Jodi D. Edwards

Motor sequence chunking is impaired by basal ganglia stroke

Our main aim was to determine whether individuals with stroke that affected the basal ganglia, organized movement sequences into chunks in the same fashion as neurologically intact individuals. To address this question, we compared motor response times during the performance of repeated sequences that were learned, and thus may be planned in advance, with random sequences where there is minimal if any advance preparation or organization of responses. The pattern of responses illustrated that, after basal ganglia stroke, individuals do not chunk elements of the repeated sequence into functional sub-sequences of movement to the same extent as neurologically intact age-matched people. Limited chunking of learned movements after stroke may explain past findings that show overall slower responses even when sequences of action are learned by this population. Further, our data in combination with other work, suggest that chunking may be a function of the basal ganglia.

A quantitative systematic review of domain-specific cognitive impairment in lacunar stroke

Objective: To quantitatively characterize domain-specific cognition in individuals with symptomatic lacunar stroke in a systematic review. Methods: Systematic searches of MEDLINE and EMBASE were conducted. Inclusion criteria were all articles published prior to December 2011 evaluating domain-specific cognitive status in individuals with a symptomatic lacunar infarct. Data extraction identified cognitive domains with reported impairment and effect size calculations and heterogeneity analyses were completed to assess the magnitude of this impairment for all studies with control group data. Results: Results of the search yielded 12 cross-sectional and 5 longitudinal studies that met inclusion criteria. Effect size calculations revealed small to medium effect sizes (ES) estimations for impairment after stroke in the domains of executive function (ES −0.44, 95% confidence interval [CI] −0.83, −0.50), memory (ES −0.55, 95% CI −0.96, −0.13), language (ES −0.63, 95% CI −0.92, −0.33), attention (ES −0.37, 95% CI −0.67, −0.07), and visuospatial abilities (ES −0.61, 95% CI −1.03, 0.19), and large effect sizes for global cognition (ES −0.90, 95% CI −1.48, −0.31) and information processing speed (ES −0.93, 95% CI −1.63, −0.23). Heterogeneity analyses revealed that a subset of these domains were heterogeneous and identified moderating factors accounting for this heterogeneity. Conclusions: Results of this systematic review are consistent with previous characterizations of cognitive impairment associated with lacunar strokes. However, impaired cognition in this stroke subtype appears less selective than previously thought, involving all major cognitive domains.

Is Health-Related Quality of Life Improving After Stroke?: A Comparison of Health Utilities Indices Among Canadians With Stroke Between 1996 and 2005

Background and Purpose— Recent innovations in diagnosis, management, and rehabilitation have resulted in measurable improvements in clinical and functional outcomes after acute stroke. However, whether gains in health-related quality of life after stroke have also occurred is not well characterized. Using 2 Canadian population surveys, the purpose of this study was to identify changes in health-related quality of life in individuals with stroke from 1996 to 2005. Methods— Data from the public use files of the National Population Health Survey, Cycle 2 (1996), and the Canadian Community Health Survey, Cycle 3.1. (2005), were used. A total of 847 individuals with stroke were included. Self-reported information on health status based on the Health Utilities Index Mark 3 was used to generate single-attribute and overall health-related quality of life scores. Analysis of covariance and multiple logistic regression were used to determine the relationship between survey year and poststroke impairment adjusting for demographic variables and clinical comorbidities. Results— A statistically significant and clinically important reduction in mean overall Health Utilities Index Mark 3 scores was observed for respondents with stroke from 1996 to 2005. In addition, 2 of the 8 single-attribute Health Utilities Index Mark 3 domains showed a significant change between survey years. Significantly more individuals with stroke reported dexterity and cognitive impairment in 2005 compared with respondents in 1996, indicating reduced health-related quality of life for these domains. Conclusion— Despite improvements in medical management, quality of life is not improving after stroke in the Canadian population. These findings are useful to generate hypotheses about the impact of advances in management on quality of life after stroke and identify specific domains that may benefit from future study in stroke populations.

