Publications by authors named "Manabu Inoue"

83 Publications

A nomogram to predict unfavourable outcome in patients receiving oral anticoagulants for atrial fibrillation after stroke.

Eur Stroke J 2020 Dec 26;5(4):384-393. Epub 2020 Nov 26.

Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.

Introduction: It is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients.

Patients And Methods: We conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (<65 years, reference; 65--79; or 80), National Institutes of Health Stroke Scale score (0--5 points, reference; 6--15; 16--25; or >25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve.

Results: A total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training ( = 1553) and test ( = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852;  = 0.276 for the Hosmer--Lemeshow test).

Discussion And Conclusion: Our nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.
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http://dx.doi.org/10.1177/2396987320945840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856583PMC
December 2020

Identifying large ischemic core volume ranges in acute stroke that can benefit from mechanical thrombectomy.

J Neurointerv Surg 2020 Dec 15. Epub 2020 Dec 15.

Neurology, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Background: We aimed to identify the large ischemic core (LIC) volume ranges in acute ischemic stroke patients that can benefit from mechanical thrombectomy (MT).

Methods: Consecutive patients within 24 hours of onset of anterior circulation ischemic stroke with large vessel occlusion and ischemic core volumes of 70-300 mL were included from our single-center prospective database from March 2014 to December 2019. Subjects were divided into three groups by baseline ischemic core volume (A: 70-100 mL; B: 101-130 mL; C: >130 mL). We compared modified Rankin Scale (mRS) score 0-2 at 3 months and parenchymal hematoma between patients receiving MT and standard medical treatment (SMT), and determined clinically treatable core volume ranges for MT.

Results: Of 157 patients (86 women; median age, 81 years; median ischemic core volume, 123 mL), 49 patients underwent MT. In Group A (n=52), MT patients (n=31) showed a higher proportion of mRS 0-2 at 3 months (52% vs 5%, P<0.05) versus SMT, respectively. Group B (n=36) MT patients (n=14) also had a higher proportion of mRS 0-2 at 3 months (29% vs 9%, P=0.13) versus SMT, respectively. In Group C (n=69), only four patients received MT. The 95% confidence intervals for the probability of mRS 0-2 at 3 months in patients with MT (n=49) versus SMT (n=108) intersected at 120-130 mL.

Conclusions: Ischemic core volumes between 70 and 100 mL may benefit from MT. The treatable upper core limit is approximately 120 mL in selected patients with LIC of 70-300 mL.
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http://dx.doi.org/10.1136/neurintsurg-2020-016934DOI Listing
December 2020

Magnetic Resonance Imaging-Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size: THAWS RCT Substudy.

Stroke 2021 01 10;52(1):12-19. Epub 2020 Dec 10.

Department of Cerebrovascular Medicine (K.T., M. Inoue, S.Y., M.F.-D., K. Miwa, M. Shiozawa, K. Minematsu, M.K.), National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Purpose: We determined to identify patients with unknown onset stroke who could have favorable 90-day outcomes after low-dose thrombolysis from the THAWS (Thrombolysis for Acute Wake-Up and Unclear-Onset Strokes With Alteplase at 0.6 mg/kg) database.

Methods: This was a subanalysis of an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients with stroke with a time last-known-well >4.5 hours who showed a mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg intravenously or standard medical treatment. The patients were dichotomized by ischemic core size or National Institutes of Health Stroke Scale score, and the effects of assigned treatments were compared in each group. The efficacy outcome was favorable outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1.

Results: The median DWI-Alberta Stroke Program Early CT Score (ASPECTS) was 9, and the median ischemic core volume was 2.5 mL. Both favorable outcome (47.1% versus 48.3%) and any intracranial hemorrhage (26% versus 14%) at 22 to 36 hours were comparable between the 68 thrombolyzed patients and the 58 control patients. There was a significant treatment-by-cohort interaction for favorable outcome between dichotomized patients by ASPECTS on DWI (=0.026) and core volume (=0.035). Favorable outcome was more common in the alteplase group than in the control group in patients with DWI-ASPECTS 5 to 8 (RR, 4.75 [95% CI, 1.33-30.2]), although not in patients with DWI-ASPECTS 9 to 10. Favorable outcome tended to be more common in the alteplase group than in the control group in patients with core volume >6.4 mL (RR, 6.15 [95% CI, 0.87-43.64]), although not in patients with volume ≤6.4 mL. The frequency of any intracranial hemorrhage did not differ significantly between the 2 treatment groups in any dichotomized patients.

