Marykay A. Pavol

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

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.

Measurement of cortical thickness asymmetry in carotid occlusive disease.

Despite being considered an important anatomical parameter directly related to neuronal density, cortical thickness is not routinely assessed in studies of the human brain in vivo. This paucity has been largely due to the size and convoluted shape of the human cortex, which has made it difficult to develop automated algorithms that can measure cortical thickness efficiently and reliably. Since the development of such an algorithm by Fischl and Dale in 2000, the number of studies investigating the relationship between cortical thickness and other physiological parameters in the brain has been on the rise. There have been no studies however that have validated cortical asymmetry against known vascular anatomy. To this aim, using high-resolution MRI, we measured cortical thickness and volume in the primary motor (M1) and primary visual (V1) cortex in patients with unilateral, high-grade carotid occlusive disease (n = 29, age = 74 ± 10 years). These regions were selected based on the hypothesis that there will be thinning of the cortical thickness of M1 in the territory supplied by the occluded carotid artery, whereas V1 will show no asymmetry since its blood supply is provided by unaffected posterior arteries. To test for an effect of handedness, cortical thickness and volume were also measured in healthy volunteers (n = 8, age = 37 ± 13 years). In patients, we found thinner cortex in M1 on the occluded side (mean = 2.07 ± 0.19 mm vs 2.15 ± 0.20 mm, p = 0.0008) but no hemispheric difference in V1 (1.80 ± 0.17 mm in occluded vs 1.78 ± 0.16 mm in unoccluded, p = 0.31). Although the mean cortical volume of M1 in the occluded hemisphere was also lower, the difference did not reach statistical significance (p = 0.09). Similarly, in healthy controls, the results showed no hemispheric asymmetry in either cortical thickness or volume in either region (p > 0.1). To test for an orientation bias in the method, the analysis was repeated with images flipped from neurological to radiological orientation. While the algorithm did not yield identical results for the two orientations, the effect did not alter the findings of the study. These results provide a method for within-subject validation of a pathophysiological effect of carotid occlusive disease on the human cortex and warrant further investigation for underlying mechanisms.

Altered cerebral hemodyamics and cortical thinning in asymptomatic carotid artery stenosis

Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascular disease is unknown. We investigated the association between regional cortical blood flow and regional cortical thickness in patients with asymptomatic unilateral high-grade internal carotid artery disease without stroke. Twenty-nine patients underwent high resolution anatomical and single-delay, pseudocontinuous arterial spin labeling magnetic resonance imaging with partial volume correction to assess gray matter baseline flow. Cortical thickness was estimated using Freesurfer software, followed by co-registration onto each patient’s cerebral blood flow image space. Paired t-tests assessed regional cerebral blood flow in motor cortex (supplied by the carotid artery) and visual cortex (indirectly supplied by the carotid) on the occluded and unoccluded side. Pearson correlations were calculated between cortical thickness and regional cerebral blood flow, along with age, hypertension, diabetes and white matter hyperintensity volume. Multiple regression and generalized estimating equation were used to predict cortical thickness bilaterally and in each hemisphere separately. Cortical blood flow correlated with thickness in motor cortex bilaterally (p = 0.0002), and in the occluded and unoccluded sides individually; age (p = 0.002) was also a predictor of cortical thickness in the motor cortex. None of the variables predicted cortical thickness in visual cortex. Blood flow was significantly lower on the occluded versus unoccluded side in the motor cortex (p<0.0001) and in the visual cortex (p = 0.018). On average, cortex was thinner on the side of occlusion in motor but not in visual cortex. The association between cortical blood flow and cortical thickness in carotid arterial territory with greater thinning on the side of the carotid occlusion suggests that altered cerebral hemodynamics is a factor in cortical thinning.

