Thalia S. Field

Weather, Chinook, and Stroke Occurrence

Background— Changes in weather and season have been linked to stroke occurrence. However, the association has been inconsistent across stroke types. Calgary is a city in the Chinook belt and is subject to high variability in weather conditions. Methods— We obtained hourly weather data over a 5-year period from 1996 to 2000; Chinook events were identified according to the accepted definition. We reviewed administrative data to determine stroke occurrence and defined stroke types to maximize specificity of diagnosis. To examine the hypothesis that weather affected the number of strokes occurring in a given day, we compared average daily stroke occurrence on Chinook days and non-Chinook days; we compared mean daily temperature, relative humidity, barometric pressure, and wind speed by the number of strokes occurring on any given day. Results— Annual variation in stroke frequency was observed. No seasonal, monthly, or weekly variation in overall stroke occurrence or occurrence by type was evident. No relationship with changes in weather parameters was observed. Conclusions— We found no association between weather changes and stroke occurrence. A cause-and-effect relationship between weather and stroke occurrence is dubious because of a lack of consistency across studies.

Post Stroke Pain: Identification, Assessment, and Therapy

Background: Pain is a common complication after stroke and is associated with the presence of depression, cognitive dysfunction, and impaired quality of life. It remains underdiagnosed and undertreated, despite evidence that effective treatment of pain may improve function and quality of life. Summary: We provide an overview of the means for clinical assessment and risk factors for the development of post-stroke pain, then review the newest available literature regarding the commonest post-stroke pain syndromes, including central post-stroke pain, complex regional pain syndrome, musculoskeletal pain including shoulder subluxation, spasticity-related pain, and post-stroke headache, as well as the available epidemiology and current treatment options. Key Messages: In the best interests of optimizing quality of life and function after stroke, clinicians should be aware of pain as a common complication after stroke, identify those patients at highest risk, directly inquire as to the presence and characteristics of pain, and should be aware of the options for treatment for the various pain syndromes.

Tenecteplase–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion

Background and Purpose— Minor stroke and transient ischemic attack with an intracranial occlusion are associated with neurological deterioration and disability. Tenecteplase (TNK–tissue-type plasminogen activator) compared with alteplase is easier to administer, has a longer half-life, higher fibrin specificity, possibly a lower rate of intracranial hemorrhage, and may be an ideal thrombolytic agent in this population. Methods— TNK–Tissue-Type Plasminogen Activator Evaluation for Minor Ischemic Stroke With Proven Occlusion (TEMPO-1) was a multicenter, prospective, uncontrolled, TNK–tissue-type plasminogen activator dose-escalation, safety, and feasibility trial. Patients with a National Institutes of Health Stroke Scale ⩽5 within 12 hours of symptom onset, intracranial arterial occlusion on computed tomographic angiography and absence of well-evolved infarction were eligible. Fifty patients were enrolled; 25 patients at a dose of 0.1 mg/kg, and 25 patients at 0.25 mg/kg. Primary outcome was the rate of drug-related serious adverse events. Secondary outcomes included recanalization and 90-day neurological outcome (modified Rankin Scale, 0–1). Results— Median baseline National Institutes of Health Stroke Scale was 2.5 (interquartile range, 1), and median age was 71 (interquartile range, 22) years. There were no drug-related serious adverse events in tier 1. In tier 2, there was 1 symptomatic intracranial hemorrhage (4%; 95% confidence interval, 0.01–20.0). Stroke progression occurred in 6% of cases. Overall, 66% had excellent functional outcome (modified Rankin Scale, 0–1) at 90 days. Recanalization rates were high; 0.1 mg/kg (39% complete and 17% partial), 0.25 mg/kg (52% complete and 9% partial). Complete recanalization was significantly related to excellent functional outcome (modified Rankin Scale, 0–1) at 90 days (relative risk, 1.65; 95% confidence interval, 1.09–2.5; P=0.026). Conclusions— Administration of TNK–tissue-type plasminogen activator in minor stroke with intracranial occlusion is both feasible and safe. A larger randomized controlled trial is needed to prove that this treatment is efficacious. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01654445.

Trends in hospital admission for stroke in Calgary.

