Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascula... more 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,...
The authors sought to determine baseline neurocognition before transcatheter aortic valve replace... more The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared t...
Aphasia is a common feature of stroke, affecting 21-38% of acute stroke patients and an estimated... more Aphasia is a common feature of stroke, affecting 21-38% of acute stroke patients and an estimated 1 million stroke survivors. Although stroke, as a syndrome, is the leading cause of disability in the USA, less is known about the independent impact of aphasia on stroke outcomes. During the acute stroke period, aphasia has been found to increase length of stay, inpatient complications, overall neurological disability, mortality, and to alter discharge disposition. Outcomes during the sub-acute and chronic stroke periods show that aphasia is associated with lower Functional Independence Measures (FIM) scores, longer stays in rehabilitation settings, poorer function in activities of daily living, and mortality. Factors that complicate the analysis of aphasia on post-stroke outcomes, however, include widely different systems of care across international settings that result in varying admission patterns to acute stroke units, allowable length of stays based on reimbursement, and criteria for rehabilitation placement. Aphasia arising from stroke is associated with worse outcomes both in the acute and chronic periods. Future research will have to incorporate disparate patterns in analytic models, and to take into account specific aphasia profiles and evolving methods of post-stroke speech-language therapy.
The ability of neuropsychological tests to predict rehabilitation outcome is unclear, particularl... more 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 neuropsy...
The Journal of clinical endocrinology and metabolism, Sep 1, 2017
Diabetes is associated with a greater risk for incident cardio-vascular disease and for cognitive... more Diabetes is associated with a greater risk for incident cardio-vascular disease and for cognitive dysfunction. This study aimed to investigate, in people with Type 2 diabetes the association of a simple measure of cognitive function to CVD events and mortality. The ACCORD trial included persons with long-standing T2D. A sub-study of 2977 (MIND) participants age => 55 years aimed to test the effect of the interventions on brain structure and function. At baseline participants were administered a cognitive battery that included the Digit Symbol Substitution Test (DSST). The associations of the DSST and the ACCORD primary outcome (the first occurrence of nonfatal myocardial infarction, or nonfatal stroke or death from cardiovascular causes) and all-cause mortality, were investigated with Cox proportional hazard models adjusting for several demographic and clinical variables. Median follow-up time was 4.27 years. An inverse relationship between the incidence of the ACCORD primary out...
International journal of stroke : official journal of the International Stroke Society, Oct 1, 2017
Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeo... more Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus int...
Restorative neurology and neuroscience, Sep 21, 2016
Reducing inhibitory neurotransmission with pharmacological agents is a potential approach for aug... more Reducing inhibitory neurotransmission with pharmacological agents is a potential approach for augmenting plasticity after stroke. Previous work in healthy subjects showed diminished intracortical inhibition after administration of theophylline. We assessed the effect of single-dose theophylline on intracortical and interhemispheric inhibition in patients with chronic stroke, in a double-blind, placebo-controlled, cross-over study. Eighteen subjects were randomly administered 300 mg of extended-release theophylline or placebo. Immediately and 5 hours following administration, transcranial magnetic stimulation was used to assess bihemispheric resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, and interhemispheric inhibition. Adverse effects on cardiovascular, neurological, and motor performance outcomes were also surveilled. Change between morning and afternoon sessions were compared across conditions. One week later, patients und...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, Jan 9, 2017
Prior studies have shown a correlation between the National Institutes of Health Stroke Scale (NI... more Prior studies have shown a correlation between the National Institutes of Health Stroke Scale (NIHSS) and stroke volume on diffusion weighted imaging (DWI); data are more limited in patients with minor stroke. We sought to determine the association between DWI lesion(s) volume and the (1) total NIHSS score and (2) NIHSS component scores in patients with minor stroke. We included all patients with minor stroke (NIHSS 0-5) enrolled in the Stroke Warning Information and Faster Treatment study. We calculated lesion(s) volume (cm(3) ) on the DWI sequence using Medical Image Processing, Analysis, and Visualization (MIPAV, NIH, Version 7.1.1). We used nonparametric tests to study the association between the primary outcome, DWI lesion(s) volume, and the predictors (NIHSS score and its components). We identified 894 patients with a discharge diagnosis of minor stroke; 709 underwent magnetic resonance imaging and 510 were DWI positive. There was a graded relationship between the NIHSS score ...
