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 \u3e 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

Neuroimaging biomarkers of cognitive recovery after ischemic stroke

Post-stroke cognitive impairment affects more than one-third of patients after an ischemic stroke (IS). Identifying markers of potential cognitive recovery after ischemic stroke can guide patients' selection for treatments, enrollment in clinical trials, and cognitive rehabilitation methods to restore cognitive abilities in post-stroke patients. Despite the burden of post-stroke cognitive impairment, biomarkers of cognitive recovery are an understudied area of research. This narrative review summarizes and critically reviews the current literature on the use and utility of neuroimaging as a predictive biomarker of cognitive recovery after IS. Most studies included in this review utilized structural Magnetic Resonance Imaging (MRI) to predict cognitive recovery after IS; these studies highlighted baseline markers of cerebral small vessel disease and cortical atrophy as predictors of cognitive recovery. Functional Magnetic Resonance Imaging (fMRI) using resting-state functional connectivity and Diffusion Imaging are potential biomarkers of cognitive recovery after IS, although more precise predictive tools are needed. Comparison of these studies is limited by heterogeneity in cognitive assessments. For all modalities, current findings need replication in larger samples. Although no neuroimaging tool is ready for use as a biomarker at this stage, these studies suggest a clinically meaningful role for neuroimaging in predicting post-stroke cognitive recovery

Women have worse cognitive, functional, and psychiatric outcomes at hospital discharge after cardiac arrest

Aim: To examine gender differences among cardiac arrest (CA) survivors’ cognitive, functional, and psychiatric outcomes at discharge. Methods: This is a prospective, observational cohort of 187 CA patients admitted to Columbia University Medical Center, considered for Targeted Temperature Management (TTM), and survived to hospital discharge between September 2015 and July 2017. Patients with sufficient mental status at hospital discharge to engage in the Repeatable Battery for Neuropsychological Status (RBANS), Modified Lawton Physical Self-Maintenance Scale (M-PSMS), Cerebral Performance Category Scale (CPC), Center for Epidemiological Studies Depression Scale (CES-D), and Post-Traumatic Stress Disorder Checklist – Civilian Version (PCL-C) were included. Fisher’s exact, Wilcoxon Rank Sum, and regression analysis were utilized. Results: 80 patients (38% women, 44% white, mean age 53 ± 17 years) were included. No significant gender differences were found for age, race, Charlson Comorbidity Index, premorbid CPC or psychiatric diagnoses, arrest related variables, discharge CPC, or PCL-C scores. Women had significantly worse RBANS (64.9 vs 74.8, p = .01), M-PSMS (13.6 vs 10.6, p = .02), and CES-D (22.8 vs 14.3, p = .02) scores. These significant differences were maintained in multivariate models after adjusting for age, initial rhythm, time to return of spontaneous circulation, and TTM. Conclusions: Women have worse cognitive, functional, and psychiatric outcomes at hospital discharge after cardiac arrest than men. Identifying factors contributing to these differences is of great importance in cardiac arrest outcomes research

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 (15)O 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

Table_1_Neuroimaging biomarkers of cognitive recovery after ischemic stroke.docx

Post-stroke cognitive impairment affects more than one-third of patients after an ischemic stroke (IS). Identifying markers of potential cognitive recovery after ischemic stroke can guide patients' selection for treatments, enrollment in clinical trials, and cognitive rehabilitation methods to restore cognitive abilities in post-stroke patients. Despite the burden of post-stroke cognitive impairment, biomarkers of cognitive recovery are an understudied area of research. This narrative review summarizes and critically reviews the current literature on the use and utility of neuroimaging as a predictive biomarker of cognitive recovery after IS. Most studies included in this review utilized structural Magnetic Resonance Imaging (MRI) to predict cognitive recovery after IS; these studies highlighted baseline markers of cerebral small vessel disease and cortical atrophy as predictors of cognitive recovery. Functional Magnetic Resonance Imaging (fMRI) using resting-state functional connectivity and Diffusion Imaging are potential biomarkers of cognitive recovery after IS, although more precise predictive tools are needed. Comparison of these studies is limited by heterogeneity in cognitive assessments. For all modalities, current findings need replication in larger samples. Although no neuroimaging tool is ready for use as a biomarker at this stage, these studies suggest a clinically meaningful role for neuroimaging in predicting post-stroke cognitive recovery.</p

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

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

Cortical thickness-rCBF coregistration.

<p>A sample patient’s left (red) and right (yellow) motor cortex ROI, coregistered on the patient’s own GM CBF pCASL images. Images are shown in coronal, sagittal, and axial orientation.</p