Sungwook Yu

Prognostic Significance of Perihematomal Edema in Acute Intracerebral Hemorrhage Pooled Analysis From the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies

Background and Purpose— Controversy exists over the prognostic significance of perihematomal edema (PHE) in intracerebral hemorrhage. We aimed to determine the association of early PHE and clinical outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) studies. Methods— Pooled analyses of computed tomographic substudies in the pilot phase (INTERACT1) and main phase (INTERACT2), both international, prospective, open, blinded end point, randomized controlled trials, of patients with spontaneous intracerebral hemorrhage (<6 hours) and elevated systolic blood pressure, randomly assigned to intensive (target systolic blood pressure, <140 mm Hg) or guideline-based (systolic blood pressure, <180 mm Hg) blood-pressure management. Substudy participants (n=1310; 346 INTERACT1, 964 INTERACT2) had blinded central analyses of digital images from standardized baseline and 24-hour computed tomography. Predictors of death or dependency (modified Rankin scale scores, ≥3) at 90 days were assessed in logistic regression models and reported with odds ratios and 95% confidence intervals. INTERACT studies are registered at ClinicalTrials.gov (NCT00226096 and NCT00716079). Results— Of 1138 (87%) patients with 2 CTs available for edema analysis and outcome information, time from intracerebral hemorrhage onset to baseline computed tomography, baseline hematoma volume, 24-hour hematoma growth, and intraventricular extension were independent predictors of 24-hour PHE growth. Absolute growth in PHE volume was significantly associated with death or dependency (adjusted odds ratio, 1.17; 95% confidence interval, 1.02–1.33 per 5 mL increase from baseline; P=0.025) at 90 days after adjustment for demographic, clinical, and hematoma parameter prognostic factors. Associations were consistent across various sensitivity analyses. Conclusion— PHE growth is an independent prognostic factor in intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00226096 and NCT00716079.

Takotsubo-Like Myocardial Dysfunction in Ischemic Stroke: A Hospital-Based Registry and Systematic Literature Review.

Background and Purpose— We investigated clinical and radiological characteristics of ischemic stroke patients with Takotsubo-like myocardial dysfunction. Methods— From multicenter stroke registry database, ischemic stroke patients who underwent transthoracic echocardiography were found. Among these, patients were classified if they had specific ventricular regional wall motion abnormalities discording with coronary artery distribution, such as apical (typical pattern) or nonapical ballooning (atypical pattern), considered as echocardiographic findings of Takotsubo cardiomyopathy. Patients with ischemic heart disease history, myocarditis, or pheochromocytoma were excluded. We compared patients with Takotsubo-like myocardial dysfunction with those without and further performed systematic literature review on those with Takotsubo cardiomyopathy. Results— This study included 23 patients (0.42%). The mean age was 70.7±13.9 years, with predominance of women (73.9%) and typical pattern of Takotsubo-like myocardial dysfunction (91.3%). They were associated with short-term poor functional outcomes, including high mortality, neurological deterioration, and functional status at discharge, compared with those without (39.1% versus 2.4%, 47.8% versus 7.4%; and median [interquartile range], 5 [5–6] versus 3 [2–4]; all P<0.001). They had a higher inflammatory marker level and lower triglyceride level. Ischemic lesions were more commonly found in the right anterior circulation with specific dominant regions being the insula and peri-insular areas. In addition, a trend toward a remarkable mortality rate and higher prevalence of insular involvement was observed in the propensity-score matching, subgroup fulfilling the strict Takotsubo cardiomyopath criteria, and was as reported in literature review. Conclusion— Stroke patients with Takotsubo-like myocardial dysfunction may differ from those without in clinical outcomes, laboratory findings, and radiological features.

Statins Improve Survival in Patients With Cardioembolic Stroke

Background and Purpose— The objective of this study was to investigate the potential benefits of statin therapy on mortality and stroke recurrence after cardioembolic stroke. Methods— In this retrospective observational study, we analyzed data from 535 patients with first-ever cardioembolic stroke. Patients were classified into nonstatin, low-potency statin, and high-potency statin groups. The primary outcomes were time to mortality and time to recurrent stroke. Results— The mean duration of follow-up was 22.2 months. The cumulative mortality rate was 7% at the end of the first year and 10% at the end of the third year. Statin therapy was independently associated with reduced mortality (hazard ratio, 0.237; 95% confidence interval, 0.080–0.703 for nonstatin versus low-potency statin; hazard ratio, 0.158; 95% confidence interval, 0.037–0.686 for nonstatin versus high-potency statin). Statin treatment did not affect the incidence of recurrent stroke in patients with cardioembolic stroke. Conclusions— Statin therapy could be associated with reduced mortality in patients with cardioembolic stroke.

