Jennifer Mandzia

Migraines Linked to Intrapulmonary Right-to-Left Shunt

Objective.—To determine if there is an association between migraines and intrapulmonary right‐to‐left shunt.

fMRI differences in encoding and retrieval of pictures due to encoding strategy in the elderly.

Functional MRI (fMRI) was used to examine the neural correlates of depth of processing during encoding and retrieval of photographs in older normal volunteers (n = 12). Separate scans were run during deep (natural vs. man‐made decision) and shallow (color vs. black‐and‐white decision) encoding and during old/new recognition of pictures initially presented in one of the two encoding conditions. A baseline condition consisting of a scrambled, color photograph was used as a contrast in each scan. Recognition accuracy was greater for the pictures on which semantic decisions were made at encoding, consistent with the expected levels of processing effect. A mixed‐effects model was used to compare fMRI differences between conditions (deep‐baseline vs. shallow‐baseline) in both encoding and retrieval. For encoding, this contrast revealed greater activation associated with deep encoding in several areas, including the left parahippocampal gyrus (PHG), left middle temporal gyrus, and left anterior thalamus. Increased left hippocampal, right dorsolateral, and inferior frontal activations were found for recognition of items that had been presented in the deep relative to the shallow encoding condition. We speculate that the modulation of activity in these regions by the depth of processing manipulation shows that these regions support effective encoding and successful retrieval. A direct comparison between encoding and retrieval revealed greater activation during retrieval in the medial temporal (right hippocampus and bilateral PHG), anterior cingulate, and bilateral prefrontal (inferior and dorsolateral). Most notably, greater right posterior PHG was found during encoding compared to recognition. Focusing on the medial temporal lobe (MTL) region, our results suggest a greater involvement of both anterior MTL and prefrontal regions in retrieval compared to encoding. Hum. Brain Mapping 21:1–14, 2004.

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.

Post-stroke depression, obstructive sleep apnea, and cognitive impairment: Rationale for, and barriers to, routine screening

Stroke can cause neurological impairment ranging from mild to severe, but the impact of stroke extends beyond the initial brain injury to include a complex interplay of devastating comorbidities including: post-stroke depression, obstructive sleep apnea, and cognitive impairment (“DOC”). We reviewed the frequency, impact, and treatment options for each DOC condition. We then used the Ottawa Model of Research Use to examine gaps in care, understand the barriers to knowledge translation, identification, and addressing these important post-stroke comorbidities. Each of the DOC conditions is common and result in poorer recovery, greater functional impairment, increased stroke recurrence and mortality, even after accounting for traditional vascular risk factors. Despite the strong relationships between DOC comorbidities and these negative outcomes as well as recommendations for screening based on best practice recommendations from several countries, they are frequently not assessed. Barriers related to the nature of the screening tools (e.g., time consuming in high-volume clinics), practice environment (e.g., lack of human resources or space), as well as potential adopters (e.g., equipoise surrounding the benefits of treatment for these conditions) pose challenges to routine screening implementation. Simple, feasible approaches to routine screening coupled with appropriate, evidence-based treatment protocols are required to better identify and manage depression, obstructive sleep apnea, and cognitive impairment symptoms in stroke prevention clinic patients to reduce the impact of these important post-stroke comorbidities. These tools may in turn facilitate large-scale randomized controlled treatment trials of interventions for DOC conditions that may help to improve cardiovascular outcomes after stroke or TIA.

Good is not Good Enough: The Benchmark Stroke Door-to-Needle Time Should be 30 Minutes.

Noreen Kamal, Oscar Benavente, Karl Boyle, Brian Buck, Ken Butcher, Leanne K. Casaubon,RobertCote,AndrewMDemchuk,YanDeschaintre,DarDowlatshahi,GordonJGubitz,GaryHunter,Tom Jeerakathil, Albert Jin, Eddy Lang, Sylvain Lanthier, Patrice Lindsay, Nancy Newcommon,Jennifer Mandzia, Colleen M. Norris, Wes Oczkowski, Celine Odier, Stephen Phillips,Alexandre Y Poppe, Gustavo Saposnik, Daniel Selchen, Ashfaq Shuaib, Frank Silver, Eric E Smith,Grant Stotts, Michael Suddes, Richard H. Swartz, Philip Teal, Tim Watson, Michael D. Hill

Infarct in a New Territory After Treatment Administration in the ESCAPE Randomized Controlled Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times)

