference at P<0.05, indicating that this medication is effective in ameliorating the swallowing function is improved in the long run. CONCLUSION: The LTSR values was significantly shortened within 180 days after the start of cilo treatment, but the result was not well explained by substance P levels as far as these were measured using the plasma, probably because this substance had diluted during blood circulation. However, it will become clinically usable as a single swallowing index, if in the future some ingeneus method of its measurement is developed. A larger-scale study would also be needed to confirm our conclusion from this pilot study.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Multiple system atrophy with predominant parkinsonism (MSA-P) usually shows poor responsiveness to dopaminergic medications. We herein describe a patient with MSA-P who exhibited a good response to pramipexole but not to an ordinary dose of L-dopa. Positron emission tomography (PET) displayed severely impaired presynaptic dopaminergic availability and relatively preserved postsynaptic D-2 receptor binding capacity. The pharmacokinetic analyses demonstrated relatively low bioavailability for L-dopa and adequate plasma levels of pramipexole, even at baseline, on a stable daily dose. The PET features and pharmacokinetic differences between L-dopa and pramipexole indicate the presence of unique therapeutic responses to dopaminergic medications in the patient.

DOI： 10.2169/internalmedicine.52.9442

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

We report a 76-year-old man with paradoxical cerebral air embolism. He developed consciousness disturbance and left hemiparesis after a postural change in rehabilitation. CT showed multiple air densities within the right hemisphere. An echocardiography showed a large right-to-left (RL) shunt. We considered the reason to be that a small amount of air entered, and the Valsalva-like maneuver with the postural change moved air into arterial circulation through the RL shunt and embolized a brain artery. The present case showed that even a small amount of air in the venous circulation may become a potential risk for cerebral air embolism, especially in the presence of a large RL shunt.

DOI： 10.2169/internalmedicine.51.7032

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

A 64-year-old female with a history of primary biliary cirrhosis and esophageal varices starting at age 39 was brought to our Stroke Care Unit by ambulance with right-side weakness and speech difficulty. Physical examination revealed right hemiparesis (including the face), sensory disturbances, pathological reflexes, and slightly decreased consciousness, with a Glasgow Coma Scale rating of E3V4M6. Flapping tremors and speech disturbance, as well as anarithmia, construction apraxia, and ideomotor apraxia, were noted, and her National Institutes of Health Stroke Scale score was 13. Initially, the patient was diagnosed with acute stroke and treated accordingly; however, subsequent findings from clinical images and electroencephalography led to a diagnosis of focal neurologic signs due to hepatic encephalopathy (HE). The patient had significantly reduced cerebral blood flow in the left side of the brain, probably due to microsurgical repair of an aneurysm done 2 years earlier. HE with exaggerated chronic liver damage might have made the previously silent ischemia clinically apparent. This interpretation is supported by the fact that the patient's neurologic deficits resolved once HE was adequately controlled. This case illustrates the need for careful assessment of background pathophysiology when diagnosing patients with stroke-like symptoms.

DOI： 10.1016/j.jstrokecerebrovasdis.2010.01.011

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

Levodopa (LD) is the most effective drug to treat the symptoms of Parkinson&apos;s disease (PD). It has been reported that the bioavailability of LD is higher in elderly patients than in young patients; however, it is not known how ageing changes the bioavailability of LD among elderly patients. In this study, we compared the pharmacokinetics of LD between two groups of elderly PD patients, early- (75 years or younger) and late-elderly (76 years or older). After oral administration of a tablet containing 100 mg LD per 10 mg carbidopa in 155 PD patients, we measured plasma LD concentrations. Peak drug concentration (C(max)), time to peak drug concentration (T(max)), halftime of drug (T1/2) and area under the curve (AUC) were determined. AUC and T1/2 were significantly higher and longer, respectively, in the late-elderly group than in the early-elderly group (p &lt; 0.05 and &lt;0.05, respectively). However, C(max) and T(max) were not statistically different between the groups. The present data indicate that LD absorption is consistent in PD patients, regardless of age. The difference in oral LD bioavailability between the groups may result from a difference in excretion ability. Physicians should consider LD pharmacokinetics when treating elderly PD patients. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.parkreldis.2010.11.002