Chronic kidney disease and intravenous thrombolysis in acute stroke: A systematic review and meta-analysis.

BACKGROUND The association between chronic kidney disease (CKD) and hemorrhagic complications or clinical outcomes in patients treated with intravenous (IV) thrombolytic agents is controversial. METHODS We searched multiple databases for studies on the association between CKD and symptomatic intracerebral hemorrhage (ICH) and/or clinical outcomes in acute stroke patients treated with IV tissue plasminogen activator (tPA). Observational studies that evaluated the association between CKD and outcomes after adjusting for other confounding factors were eligible. We assessed study quality and performed a meta-analysis. The main outcome was symptomatic ICH. The secondary outcomes were poor functional status at 3 months using the modified Rankin Scale, mortality at 3 months, and any ICH. RESULTS Seven studies were selected based on our eligibility criteria. Of 7168 patients treated with IV tPA, 2001 (27.9%) had CKD. Patients with CKD had a higher risk of symptomatic ICH and mortality [pooled odds ratio (OR) 1.56, 95% confidence interval (CI) 1.05-2.33 and pooled OR 1.70, 95% CI 1.03-2.81, respectively]. Patients with CKD were likely to have an increased risk of poor outcome at 3 months. There was no significant association between CKD and any ICH. CONCLUSIONS Chronic kidney disease may significantly affect symptomatic hemorrhagic complications and poor clinical outcomes following administration of IV tPA.

White blood cell count and clinical outcomes after intracerebral hemorrhage: The INTERACT2 trial

BACKGROUND Increased inflammatory reaction can aggravate brain injury after acute intracerebral hemorrhage, but the clinical effect of such response is not fully understood. The aim of this study was to determine associations of peripheral white blood cell (WBC) count on clinical outcome among participants of the INTERACT2 study. METHODS INTERACT2 was a randomized controlled trial of early intensive (target systolic level<140 mm Hg) compared to guideline-recommended (target systolic level < 180 mm Hg) blood pressure (BP) lowering in 2839 patients with acute ICH (<6h) and elevated systolic BP (150-220 mm Hg). Blood samples were collected on admission and WBC count was measured at local laboratories. The primary outcome was death or major disability, defined by scores 3-6 on the modified Rankin Scale at 90 days. Secondary outcome was death at 90 days. Associations of baseline WBC count and outcomes were evaluated in logistic regression models. INTERACT2 is registered with http://www.clinicaltrials.gov NCT00716079. RESULTS There were 2630 participants with relevant data who were classified into quartiles of WBC counts (≤ 6.22, 6.24-7.89, 7.90-10.17, and ≥ 10.20 × 10(9)/L, respectively). Increased WBC count was associated with younger age, elevated body temperature, increased glucose level, stroke severity, larger baseline hematoma volume, and intraventricular extension. Risks of death or major disability at 90 days increased progressively with higher WBC count: frequencies of 49.9%, 52.0%, 52.3% and 58.1% for quartile groups, respectively (P=0.004 for trend). However, after adjustment for baseline clinical and imaging variables including age, sex, region, lipid lowering therapy, body temperature, glucose, systolic BP, heart rate, high NIHSS scores, volume and location of hematoma, intraventricular extension, time from onset to CT scan, and randomized treatment, the association between WBC count and primary outcome was no longer significant (P=0.426 for trend). Patients with increased WBC count had significantly higher risk of death (P=0.0003 for trend), but again the association was no longer significant after adjustment for baseline clinical and imaging variables. CONCLUSIONS Elevated WBC count on admission is not an independent prognostic variable in patients with acute ICH.