Conclusions: Patients developing unknown onset stroke with DWI-ASPECTS 5 to 8 showed favorable outcomes more commonly after low-dose thrombolysis than after standard treatment. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT02002325. URL: https://www.umin.ac.jp/ctr; Unique Identifier: UMIN000011630.
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http://dx.doi.org/10.1161/STROKEAHA.120.030848DOI Listing
January 2021

Left Atrial Size and Ischemic Events after Ischemic Stroke or Transient Ischemic Attack in Patients with Nonvalvular Atrial Fibrillation.

Cerebrovasc Dis 2020 11;49(6):619-624. Epub 2020 Nov 11.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background: The present study aimed to clarify the association between left atrial (LA) size and ischemic events after ischemic stroke or transient ischemic attack (TIA) in patients with nonvalvular atrial fibrillation (NVAF).

Methods: Acute ischemic stroke or TIA patients with NVAF were enrolled. LA size was classified into normal LA size, mild LA enlargement (LAE), moderate LAE, and severe LAE. The ischemic event was defined as ischemic stroke, TIA, carotid endarterectomy, carotid artery stenting, acute coronary syndrome or percutaneous coronary intervention, systemic embolism, aortic aneurysm rupture or dissection, peripheral artery disease requiring hospitalization, or venous thromboembolism.

Results: A total of 1,043 patients (mean age, 78 years; 450 women) including 1,002 ischemic stroke and 41 TIA were analyzed. Of these, 351 patients (34%) had normal LA size, 298 (29%) had mild LAE, 198 (19%) had moderate LAE, and the remaining 196 (19%) had severe LAE. The median follow-up duration was 2.0 years (interquartile range, 0.9-2.1). During follow-up, 117 patients (11%) developed at least one ischemic event. The incidence rate of total ischemic events increased with increasing LA size. Severe LAE was independently associated with increased risk of ischemic events compared with normal LA size (multivariable-adjusted hazard ratio, 1.75; 95% confidence interval, 1.02-3.00).

Conclusion: Severe LAE was associated with increased risk of ischemic events after ischemic stroke or TIA in patients with NVAF.
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http://dx.doi.org/10.1159/000511393DOI Listing
March 2021

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data.

Lancet 2020 11 8;396(10262):1574-1584. Epub 2020 Nov 8.

Department of Neurology, University of Erlangen-Nuremberg, Erlangen, Germany.

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.

Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.

Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).

Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.

Funding: None.
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http://dx.doi.org/10.1016/S0140-6736(20)32163-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734592PMC
November 2020

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

J Stroke Cerebrovasc Dis 2020 Dec 16;29(12):105321. Epub 2020 Sep 16.

Westchester Medical Center Health Network, Director of Neurocritical Care and Emergency Neurological Services, Valhalla, NY, USA; Westchester Medical Center Health Network, New York Medical College, Valhalla, NY, USA.

Background: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran.

Methods: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model.

Results: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001).

Conclusion: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494258PMC
December 2020

Treatment Outcomes by Initial Neurological Deficits in Acute Stroke Patients with Basilar Artery Occlusion: The RESCUE Japan Registry 2.

J Stroke Cerebrovasc Dis 2020 Nov 4;29(11):105256. Epub 2020 Sep 4.

Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya, Japan.

Background And Purpose: We hypothesized that the relationships between treatments and outcomes in acute basilar artery occlusion (BAO) are different, depending on the severity of initial neurological deficits.

Methods: Of 2420 ischemic stroke patients with large vessel occlusion in a prospective, multicenter registry in Japan, patients with acute BAO were enrolled. Subjects were divided into two severity groups according to the baseline NIH Stroke Scale score: severe (≥10) and mild (<10) groups. The primary effectiveness outcome was favorable outcome, defined as modified Rankin Scale score 0-3 at 3 months. Safety outcomes included any intracranial hemorrhage (ICH) within 72 h. Outcomes in each group were compared between patients who received endovascular therapy (EVT) and those with standard medical treatment (SMT).

Results: In this study, 167 patients (52 female; median age 75 years) were analyzed. The favorable outcome was seen in 93 patients (56%) overall. In the severe group (n = 128), the proportion of favorable outcome was higher in patients who received EVT (60/111, 54%) than those with SMT (2/17, 12%, P < 0.01). In the mild group (n = 39), the rates of favorable outcome were comparable between the EVT (13/18, 72%) and SMT patients (18/21, 86%, P = 0.43). No significant differences in the rates of any ICH were seen among any groups.