Background and Purpose— Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Methods— The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I–III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days. Results— From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow-up noncontrast computed tomography, 11.7% on follow-up magnetic resonance imaging) were identified (5.0% in endovascular treatment arm versus 4.0% in control arm [P=0.7]). The use of intravenous alteplase was associated with a 68% reduction in the odds of INT occurrence (3.0% with versus 9.1% without; odds ratio, 0.32; 95% confidence interval, 0.11–0.96; adjusted for age, sex, and treatment type). No other variables were associated with INTs. INT occurrence was associated with reduced probability of good clinical outcome (common odds ratio, 0.25; 95% confidence interval, 0.09–0.74; adjusted for age, type of treatment, and follow-up scan). Conclusions— INTs are uncommon, detected more frequently on follow-up magnetic resonance imaging, and affect clinical outcome. In experienced centers, endovascular treatment is likely not causal, whereas intravenous alteplase may be therapeutic. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Rapid Assessment and Treatment of Transient Ischemic Attacks and Minor Stroke in Canadian Emergency Departments: Time for a Paradigm Shift.

A majority of acute cerebrovascular syndromes are transient ischemic attacks (TIA) or minor ischemic strokes. They are often thought of and managed as though benign, but are in fact a warning of impending disabling stroke. The risk of stroke progression or recurrence is highest in the first hours to days from initial symptom onset, with a 6.7% risk at 48 hours and a 10% risk by 7 days after a TIA.1,2 The highest risk period is early, with a median time to a recurrence or progression event of 1 day; many events occur overnight after the initial ictus.3 Many strokes are preventable after a TIA. Rapid diagnosis and treatment reduces the risk of stroke by as much as 80%4,5 and significantly reduces mortality, long-term disability, and costs.6,7 The estimated annual cost avoidance in Canada from the rapid assessment and treatment of TIA is

Imaging and Baseline Predictors of Cognitive Performance in Minor Ischemic Stroke and Patients With Transient Ischemic Attack at 90 Days

313.8 million (of which

Regional Comparison of Multiphase Computed Tomographic Angiography and Computed Tomographic Perfusion for Prediction of Tissue Fate in Ischemic Stroke

269.2 million are indirect costs).8 To be most effective, the diagnosis and treatment of all TIAs and minor strokes must recognize the natural biology of the condition and should ideally occur on the same day as the event. Currently, this is not consistently achieved in Canada. There are several overlapping challenges with TIA/minor stroke management, including (1) establishing an accurate diagnosis of brain ischemia quickly; (2) establishing accurate triage approaches to risk-stratify patients; and (3) establishing systems of care that expedite both the diagnostic evaluation and initiation of treatment. Rapid access to both brain and vascular imaging is a unifying component of the solution to all these challenges. The clinical diagnosis of TIA/minor stroke is not always straightforward because a …

Acute stroke management in patients with known or suspected atrial fibrillation.

Background and Purpose— Few studies have examined predictors of cognitive impairment after minor ischemic stroke and transient ischemic attack (TIA). We examined clinical and imaging features associated with worse cognitive performance at 90 days. Methods— TIA or patients with minor stroke underwent neuropsychological testing 90 days post event. Z scores were calculated for cognitive tests, and then grouped into domains of executive function (EF), psychomotor processing speed (PS), and memory. White matter hyperintensity and diffusion-weighted imaging volumes were measured on baseline magnetic resonance imaging. Ninety-day outcomes included modified Rankin Scale (mRS) and Centre for Epidemiological Studies Depression Scale (CES-D) score. Results— Ninety-two patients were included, 76% male, 54% TIA, and mean age 65.1±12.0. Sixty-four percent were diffusion-weighted imaging positive. Median domain z scores were not significantly different from published norms (P>0.05): memory −0.03, EF −0.12, and PS −0.05. Patient performance ≥1 SD below normal was 20% on memory, 16% on PS, and 17% on EF. Cognitive scores did not differ by diagnosis (stroke versus TIA), stroke pathogenesis, presence of obstructive sleep apnea, and diffusion-weighted imaging or white matter hyperintensity volumes. In multivariable analyses, lower EF was associated with previous cortical infarct on magnetic resonance imaging (P=0.03), mRS score of >1; P=0.0003 and depressive symptoms (CES-D ≥16; P=0.03). Lower PS scores were associated with previous cortical infarct (P=0.02), acute bilateral positive diffusion-weighted imaging (P=0.02), mRS score of >1 (P=0.003), and CES-D ≥16 (P=0.03). Conclusions— Despite average-range cognitive performance in this TIA and population with minor stroke, we found associations of EF and PS with evidence of previous stroke, postevent disability, and depression.