Changes in thresholds for intracortical excitability in chronic stroke: more than just altered intracortical inhibition.

PURPOSE The purpose of the present study was to assess changes in thresholds for the onset of short intracortical inhibition (SICI) and intracortical facilitation (ICF) in individuals with chronic stroke compared to age-matched healthy adults and evaluate the relationship between these thresholds and motor function in the chronic stroke group. METHODS Paired-pulse transcranial magnetic stimulation was used to derive thresholds for the onset of SICI and ICF in 12 neurologically healthy and 12 individuals with chronic stroke. Motor evoked potentials were elicited by a test stimulus of fixed intensity preceded by a conditioning stimulus ranging from 0%-125% of active motor threshold to generate recruitment curves. Regression functions were fit to these recruitment curves to identify thresholds for the onset of SICI and ICF. Mixed measures analysis of variance was used to compare thresholds for each hemisphere within and between groups. RESULTS Results showed a significant three-way interaction between Group (stroke, healthy), Hemisphere (ipsilesional, contralesional) and Stimulus interval (2 ms, 12 ms). Significant differences in the thresholds for the onset of both SICI and ICF were present in individuals with chronic stroke, with no between hemisphere differences for the control group. When compared to age-matched controls, comparisons revealed significant reductions in ipsilesional, but not contralesional thresholds for the onset of ICF, and significant reductions in contralesional, but not ipsilesional, thresholds for the onset of SICI in individuals with chronic stroke. In addition, as thresholds for ICF and SICI in stroke patients approached the level of healthy adults, higher function on the Wolf Motor Function Test was observed. CONCLUSIONS Reduced thresholds for the onset of SICI and ICF observed in the present study indicate that both inhibitory and facilitatory systems mediate changes in cortical excitability in chronic stroke patients. The association between higher onset thresholds and motor function in the stroke group also suggests that these thresholds have potential utility for tracking functional motor improvements in patients with chronic stroke. This study provides new insights to further characterize changes in intracortical neurotransmission that play an important role in modulating neuroplasticity and the potential relationship between inhibitory and facilitatory networks and motor function post-stroke.

Underutilization of Ambulatory ECG Monitoring After Stroke and Transient Ischemic Attack Missed Opportunities for Atrial Fibrillation Detection

Background and Purpose— Detection and treatment of atrial fibrillation is a major goal in secondary stroke prevention. Guidelines recommend at least 24 hours of ECG monitoring after stroke. However, it is unclear how often this is done in routine practice. Methods— In this longitudinal cohort study using data from the Ontario Stroke Registry, we analyzed consecutive patients presenting to designated stroke centers in Ontario, Canada (2003–2013) with a first acute ischemic stroke or transient ischemic attack (TIA) in sinus rhythm and without known atrial fibrillation. The primary outcome was the proportion of patients who received at least 24-hour Holter monitoring within 30 days after stroke/TIA. Secondary analyses assessed total duration of ECG monitoring completed within 90 days after stroke/TIA, temporal trends in monitoring use, and use of Holter monitoring relative to echocardiography. Results— Among 17 398 consecutive eligible patients (mean age 68.8±14.3 years), 30.6% had at least 24 hours of Holter monitoring within 30 days after stroke/TIA. Less than 1% of patients received prolonged monitoring beyond 48 hours. The median time to start monitoring was 9 days poststroke (interquartile range 3–25). Stroke/TIA patients were nearly twice as likely to receive an echocardiogram than a Holter monitor within 90 days (odds ratio 1.8, 95% confidence interval 1.67–2.01). Conclusions— Less than one third of patients in our cohort received guideline-recommended 24-hour Holter monitoring, and <1% received prolonged ambulatory ECG monitoring. These findings highlight a modifiable evidence-practice gap that likely contributes to an overdiagnosis of strokes as cryptogenic, an underdiagnosis of atrial fibrillation, and missed anticoagulant treatment opportunities for secondary stroke prevention.