Conclusions: In acute BAO stroke with severe neurological deficit, independent ambulation was more frequently seen in patients who received EVT than those with SMT. Patients with mild neurological deficits showed similar rates of independent ambulation between the two treatment selections.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105256DOI Listing
November 2020

[MRI and intravenous thrombolysis for unclear-onset stroke during the COVID-19 pandemic: a case report].

Rinsho Shinkeigaku 2020 Oct 5;60(10):706-711. Epub 2020 Sep 5.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center.

During the COVID-19 pandemic in 2020, an 81-year-old afebrile woman was transported to our institute at 44 minutes after she was found to have global aphasia and weakness of the right extremities. The onset time was unclear. CT showed an occlusion of the left middle cerebral artery without early ischemic changes. MRI revealed a negative fluid-attenuated inversion recovery (FLAIR) pattern, in which several small acute infarcts were seen in diffusion-weighted images with no corresponding hyperintensity lesions on FLAIR. Accordingly, intravenous thrombolysis with alteplase (0.6 mg/kg, the dose approved in Japan) was administered at 1,660 minutes after the last known well and 116 minutes after the symptom recognition. An immediate internal carotid angiogram showed severe stenosis at the distal end of the horizontal portion of the left middle cerebral artery. In the follow-up angiogram at 164 minutes after the symptom recognition, the stenotic lesion almost resolved with the restoration of quick and nearly complete antegrade flow. Her symptoms also resolved promptly. Although the use of MRI is recommended to be minimized in the emergency stroke management during the COVID-19 pandemic, MRI is occasionally mandatory for patient selection, such as cases with unclear onset to perform intravenous thrombolysis. The individualized protected code stroke is essential and must be well considered by each institute for diagnosing patients by selecting appropriate modalities.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001481DOI Listing
October 2020

Cerebral embolism accompanied by remarkable diffusion-weighted imaging reversal in a 10 month-old infant with congenital heart disease.

eNeurologicalSci 2020 Sep 12;20:100260. Epub 2020 Aug 12.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, 6-1, Kishibe-shimmachi, Suita, Osaka 564-8565, Japan.

•The case of infant ischemic stroke with remarkable DWI reversal.•A mismatch between core volume and visually DWI lesion predicts DWI reversal.•Chronic hypoxia and early recanalization may contribute to large DWI reversal.•Mismatch between DWI-ASPECTS and core volume may occur in infant brain.
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http://dx.doi.org/10.1016/j.ensci.2020.100260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452634PMC
September 2020

Call to Action: SARS-CoV-2 and CerebrovAscular DisordErs (CASCADE).

J Stroke Cerebrovasc Dis 2020 Sep 8;29(9):104938. Epub 2020 May 8.

Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.

Background And Purpose: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic.

Methods: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center.

Conclusion: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205703PMC
September 2020

Prognostic impact of primary tumor location in Stage III colorectal cancer-right-sided colon versus left-sided colon versus rectum: a nationwide multicenter retrospective study.

J Gastroenterol 2020 Oct 10;55(10):958-968. Epub 2020 Jul 10.

Department of Colorectal Surgery, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 1040045, Japan.

Background: Previous studies investigating the impact of tumor location on colorectal cancer prognosis only compared two groups by location, e.g., 'right-sided colon vs. left-sided colon,' 'colon vs. rectum,' and 'right-sided (right-sided colon) vs. left-sided (left-sided colon and rectum).' This nationwide multicenter retrospective study aimed to clarify the prognostic impact of tumor location in patients with stage III colorectal cancer by classifying tumors into three groups: right-sided colon, left-sided colon, and rectum.

Methods: Subjects were 9194 patients with stage III colorectal cancer who underwent curative surgery from 1997 to 2012. Relapse-free survival (RFS) after primary surgery and overall survival (OS) after recurrence were examined.

Results: Rectal cancer (n = 2922) was associated with worse RFS compared to right-sided colon cancer (n = 2362) (hazard ratio (HR) 0.65; 95% CI 0.59-0.72; p < 0.001) and left-sided colon cancer (n = 3910) (HR 0.72; 95% CI 0.66-0.78; p < 0.001) after adjusting for key clinical factors (i.e., sex, age, histological type, CEA, adjuvant therapy, T category, and N category). Among patients with recurrence (n = 2823), rectal cancer was associated with better OS compared to right-sided colon cancer (HR 1.23; 95% CI 1.08-1.40; p = 0.002) and worse OS compared to left-sided colon cancer (HR 0.88; 95% CI 0.79-0.99; p = 0.029). Twenty percent of right-sided colon cancer recurrences exhibited peritoneal dissemination, 42% of left-sided colon cancer recurrences were liver metastases, and 33% of rectal cancer recurrences were local recurrences.