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記述言語：日本語   出版者・発行元：(株)先端医学社  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aim: It remains unclear whether the decrease in the ADMA level associated with statin treatment results from the LDL-C-lowering effect or the pleiotropic effects of statins. A prospective, controlled study was conducted to examine whether statin treatment affects serum ADMA concentrations in ischemic stroke patients. Methods: Consecutive outpatients with non-cardiogenic ischemic stroke who had never been treated with statins and whose LDL-cholesterol level was higher than 140 mg/dL were enrolled and compared with control patients whose LDL-cholesterol level was lower than 140 mg/dL. Overall, 114 patients were enrolled in the study (56 and 58 in statin-treated and non-statin-treated groups, respectively). Patients in the statin group were treated with pravastatin 10 mg/day (n = 15), fluvastatin 20 mg/day (n = 14), pitavastatin 1 mg/day (n = 14), or atorvastatin 10 mg/day (n = 13). Results: The serum ADMA concentration and LDL-C level were significantly decreased by statin treatment (p = 0.003 and p<0.001, respectively), and the ADMA concentration in subjects treated with statins was significantly lower than that of the control (p = 0.028). Multiple linear regression analysis showed that age (β= 0.26, p<0.05) and statin use (β= 0.20, p<0.05) were independently associated with the ADMA level. Conclusions: A significant relation between statin treatment and decreased levels of ADMA was demonstrated in ischemic stroke patients with an adequately controlled lipid profile, suggesting the statin treatment might prevent atherosclerotic disease in ischemic stroke patients through suppression of ADMA concentration.

DOI： 10.5551/jat.5553

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掲載種別：研究論文（学術雑誌）  

Although a decrease in cerebrovascular reserves (CVR) is known to enhance the risk of stroke, changes in this parameter after carotid artery stenting (CAS) have rarely been investigated. The present study is the first to compare CVR recoveries after applying CAS to patients with symptomatic carotid artery disease. CAS was performed for 31 consecutive patients with symptomatic carotid artery disease. They underwent acetazolamide-challenged single photon emission computed tomography (SPECT) before and after CAS to obtain data on resting stage cerebral blood flow (CBFrest values) in various regions of interest (ROIs) defined by a three-dimensional stereotactic ROI template. CVR values on ipsilateral and contralateral hemispheric sides were then calculated based on the CBFrest data. The 31 patients were dichotomized into unilateral (n=22) and bilateral (n=9) lesion groups, and no significant between-group differences were observed in CBFrest before and after CAS. In the unilateral group, there were no differences in CVR values before and after CAS. In the bilateral group, however, the CVR values significantly increased in nearly all the investigated ROIs on the contralateral side. Also, the hemispheric CVR values on both sides significantly increased after CAS in the bilateral group, while no such increase was observed in the unilateral group. CAS in patients with symptomatic bilateral carotid artery disease has the potential utility for their haemodynamic improvement even on the contralateral hemispheric side.

DOI： 10.1177/159101991001600408

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: We investigated whether a correlation exists between insulin resistance and the severity of cerebral white matter lesions among non-diabetic patients with ischemic stroke. METHODS: The subjects were 105 consecutive patients without diabetes who were hospitalized due to non-cardioembolic stroke. The insulin resistance was evaluated by a homeostasis model assessment of insulin resistance (HOMA-IR). The degrees of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) were evaluated by the brain MRI. The HOMA-IR values >or=2.5 were indicative of the insulin resistance. RESULTS: The presence of PVH and DSWMH were 86.7 and 83.8%, respectively. The ratio of insulin resistance increased with higher grades of PVH and DSWMH. The HOMA-IR level in grade 3 PVH was significantly higher than those in grades 0 and 1. The HOMA-IR level in grade 3 DSWMH was significantly higher than those in grades 0-2. Multiple linear regression analysis showed that HOMA-IR was significantly associated with PVH or DSWMH. CONCLUSION: It was found that insulin resistance correlated with white matter lesions among non-diabetic patients with non-cardiogenic ischemic stroke.

