Recurrence after Spontaneous Resolution of an Idiopathic Epiretinal Membrane

We report a case of recurrent epiretinal membrane (ERM) after spontaneous resolution of an idiopathic ERM. A 65-year-old female demonstrated a spontaneous improvement in visual acuity from 0.1 to 1.2 in her left eye attributable to spontaneous resolution of idiopathic ERM due to posterior vitreous detachment. Thereafter, however, her visual acuity again decreased to 0.2 because of the recurrence of ERM. Her visual acuity improved to 0.8 after surgical removal. A microscopic examination of the excised specimen showed a characteristic undulating internal limiting membrane (ILM) and a continuous sheet of cells overlying the inner surface of the ILM. This case report illustrates that although spontaneous ERM resolution is rare, there is a possibility of recurrence even after spontaneous ERM resolution

Intravenous thrombolysis in patients with acute ischemic stroke and cerebral microbleeds:results from the ENCHANTED trial

OBJECTIVE: To determine associations between cerebral microbleeds (CMB) and intracerebral hemorrhage (ICH) as well as functional recovery after thrombolysis in participants of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).METHODS: ENCHANTED recruited acute ischemic stroke (AIS) patients eligible for thrombolytic therapy from 111 clinical centres in 13 countries. We included those with T2*-weighted or susceptibility-weighted brain magnetic resonance imaging within 6 hours after AIS. Associations between CMB (primary predictor), burden (0, 1, 2-4, or ≥5 CMBs), and location (deep, lobar, mixed) and any intracerebral hemorrhage (ICH) (primary outcome), symptomatic ICH (sICH), 90-day disability or death (modified Rankin scale [mRS] score 2-6), and other unfavorable functional outcomes (mRS 3-6, 6, and shift) were explored in logistic regression models, and in a stratification by alteplase dose.RESULTS: Of 311 eligible AIS participants, 111 (35.7%) had CMB(s) and this was not associated with an increase in any ICH (adjusted odds ratio 1.49, 95% confidence interval [CI] 0.87-2.54) or sICH (2.05, 0.92-4.56). However, the presence of CMB(s) was associated with 90-day disability or death (1.75, 1.04-2.94) and other unfavorable functional outcomes. Comparable associations were seen between CMB burden (defined ordinally categorical; any ICH 1.16 [0.90-1.50]; mRS 2-6 1.44 [1.11-1.87]) or mixed deep-lobar distribution (any ICH 1.42 [0.61-3.29]; mRS 2-6 3.66 [1.48-9.05]) and these outcomes. There were no differences in associations between CMB presence/burden/distribution and outcomes between two different alteplase doses (Pinteraction &gt;0.087).CONCLUSIONS: In ENCHANTED, CMB(s) was associated with 90-day unfavorable function recovery but not with a significantly increased likelihood of ICH in post-intravenous thrombolytic AIS. Low-dose alteplase may not offer a better profile for AIS with CMB(s).REGISTRATION NO: Clinicaltrials.gov (identifier no. NCT01422616).</p

Effect of Hospital Arrival Time on Functional Prognosis of Stroke Patients: Japan Stroke Data Bank Over 20 Years