Conclusions: The three tumor locations (right-sided colon, left-sided colon, rectum) had different prognostic implications for recurrence after curative resection and overall mortality, suggesting that tumor location serves as a prognostic biomarker in stage III colorectal cancer.
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http://dx.doi.org/10.1007/s00535-020-01706-7DOI Listing
October 2020

Laparoscopic versus Open Colectomy for Elderly Patients with Colon Cancer: A Propensity Score Analysis with the Controlling Nutritional Status (CONUT) Score.

Nutr Cancer 2021 7;73(2):246-251. Epub 2020 Apr 7.

Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan.

The feasibility of laparoscopic surgery for elderly patients remains unclear, as these patients usually present with comorbidities. Recently, the controlling nutritional status (CONUT) score has drawn attention as an evaluation score of patients' general status as well as a predictor of survival. We retrospectively analyzed overall survival in 424 patients aged ≥75 years with colon cancer, who underwent curative surgery (laparoscopic ( = 167) or open surgery ( = 257)) between January 2004 and December 2013. To adjust for heterogeneity in both groups, a propensity score-matched analysis was performed, with the CONUT score as a confounding covariate. 5-year overall survival rates of patients with normal (0-1), mildly abnormal (2-4), or abnormal (≥5) CONUT score were 88.6%, 79.4%, and 41.4%, respectively ( < 0.001). T3 or less, N negative, late period (2009-2013), and normal CONUT score were associated with the tendency to undergo laparoscopic surgery ( < 0.001). The analysis of the propensity score-matched cohort (124 pairs) revealed that patients in the laparoscopic surgery group had a similar prognosis to those in the open surgery group, with a 5-year overall survival of 91.9% vs. 82.0%, respectively ( = 0.102). Laparoscopic surgery for colon cancer is an acceptable surgical approach in elderly patients.
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http://dx.doi.org/10.1080/01635581.2020.1743868DOI Listing
April 2020

Thrombolysis With Alteplase at 0.6 mg/kg for Stroke With Unknown Time of Onset: A Randomized Controlled Trial.

Stroke 2020 05 6;51(5):1530-1538. Epub 2020 Apr 6.

Department of Neurosurgery, Hyogo College of Medicine, Nishinomiya (S. Yoshimura).

Background and Purpose- We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods- This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0-1). Results- Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68-1.41]; =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06-12.58]; >0.999), respectively. Conclusions- No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02002325.
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http://dx.doi.org/10.1161/STROKEAHA.119.028127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185058PMC
May 2020

[A rare case of inclusion body myositis associated with anti-PM/Scl-75 antibodies].

Rinsho Shinkeigaku 2020 Apr 31;60(4):264-267. Epub 2020 Mar 31.

Department of Neurology, Kansai Electric Power Hospital.

A 71-year-old man presented with progressive muscle weakness of the four limbs in November 2014. His symptoms had started from the left leg in 2008, resulting in frequent falls. In 2011, he became unable to stand up without a handrail due to weakness of the both legs. Physical examination showed almost symmetric muscle weakness of the arms and legs; MMT4. The CK level was slightly elevated of 304 IU/l. The patient was diagnosed as having inclusion body myositis based on the muscle biopsy findings showing many fibers with rimmed vacuoles in addition to mononuclear cell infiltrating into the endomysium, surrounding and sometimes invading into non-necrotic muscle fibers. Anti-PM/Scl-75 antibodies were positive. Muscle strength improved after intravenous immunoglobulin therapy, although the effect was only temporary. This rare case suggests the autoimmunological etiology in inclusion body myositis.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001363DOI Listing
April 2020

Ischemic Stroke despite Oral Anticoagulant Therapy in Patients with Atrial Fibrillation.

Ann Neurol 2020 Feb 12. Epub 2020 Feb 12.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Objective: It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.

Methods: We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OAC ) with those without prior oral anticoagulation (OAC ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OAC ) with those who continued the same anticoagulation as secondary prevention (OAC ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA DS -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OAC (n = 1,195) and OAC (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OAC was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OAC (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OAC (n = 585).