DOI： 10.1179/016164109X12608733393755

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

[(123)I]-Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is useful for distinguishing multiple system atrophy (MSA) from Parkinson disease. In this study, longitudinal observation using MIBG myocardial scintigraphy was carried out in patients with MSA to evaluate the association of myocardial MIBG uptake with clinical features. A total of 96 MIBG examinations were performed in 52 patients with MSA. The heart/mediastinum (H/M) ratio of MIBG uptake at 240 minutes after injection was below the lower limit in 16 patients with MSA (31.3%). Overall, the H/M ratio correlated with neither disease duration nor severity. In the follow-up observations, the H/M ratio did not show any specific trends, in contrast with the continuous decrease observed in patients with Parkinson's disease. This data clearly showed that cardiac MIBG uptake cannot necessarily be preserved in patients with MSA and that approximately 30% of patients with MSA showed decreased MIBG uptake without any correlation to disease duration or severity.

DOI： 10.1002/mds.23338

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE BV  

Background: Poststroke depression is one of the most frequent and important complications of stroke. Although many studies of depression after stroke have been reported, clinical association between the risk of depression after stroke and the lesion location remains unclear. The presence of depression after stroke reportedly confers a poor prognosis; however, early recognition of depressive symptoms may improve outcomes. We examined the relation between lesion location and presence of depressive symptoms 1 month after ischemic stroke, with a view toward early management of depressive symptoms. Methods: In all, 134 consecutive patients with ischemic stroke were followed up to determine whether depression was present 1 month after stroke onset. Depressive symptoms were assessed by means of the Zung Self-rating Depression Scale. The lesion location was determined on magnetic resonance or computed tomography images. Results: The incidence of depressive symptoms 1 month after stroke onset was 34.3%. Backward stepwise logistic regression analysis showed hypertension, education, and the presence of a left lenticulocapsular infarct, in particular, to be independent predictors of depressive symptoms. Conclusions: Patients with ischemic stroke, particularly in the left lenticulocapsular area, should be carefully evaluated for early detection and treatment of depressive symptoms, which may greatly influence outcome.

DOI： 10.1016/j.jstrokecerebrovasdis.2009.04.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Asymmetric dimethylarginine (ADMA) affects vascular function by blocking nitric oxide synthesis. We examined the relationship of ADMA concentration to vascular risk factors in subjects who have undergone annual medical check-up. Methods: ADMA concentration, lipid profile and vascular risk factors were assessed during an annual medical examination in 116 subjects (mean age 58.7 years). Univariate and multivariate analyses were carried out to assess factors associated with ADMA concentration. ADMA concentration was also assessed in 50 age-matched patients with ischemic stroke. Results: Mean serum ADMA concentration was significantly higher in the ischemic stroke patients than the medical check-up subjects (0.461 ± 0.076 versus 0.433 ± 0.056 μmol/l; P = 0.022). Univariate analysis showed that ADMA concentration in the medical check-up subjects was significantly associated with age, hypertension, dyslipidemia, fasting blood glucose, total and LDL cholesterol concentrations. Multiple stepwise linear regression analysis showed that hypertension (β = 0.25, P = 0.008) and dyslipidemia (β = 0.19, P = 0.048) were significant independent determinants of ADMA concentration. ADMA concentration increased progressively with number of vascular risk factors, with a significant (P = 0.001) difference between subjects with no risk factors and subjects with ≥ 2 risk factors. Conclusions: Serum ADMA concentration was significantly associated with vascular risk factors in subjects undergoing routine medical check-up. ADMA concentration warrants further examination as a possible marker of future development of ischemic stroke. © 2009 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jns.2009.12.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：KARGER  

Background: Aspiration pneumonia is one of the most important complications following ischaemic stroke, and a leading cause of mortality in stroke patients. This is particularly prevalent in patients with involvement of the basal ganglia, which may be due to impaired neurotransmission through lack of production of substance P. Methods: Consecutive patients in the chronic stage, 1-3 months after cerebral ischaemic infarction, were assessed for basal ganglia involvement by magnetic resonance imaging. The patients were randomised to 4 weeks of treatment with (n = 25) or without (n = 25) nicergoline (15 mg t.i.d.). Serum concentration of substance P was measured by radioimmunoassay. Results: At entry to the study, mean concentration of substance P was significantly (p &lt; 0.001) lower in patients with bilateral basal ganglia lesions than in patients with no or unilateral basal ganglia involvement. Nicergoline administration caused a significant (p = 0.021) increase from baseline in mean substance P concentration. No significant change was seen in the nicergoline-untreated patients (p = 0.626). Among the patients who received nicergoline, 11 patients had bilateral basal ganglia involvement and there was no significant mean change in substance P in these patients, whereas there was a significant increase (p = 0.032) in the 14 nicergoline-treated patients with no or unilateral basal ganglia involvement. Conclusions: The present study suggests a possible effect of nicergoline to increase substance P level in ischaemic stroke patients with partial damage to basal ganglia, who have a decreased swallowing response and consequent risk of aspiration pneumonia. Further trials of nicergoline treatment in patients at risk for aspiration pneumonia are warranted. Copyright (C) 2009 S. Karger AG, Basel