Journal of the American College of Cardiology, Jan 14, 2017
Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inheren... more Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assess...
Journal of the American College of Cardiology, Jan 27, 2016
Neurological events and brain infarction after transcatheter aortic valve replacement (TAVR) are ... more Neurological events and brain infarction after transcatheter aortic valve replacement (TAVR) are concerns which may be reduced with transcatheter embolic protection (TEP). Evaluate the safety and efficacy of TEP during TAVR. Nineteen centers randomized 363 patients undergoing TAVR to safety (n=123), device imaging (n=121), and control imaging (n=119). The primary safety endpoint was major adverse cardiac and cerebrovascular events (MACCE) at 30 days and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on MRI scans at 2-7 days. Patients underwent neurocognitive assessments and the debris captured was analyzed. MACCE (7.3%) was non-inferior to the performance goal (18.3%, pnoninferior<0.001) and not statistically different from control (9.9%, p=0.41). New lesion volume was 178.0 mm(3) in controls and 102.8 mm(3) in the device arm (p=0.33). A post hoc multivariable analysis identified preexisting lesion volume and valve type to be predi...
The definition of stroke has changed over time, from a clinical only-based diagnosis to a more co... more The definition of stroke has changed over time, from a clinical only-based diagnosis to a more complex classification, including both clinical and imaging-based criteria, in part due to widespread use of magnetic resonance imaging (MRI). The increasing number of transcatheter aortic valve replacement (TAVR) procedures in patients with severe aortic valvular stenosis who are considered high-risk surgical candidates has influenced our view on the diagnosis, interpretation, and significance of perioperative stroke during these procedures. Areas covered: In this perspective, we summarize changes in the definition and diagnostic criteria for stroke and transient ischemic attacks. We examine how the introduction of MRI and standardized cognitive tests has affected our understanding of the safety of TAVR procedures. Finally, we review the growing evidence regarding the role of cerebral protection technology during TAVR procedures on cognitive function. Expert Commentary: Standardized MRI-b...
Despite being considered an important anatomical parameter directly related to neuronal density, ... more 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, highgrade 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 N 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.
Cerebral blood flow (CBF) regulation is a critical element in cerebrovascular pathophysiology, pa... more 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. 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. CBF (p=0.001), MFV (p&amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;lt;0.233 and p-values &amp;amp;amp;amp;gt;0.468). 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.
Background: Most stroke recovery occurs by 90 days after onset, with proportional recovery models... more Background: Most stroke recovery occurs by 90 days after onset, with proportional recovery models showing an achievement of about 70% of the maximal remaining recovery. Little is known about recovery during the acute stroke period. Moreover, data are described for groups, not for individuals. In this observational cohort study, we describe for the first time the daily changes of acute stroke patients with motor and/or language deficits over the first week after stroke onset. Methods: Patients were enrolled within 24-72 h after stroke onset with upper extremity hemiparesis, aphasia, or both, and were tested daily until day 7 or discharge with the upper-extremity Fugl-Meyer Assessment of Motor Recovery after Stroke, the Boston Naming Test, and the comprehension domain from the Western Aphasia Battery. Discharge scores, and absolute and proportional changes were examined using t-tests for pairwise comparisons and linear regression to determine relative contributions of initial impairme...
Cortical thinning is a potentially important biomarker, but the pathophysiology in cerebrovascula... more 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,...
The authors sought to determine baseline neurocognition before transcatheter aortic valve replace... more The authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. TAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. SENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤-1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared t...
Aphasia is a common feature of stroke, affecting 21-38% of acute stroke patients and an estimated... more Aphasia is a common feature of stroke, affecting 21-38% of acute stroke patients and an estimated 1 million stroke survivors. Although stroke, as a syndrome, is the leading cause of disability in the USA, less is known about the independent impact of aphasia on stroke outcomes. During the acute stroke period, aphasia has been found to increase length of stay, inpatient complications, overall neurological disability, mortality, and to alter discharge disposition. Outcomes during the sub-acute and chronic stroke periods show that aphasia is associated with lower Functional Independence Measures (FIM) scores, longer stays in rehabilitation settings, poorer function in activities of daily living, and mortality. Factors that complicate the analysis of aphasia on post-stroke outcomes, however, include widely different systems of care across international settings that result in varying admission patterns to acute stroke units, allowable length of stays based on reimbursement, and criteria for rehabilitation placement. Aphasia arising from stroke is associated with worse outcomes both in the acute and chronic periods. Future research will have to incorporate disparate patterns in analytic models, and to take into account specific aphasia profiles and evolving methods of post-stroke speech-language therapy.