Interpretation: Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA DS -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group. ANN NEUROL 2020.
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http://dx.doi.org/10.1002/ana.25700DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383617PMC
February 2020

Concentrations of dabigatran administered after acute ischemic stroke.

J Neurol Sci 2020 Apr 22;411:116704. Epub 2020 Jan 22.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Background And Purpose: The aim of this study was to evaluate the anticoagulation intensity of dabigatran for acute ischemic stroke patients and hemorrhagic/ischemic events after early initiation of dabigatran.

Methods: Acute ischemic stroke/transient ischemic attack (TIA) patients admitted to our hospital who started dabigatran from January 2012 to December 2017 were studied. Blood samples were drawn just before (0 h) and 4 h after dabigatran at a median of 5 days after starting dabigatran to measure dabigatran concentrations (C, C) based on the thrombin clotting time assay (Hemoclot®).

Results: Of the 70 patients (54 men, 69 ± 9 y), 14 started dabigatran after a TIA, and 56 started it after an ischemic stroke a median of 5 days after onset. C, C was 82.5 ± 58.0, 143.1 ± 98.2 ng/dl (150 mg BID, 35 patients) and 50.6 ± 40.9, 91.2 ± 64.7 ng/ml (110 mg BID, 35 patients). During a median follow-up of 382 (IQR 109-688) days of all 70 patients, five had clinical events. Three patients had bleeding events, two with nasal bleeding (C, C: 50, 80 ng/ml, C, C: 91, 173 ng/ml) and one with GI bleeding (C, C: 5, 5 ng/ml). Two patients had ischemic events, one with ischemic stroke (C, C: 10, 50 ng/ml) and another with acute myocardial infarction (C, C: 40, 40 ng/ml).

Conclusions: There was no obvious relationship between dabigatran concentration and hemorrhagic/ischemic events in this study. Larger sample study will be needed to examine the relationship between the concentration and events in clinical practice.
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http://dx.doi.org/10.1016/j.jns.2020.116704DOI Listing
April 2020

Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation.

Stroke 2020 03 22;51(3):883-891. Epub 2020 Jan 22.

From the Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan (T.M., K. Toyoda, S.Y., M.T., M.S., M. Inoue, M.K.).

Background and Purpose- We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods- From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results- DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2-7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68-81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69-82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47-1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42-4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28-1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions- Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation-associated ischemic stroke or transient ischemic attack. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01581502.
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http://dx.doi.org/10.1161/STROKEAHA.119.028118DOI Listing
March 2020

Use of Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) and Ischemic Core Volume to Determine the Malignant Profile in Acute Stroke.

J Am Heart Assoc 2019 11 8;8(22):e012558. Epub 2019 Nov 8.

Department of Cerebrovascular Medicine National Cerebral and Cardiovascular Center Suita Japan.

Background Malignant profiles were identified by imaging profiles and unfavorable outcomes that have poor response to reperfusion therapy. Many trials have used this profile in their inclusion criteria including large-vessel occlusion acute ischemic stroke trials. We aimed to redefine the cutoff values for malignant profile in acute ischemic stroke patients with large-vessel occlusion regardless of reperfusion therapy. Methods and Results Consecutive acute ischemic stroke patients with anterior large-vessel occlusion were prospectively extracted from the National Cerebral and Cardiovascular Center Stroke Registry between March 2014 and December 2017. Diffusion-Weighted Imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) and diffusion-weighted imaging lesion ischemic core volume (Vol) were measured in acute ischemic stroke patients with large-vessel occlusion with or without treatment. Unfavorable outcome was defined as a modified Rankin Scale score 5 to 6 at 3 months, and optimal DWI-ASPECTS and Vol for unfavorable outcome were assessed. In total, 198 patients (111 men, 77±13 years old) were enrolled. Median DWI-ASPECTS was 7 (5-9), and median Vol was 55 (6-134) mL. Among the patients, 72 (36%) patients underwent reperfusion therapy, and 83 (42%) had unfavorable outcomes. The threshold values for a malignant profile on receiver operating characteristic curve analysis for DWI-ASPECTS and Vol were 4 (area under the curve 0.78, <0.01; sensitivity 0.71, specificity 0.75) and 71 mL (area under the curve 0.80, <0.01; sensitivity 0.76, specificity 0.77), respectively. Conclusions The cutoff values for our redefined malignant profile were DWI-ASPECTS 4 and Vol 71 mL with no selection bias for reperfusion therapy in the real-world clinical practice. Clinical Trial Registration URL: http://www.clinicaltrials.gov Unique identifier: NCT02251665.
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http://dx.doi.org/10.1161/JAHA.119.012558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915267PMC
November 2019

Tissue Plasminogen Activator for Cortical Embolism Stroke with Magnetic Resonance Perfusion Imaging: A Report of Two Cases.