Changes in Intracortical Excitability After Transient Ischemic Attack Are Associated With ABCD2 Score

Background and Purpose— A transient ischemic attack (TIA) is a brief ischemic episode characterized by rapid clinical resolution and not associated with permanent cerebral infarction. Whether changes in intracortical excitability persist and are related to clinical predictors of stroke risk after TIA remains unknown. Methods— Participants were individuals with clinically resolved motor TIA with no structural lesions and healthy age-matched control participants. Single and paired-pulse transcranial magnetic stimulation was used to measure intracortical excitability. Recruitment curves for percent inhibition and facilitation were used to derive excitability thresholds. Correlations between threshold asymmetries and ABCD2 score were performed. Results— Results showed a significant 3-way interaction with reduced inhibition and enhanced facilitation in the affected compared with unaffected hemisphere after TIA. No significant differences were present in healthy participants. Asymmetries in intracortical inhibition and facilitation were significantly correlated with ABCD2 score. Conclusions— The present study is the first, to our knowledge, to demonstrate altered intracortical inhibition and facilitation in the affected hemisphere after TIA. These changes occurred on average 2 weeks after clinical signs of TIA resolved and in the absence of structural lesions and were not present in healthy age-matched control participants. Furthermore, this study is the first, to our knowledge, to report that changes in intracortical excitability after TIA are associated with ABCD2 score.

Manual and oculomotor performance develop contemporaneously but independently during continuous tracking

The coordination of the oculomotor and manual effector systems is an important component of daily motor behavior. Previous work has primarily examined oculomotor/manual coordination in discrete targeting tasks. Here we extend this work to learning a tracking task that requires continuous response and movement update. Over two sessions, participants practiced controlling a computer mouse with movements of their arm to follow a target moving in a repeated sequence. Eye movements were also recorded. In a retention test, participants demonstrated sequence-specific learning with both effector systems, but differences between effectors also were apparent. Time series analysis and multiple linear regression were employed to probe spatial and temporal contributions to overall tracking accuracy within each effector system. Sequence-specific oculomotor learning occurred only in the spatial domain. By contrast, sequence-specific learning at the arm was evident only in the temporal domain. There was minimal interdependence in error rates for the two effector systems, underscoring their independence during tracking. These findings suggest that the oculomotor and manual systems learn contemporaneously, but performance improvements manifest differently and rely on different elements of motor execution. The results may in part be a function of what the motor learning system values for each effector as a function of its effector’s inertial properties.

Long-term morbidity and mortality in patients without early complications after stroke or transient ischemic attack

BACKGROUND: Secondary prevention after stroke and transient ischemic attack (TIA) has focused on high early risk of recurrence, but survivors of stroke can have substantial long-term morbidity and mortality. We quantified long-term morbidity and mortality for patients who had no early complications after stroke or TIA and community-based controls. METHODS: This longitudinal case–control study included all ambulatory or hospitalized patients with stroke or TIA (discharged from regional stroke centres in Ontario from 2003 to 2013) who survived for 90 days without recurrent stroke, myocardial infarction, all-cause admission to hospital, admission to an institution or death. Cases and controls were matched on age, sex and geographic location. The primary composite outcome was death, stroke, myocardial infarction, or admission to long-term or continuing care. We calculated 1-, 3- and 5-year rates of composite and individual outcomes and used cause-specific Cox regression to estimate long-term hazards for cases versus controls and for patients with stroke versus those with TIA. RESULTS: Among patients who were initially stable after stroke or TIA (n = 26 366), the hazard of the primary outcome was more than double at 1 year (hazard ratio [HR] 2.4, 95% confidence interval [CI] 2.3–2.5), 3 years (HR 2.2, 95% CI 2.1–2.3) and 5 years (HR 2.1, 95% CI 2.1–2.2). Hazard was highest for recurrent stroke at 1 year (HR 6.8, 95% CI 6.1–7.5), continuing to 5 years (HR 5.1, 95% CI 4.8–5.5), and for admission to an institution (HR 2.1, 95% CI 1.9–2.2). Survivors of stroke had higher mortality and morbidity, but 31.5% (1789/5677) of patients with TIA experienced an adverse event within 5 years. INTERPRETATION: Patients who survive stroke or TIA without early complications are typically discharged from secondary stroke prevention services. However, these patients remain at substantial long-term risk, particularly for recurrent stroke and admission to an institution. Novel approaches to prevention, potentially embedded in community or primary care, are required for long-term management of these initially stable but high-risk patients.