Aims: The impact of weekend/holiday and nighttime hospitalization on functional outcomes and long-term trends in stroke patients is unclear. We examined functional and life outcomes and changes over time. Methods: We analyzed the clinical data of 203,176patients for hospital arrival day of week and 76,442patients for arrival times using Japan Stroke Data Bank. The endpoints were favorable outcome (Modified Rankin Scale[mRS]0-2), unfavorable outcome(mRS 5-6), and in-hospital mortality. We calculated odds ratios(OR) and 95% confidence interval(CI) of weekends/holidays and off-hours versus weekdays and on-hours for 2000-2009 and 2010-2020 using a mixed-effect multivariate model adjusted for confounding factors and evaluated interactions. Thereafter, we performed to check for year trends. Results: All endpoints were worse in weekend/holiday admissions for all stroke and in off-hours hospitalization for total stroke(TS), ischemic stroke(IS), and intracerebral hemorrhage(ICH). The adjusted ORs for favorable outcomes of weekend/holiday admissions were TS, 0.90(0.87-0.93); IS, 0.89(0.86-0.93); ICH, 0.91(0.84-0.98) and unfavorable outcome TS, 1.04(1.002-1.08) IS, 1.06(1.01-1.11). Off-hour hospitalization had adjusted ORs for favorable outcome(TS, 0.86 [95% CI: 0.82-0.91]; IS, 0.90 [0.84-0.95]; ICH, 0.85 [0.75-0.96]), unfavorable outcome(TS, 1.14 [1.07-1.22]; IS, 1.13 [1.04-1.23]; ICH, 1.15 [1.01-1.31]), and mortality (TS, 1.15 [1.05-1.26]; IS, 1.17 [1.04-1.32]). For IS, the incidence of unfavorable outcomes during off-hours was significantly lower in 2010-2020 than in 2000-2009; after adjusting for reperfusion therapy, it was no longer significant. Conclusion: Stroke patients admitted on weekends/holidays and off-hours had worse functional and life outcomes. Functional outcomes for off-hour admission for IS improved at 10-year intervals, possibly due to improvements in stroke care systems

Clinical Characteristics, Risk Factors, and Outcomes of Arterial Dissection-Associated Stroke: A 21-Year Cohort Study from the Japan Stroke Data Bank

Aim: To evaluate the risk factors, location, treatment, and outcomes of stroke due to arterial dissection, we examined these characteristics in a substantial, long-standing, nationwide stroke cohort. Methods: The study participants were patients with acute stroke who were registered in the Japan Stroke Data Bank between January 1999 and December 2020. We focused on patients with stroke caused by extracranial or intracranial artery dissection and examined their clinical characteristics, treatments, and outcomes. In addition, we compared the results between clinical subtypes with and without dissection. Results: Among the 218,799 registered patients with acute stroke, 1,353 (0.62%) were attributed to artery dissection. Of these, 880 patients had ischemic stroke, 16 had intracerebral hemorrhage, and 457 had subarachnoid hemorrhage (SAH). Dissection cases were most prevalent among individuals in their 40s and 50s, with intracranial vertebral artery dissection being the primary cause of ischemic stroke and SAH. Male sex, dyslipidemia, diabetes mellitus, and a history of smoking were associated with a higher likelihood of ischemic stroke than SAH. Unfavorable outcomes, defined as a modified Rankin score ≥ 4 at discharge, were observed in 18.9% of ischemic stroke cases and 42.6% of SAH cases with dissection. Neurological severity and older age at admission are associated with unfavorable outcomes in patients with ischemic stroke and SAH. Conclusions: Ischemic stroke was the most frequent subtype of stroke in patients with arterial dissection, followed by SAH. Patients with stroke due to dissection were younger than those without. Neurological severity and older age at admission are substantial risk factors for unfavorable stroke outcomes due to artery dissection

Practical "1-2-3-4-Day" Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study

BACKGROUND: The "1-3-6-12-day rule" for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. METHODS: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0-7), moderate (8-15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. RESULTS: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)-initiating DOACS within 1, 2, 3, and 4 days, respectively-than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27-0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27-0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. CONCLUSIONS: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation

Practical "1-2-3-4-Day" Rule for Starting Direct Oral Anticoagulants After Ischemic Stroke With Atrial Fibrillation: Combined Hospital-Based Cohort Study