BACKGROUND Stroke incidence has fallen since 1950. Recent trends suggest that stroke incidence may be stabilizing or increasing. We investigated time trends in stroke occurrence and in-hospital morbidity and mortality in the Calgary Health Region. METHODS All patients admitted to hospitals in the Calgary Health Region between 1994 and 2002 with a primary discharge diagnosis code (ICD-9 or ICD-10) of stroke were included. In-hospital strokes were also included. Stroke type, date of admission, age, gender, discharge disposition (died, discharged) and in-hospital complications (pneumonia, pulmonary embolism, deep venous thrombosis) were recorded. Poisson and simple linear regression was used to model time trends of occurrence by stroke type and age-group and to extrapolate future time trends. RESULTS From 1994 to 2002, 11642 stroke events were observed. Of these, 9879 patients (84.8%) were discharged from hospital, 1763 (15.1%) died in hospital, and 591 (5.1%) developed in-hospital complications from pneumonia, pulmonary embolism or deep venous thrombosis. Both in-hospital mortality and complication rates were highest for hemorrhages. Over the period of study, the rate of stroke admission has remained stable. However, total numbers of stroke admission to hospital have faced a significant increase (p=0.012) due to the combination of increases in intracerebral hemorrhage (p=0.021) and ischemic stroke admissions (p=0.011). Sub-arachnoid hemorrhage rates have declined. In-hospital stroke mortality has experienced an overall decline due to a decrease in deaths from ischemic stroke, intracerebral hemorrhage and sub-arachnoid hemorrhage. CONCLUSIONS Although age-adjusted stroke occurrence rates were stable from 1994 to 2002, this is associated with both a sharp increase in the absolute number of stroke admissions and decline in proportional in-hospital mortality. Further research is needed into changes in stroke severity over time to understand the causes of declining in-hospital stroke mortality rates.

Achieved Blood Pressure and Outcomes in the Secondary Prevention of Small Subcortical Strokes Trial

Abstract—Studies suggest a J-shaped association between blood pressure and cardiovascular events in the setting of intensive systolic blood pressure control; whether there is a similar association with stroke remains less well established. The Secondary Prevention of Small Subcortical Strokes was a randomized trial to evaluate higher (130–149 mm Hg) versus lower (<130 mm Hg) systolic blood pressure targets in participants with recent lacunar infarcts. We evaluated the association of mean achieved blood pressure, 6 months after randomization, and recurrent stroke, major vascular events, and all-cause mortality. After a mean follow up of 3.7 years, there was a J-shaped association between achieved blood pressure and outcomes; the lowest risk was at ≈124 and 67 mm Hg systolic and diastolic blood pressure, respectively. For example, above a systolic blood pressure of 124 mm Hg, 1 standard deviation higher (11.1 mm Hg) was associated with increased mortality (adjusted hazard ratio: 1.9; 95% confidence interval: 1.4, 2.7), whereas below this level, this relationship was inverted (0.29; 0.10, 0.79), P<0.001 for interaction. Above a diastolic blood pressure of 67 mm Hg, a 1 standard deviation higher (8.2 mm Hg) was associated with an increased risk of stroke (2.2; 1.4, 3.6), whereas below this level, the association was in the opposite direction (0.34; 0.13, 0.89), P=0.02 for interaction. The lowest risk of all events occurred at a nadir of ≈120 to 128 mm Hg systolic blood pressure and 65 to 70 mm Hg diastolic blood pressure. Future studies should evaluate the impact of excessive blood pressure reduction, especially in older populations with preexisting vascular disease. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Relationship between Supra-Annual Trends in Influenza Rates and Stroke Occurrence

Background: Stroke occurrence appears to be a random event, yet annual and supra-annual periodicity is observed. Recent attention in atherosclerotic disease etiology has focused on infectious and inflammatory mechanisms. Influenza is one such infection that may influence stroke occurrence. Methods: We explored population-based time series data on stroke occurrence and influenza activity. Using Fourier transformation to isolate low-frequency signals in the data, the inverse transformed time series were regressed using Prais-Winsten regression to correct for serially auto-correlated residuals, to assess the relationship between influenza rates and stroke occurrence rates. Results: Changes in the low-frequency components of influenza activity predicted the changes in low-frequency components of the stroke occurrence data with a delay of about 20 weeks. The delay between changes in influenza activity and subsequent stroke activity was different for different stroke types. Overall, the effect size was small with a tripling of the influenza rate associated with about a 6% change in stroke occurrence rate. Conclusions: A small proportion of the patterns of stroke occurrence may be explained by variation in influenza activity. Further evaluation of influenza as a triggering agent in stroke is needed.