The ability of neuropsychological tests to predict rehabilitation outcome is unclear, particularl... more 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 neuropsy...
The Journal of clinical endocrinology and metabolism, Sep 1, 2017
Diabetes is associated with a greater risk for incident cardio-vascular disease and for cognitive... more Diabetes is associated with a greater risk for incident cardio-vascular disease and for cognitive dysfunction. This study aimed to investigate, in people with Type 2 diabetes the association of a simple measure of cognitive function to CVD events and mortality. The ACCORD trial included persons with long-standing T2D. A sub-study of 2977 (MIND) participants age => 55 years aimed to test the effect of the interventions on brain structure and function. At baseline participants were administered a cognitive battery that included the Digit Symbol Substitution Test (DSST). The associations of the DSST and the ACCORD primary outcome (the first occurrence of nonfatal myocardial infarction, or nonfatal stroke or death from cardiovascular causes) and all-cause mortality, were investigated with Cox proportional hazard models adjusting for several demographic and clinical variables. Median follow-up time was 4.27 years. An inverse relationship between the incidence of the ACCORD primary out...
International journal of stroke : official journal of the International Stroke Society, Oct 1, 2017
Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeo... more Rationale Trials conducted decades ago demonstrated that carotid endarterectomy by skilled surgeons reduced stroke risk in asymptomatic patients. Developments in carotid stenting and improvements in medical prevention of stroke caused by atherothrombotic disease challenge understanding of the benefits of revascularization. Aim Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST-2) will test whether carotid endarterectomy or carotid stenting plus contemporary intensive medical therapy is superior to intensive medical therapy alone in the primary prevention of stroke in patients with high-grade asymptomatic carotid stenosis. Methods and design CREST-2 is two multicenter randomized trials of revascularization plus intensive medical therapy versus intensive medical therapy alone. One trial randomizes patients to carotid endarterectomy plus intensive medical therapy versus intensive medical therapy alone; the other, to carotid stenting plus int...
Restorative neurology and neuroscience, Sep 21, 2016
Reducing inhibitory neurotransmission with pharmacological agents is a potential approach for aug... more Reducing inhibitory neurotransmission with pharmacological agents is a potential approach for augmenting plasticity after stroke. Previous work in healthy subjects showed diminished intracortical inhibition after administration of theophylline. We assessed the effect of single-dose theophylline on intracortical and interhemispheric inhibition in patients with chronic stroke, in a double-blind, placebo-controlled, cross-over study. Eighteen subjects were randomly administered 300 mg of extended-release theophylline or placebo. Immediately and 5 hours following administration, transcranial magnetic stimulation was used to assess bihemispheric resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, and interhemispheric inhibition. Adverse effects on cardiovascular, neurological, and motor performance outcomes were also surveilled. Change between morning and afternoon sessions were compared across conditions. One week later, patients und...
Journal of neuroimaging : official journal of the American Society of Neuroimaging, Jan 9, 2017
Prior studies have shown a correlation between the National Institutes of Health Stroke Scale (NI... more Prior studies have shown a correlation between the National Institutes of Health Stroke Scale (NIHSS) and stroke volume on diffusion weighted imaging (DWI); data are more limited in patients with minor stroke. We sought to determine the association between DWI lesion(s) volume and the (1) total NIHSS score and (2) NIHSS component scores in patients with minor stroke. We included all patients with minor stroke (NIHSS 0-5) enrolled in the Stroke Warning Information and Faster Treatment study. We calculated lesion(s) volume (cm(3) ) on the DWI sequence using Medical Image Processing, Analysis, and Visualization (MIPAV, NIH, Version 7.1.1). We used nonparametric tests to study the association between the primary outcome, DWI lesion(s) volume, and the predictors (NIHSS score and its components). We identified 894 patients with a discharge diagnosis of minor stroke; 709 underwent magnetic resonance imaging and 510 were DWI positive. There was a graded relationship between the NIHSS score ...