DOI： 10.1159/000267279

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1272/jnms.76.323

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記述言語：英語   出版者・発行元：ELSEVIER SCI LTD  

DOI： 10.1016/j.jocn.2008.11.005

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掲載種別：研究論文（学術雑誌）  

No information has been available regarding middle cerebral artery (MCA) dissection occurring as a result of athletics. We describe a case of cerebral infarction in the right MCA region that occurred in young, right-handed tennis player while he was serving. Angiography with a contrast medium and a 3-dimensional rotational system revealed proximal M2 stenosis, and emergency superficial temporal artery-MCA anastomosis was performed. As a result, the patient showed a complete recovery and resumed all activities of daily life, including playing tennis. Because sports such as tennis, in which players vigorously swing their heads while serving, could lead to intracranial artery dissection, we advise that the possibility of MCA dissection should be considered in athletes with certain neurological symptoms, including headache.

DOI： 10.1272/jnms.76.209

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Transplantation of bone marrow cells has been reported to exert neuroprotection against cerebral ischemia. However, the effect of bone marrow mononuclear cells (BMMCs) administered immediately after reperfusion has rarely been investigated. The present study was designed to examine whether brain injury in response to transient focal ischemia can be ameliorated by BMMC administration immediately after reperfusion in rats, and to determine whether there are differences in the route of administration. MAIN METHODS: Autologous BMMCs were obtained from each rat. Rats were then subjected to transient focal ischemia followed by BMMC administration via the ipsilateral carotid artery (IA group) or the femoral vein (IV group) immediately after reperfusion. Control rats underwent the same procedure but received vehicle injection. Infarct volume was compared among the groups 24 h and 7 days after reperfusion. BMMCs were fluorescently labeled with PKH26 prior to administration to track transplanted cells. KEY FINDINGS: Total infarct volume decreased in the IA group, but not in the IV group, when compared to the vehicle group. In the ipsilateral hemisphere, PKH26 positive cell count was greater in the IA group than in the IV group. Motor function, assessed with a rotarod test, improved in the IA group compared to the vehicle group. SIGNIFICANCE: These results show significant neuroprotection after transient focal ischemia by 1 x 10(7) autologous BMMCs administered intra-arterially, but not intravenously, immediately after reperfusion in rats. The larger number of transplanted BMMCs in the brain during the early stage of reperfusion may be responsible for the protective effect.

DOI： 10.1016/j.lfs.2008.07.018

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記述言語：英語  

DOI： 10.1002/mds.22031

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Priming of CTLs at mucosal sites, where various tumors are originated, seems critical for controlling tumors. In the present study, the effect of the oral administration of OVA plus adjuvant cholera toxin (CT) on the induction of Ag-specific mucosal CTLs as well as their effect on tumor regression was investigated. Although OVA-specific TCRs expressing lymphocytes requiring in vitro restimulation to gain specific cytotoxicity could be detected by OVA peptide-bearing tetramers in both freshly isolated intraepithelial lymphocytes and spleen cells when OVA was orally administered CT, those showing direct cytotoxic activity without requiring in vitro restimulation were dominantly observed in intraepithelial lymphocytes. The magnitude of such direct cytotoxicity at mucosal sites was drastically enhanced after the second oral administration of OVA with intact whole CT but not with its subcomponent, an A subunit (CTA) or a B subunit (CTB). When OVA plus CT were orally administrated to C57BL/6 mice bearing OVA-expressing syngeneic tumor cells, E.G7-OVA, in either gastric tissue or the dermis, tumor growth was significantly suppressed after the second oral treatment; however, s.c. or i.p. injection of OVA plus CT did not show any remarkable suppression. Those mucosal OVA-specific CTLs having direct cytotoxicity expressed CD8alphabeta but not CD8alphaalpha, suggesting that they originated from thymus-educated cells. Moreover, the infiltration of such OVA-specific CD8(+) CTLs was observed in suppressed tumor tissues. These results indicate that the growth of ongoing tumor cells can be suppressed by activated CD8alphabeta CTLs with tumor-specific cytotoxicity via an orally administered tumor Ag with a suitable mucosal adjuvant.