Dissociation among hemodynamic measures in asymptomatic high grade carotid artery stenosis

BACKGROUND Cerebral blood flow (CBF) regulation is a critical element in cerebrovascular pathophysiology, particularly in large vessel disease, but the best method to use for hemodynamic assessment is not clear. We examined 4 different blood-flow related measures in patients with unilateral high-grade carotid artery disease, assessing asymmetry between the occluded vs non-occluded side, and the correlations among the measures. METHODS Thirty-three patients (age 50-93, 19 M) with unilateral 80-100% ICA occlusion but no stroke underwent: 1) mean flow velocity (MFV) in both middle cerebral arteries by transcranial Doppler (TCD), 2) quantitative resting CBF using pseudo-continuous arterial spin labeling (pCASL) MRI, 3) vasomotor reactivity (VMR) in response to 5% CO2 inhalation, and 4) dynamic cerebral autoregulation (DCA) assessing the counter-regulation of blood flow to spontaneous changes in blood pressure using TCD monitoring and finger photoplethysmography. Paired t-tests and Pearson correlations assessed side-to-side differences within each measure, and correlations between measures. RESULTS CBF (p=0.001), MFV (p<0.001), VMR (p=0.008), and DCA (p=0.047) all showed significantly lower values on the occluded side. The 4 measures were independent of each other on correlation analysis, even when controlling for age and anterior circle of Willis collateral (all partial correlations <0.233 and p-values >0.468). CONCLUSIONS These 4 measures showed high sensitivity to the occluded carotid artery, but their dissociation suggests that any given measure only partially characterizes the hemodynamic state. Additional research is needed to explore the multifaceted biology of cerebral blood flow regulation.

Modified Approach to Stroke Rehabilitation (MAStR): feasibility study of a method to apply procedural memory concepts to transfer training

Abstract Objective: Training and implementation for a multidisciplinary stroke rehabilitation method emphasizing procedural memory. Background: Current practice in stroke rehabilitation relies on explicit memory, often compromised by stroke, failing to capitalize on better-preserved procedural memory skills. Recruitment of procedural memory requires consistency and practice, characteristics difficulty to promote on inpatient rehabilitation units. We designed a method Modified Approach to Stroke Rehabilitation (MAStR) to maximize consistency and practice for transfer training with stroke patients. Design: Phase I, single-group study. MAStR has two innovations: (1) simplification of instructions to only three words, other direction provided non-verbally; (2) having all rehabilitation staff apply the same approach for transfers. Staff training in MAStR included review of written material describing the rationale for MAStR and demonstration of a transfer using MAStR. Enrolled patients completed each transfer with MAStR in addition to standard rehabilitation therapy. Results: The MAStR method was taught to a large, multidisciplinary rehabilitation staff (n = 31). Training and certification required 15 min per staff member. Five stroke patients were enrolled. No transfers with MAStR resulted in injury, no negative feedback was received from staff or patients. Staff reported satisfaction with the brief MAStR training and reported transfers were easier to complete with the MAStR method. Conclusions: Feasibility was demonstrated for an innovative application of procedural memory concepts to stroke rehabilitation. All rehabilitation disciplines were successfully trained. MAStR was well-tolerated and liked by rehabilitation staff and patients. These results support pursuit of a Phase II pilot study.

Advancing the Science of Self-Management in Adults With Long-Term Left Ventricular Assist Devices: Thoughts and Progress

This study tested the applicability of the individual and family self-management theory (IFSMT) to self-management (SM) in patients with left ventricular assist devices (LVADs). From an existing data set, we extracted the following variables that correspond to IFSMTs conceptual dimensions: anxiety, depression, and cognition (context dimension); self-efficacy (SM process dimension); adherence and quality of life (QOL; outcome dimensions). Descriptive statistics and partial least squares path modeling procedures were used for data analyses. A total of 100 patients (mean age 52 ± 13.4 years) with continuous flow LVAD designs comprised the present study. Most patients were White (78%), married (69%), college-educated (72%), and on disability (53%). Their mean anxiety and depression scores were slightly above normal, while their cognitive function scores were slightly lower than normal. LVAD care self-efficacy, adherence, and QOL were within normal ranges. Factor loadings ranged from 0.50 to 1.0, and there were significant forward path relationships among the context, process, and outcome dimensions (β ranges from 0.02 to 0.60, all P values < 0.05). In conclusion, the IFSMT provides a good fit for SM in LVAD. Further research is needed to clarify how best to improve LVAD SM practice and treatment outcomes.