Journal of the American College of Cardiology, Jan 14, 2017
Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inheren... more Surgical and catheter-based cardiovascular procedures and adjunctive pharmacology have an inherent risk of neurological complications. The current diversity of neurological endpoint definitions and ascertainment methods in clinical trials has led to uncertainties in the neurological risk attributable to cardiovascular procedures and inconsistent evaluation of therapies intended to prevent or mitigate neurological injury. Benefit-risk assessment of such procedures should be on the basis of an evaluation of well-defined neurological outcomes that are ascertained with consistent methods and capture the full spectrum of neurovascular injury and its clinical effect. The Neurologic Academic Research Consortium is an international collaboration intended to establish consensus on the definition, classification, and assessment of neurological endpoints applicable to clinical trials of a broad range of cardiovascular interventions. Systematic application of the proposed definitions and assess...
Journal of the American College of Cardiology, Jan 27, 2016
Neurological events and brain infarction after transcatheter aortic valve replacement (TAVR) are ... more Neurological events and brain infarction after transcatheter aortic valve replacement (TAVR) are concerns which may be reduced with transcatheter embolic protection (TEP). Evaluate the safety and efficacy of TEP during TAVR. Nineteen centers randomized 363 patients undergoing TAVR to safety (n=123), device imaging (n=121), and control imaging (n=119). The primary safety endpoint was major adverse cardiac and cerebrovascular events (MACCE) at 30 days and the primary efficacy endpoint was reduction in new lesion volume in protected brain territories on MRI scans at 2-7 days. Patients underwent neurocognitive assessments and the debris captured was analyzed. MACCE (7.3%) was non-inferior to the performance goal (18.3%, pnoninferior<0.001) and not statistically different from control (9.9%, p=0.41). New lesion volume was 178.0 mm(3) in controls and 102.8 mm(3) in the device arm (p=0.33). A post hoc multivariable analysis identified preexisting lesion volume and valve type to be predi...
The definition of stroke has changed over time, from a clinical only-based diagnosis to a more co... more The definition of stroke has changed over time, from a clinical only-based diagnosis to a more complex classification, including both clinical and imaging-based criteria, in part due to widespread use of magnetic resonance imaging (MRI). The increasing number of transcatheter aortic valve replacement (TAVR) procedures in patients with severe aortic valvular stenosis who are considered high-risk surgical candidates has influenced our view on the diagnosis, interpretation, and significance of perioperative stroke during these procedures. Areas covered: In this perspective, we summarize changes in the definition and diagnostic criteria for stroke and transient ischemic attacks. We examine how the introduction of MRI and standardized cognitive tests has affected our understanding of the safety of TAVR procedures. Finally, we review the growing evidence regarding the role of cerebral protection technology during TAVR procedures on cognitive function. Expert Commentary: Standardized MRI-b...
Despite being considered an important anatomical parameter directly related to neuronal density, ... more 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, highgrade 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 N 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.
Cerebral blood flow (CBF) regulation is a critical element in cerebrovascular pathophysiology, pa... more 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. 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. CBF (p=0.001), MFV (p&amp;amp;amp;amp;lt;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 &amp;amp;amp;amp;lt;0.233 and p-values &amp;amp;amp;amp;gt;0.468). 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.
Background: Most stroke recovery occurs by 90 days after onset, with proportional recovery models... more Background: Most stroke recovery occurs by 90 days after onset, with proportional recovery models showing an achievement of about 70% of the maximal remaining recovery. Little is known about recovery during the acute stroke period. Moreover, data are described for groups, not for individuals. In this observational cohort study, we describe for the first time the daily changes of acute stroke patients with motor and/or language deficits over the first week after stroke onset. Methods: Patients were enrolled within 24-72 h after stroke onset with upper extremity hemiparesis, aphasia, or both, and were tested daily until day 7 or discharge with the upper-extremity Fugl-Meyer Assessment of Motor Recovery after Stroke, the Boston Naming Test, and the comprehension domain from the Western Aphasia Battery. Discharge scores, and absolute and proportional changes were examined using t-tests for pairwise comparisons and linear regression to determine relative contributions of initial impairme...
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Papers by Ronald Lazar