Quality of Life After Intravenous Thrombolysis for Acute Ischemic Stroke: Results From the AcT Randomized Controlled Trial.

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Do Intracerebral Hemorrhage Nonexpanders Actually Expand Into the Ventricular Space?

BACKGROUND AND PURPOSE: The computed tomographic angiography spot sign as a predictor of hematoma expansion is limited by its modest sensitivity and positive predictive value. It is possible that hematoma expansion in spot-positive patients is missed because of decompression of intracerebral hemorrhage (ICH) into the ventricular space. We hypothesized that revising hematoma expansion definitions to include intraventricular hemorrhage (IVH) expansion will improve the predictive performance of the spot sign. Our objectives were to determine the proportion of ICH nonexpanders who actually have IVH expansion, determine the proportion of false-positive spot signs that have IVH expansion, and compare the known predictive performance of the spot sign to a revised definition incorporating IVH expansion. METHODS: We analyzed patients from the multicenter PREDICT ICH spot sign study. We defined hematoma expansion as ≥6 mL or ≥33% ICH expansion or >2 mL IVH expansion and compared spot sign performance using this revised definition with the conventional 6 mL/33% definition using receiver operating curve analysis. RESULTS: Of 311 patients, 213 did not meet the 6-mL/33% expansion definition (nonexpanders). Only 13 of 213 (6.1%) nonexpanders had ≥2 mL IVH expansion. Of the false-positive spot signs, 4 of 40 (10%) had >2 mL ventricular expansion. The area under the curve for spot sign to predict significant ICH expansion was 0.65 (95% confidence interval, 0.58-0.72), which was no different than when IVH expansion was added to the definition (area under the curve, 0.66; 95% confidence interval, 0.58-0.71). CONCLUSIONS: Although IVH expansion does indeed occur in a minority of ICH nonexpanders, its inclusion into a revised hematoma expansion definition does not alter the predictive performance of the spot sign.

Dysmetropsia and Cotard's syndrome due to migrainous infarction - or not?

INTRODUCTION: Migrainous infarction accounts for 12.8% of ischemic strokes of unusual etiology. CASE REPORT: A 59-year-old woman with longstanding migraine with aura experienced what appeared to be migrainous infarction characterized by dysmetropsia and transient Cotard's syndrome. Imaging demonstrated right temporal-parietal-occipital changes with apparent cortical laminar necrosis. CONCLUSION: The spectrum of the pathophysiology of migrainous infarction has not been established; however, cortical spreading depression may explain the appearance of imaging findings that do not obey a vascular territory.

Fatigue impact scale demonstrates greater fatigue in younger stroke survivors.

BACKGROUND: Fatigue affects 33-77% of stroke survivors. There is no consensus concerning risk factors for fatigue post-stroke, perhaps reflecting the multifaceted nature of fatigue. We characterized post-stroke fatigue using the Fatigue Impact Scale (FIS), a validated questionnaire capturing physical, cognitive, and psychosocial aspects of fatigue. METHODS: The Stroke Outcomes Study (SOS) prospectively enrolled ischemic stroke patients from 2001-2002. Measures collected included basic demographics, pre-morbid function (Oxford Handicap Scale, OHS), stroke severity (Stroke Severity Scale, SSS), stroke subtype (Oxfordshire Community Stroke Project Classification, OCSP), and discharge function (OHS; Barthel Index, BI). An interview was performed at 12 months evaluating function (BI; Modified Rankin Score, mRS), quality of life (Reintegration into Normal living Scale, RNL), depression (Geriatric Depression Scale, GDS), and fatigue (FIS). RESULTS: We enrolled 522 ischemic stroke patients and 228 (57.6%) survivors completed one-year follow-up. In total, 36.8% endorsed fatigue (59.5% rated one of worst post-stroke symptoms). Linear regression demonstrated younger age was associated with increased fatigue frequency (ß=-0.20;p=0.01), duration (ß=-0.22;p<0.01), and disability (ß=-0.24;p<0.01). Younger patients were more likely to describe fatigue as one of the worst symptoms post-stroke (ß=-0.24;p=0.001). Younger patients experienced greater impact on cognitive (ß=-0.27;p<0.05) and psychosocial (ß=-0.27;p<0.05) function due to fatigue. Fatigue was correlated with depressive symptoms and diminished quality of life. Fatigue occurred without depression as 49.0% of respondents with fatigue as one of their worst symptoms did not have an elevated GDS. CONCLUSIONS: Age was the only consistent predictor of fatigue severity at one year. Younger participants experienced increased cognitive and psychosocial fatigue.

Medication persistence rates and factors associated with persistence in patients following stroke: a cohort study.