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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掲載種別：研究論文（学術雑誌）  

The main symptoms of acute primary angle-closure glaucoma (PACG) include pain in the head and/or the eyes in addition to the characteristic halo and blurred vision. When loss of vision is accompanied by such pain, PACG is usually suspected. However, no information has been available regarding painless acute angle-closure glaucoma. Recently, we treated a patient with painless acute PACG mimicking amaurosis fugax as a type of transient ischemic attack. Generally, amaurosis fugax causes transient monocular loss of vision due to occlusion of the ophthalmic artery. The formation of microemboli derived from the heart or carotid artery and/or the occurrence of some hemodynamic abnormality due to arteriosclerosis is closely related to amaurosis fugax, and most cases are complicated by intracranial or extracranial arterial lesions. In the present case, we provisionally diagnosed transient amaurosis fugax which, however, was shown by additional ocular testing to be painless PACG. Herein we describe our diagnostic process and the outcome. © 2007 the Authors.

DOI： 10.1111/j.1526-4610.2007.00866.x

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記述言語：英語   出版者・発行元：日本脳循環代謝学会  

著者らは,ラット光感受性脳血栓モデルの虚血72時間後における脳保護薬エダラボン(ED)の神経保護作用を検討し,更にトロンボキサン合成酵素阻害薬オザグレルナトリウム(OZG)を併用することで,その脳保護効果が増強するかどうかを検討した.実験動物は,I:対照群,II:OZG群,III:ED群,IV:OZG/ED群の4群に分類した. 1)脳梗塞体積の検討では,ED群とOZG群は対照群に比し共に縮小傾向を認めたが,有意差は認めなかった.しかし,OZG/ED群では,対照群に比し脳梗塞の有意な縮小を認め,脳浮腫体積や神経症候も有意に改善した(p&lt;0.05). 2)EDはラット脳血栓モデルにおいて脳梗塞抑制効果を示し,またOZGを併用することによりEDの脳保護効果が増強する可能性が示され,この併用療法の臨床応用の有用性が示唆された

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Plasmodium yoelii-infected erythrocytes were injected into mice with or without 6.5 Gy irradiation. This irradiation suppressed erythropoiesis and induced severe immunosuppression. However, these mice showed a rather delayed infection, suggesting that fresh erythrocytes may become malarial targets. In other words, malarial infection did not persist without newly generated erythrocytes in mice. We then examined erythropoiesis in the liver and bone marrow of mice with malaria. Surprisingly, erythropoiesis began in the liver. At this time, the serum level of erythropoietin (EPO) was prominently elevated and the EPO mRNA also became detectable in the kidney. Many clusters of red blood cells appeared de novo in the parenchymal space of the liver. These results revealed that malarial infection had a potential to induce the onset of hepatic erythropoiesis in mice.

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

The frequency of post-stroke depression (PSD) was evaluated in an ischemic stroke cohort four weeks after onset, and the relationship between self-rating depression scale (SDS)/and infarct size, number and location of the ischemic brain lesions was also studied. The effects of a newly developed antidepressant SSRI (selective serotonin reuptake inhibitor), fluvoxamine maleate, on PSD and cerebral blood flow (CBF) was investigated in other ischemic stroke patients. The frequency of patients who had more than 40 on SDS score was 46% (18/39), and that of patients who had more than 50 was 13% (5/39). There were no differences in SDS score in infarct size, number and location of ischemic brain lesions, however there were significant differences in the lesion side. The score of the patients who had lesions in the left hemisphere was significantly higher than that of those who had them in the right. Administration of fluvoxamine maleate for four weeks improved the score on the Hamilton rating scale for depression (HAM-D) from 16.6 ±4.7 (n = 5) to 8.4±4.3 (n = 5), however it did not influence the mean cortical CBF. This study shows that the patients frequently had depression after ischemic stroke, and that left side lesion had a significant relationship with PSD. Therefore it is important that psychiatric examination of post-stroke patients is conducted. This study also shows that a newly developed antidepressant, fluvoxamine maleate, was effective for PSD.