Understanding the Connection between Cognitive Impairment and Mobility: What Can Be Gained from Neuropsychological Assessment?

The ability of neuropsychological tests to predict rehabilitation outcome is unclear, particularly when other ratings of cognition are available. Neuropsychological test scores and functional ratings of cognition (Functional Independence Measure (FIM) Cognition score) were used to predict improvement in patient mobility and self-care skill, as measured by the FIM Motor score. Regression models used both raw neuropsychology test scores and age-adjusted scores. Retrospective chart review was performed for patients on an inpatient rehabilitation unit and referred for neuropsychological assessment. The group included 126 subjects (average age 64.2 ± 17.1 years) and a variety of medical diagnoses. Neuropsychological tests included the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). After forcing the Admission FIM Cognition score into the model, RBANS scores and duration of rehabilitation predicted FIM Motor improvements (F = 11.42, p < 0.0001). Raw neuropsychological test scores performed better than the model with age-adjusted test scores. FIM Cognition alone did not predict FIM Motor improvements. Neuropsychological tests, combined with duration of rehabilitation, predicted mobility gains for patients undergoing inpatient rehabilitation beyond what was predicted by another, readily available, assessment of cognition. Neuropsychology raw scores performed better than age-adjusted scores, raising questions about the standard use of demographic adjustments for predicting real-world function.

Severe aphasia following infarction in the territory of the left anterior choroidal artery

language deficit with right and left hemisphere infarction, respectively [4–7] . The language deficits, when described, tended to be fairly mild. Our patient is a 74-year-old, right-handed woman hospitalized with acute onset of aphasia and right hemiparesis. Brain MRI revealed acute infarction in the area of the left AChA, including the posterior limb of the left internal capsule and thalamus, as seen on diffusion-weighted imaging in figure 1 . The patient was referred for functional neuroimaging but, unfortunately, was considered too agitated to participate. She had no neurological deficits prior to hospitalization. After transfer to an inpatient rehabilitation program, follow-up neurological examination revealed right hemianopia with adequate attention to the right, and spontaneous crossing of midline, right facial asymmetry at rest, 2/5 in right-upper and right-lower extremity strength, 5/5 in left-upper and left-lower extremity strength, and sensory exam was intact to light touch, temperature, and vibration throughout. Neuropsychological examination revealed possible signs of right neglect but this was difficult to verify. Otherwise fully alert, she made no spontaneous verbalizations, and responses to prompts were delayed and sparse. Because her communication skills were so impaired, language was evaluated with the Mississippi Aphasia Screening Test. She was able to name 2/5 objects and perform 3/5 automatic speech tasks (expressive subscale 10/50). She was accurate for 6/10 yes/no questions and followed 2/5 auditory commands (receptive subscale 16/50). Her total Mississippi Aphasia Screening Test score was 26/100. Repetition was impaired with We present a case of severe aphasia resulting from infarction in the territory of the left anterior choroidal artery (AChA). The AChA typically originates from the internal carotid artery, although it may also arise from the middle cerebral artery or posterior communicating artery [1] . Regions supplied by the AChA include the optic tract, posterior limb of the internal capsule, cerebral peduncle and choroid plexus. Additional areas often include portions of the paraventricular corona radiata, lateral geniculate body, medial temporal lobe, hippocampus, thalamus and basal ganglia [2] . Infarction of the AChA was initially associated with a syndrome of hemiparesis, hemianopia and hemianesthesia [1, 3] , but more recently with some degree of neglect and Published online: August 15, 2011