BACKGROUND: Medication nonadherence can be as high as 50% and results in suboptimal patient outcomes. Stroke patients in particular can benefit from pharmacotherapy for thrombosis, hypertension, and dyslipidemia but are at high risk for medication nonpersistence. METHODS: Patients who were admitted to the Queen Elizabeth II Health Sciences Centre in Halifax, Nova Scotia, with stroke between January 1, 2001 and December 31, 2002 were analyzed. Data collected were pre-stroke function, stroke subtype, stroke severity, patient outcomes, and medication use at discharge, and six and 12 months post discharge. Medication persistence at six and 12 months and the factors associated with nonpersistence at six months were examined using multivariable stepwise logistic regression. RESULTS: At discharge, 420 patients (mean age 68.2 years, 55.7% male) were prescribed an average of 6.4 medications and mean prescription drug cost was $167 monthly. Antihypertensive (91%) and antithrombotic (96%) drug use at discharge were frequent, antilipidemic (73%) and antihyperglycemic (25%) drug use were less common. Self-reported persistence at six and 12 months after stroke was high (> 90%) for all categories. In the multivariable model of medication nonpersistence at six months, people aged 65 to 79 years were less likely to be nonpersistent with antihypertensive medications than people aged 80 years or more (Odds ratio (OR) 0.11, 95% Confidence Interval (CI) 0.03-0.39). Monthly drug costs of < $90 or $90-199.99 were associated with greater nonpersistence, compared to monthly drug costs > or =$200 (OR 6.74, 95% CI 1.32-34.46 for < $90; OR 5.25, 95% CI 1.14-24.25 for $90-199.99). For the antithrombotic drug category, people aged 65 to 79 years were less likely to be nonpersistent than people aged 80 years or more (OR 0.23, 95% CI 0.06-0.81), and people who were disabled before admission were more likely to be nonpersistent than those not disabled (OR 7.01, 95% CI 1.66-29.58). CONCLUSION: Patients reported high medication persistence rates six and 12 months after stroke. Identification of factors associated with nonpersistence (such as older age and prior disability) will help predict which patients are at higher risk for discontinuing their medications.

Diagnostic accuracy of neurological problems in the emergency department.

BACKGROUND: Previous studies describe significant rates of misdiagnosis of stroke, seizure and other neurological problems, but there are few studies examining diagnostic accuracy of all emergency referrals to a neurology service. This information could be useful in focusing the neurological education of physicians who assess and refer patients with neurological complaints in emergency departments. METHODS: All neurological consultations in the emergency department at a tertiary-care teaching hospital were recorded for six months. The initial diagnosis of the requesting physician was recorded for each patient. This was compared to the initial diagnosis of the consulting neurologist and to the final diagnosis, as determined by retrospective chart review. RESULTS: Over a six-month period, 493 neurological consultations were requested. The initial diagnosis of the requesting physician agreed with the final diagnosis in 60.4% (298/493) of cases, and disagreed or was uncertain in 35.7% of cases (19.1% and 16.6% respectively). In 3.9% of cases, the initial diagnosis of both the referring physician and the neurologist disagreed with the final diagnosis. Common misdiagnoses included neurocardiogenic syncope, peripheral vertigo, primary headache and psychogenic syndromes. Often, these were initially diagnosed as stroke or seizure. CONCLUSIONS: Our data indicate that misdiagnosis or diagnostic uncertainty occurred in over one-third of all neurological consultations in the emergency department setting. Benign neurological conditions, such as migraine, syncope and peripheral vertigo are frequently mislabeled as seizure or stroke. Educational strategies that emphasize emergent evaluation of these common conditions could improve diagnostic accuracy, and may result in better patient care.

Antiplatelet therapy for acute ischaemic stroke.

BACKGROUND: In patients with acute ischaemic stroke, platelets become activated. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and reduce the risk of early recurrent ischaemic stroke. This might reduce the risk of early death and improve long-term outcome in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage. OBJECTIVES: To assess the efficacy and safety of antiplatelet therapy in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched June 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2007), MEDLINE (June 1998 to May 2007), and EMBASE (June 1998 to May 2007). In 1998, for a previous version of this review, we searched the register of the Antiplatelet Trialists' Collaboration, MedStrategy and contacted relevant drug companies. SELECTION CRITERIA: Randomised trials comparing antiplatelet therapy (started within 14 days of the stroke) with control in patients with definite or presumed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and assessed trial quality, and for the included trials, extracted and cross-checked the data. MAIN RESULTS: Twelve trials involving 43,041 participants were included. Two trials testing aspirin 160 mg to 300 mg once daily started within 48 hours of onset contributed 94% of the data. The maximum follow up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow up (odds ratio 0.95, 95% confidence interval 0.91 to 0.99). For every 1000 patients treated with aspirin, 13 patients will avoid death or dependency (number needed to treat to benefit: 79). Antiplatelet therapy was associated with a small but definite excess of symptomatic intracranial haemorrhages, but this was more than offset by the reduction of recurrent ischaemic strokes and pulmonary embolus. AUTHORS' CONCLUSIONS: Antiplatelet therapy with aspirin 160 mg to 300 mg daily, given orally (or by nasogastric tube or per rectum in patients who cannot swallow), and started within 48 hours of onset of presumed ischaemic stroke reduces the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications and improves long-term outcome.

