Joanne R. Festa

White Matter Hyperintensities and Subclinical Infarction Associations With Psychomotor Speed and Cognitive Flexibility

Background and Purpose— We examined white matter hyperintensity volume (WMHV) and subclinical infarction (no history of clinical stroke; SI) in relation to performance on tests of sequencing, cognitive flexibility, and sensorimotor ability. Methods— The Northern Manhattan Study includes a stroke-free community-based sample of Hispanic, Black, and White participants. A subsample (n=656) has undergone measurement of WMHV, SI, and neuropsychological testing. Linear regression was used to examine WMHV and SI in relation to performance on tests of sequencing as measured by Color Trails 1, cognitive flexibility as measured by Color Trails 2, and sensorimotor ability as measured by Grooved Pegboard, using generalized estimating equations (GEE) to account for the correlation among the cognitive tests and other covariates. Results— Considering performance on the tests of sequencing, cognitive flexibility, and sensorimotor ability simultaneously using GEE, WMHV and subclinical infarction were each associated with worse cognitive performance globally. There was a threshold effect for WMHV with those in the upper quartile performing significantly worse on the tests of cognitive flexibility and sensorimotor ability. Those with frontal SI performed worse on the test of cognitive flexibility and those with deep SI, worse on the test of sequencing. Conclusions— Both SI and WMHV were associated with globally worse cognitive performance. Participants with WMH affecting more than 0.75% of cranial volume had significantly slower performance on a task of cognitive flexibility and sensorimotor ability than those in the lowest quartile. The effects of SI on cognitive performance varied by location.

Improvement in Aphasia Scores After Stroke Is Well Predicted by Initial Severity

Background and Purpose— Most improvement from poststroke aphasia occurs within the first 3 months, but there remains unexplained variability in recovery. Recently, we reported a strong correlation between initial impairment and change scores in motor recovery at 90 days. We wanted to determine whether aphasia recovery (defined as a change from baseline to 90 days) shows a comparably strong correlation and whether the relation was similar to that in motor recovery. Methods— Twenty-one stroke patients had aphasia scores on the Western Aphasia Battery (WAB) obtained on stroke admission (WABinitial) and at 90 days (WAB3 mo). The relation between actual change (&Dgr;) scores (defined as WAB3 mo− WABinitial) and WABinitial was calculated in multiple-regression analysis. Results— Regression analysis demonstrated that WABinitial was highly correlated with &Dgr;WAB (R2=0.81, P<0.001) and that, in addition, the relation between WABinitial and &Dgr;WAB was proportional, such that patients recovered 0.73 of maximal potential recovery (WABmaximum−WABinitial). Conclusions— We show that, like motor recovery, there is a highly predictable relation between aphasia recovery and initial impairment, which is also proportional in nature. The comparability of recovery from motor and language impairment suggests that common mechanisms may govern reduction of poststroke neurologic impairment across different functional domains and that they could be the focus of therapeutic intervention.

Variability in language recovery after first-time stroke

Background: Predicting aphasia recovery after stroke has been difficult due to substantial variability in outcomes. Few studies have characterised the nature and extent of recovery, beginning with baselines at 24–72 hours after stroke onset. Aim: To characterise the course of language recovery after first-time stroke. Methods: Using our Performance and Recovery in Stroke Study (PARIS) database, we evaluated consecutive first-time stroke patients with aphasia and diffusion-weighted-image-positive lesions on admission and at 90 days. Results: Twenty-two of 91 patients had language disorders. Initial syndrome scores were positively correlated with 90-day scores (r = 0.60) and negatively correlated with the change in score from baseline to follow-up (r = −0.66). Neither lesion size, age nor education correlated with initial syndrome severity or with performance at 90 days. Level of education was not associated with degree of recovery. A multiple regression model that combined lesion size, age and initial syndrome was significant (p = 0.03) but only explained 29% of the variance. Patients with severe deficits at baseline in individual language domains could recover, improve to a less severe deficit or not improve at all. Conclusion: There was significant variability in language recovery after first-time stroke, even in more severe, initial syndromes. Traditional predictors of post-stroke language outcomes did not reliably predict function at 90 days. These data suggest that other factors that account for functional stroke recovery have not yet been identified.

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article.

Object To report the clinical features, surgical treatment, and long-term outcomes of adults with moyamoya phenomenon treated at a single institution in the United States.