Temporal Trends in the Use of Investigations After Stroke or Transient Ischemic Attack.

Background:Guidelines recommend that patients with stroke or transient ischemic attack (TIA) undergo neuroimaging and cardiac investigations to determine etiology and guide treatment. It is not known how the use of these investigations has changed over time and whether there have been associated changes in management. Objectives:To evaluate temporal trends in the use of brain and vascular imaging, echocardiography, and antithrombotic and surgical therapy after stroke or TIA. Research Design:We analyzed 42,738 patients with stroke or TIA presenting to any of the 11 regional stroke centers in Ontario, Canada between 2003 and 2012 using the Ontario Stroke Registry database. The study period was divided into 1-year intervals and we used the Cochran-Armitage test to determine trends over time. Results:Between 2003/2004 and 2011/2012, the proportion of patients undergoing brain imaging increased from 96% to 99%, as did the proportion receiving ≥3 brain scans (21%–39%), magnetic resonance imaging (13%–50%), vascular imaging (62%–88%), or echocardiography (52%–70%) (P<0.0001 for all comparisons). There was an increase in the proportion receiving any antithrombotic therapy (83%–91%, P<0.0001) but no change in use of anticoagulation (25% overall and 68% in subgroup with atrial fibrillation) or carotid revascularization (1.4%–1.5%, P=0.49). Conclusions:The use of investigations after stroke has increased over time without concomitant changes in medical or surgical management. Although initial neurovascular imaging is in accordance with practice guidelines, the use of multiple imaging procedures and routine echocardiography are of uncertain clinical effectiveness.

The effect of white matter hyperintensities on verbal memory: Mediation by temporal lobe atrophy

Objective To determine the relationship between white matter hyperintensities (WMH) presumed to indicate disease of the cerebral small vessels, temporal lobe atrophy, and verbal memory deficits in Alzheimer disease (AD) and other dementias. Methods We recruited groups of participants with and without AD, including strata with extensive WMH and minimal WMH, into a cross-sectional proof-of-principle study (n = 118). A consecutive case series from a memory clinic was used as an independent validation sample (n = 702; Sunnybrook Dementia Study; NCT01800214). We assessed WMH volume and left temporal lobe atrophy (measured as the brain parenchymal fraction) using structural MRI and verbal memory using the California Verbal Learning Test. Using path modeling with an inferential bootstrapping procedure, we tested an indirect effect of WMH on verbal recall that depends sequentially on temporal lobe atrophy and verbal learning. Results In both samples, WMH predicted poorer verbal recall, specifically due to temporal lobe atrophy and poorer verbal learning (proof-of-principle −1.53, 95% bootstrap confidence interval [CI] −2.45 to −0.88; and confirmation −0.66, 95% CI [−0.95 to −0.41] words). This pathway was significant in subgroups with (−0.20, 95% CI [−0.38 to −0.07] words, n = 363) and without (−0.71, 95% CI [−1.12 to −0.37] words, n = 339) AD. Via the identical pathway, WMH contributed to deficits in recognition memory (−1.82%, 95% CI [−2.64% to −1.11%]), a sensitive and specific sign of AD. Conclusions Across dementia syndromes, WMH contribute indirectly to verbal memory deficits considered pathognomonic of Alzheimer disease, specifically by contributing to temporal lobe atrophy.