BACKGROUND: The "1-3-6-12-day rule" for starting direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation after acute ischemic stroke or transient ischemic attack recommends timings that may be later than used in clinical practice. We investigated more practical optimal timing of DOAC initiation according to stroke severity. METHODS: The combined data of prospective registries in Japan, Stroke Acute Management with Urgent Risk-factor Assessment and Improvement-nonvalvular atrial fibrillation (September 2011 to March 2014) and RELAXED (February 2014 to April 2016) were used. Patients were divided into transient ischemic attack and 3 stroke subgroups by the National Institutes of Health Stroke Scale score: mild (0-7), moderate (8-15), and severe (≥16). The early treatment group was defined as patients starting DOACs earlier than the median initiation day in each subgroup. Outcomes included a composite of recurrent stroke or systemic embolism, ischemic stroke, and severe bleeding within 90 days. Six European prospective registries were used for validation. RESULTS: In the 1797 derivation cohort patients, DOACs were started at median 2 days after transient ischemic attack and 3, 4, and 5 days after mild, moderate, and severe strokes, respectively. Stroke or systemic embolism was less common in Early Group (n=785)-initiating DOACS within 1, 2, 3, and 4 days, respectively-than Late Group (n=1012) (1.9% versus 3.9%; adjusted hazard ratio, 0.50 [95% CI, 0.27-0.89]), as was ischemic stroke (1.7% versus 3.2%, 0.54 [0.27-0.999]). Major bleeding was similarly common in the 2 groups (0.8% versus 1.0%). On validation, both ischemic stroke (2.4% versus 2.2%) and intracranial hemorrhage (0.2% versus 0.6%) were similarly common in Early (n=547) and Late (n=1483) Groups defined using derivation data. CONCLUSIONS: In Japanese and European populations, early DOAC initiation within 1, 2, 3, or 4 days according to stroke severity seemed to be feasible to decrease the risk of recurrent stroke or systemic embolism and no increase in major bleeding. These findings support ongoing randomized trials to better establish the optimal timing of DOAC initiation

Severity, Outcomes, and their Secular Changes in 33,870 Ischemic Stroke Patients with Atrial Fibrillation in a Hospital-Based Registry: Japan Stroke Data Bank

Aim: Severity, functional outcomes, and their secular changes in acute atrial fibrillation (AF)-associated stroke patients were determined. Methods: Acute ischemic stroke patients with AF in a hospital-based, multicenter, prospective registry from January-2000 through December-2020, were compared with those without AF. The co-primary outcomes were the initial severity assessed by the NIH Stroke Scale (NIHSS) score and favorable outcome assessed by the modified Rankin Scale scores 0-2 at hospital discharge. Results: Of the 142,351 patients studied, 33,870 had AF. AF patients had higher NIHSS scores (median 9 vs. 3, adjusted coefficient 5.468, 95% CI 5.354-5.582) than non-AF patients. Favorable outcome was less common in AF patients than in non-AF patients in the unadjusted analysis (48.4% vs. 70.4%), but it was more common with adjustment for the NIHSS score and other factors (adjusted OR 1.110, 95% CI 1.061-1.161). In AF patients, the NIHSS score decreased throughout the 21-year period (adjusted coefficient -0.088, 95% CI -0.115 – -0.061 per year), and the reduction was steeper than in non-AF patients (P＜0.001). In AF patients, favorable outcome became more common over the period (adjusted OR 1.018, 95% CI 1.010-1.026), and the increase was steeper than in non-AF patients (P＜0.001); the increase was no longer significant after further adjustment by reperfusion therapy. Conclusions: Initial stroke severity became milder and functional outcomes improved in AF patients over the 21-year period. These secular changes were steeper than in non-AF patients, suggesting that AF-associated stroke seemed to reap more benefit of recent development of stroke care than stroke without AF

Brain Imaging Signs and Health-Related Quality of Life after Acute Ischemic Stroke: Analysis of ENCHANTED Alteplase Dose Arm.

The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24-2.29) and deep (OR 1.50, 95% CI: 1.03-2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty - atrophy, white matter change, and old infarcts - were significantly associated with adverse physical but not emotional HRQoL domains. In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL. [Abstract copyright: © 2020 S. Karger AG, Basel.

Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke

ObjectiveTo determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.MethodsIn a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2–6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.ResultsOf 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2–6, adjusted odds ratio [95% confidence interval] 0.60 [0.47–0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2–6, 1.04 [0.87–1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07).ConclusionsWe found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.Classification of EvidenceThis study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.Clinical Trial RegistrationClinicaltrials.gov identifier NCT01422616