Case Rep Neurol 2019 May-Aug;11(2):222-229. Epub 2019 Jul 16.

Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

Computerized tomography (CT) or magnetic resonance imaging (MRI) is indispensable for diagnosing acute ischemic stroke (AIS) patients who are candidates for recombinant tissue plasminogen activator (rt-PA) therapies, but further investigation concerning appropriate selection of therapy following advanced imaging including perfusion imaging has not yet been done. The 2018 AHA guidelines have recommended not to perform excessive time-consuming imaging before rt-PA. Here we describe two cases in which reperfusion therapy was decided based on advanced imaging. The first case was a 70-year-old woman with complaints of total aphasia and right unilateral spatial neglect. Her MRI revealed no apparent high signal area in diffusion-weighted image (DWI), and her magnetic resonance angiography (MRA) showed no large vessel occlusion. Subsequent perfusion-weighted image (PWI) analysis showed a unilateral perfusion deficit in the left middle cerebral artery (MCA) region. The other case was an 88-year-old man with complaints of minor unilateral spatial neglect, right conjugate deviation of the eyes, and dysarthria. His MRI also revealed no apparent high signal area in DWI, and MRA showed slight stenosis in the right middle MCA. Subsequent PWI analysis showed a unilateral perfusion deficit in the right MCA region. In both cases, intravenous rt-PA therapy was administered after the diagnosis of AIS and the patients responded well to the reperfusion therapy. When DWI is performed too early, detecting the ischemic core and differentiating between a diagnosis of stroke and stroke mimics is sometimes difficult. Evaluation of perfusion abnormalities in acute cases can be performed quickly, as shown in these cases. Although rt-PA can be given just by non-contrast CT with no hemorrhage, advanced imaging may be an option to identify difficult-to-diagnose patients who require reperfusion therapy.
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http://dx.doi.org/10.1159/000501547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738249PMC
July 2019

Small but Steady Steps in Stroke Medicine in Japan.

J Am Heart Assoc 2019 08 8;8(16):e013306. Epub 2019 Aug 8.

Department of Cerebrovascular Medicine National Cerebral and Cardiovascular Center Suita Japan.

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http://dx.doi.org/10.1161/JAHA.119.013306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759910PMC
August 2019

[Postoperative Dysfunction and Quality of Life in Patients with Rectal Cancer].

Gan To Kagaku Ryoho 2019 Jun;46(6):990-996

Division of Colorectal Surgery, National Cancer Center Hospital.

Standard treatment for low advanced rectal cancer is total mesorectal excision(TME)plus bilateral pelvic lymph node dissection in Japan. It has been expanded sphincter-preserving rectal surgery due to improvement of surgical procedures for rectal cancer. However, autonomic nerves are close to rectum, it is important to establish a treatment strategy that is considering the patients of quality of life(QOL)after rectal cancer surgery. Here, we investigated the frequency and how to deal with dysuria, sexual dysfunction, defecation dysfunction and stoma related complications after rectal cancer surgery. It is considered that it is more important to increase the number of patients with rectal cancer, especially of elderly patients, to evaluate the preoperative function of each patient and select individual treatment based on the progress of the cancer.
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June 2019

[Reliability of modified Rankin Scale assessment with a Japanese version of simplified modified Rankin Scale Questionnaire (J-RASQ)].

Rinsho Shinkeigaku 2019 Jul 27;59(7):399-404. Epub 2019 Jun 27.

Department of Neurology, National Cerebral and Cardiovascular Center.