Detection of occult atrial fibrillation in patients with embolic stroke of uncertain source: a work in progress

Atrial fibrillation accounts for a substantial proportion of ischemic strokes of known etiology and may be responsible for an additional subset of the 25–40% of strokes of unknown cause (so-called cryptogenic). Oral anticoagulation is significantly more effective than antiplatelet therapy in the secondary prevention of atrial fibrillation-related strokes, providing justification for developing more sensitive approaches to detecting occult paroxysms of atrial fibrillation. In this article, we summarize the current state of knowledge regarding the value of in-hospital and out-patient monitoring for detecting atrial fibrillation in the context of cryptogenic stroke. We review the evidence for and against screening with standard Holter monitors, external loop recorders, the newer real-time continuous attended cardiac monitoring systems, cardiac implantable electronic devices, and insertable loop recorders. We review key questions regarding prolonged cardiac arrhythmia monitoring, including the relationship between duration of the atrial fibrillation episode and risk of thromboembolism, frequency of monitoring and its impact on the diagnostic yield in detecting occult or subclinical atrial fibrillation, and the temporal proximity of device-detected atrial fibrillation to stroke events. We conclude by proposing avenues for further research.

CYP2C19 Metabolizer Status and Clopidogrel Efficacy in the Secondary Prevention of Small Subcortical Strokes (SPS3) Study

Background The role of the CYP2C19 genotype on clopidogrel efficacy has been studied widely, with data suggesting reduced clopidogrel efficacy in loss-of-function variant carriers taking clopidogrel after percutaneous coronary intervention; however, data are limited regarding the association between CYP2C19 genetic variants and outcomes in stroke patients. We investigated whether CYP2C19 metabolizer status affects the risk of recurrent stroke or major bleeding in subcortical stroke patients taking dual antiplatelet therapy with aspirin and clopidogrel. Methods and Results CYP2C19*2 and CYP2C19*17 were genotyped in 522 patients treated with dual antiplatelet therapy from the Secondary Prevention of Small Subcortical Strokes (SPS3) study. CYP2C19 metabolizer status was inferred from genotype, and associations with the risk of recurrent stroke and major bleeding were assessed in the overall cohort and by race/ethnic group with logistic regression modeling. In the overall cohort, there were no differences in outcomes by CYP2C19 metabolizer status (recurrent stroke, odds ratio 1.81 [95% CI 0.76 to 4.30]; major bleeding, odds ratio 0.67 [95% CI 0.22 to 2.03]). In white participants, those with CYP2C19 intermediate or poor metabolizer status had higher odds of recurrent stroke (odds ratio 5.19 [95% CI 1.08 to 24.90]) than those with extensive or ultrarapid metabolizer status, but there was no evidence of difference in major bleeding. Conclusions There were significant differences in recurrent stroke by CYP2C19 genotype-inferred metabolizer status in white subcortical stroke patients receiving dual antiplatelet therapy with aspirin and clopidogrel, consistent with cardiovascular studies on CYP2C19 and clopidogrel; however, the bleeding risk that led to early termination of the antiplatelet arm of the SPS3 trial does not appear to be explained by CYP2C19 genotype. This study was relatively underpowered; therefore, these findings should be interpreted with caution and warrant replication. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

Prevention of deep vein thrombosis and pulmonary embolism in patients with stroke.

Venous thromboembolism (VTE), encompassing deep venous thrombosis and pulmonary embolism, is a potentially fatal but preventable complication of stroke. Reported rates of VTE after stroke have decreased over the last four decades, possibly due to the implementation of stroke units, early mobilization and hydration, and increased early use of antiplatelets. Additional means of thromboprophylaxis in stroke include mechanical methods (ie, compression stockings) to prevent venous stasis and medical therapy including antiplatelets, heparins, and heparinoids. Risk of VTE must be balanced by potential risk of hemorrhagic complications from pharmacotherapy. Unfractionated heparin, low-molecular-weight heparin (LMWH), and danaparoid are acceptable options for chemoprophylaxis though none have shown superior efficacy for VTE prevention without an associated increase in major hemorrhage. The efficacy and timing of pharmacological thromboprophylaxis in hemorrhagic stroke are not well defined. Graduated compression stockings are associated with an increased rate of adverse events and are not recommended and intermittent pneumatic compression stockings require further investigation.

Current Status of Antiplatelet Agents to Prevent Stroke

Stroke is one of the leading causes of disability; most are due to atherothrombotic mechanisms. About one third of ischemic strokes are preceded by other stroke or transient ischemic attacks. Stroke survivors are at high risk for vascular events (i.e., cerebrovascular and cardiovascular). Prevention of recurrent stroke and other major vascular events can be accomplished by control of risk factors. Nonetheless, the use of antiplatelet agents remains the fundamental component of secondary stroke prevention strategy in patients with noncardioembolic disease. Currently, the uses of aspirin, clopidogrel, or aspirin plus extended-release dipyridamole are valid alternatives for stroke or transient ischemic attack patients. To maximize the beneficial effects of these agents, the treatment should be initiated as early as possible and continue on a lifelong basis.