Neck–tongue syndrome precipitated by prolonged poor sitting posture

Neck–tongue syndrome (NTS) is a rare manifestation of cervicogenic headache, which is characterized by unilateral upper neck or occipital pain with ipsilateral numbness of the tongue upon sudden turning of the head [1]. NTS is known to occur in association with trauma, during physical activities, or in otherwise normal patients [1–3]. Poor fixed sitting postures that are maintained for lengthy periods may be an important contributing factor to the development of headache and neck pain [2]. However, the association between NTS and prolonged static sitting postures has not yet been clearly described. Here, we describe a case with NTS that was precipitated by prolonged slouching sitting posture. A 24-year-old woman presented with recurrent episodes of right upper neck and occipital pain that was provoked by head turning. Eight months before she had a mild neck pain, but it subsided spontaneously. One month before admission, she had spent at least 10 h a day in the sitting position to prepare for an examination. The usual sitting posture involved a forward head posture with a highly flexed neck and rounded shoulders and with the body leaning forward and toward the right side. One day before admission, she experienced unusually intense pain in the occipital area and the right upper neck. The pain attacks were severe, sharp, and short-lasting and were typically provoked by abrupt head rotation toward the right side or neck flexion, which was accompanied by an ipsilateral tingling sensation and numbness of her tongue. She did not have any medical history, including inflammatory arthritis or trauma. Her neurological examination, including the sensation and movement of the tongue, was unremarkable. Her range of motion in cervical rotation was not limited. Laboratory findings, including rheumatoid factors, were normal. Cervical spine radiographs showed an asymmetry of the para-odontoid space (Fig. 1a). Cervical computed tomographic (CT) scans of the neutral supine position revealed a narrowing of the left para-odontoid space, which was possibly due to an atlantoaxial rotatory fixation (Fig. 1b). There was no degenerative change of the cervical spine. A dynamic CT scan with head turning demonstrated little change in the asymmetry of the para-odontoid spaces with the normal rotation of the atlas (Fig. 1c, d). She was treated conservatively with medication, including a non-steroidal anti-inflammatory drug and gabapentin. She rested in bed to provide stabilization of the cervical spine by limiting head rotation. In addition, we corrected her sitting posture to achieve a neutral body posture with the head upright avoiding slouching including leaning forward or to the side and recommended exercises for relaxing the neck muscles. Three days after admission, her pain was significantly relieved. Three weeks after the onset of symptoms, the pain attacks were completely resolved. She had no recurrence of symptoms up to 8 months thereafter. It was noteworthy that static slouching sitting posture could be a precipitating factor for the development of NTS in this otherwise healthy patient. Neck and shoulder pains are relatively common among adolescents, which can be predisposed by prolonged sitting in a fixed posture [2, 4]. Therefore, poor static posture could be considered a precipitating factor for NTS. The pathogenesis of NTS has been suggested to involve compression or mechanical irritation of the C2 ventral ramus by an abnormal subluxation of the lateral atlantoaxial joints [1, 5]. Another proposed mechanism is a spasm J. B. Kim J.-K. Yoo S. Yu (&) Department of Neurology, Korea University College of Medicine, #126-1, Anam-Dong 5-Ga, Seongbuk-Gu, Seoul 136-705, Republic of Korea e-mail: song4yu@korea.ac.kr

Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial

BACKGROUND The optimal treatment for patients with ischaemic stroke with a high risk of cerebral haemorrhage is unclear. We assessed the efficacy and safety of cilostazol versus aspirin, with and without probucol, in these patients. METHODS In this randomised, controlled, 2 × 2 factorial trial, we enrolled patients with ischaemic stroke with a history of or imaging findings of intracerebral haemorrhage or two or more microbleeds from 67 centres in three Asian countries. Patients were randomly assigned (1:1:1:1) to receive oral cilostazol (100 mg twice a day), aspirin (100 mg once a day), cilostazol plus probucol (250 mg twice a day), or aspirin plus probucol with centralised blocks stratified by centre. Cilostazol versus aspirin was investigated double-blinded; probucol treatment was open-label, but the outcome assessor was masked to assignment. The co-primary outcomes were incidence of the composite of stroke, myocardial infarction, or vascular death (efficacy) and incidence of haemorrhagic stroke (safety), which were assessed in intention-to-treat and modified intention-to-treat populations. Efficacy was analysed with a non-inferiority test and a superiority test if non-inferiority was satisfied. Safety was assessed with a superiority test only. This trial is registered with ClinicalTrials.gov, NCT01013532. FINDINGS Between Aug 1, 2009, and Aug 31, 2015, we randomly assigned 1534 patients to one of the four study groups, of whom 1512 were assessed for the co-primary endpoints. During a median follow-up of 1·9 years (IQR 1·0-3·0), the incidence of composite vascular events was 4·27 per 100 person-years in patients who received cilostazol and 5·33 per 100 person-years in patients who received aspirin (HR 0·80, 95% CI 0·57-1·11; non-inferiority p=0·0077; superiority p=0·18). Incidence of cerebral haemorrhage was 0·61 per 100 person-years in patients who received cilostazol and 1·20 per 100 person-years in those who received aspirin (HR 0·51, 97·5% CI 0·20-1·27; superiority p=0·18). The incidence of vascular events was 3·91 per 100 person-years in the probucol group compared with 5·75 per 100 person-years in the non-probucol group (HR 0·69, 95% CI 0·50-0·97; superiority p=0·0316). The incidence of cerebral haemorrhage was 0·72 per 100 person-years in the probucol group and 1·11 per 100 person-years in the non-probucol group (HR 0·65, 97·5% CI 0·27-1·57; p=0·55). Adverse events were similar across the four study groups; the most common events were dizziness, headache, diarrhoea, and constipation. INTERPRETATION In patients with ischaemic stroke at high risk of cerebral haemorrhage, cilostazol was non-inferior to aspirin for the prevention of cardiovascular events, but did not reduce the risk of haemorrhagic stroke. Addition of probucol to aspirin or cilostazol could be beneficial for reducing the incidence of cardiovascular events. FUNDING Korea Otsuka Pharmaceutical.