Modified Rankin Scale (mRS) is widely used as an indicator of physical disability after the onset of stroke and a main evaluation scale in clinical stroke trials but sometimes has discrepancies among raters. We designed a Japanese version of simplified mRS questionnaire (J-RASQ) to evaluate mRS using closed question to assess the difference from the original. Currently there are no Japanese version of mRS questionnaire and its validity and reliability assessment has been warranted. Patients with planned visit to our hospital between 60 and 120 days after the onset of cerebral hemorrhage or infarction between August 2017 and March 2018 were recruited. J-RASQ was distributed before the outpatient visit to stroke patients, families or caregivers, and response was obtained. Thereafter, outpatient attending physicians qualified as stroke or neurological specialists evaluated mRS according to the Japanese version of guidance scheme for mRS. Subsequently, 130 patients (mean age, 72 ± 12 years old) were enrolled, and the difference between the two scale scores (mRS vs. J-RASQ) were statistically examined by the κ statistic and the weighted κ statistic. The κ statistic was 0.42 (95% CI, 0.31-0.52), and the weighted κ statistic calculated taking into account the extent of disagreement was 0.78 (95% CI, 0.70-0.86). We conclude that the J-RASQ appears to have decent reliability and is similar to the existing mRS.
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http://dx.doi.org/10.5692/clinicalneurol.cn-001295DOI Listing
July 2019

Direct oral anticoagulants versus vitamin K antagonists after recent ischemic stroke in patients with atrial fibrillation.

Ann Neurol 2019 06 30;85(6):823-834. Epub 2019 Apr 30.

Stroke Unit and Division of Cardiovascular Medicine, University of Perugia, Perugia, Italy.

Objective: We compared outcomes after treatment with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and a recent cerebral ischemia.

Methods: We conducted an individual patient data analysis of seven prospective cohort studies. We included patients with AF and a recent cerebral ischemia (<3 months before starting oral anticoagulation) and a minimum follow-up of 3 months. We analyzed the association between type of anticoagulation (DOAC versus VKA) with the composite primary endpoint (recurrent ischemic stroke [AIS], intracerebral hemorrhage [ICH], or mortality) using mixed-effects Cox proportional hazards regression models; we calculated adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs).

Results: We included 4,912 patients (median age, 78 years [interquartile range {IQR}, 71-84]; 2,331 [47.5%] women; median National Institute of Health Stroke Severity Scale at onset, 5 [IQR, 2-12]); 2,256 (45.9%) patients received VKAs and 2,656 (54.1%) DOACs. Median time from index event to starting oral anticoagulation was 5 days (IQR, 2-14) for VKAs and 5 days (IQR, 2-11) for DOACs (p = 0.53). There were 262 acute ischemic strokes (AISs; 4.4%/year), 71 intracranial hemorrrhages (ICHs; 1.2%/year), and 439 deaths (7.4%/year) during the total follow-up of 5,970 patient-years. Compared to VKAs, DOAC treatment was associated with reduced risks of the composite endpoint (HR, 0.82; 95% CI, 0.67-1.00; p = 0.05) and ICH (HR, 0.42; 95% CI, 0.24-0.71; p < 0.01); we found no differences for the risk of recurrent AIS (HR, 0.91; 95% CI, 0.70-1.19; p = 0.5) and mortality (HR, 0.83; 95% CI, 0.68-1.03; p = 0.09).

Interpretation: DOAC treatment commenced early after recent cerebral ischemia related to AF was associated with reduced risk of poor clinical outcomes compared to VKA, mainly attributed to lower risks of ICH. ANN NEUROL 2019;85:823-834.
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http://dx.doi.org/10.1002/ana.25489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563449PMC
June 2019

Rivaroxaban concentrations in acute stroke patients with different dosage forms.

PLoS One 2019 21;14(3):e0214132. Epub 2019 Mar 21.

Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.

Background: The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form.

Methods And Findings: Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)].

Conclusions: The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428291PMC
December 2019

Validation and iteration of CT perfusion defined malignant profile thresholds for acute ischemic stroke.

Int J Stroke 2020 01 22;15(1):55-60. Epub 2019 Feb 22.

Department of Neurology, University of California, San Francisco, CA, USA.

Background: Malignant profile computed tomography perfusion (CTP) lesions are associated with poor outcomes after administration of intravenous tissue-plasminogen activator (IV-tPA) for ischemic stroke.

Aims: To determine whether published CTP-based lesion thresholds predictive of poor outcomes in a predominantly 8 cm of CTP anatomic coverage cohort would predict poor outcomes in an independent 4 cm of CTP anatomic coverage cohort and to generate optimized 4 cm CTP thresholds.

Methods: Ischemic stroke patients with baseline CTP imaging with 4 cm of anatomic coverage before receiving IV-tPA at a single institution were retrospectively studied. Perfusion lesion time to maximum of tissue residue function (Tmax) and cerebral blood flow (CBF) volumes were determined using RAPID automated software. Fisher's exact tests assessed associations between lesion thresholds and outcomes. Receiver operating characteristic (ROC) curves generated optimized thresholds for 4 cm of CTP coverage.