Ipsilateral motor dysfunction from unilateral stroke: Implications for the functional neuroanatomy of hemiparesis

Background: Motor dysfunction in the contralateral hand has been well characterised after stroke. The ipsilateral hand has received less attention, yet may provide valuable insights into the structure of the motor system and the nature of the recovery process. By tracking motor function of both hands beginning in the acute stroke period in patients with cortical versus subcortical lesions, we sought to understand the functional anatomy of the ipsilateral deficit. Methods: We examined 30 patients with first-ever unilateral hemiparetic stroke, 23 with subcortical lesions affecting the corticospinal tract, seven with cortical involvement. Patients performed hand dynamometry and the 9-Hole Peg Test (9HPT) with each hand at 24–48 h, 1 week, 3 months and 1 year after stroke. Linear regression was used to compare the two different motor tasks in each hand. Repeated measures ANOVA was used to compare recovery rates of the two tasks in the first 3 months. Results: Ipsilateral 9HPT scores averaged z = −7.1, −3.6, −2.5 and −2.3 at the four time points whereas grip strength was unaffected. The initial degree of impairment of grip strength in the contralateral hand did not correlate with the degree of impairment of 9HPT in either the contralateral or ipsilateral hand (r = 0.001, p = 0.98), whereas the initial degree of impairment of 9HPT in the contralateral hand correlated with the degree of impairment of 9HPT in the ipsilateral hand (r = 0.79, p = 0.035). The rate of recovery also differed for the two tasks (p = 0.005). Conclusion: Ipsilateral motor deficits are demonstrable immediately after stroke and extend into the subacute and chronic recovery period. Dissociation between grip strength and dexterity support the notion that dexterity and grip strength operate as anatomically and functionally distinct entities. Our findings in patients with subcortical lesions suggest that the model of white matter tract injury needs to be refined to reflect the influence of a subcortical lesion on bi-hemispheral cortical networks, rather than as a simple “severed cable” model of disruption of corticofugal fibres. Our data have implications for both stroke clinical trials and the development of new strategies for therapeutic intervention in stroke recovery.

Cerebral hemodynamics and cognitive impairment Baseline data from the RECON trial

Objective: To determine whether unihemispheral hemodynamic failure is independently associated with cognitive impairment among participants in the National Institute of Neurological Disorders and Stroke–sponsored, multicenter, randomized clinical trial, Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON). Methods: Forty-three patients were randomized into RECON after recent symptomatic carotid artery occlusion and asymmetrically increased oxygen extraction fraction (OEF) by PET (OEF ratio >1.13), indicating stage II hemodynamic failure on the side of occlusion. The PET-positive patients were compared with 28 RECON-enrolled patients who met all clinical and radiographic inclusion/exclusion criteria but had no OEF asymmetry. A multivariable regression compared patients with PET OEF >1.13 or ≤1.13, stratifying by TIA vs stroke as the qualifying event. The dependent variable was a composite neurocognitive score derived from averaging age-normalized z scores on a test battery that included global and internal carotid artery (ICA) side-relevant hemisphere-specific tests. Results: There were no differences in demographic, clinical, or radiologic characteristics between the PET-positive and PET-negative patients except for PET OEF asymmetry. The unadjusted average neurocognitive z score was −1.45 for the PET-positive and −1.25 for the PET-negative patients, indicating cognitive impairment in both groups but no difference between them (p = 0.641). After adjustment for age, education, side of occlusion, depression, and previous stroke, there was a significant difference between PET-positive and PET-negative patients among those with TIA as a qualifying event (average z score = −1.41 vs −0.76, p = 0.040). Older age and right ICA side were also significant in this model. Conclusion: Hemodynamic failure is independently associated with cognitive impairment in patients with carotid occlusion. This finding establishes the physiologic parameter upon which the extracranial-intracranial bypass will be tested. Neurology® 2012;78:250–255

Association of Low Ejection Fraction With Impaired Verbal Memory in Older Patients With Heart Failure