Left ventricular wall motion abnormalities are associated with stroke recurrence

Objective: To investigate the role of left ventricular wall motion abnormalities (LVWMA), unrelated to high-risk cardioembolic conditions, in stroke recurrence. Methods: This study included consecutive acute ischemic stroke patients. Transthoracic echocardiography was performed as a routine evaluation for stroke patients. The outcomes were the time to recurrent any stroke and ischemic stroke. Results: Among 4,316 acute ischemic stroke patients, 430 had LVWMA without high-risk cardioembolic sources. The median observation periods of patients at risk of any stroke and ischemic stroke were 24.5 and 24.7 months. During the follow-up, any stroke and ischemic stroke recurrence were observed in 310 (7.2%) and 250 (5.8%) patients. LVWMA were associated with outcomes after adjustment for traditional cardiovascular risk factors, laboratory and imaging variables, and therapeutic interventions (hazard ratio [HR] 1.707, 95% confidence interval [CI] 1.262–2.310 for any stroke; HR 1.709, 95% CI 1.222–2.390 for ischemic stroke). Moreover, LVWMA could still be considered as independent risk factors after correction for covariates that were significantly associated with outcomes in univariable regression (HR 1.747, 95% CI 1.292–2.364 for any stroke; HR 1.704, 95% CI 1.219–2.382 for ischemic stroke). There were no significant interactions between LVWMA and outcomes between the subgroups except for the statin treatment subgroup. Conclusions: This study suggests that LVWMA, even when unassociated with high-risk cardioembolic sources, could be an independent predictor for stroke recurrence in patients with ischemic stroke.

Acute middle cerebral artery stroke and an innominate steal from a ruptured brachiocephalic trunk atheroma

A 59-year-old man developed sudden left hemiparesis and dysarthria 35 min before arrival at the emergency room. He was a current smoker. He had facial palsy, hemiparesis and sensory extinction on the left side. His baseline National Institutes of Health Stroke Scale score was 9. The right radial pulse was diminished. An initial diffusion weighted image showed areas of subtle diffusion restriction in the right middle cerebral artery (MCA) territory (fig 1A). CT angiography after administration of intravenous tissue plasminogen activator demonstrated right distal MCA stem occlusion (fig 1B). Intra-arterial thrombolysis was attempted 4 h after the onset of symptoms. Figure 1 (A) An initial diffusion weighted image shows areas of subtle diffusion restriction at the right insular cortex and corona radiata (broken arrows). (B) CT angiography shows right distal middle cerebral artery stem occlusion (arrow) and leptomeningeal collaterals (broken …

Driving in stroke survivors aged 18–65 years: The Psychosocial Outcomes In StrokE (POISE) Cohort Study:

Background There is limited information regarding return to driving after stroke. Aims To determine the frequency and predictors of return to driving within 1 month of acute stroke in younger (age 18–65 years) adults. Methods POISE (Psychosocial Outcomes In StrokE) was a cohort study conducted in Australia between October 2008 and June 2010. Consecutive patients (age 18–65 years) with a recent (≤28 days) acute stroke were recruited. Validated demographic, clinical, mental health, cognitive, and disability measures including return to driving were obtained. Multivariable logistic regression was used to determine factors associated with return to driving within 1 month of stroke. Results Among 359 participants who were legally able to drive before stroke, 96 (26.7%) returned to driving within 1 month. Compared to those without an early return to driving (n = 263), drivers were more often male, the main income earner, in paid work before stroke and without symptoms of depression or fatigue. Independence in activities of daily living (odds ratio (OR) 30.05, 95% confidence interval (CI) 3.85–234.45), not recalling receiving advice on driving cessation (OR 5.55, 95% CI 2.86–11.11), and having returned to paid work (OR 3.93, 95% CI 1.94–7.96) were associated with early return to driving. Conclusions One in four young adults resumed driving within a month, contrary to guideline recommendations. These data reinforce the importance of deciding who is responsible for determining fitness to drive after stroke, when, and whether it is reasonable to enforce driving restrictions on those with minimal disability who are fit to return to work. Registration Australian New Zealand Clinical Trials Registry ANZCTRN 12608000459325.