Results: Sixty-three patients were included. Poor outcomes were associated with published thresholds of Tmax >6 s > 103 mL, Tmax > 8 s > 86 mL, and Tmax > 10 s > 78 mL but not CBF core >53 mL. Thresholds optimized for 4 cm of CTP coverage and associated with poor outcomes were Tmax > 6 s > 100 mL, Tmax > 8 s > 65 mL, Tmax >10 s > 46 mL, and CBF core >39 mL.

Conclusions: We validated the ability of published CTP Tmax lesion volume thresholds to predict poor outcomes despite IV-tPA in an independent cohort using only 4 cm of CTP anatomical coverage. A CBF > 39 mL threshold, rather than the predominantly 8 cm CTP coverage derived CBF threshold of >53 mL, was associated with poor outcomes in this 4 cm CTP coverage cohort.
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http://dx.doi.org/10.1177/1747493019832987DOI Listing
January 2020

Prior Anticoagulation and Short- or Long-Term Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients With Nonvalvular Atrial Fibrillation.

J Am Heart Assoc 2019 02;8(3):e010593

1 Department of Cerebrovascular Medicine National Cerebral and Cardiovascular Center Suita Japan.

Background We aimed to clarify associations between prior anticoagulation and short- or long-term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio ( INR ) <2 on admission, 28 (2.4%) received prior warfarin treatment with an INR ≥2 on admission, and the remaining 38 (3.2%) received prior direct oral anticoagulant treatment. Prior warfarin treatment was associated with a lower risk of death or disability at 3 months compared with no prior anticoagulation ( INR <2: adjusted odds ratio: 0.58; 95% CI, 0.42-0.81; P=0.001; INR ≥2: adjusted odds ratio: 0.40; 95% CI, 0.16-0.97; P=0.043) but was not associated with a lower risk of death or disability at 2 years. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years compared with no prior anticoagulation (adjusted hazard ratio: 2.94; 95% CI, 1.20-6.15; P=0.021). Conclusions Prior warfarin treatment was associated with a lower risk of death or disability at 3 months but was not associated with a lower risk of death or disability at 2 years in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Prior warfarin treatment with an INR ≥2 on admission was associated with a higher risk of ischemic events within 2 years. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01581502.
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http://dx.doi.org/10.1161/JAHA.118.010593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405591PMC
February 2019

Capecitabine-induced Leukoencephalopathy.

Intern Med 2019 Feb 17;58(4):621-622. Epub 2018 Oct 17.

Department of Neurology, Osaka City General Hospital, Japan.

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http://dx.doi.org/10.2169/internalmedicine.0961-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421135PMC
February 2019

Large fasciculation can clinically manifest as spinal myoclonus; electromyographic and dynamic echomyographic studies of four cases with motor neuron disease.

Clin Neurophysiol Pract 2018 26;3:6-10. Epub 2017 Nov 26.

Kyoto University Graduate School of Medicine, Kyoto, Japan.

Objective: Patients with motor neuron disease rarely present with fasciculation which is large enough to be clinically recognized as myoclonus. This study is aimed at elucidating the features of large fasciculation manifesting as myoclonus by using surface electromyography (surface EMG) and dynamic echomyography (dynamic Echo).

Methods: Four patients with amyotrophic lateral sclerosis, two of whom clinically presented with both fasciculation and myoclonus, were studied by using the surface EMG and the dynamic Echo.

Results: At rest, all patients had fasciculation in atrophic muscles, and the surface EMG showed occasional discharges of different waveforms corresponding to fasciculation. During voluntary gentle muscle contraction, the surface EMG showed repetitive discharges in the contracting muscle, which were constant in size and waveform within each muscle. The muscle Echo at rest revealed occasional contractions of a small number of muscle fibers corresponding to fasciculation. During voluntary muscle contraction, the number of muscle fibers involved in the involuntary motor phenomena was larger in the patients who clinically presented with myoclonus compared with other patients who clinically presented only with fasciculation. In a patient who presented with myoclonus, there was no contraction in the antagonist muscle.

Conclusions: Fasciculation involving a large number of muscle fibers clinically manifests as spinal myoclonus.

Significance: Fasciculation involving a large number of muscle fibers can be a cause of spinal myoclonus.
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http://dx.doi.org/10.1016/j.cnp.2017.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133775PMC
November 2017