DOI： 10.3143/geriatrics.40.127

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The epithelial cell of the small intestine is one of the most rapidly regenerating cells in the body. However, the cellular mechanism and biological significance underlying this rapid regeneration remain elusive. In this study we examined the intestinal epithelia of mutant mice that lack B and/or T cells and those of normal littermates. The absence of B cells in Ig mu-chain mutant mice or B and T cells in recombination-activating gene (RAG)-2(-/-) as well as SCID mutant mice was associated with a marked acceleration of epithelial cell turnover and an up-regulation of the expression of MHC class II molecules. No such effects were observed in T cell-deficient TCR-delta and -beta double-mutant mice. As far as the goblet cells of villous epithelium are concerned, absolute numbers of them remained the same among these mutant mice that have no B and/or T cells. Alymphoplasia (aly/aly) mutant mice that lacked Peyer's patches and Ig-producing cells in the lamina propria, but harbored a large number of intestinal mucosal T cells, also displayed a significant acceleration of epithelial cell turnover and, to some extent, up-regulated expression of MHC class II molecules. Notably, the accelerated epithelial cell turnover was not observed and returned to normalcy in the Ig mu-chain mutant mice that had been given antibiotic-containing water. These findings indicate that B cells down-regulate the generation and differentiation of intestinal epithelial cells in the normal wild-type condition and suggest that enteric microorganisms are implicated in the accelerated generation of epithelial cells in mice that have no B cells.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We have revealed that 100-200 clusters, filled with closely packed lymphocytes, can be found throughout the length of the antimesenteric wall of the mouse small intestine. They are composed of a large B cell area, including a germinal center, and epithelia overlying the clusters contain M cells. A large fraction of B cells displays B220+ CD19+ CD23+ IgM(low)IgD(high)CD5(-)Mac-1(-) phenotype, and the composition of IgA+ B cells is smaller but substantial. To our knowledge, these clusters are the first identification of isolated lymphoid follicles (ILF) in mouse small intestine. ILF can be first detected at 7 (BALB/c mice) and 25 (C57BL/6 mice) days after birth, and lymphoid clusters equivalent in terms of cellular mass to ILF are present in germfree, athymic nude, RAG-2(-/-), TCR-beta(-/-), and Ig mu-chain mutant (mu(-/-)) mice, although c-kit+ cells outnumber B220+ cells in germfree and athymic nude mice, and most lymphoid residents are c-kit+ B220(-) in RAG-2(-/-), TCR-beta(-/-), and mu(-/-) mice. ILF develop normally in the progeny of transplacentally manipulated Peyer's patch (PP)-deficient mice, and decreased numbers of conspicuously atrophied ILF are present in IL-7Ralpha(-/-) PP(null) mice. Neither ILF nor PP are detectable in lymphotoxin alpha(-/-) and aly/aly mice that retain well-developed cryptopatches (CP) and thymus-independent subsets of intraepithelial T cells, whereas ILF, PP, CP, and thymus-independent subsets of intraepithelial T cells disappear from common cytokine receptor gamma-chain mutant mice. These findings indicate that ILF, PP, and CP constitute three distinct organized gut-associated lymphoid tissues that reside in the lamina propria of the mouse small intestine.

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掲載種別：研究論文（学術雑誌）  

A 50-year-old woman treated for breast cancer with mitomycin C developed severe hypertension, followed by deep coma 3 days later. Computed tomography of the brain showed frontoparietal intracranial hemorrhage accompanied by subarachnoid hemorrhage. The patient was diagnosed additionally with hemolytic uremic syndrome (HUS) based on hemolytic anemia with schistocytosis, thrombocytopenia, and acute renal failure. The patient underwent hemodialysis and plasmapheresis with no improvement. We present the pathologic findings of the general vessels, which has been reported rarely. This case represents the first reported intracranial hemorrhage in HUS following mitomymycin C administration. We emphasize the need to control blood pressure in patients with HUS.