Clinical diagnosis of lacunar stroke in the first 6 hours after symptom onset: analysis of data from the glycine antagonist in neuroprotection (GAIN) Americas trial.

BACKGROUND AND PURPOSE: Although the pathophysiological heterogeneity of stroke may be highly relevant to the development of acute-phase therapies, discriminating between ischemic stroke subtypes soon after onset remains a challenge. We conducted a study of the accuracy of a clinical diagnosis of lacunar stroke in the first 6 hours after symptom onset. METHODS: We analyzed data from 1367 patients in the Glycine Antagonist In Neuroprotection (GAIN) Americas trial. The Trial of ORG10172 in Acute Stroke Treatment (TOAST) category "small vessel (lacunar)" disease at day 7 or at hospital discharge was used as the reference standard to determine the accuracy of a diagnosis of a lacunar stroke made within 6 hours of symptom onset using the Oxfordshire Community Stroke Project (OCSP) classification "LACS." Outcome was analyzed by comparing the proportions of patients classified as "LACS" at baseline or "small vessel (lacunar)" at 7 days who were dead or dependent at 3 months. RESULTS: The positive predictive value of an OCSP diagnosis of a lacunar stroke was 76% (95% CI: 69% to 81%; sensitivity 64% [95% CI: 58% to 70%]; specificity 96% [95% CI: 95% to 97%]; negative predictive value 93% [95% CI: 92% to 94%]; accuracy 91% [95% CI: 89% to 92%]). The 3-month outcomes of patients classified as either OCSP "LACS" within 6 hours of onset or TOAST "small vessel (lacunar)" at 7 days were not significantly different. CONCLUSIONS: An OCSP LACS diagnosis made within 6 hours of stroke onset is reasonably predictive of a final diagnosis of "small vessel (lacunar)" disease made using TOAST criteria and has a similar relationship to outcome at 3 months.

Transient ischemic attack: management in the emergency department and impact of an outpatient neurovascular clinic.

OBJECTIVES: 1) To evaluate whether transient ischemic attack (TIA) management in emergency departments (EDs) of the Nova Scotia Capital District Health Authority followed Canadian Best Practice Recommendations, and 2) to assess the impact of being followed up in a dedicated outpatient neurovascular clinic. METHODS: Retrospective chart review of all patients discharged from EDs in our district from January 1, 2011 to December 31, 2012 with a diagnosis of TIA. Cox proportional hazards models, Kaplan-Meier survival curve, and propensity matched analyses were used to evaluate 90-day mortality and readmission. RESULTS: Of the 686 patients seen in the ED for TIA, 88.3% received computed tomography (CT) scanning, 86.3% received an electrocardiogram (ECG), 35% received vascular imaging within 24 hours of triage, 36% were seen in a neurovascular clinic, and 4.2% experienced stroke, myocardial infarction, or vascular death within 90 days. Rates of antithrombotic use were increased in patients seen in a neurovascular clinic compared to those who were not (94% v. 86.3%, p<0.0001). After adjustment for age, sex, vascular disease risk factors, and stroke symptoms, the risk of readmission for stroke, myocardial infarction, or vascular death was lower for those seen in a neurovascular clinic compared to those who were not (adjusted hazard ratio 0.28; 95% confidence interval 0.08-0.99, p=0.048). CONCLUSION: The majority of patients in our study were treated with antithrombotic agents in the ED and investigated with CT and ECG within 24 hours; however, vascular imaging and neurovascular clinic follow-up were underutilized. For those with neurovascular clinic follow-up, there was an association with reduced risk of subsequent stroke, myocardial infarction, or vascular death.

Description and evaluation of an acute stroke unit.

Clinical trials have demonstrated the superiority of coordinated interdisciplinary stroke unit care over conventional treatment of stroke patients on general medical wards. The evidence is so strong that several national bodies have recommended that stroke unit care be widely implemented. Translation of these research findings and care guidelines into clinical practice, however, represents a challenge for health care systems unaccustomed to managing stroke in a coordinated manner. This report describes the organization, operation and outcomes of the Acute Stroke Unit at the Queen Elizabeth II Health Sciences Centre in Halifax. By replicating and adapting the core characteristics identified in the randomized trials, we have been able to demonstrate the effectiveness of stroke unit care in a routine clinical setting. Our experience may help facilitate the development of organized stroke care in Canada.