BACKGROUND Cognitive dysfunction has a major role in health outcomes for cardiac patients. The association of cognitive dysfunction with heart failure is well established, but the cardiac variables that contribute to cognition are not well understood. OBJECTIVES To investigate the relationships among age, memory, and left ventricular ejection fraction (EF) in patients with heart failure. DESIGN Retrospective study. SETTING Academic medical center. PARTICIPANTS A total of 207 patients with heart failure underwent neuropsychological assessment of memory on standardized tests. MAIN OUTCOME MEASURES Patients were grouped by age quartiles, and memory function was compared in those with an EF below 30% vs those with an EF of 30% or higher. RESULTS Demographic, cognitive, and medical variables having a significant association with a memory composite score were identified in a univariate linear regression analysis. In a multivariate linear model that adjusted for significant covariates, there was a significant interaction between age and EF for memory function. Patients younger than 63 years maintained stable memory function across EF levels, but patients 63 years or older showed a significant decline in memory performance when EF dropped below 30% (P < .02). Post hoc multivariate analysis showed that verbal delayed recall and recognition were the components of memory most affected by low EF. CONCLUSION The effect of EF on memory differs by age such that older patients with lower EFs have significantly reduced verbal memory function.

Randomized Evaluation of Carotid Occlusion and Neurocognition (RECON) trial: Main results

Objective: To determine whether extracranial-intracranial (EC-IC) bypass can improve cognition over 2 years compared to best medical therapy alone in patients with symptomatic internal carotid artery (ICA) occlusion and increased oxygen extraction fraction (OEF) on PET. Methods: Patients underwent 15O PET and were randomized if OEF ratio was >1.13 on the occluded side. Using blinded baseline and 2-year cognitive assessments, age-adjusted composite z scores were generated from subtests sensitive to right/left hemisphere plus global cognitive functioning. Multiple regression predicted 2-year cognitive change. Results: Eighty-nine patients were enrolled; 41 had increased OEF and were randomized. Two died, 2 were lost to follow-up, and 2 refused 2-year testing. Of the 35 remaining, 6 had ipsilateral stroke or death, leaving 13 surgical and 16 medical patients. Controlling for age, education, and depression, there was no difference in 2-year cognitive change between the medical and surgical arms (95% confidence interval −0.5 to 0.5, p = 0.9). In post hoc analysis of 26 patients with no stroke in the follow-up period, cognitive improvement was associated with less impaired PET OEF at baseline (p = 0.045). Conclusion: Cognitive improvement following bypass surgery was not superior to medical therapy among patients with recently symptomatic carotid occlusion and increased OEF. Among those with no recurrent stroke, less hemodynamic impairment at baseline was associated with greater cognitive gain in both groups. Reversing cognitive impairment in hemodynamic failure remains an open challenge. Classification of evidence: This study provides Class II evidence that for patients with symptomatic ICA occlusion and increased OEF on PET, EC-IC bypass compared to no bypass does not improve cognitive function after 2 years.

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease

Object To report the clinical features, surgical treatment, and long-term outcomes of adults with moyamoya phenomenon treated at a single institution in the United States.

GABAergic but not anti-cholinergic agents re-induce clinical deficits after stroke

Our goal was to determine whether the excitatory (i.e., GABA) neurotransmitter system was important in human stroke recovery. We hypothesized that giving midazolam, a GABA(A) agonist, to patients would re-induce clinical deficits to a greater extent than the anti-cholinergic scopolamine. Twelve patients (7 M) who had recovered from hemiparesis and/or aphasia after first-time stroke and 10 age-matched, healthy controls underwent double-blinded drug challenge with midazolam and 90 days later with scopolamine, or vice versa. Language was scored for comprehension, naming and repetition, and motor function was tested with the 9-Hole Peg Test (9HPT) in each hand. The drugs were administered intravenously in small aliquots until mild awake sedation was achieved. The primary outcome was the change scores from baseline to the two drug conditions, with higher scores denoting greater loss of function. Ten of the 12 patients had recovered from hemiparesis and 7 from aphasia. The median time from stroke to participation was 9.3 months (range=0.3-77.9 months). For motor function, analysis of variance showed that change scores on the 9HPT were significantly greater in patients using the previously paretic hand during the drug state with midazolam (p=0.001). Similarly, language change scores were significantly greater among recovered aphasics during the midazolam challenge (p=0.01). In our study, patients demonstrated transient re-emergence of former stroke deficits during midazolam but not scopolamine. These data provide beginning clinical evidence for the specificity of GABA-sensitive pathways for stroke recovery.