DOI： 10.2169/internalmedicine.40.237

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1046/j.1365-2796.2001.00761.x

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掲載種別：研究論文（学術雑誌）  

Natural killer T (NKT) cells are mainly present in the liver and thymus, and the majority of these T cells express either a CD4+ or a double-negative (DN) CD4-8- phenotype. In the present study, we examined whether such NKT cells were present in the intestine. NKT cells were rare in all sites of the small intestine, including an intraepithelial site. However, a considerable number of NKT cells were found at an intraepithelial site in the large intestine. This result was confirmed by both immunofluorescence and immunohistochemistry. In contrast to conventional NKT cells, NKT cells in the large intestine were CD8+ or DN CD4-8-. In the case of conventional NKT cells, their existence is known to depend on non-classical MHC class I-like antigens (i. e. CD1d) but not on classical MHC class I antigens. However, the NKT cells in the large intestine were independent of the presence of both CD1d and classical MHC class I antigens. These results were obtained using knockout mice lacking the corresponding genes and molecules. NKT cells in the large intestine were mainly αβTCR+ (> 75%) but did not use an invariant chain of Vα14Jα281, which is preferentially used by conventional NKT cells. These NKT cells did not bias the TCR-Vβ usage toward Vβ8. These findings suggest that the large intestine is a site in which unconventional NKT cells carrying the CD8+ phenotype (or DN CD4-8-) are abundant and that these cells are independent of MHC and MHC-like antigens.

DOI： 10.1002/1521-4141(200111)31:11<3361::AID-IMMU3361>3.0.CO;2-Z

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J06376&link_issn=&doc_id=20201225180001&doc_link_id=%2Fai1ccoad%2F2020%2F000704%2F001%2F0186-0193%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fai1ccoad%2F2020%2F000704%2F001%2F0186-0193%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(NPO)日本脳神経血管内治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)にゅーろん社  

虚血性脳卒中の原因として椎骨動脈解離(以下sVAD)が疑われた症例のなかには、最終的に動脈硬化性変化と診断されるものもある。今回、虚血性脳卒中で入院しMRA所見からsVADが疑われた患者30例をsVAD確定診断群(15例)とsVAD疑診群(15例)に分けて患者データを比較することにより、sVADとアテローム硬化の鑑別に役立つデータは何か検討した。その結果、確定診断群は疑診群に比べて平均年齢が有意に若く、糖尿病合併例の割合と冠疾患合併例の割合が有意に低いという特徴が認められた。

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：(株)にゅーろん社  

著者らのSCUにおけるrt-PAの使用状況と有効性について、使用時期で前半(n=11)と後半(n=11)に分け、比較検討した。その結果、患者の年齢は前半が74±13歳、後半が69±13歳であり、後半で若年の傾向がみられた。慎重投与の有無は前半でありの割合が多い傾向にあった。病型、発症から治療までの平均時間は前半後半ともほぼ同様の結果であった。治療効果は入院時のNIHSSでは後半でやや重症症例が多かったが、24時間後のNIHSSでは後半で有効例が多かった。退院時の有効例(mRS 0-1)は前半18%、後半55%で、死亡例(mRS 6)は前半36%、後半0%であり、後半で治療成績が良かった。この成績はJ-ACT、市販後使用成績調査と比較しても良好な結果であった。累積症例数と使用時期、SCUスタッフ数を検討すると人員の充実に伴って使用ペースも増加していた。尚、いずれの期間も症候性頭蓋内出血は0例であった。

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記述言語：日本語   出版者・発行元：日本神経治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本神経治療学会  

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脳梗塞急性期に対して使用されたクロピドグレルの有用性を後ろ向きに検討した。急性期脳梗塞または一過性脳虚血発作(TIA)で入院し、7日以内にクロピドグレルの投与を開始した、非心原性の脳血管障害患者19例を対象とした。合併症は、高血圧症は19例全員が有し、喫煙の習慣のある症例は8例であった。急性期治療としての静注剤は、オザグレルナトリウムが13例、アルガトロバンが7例に使用された。クロピドグレルは、入院後平均3.1日目に投与された。入院時NIHSSとmRSは有意に改善した。凝固線溶系マーカーと血小板系マーカーは上昇した。白血球数、血小板数、肝機能検査値に異常変動はみられなかった。機能検査値では、ALTで正常範囲内での上昇を認めたが、他の肝酵素値に有意な変動はなかった。クロピドグレルを第一選択薬とした急性期治療は安全であることが示唆された。

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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記述言語：日本語   出版者・発行元：日本脳循環代謝学会  

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その他リンク： http://search.jamas.or.jp/link/ui/2008091993

記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本神経学会  

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記述言語：日本語   出版者・発行元：日本医科大学医学会  

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記述言語：日本語   出版者・発行元：日本内科学会-関東地方会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本脳卒中学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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