ABSTRACT
Imaging studies have described hemodynamic activity during fear conditioning protocols with stimulus trains in which a visual conditioned stimulus (CS+) is paired with an aversive unconditioned stimulus (US, painful laser pulse) while another visual stimulus is unpaired (CS-). We now test the hypothesis that CS Event Related Spectral Perturbations (ERSPs) are related to ratings of CS Expectancy (likelihood of pairing with the US), Valence (unpleasantness) and Salience (ability to capture attention). ERSP windows in EEG were defined by both time after the CS and frequency, and showed increased oscillatory power (Event Related Synchronization, ERS) in the Delta/Theta Windows (0-8Hz) and the Gamma Window (30-55Hz). Decreased oscillatory power (Event Related Desynchronization - ERD) was found in Alpha (8-14Hz) and Beta Windows (14-30Hz). The Delta/Theta ERS showed a differential effect of CS+ versus CS- at Prefrontal, Frontal and Midline Channels, while Alpha and Beta ERD were greater at Parietal and Occipital Channels early in the stimulus train. The Gamma ERS Window increased from habituation to acquisition over a broad area from frontal and occipital electrodes. The CS Valence and Salience were greater for CS+ than CS-, and were correlated with each other and with the ERD at overlapping channels, particularly in the Alpha Window. Expectancy and CS Skin Conductance Response were greater for CS+ than CS- and were correlated with ERSP at fewer channels than Valence or Salience. These results suggest that Alpha ERSP activity during fear conditioning reflects Valence and Salience of the CSs more than conditioning per se.
Subject(s)
Attention/physiology , Brain Waves , Cerebral Cortex/physiology , Conditioning, Classical/physiology , Fear/physiology , Adult , Delta Rhythm , Electroencephalography , Evoked Potentials , Female , Gamma Rhythm , Humans , Male , Middle Aged , Psychophysics , Theta Rhythm , Young AdultABSTRACT
During Sustained Attention to stimuli across many modalities neural activity often decreases over time on task, while Errors in task performance increase (Vigilance Decrement). Sustained Attention to pain has rarely been investigated experimentally despite its clinical significance. We have employed a Sustained Attention protocol (Continuous Performance Task, CPT) in which the subject counts painful laser stimuli (targets) when they occur randomly in a prolonged train of nonpainful nontargets. We hypothesize that the magnitude of the poststimulus oscillatory power divided by baseline power (Event-Related Spectral Perturbation, ERSP - scalp EEG) over Frontoparietal structures will decrease at all frequencies with time on task, while Beta ERSP (14-30Hz) will be correlated with Error Rates in performance of the CPT. During the CPT with a painful target ERSP was found in four separate Windows, as defined by both their frequency band and the time after the stimulus. A Vigilance Decrement was found which confirms that Sustained Attention to pain was produced by this CPT. In addition, Error Rates was correlated inversely with laser energy, and with ratings of pain unpleasantness and salience. Error Rates also were related directly to the Beta ERSP Window at scalp EEG electrodes over the central sulcus. Over time on task, the ERSP magnitude decreased in Alpha (8-14Hz) Window, was unchanged in early and late Delta/Theta Windows (0-8Hz), and increased in the Beta Window. The increase in Beta ERSP and a decrease in the Alpha ERSP occurred at the same EEG electrode over the parietal lobe to a significant degree across subjects. Overall, Beta activity increases with time on task, and with higher Error Rates as in the case of other modalities. In the case of pain increased Errors correspond to misidentification of painful and nonpainful stimuli and so modulate the sensation of pain under the influence of Sustained Attention.
ABSTRACT
We investigated the relationship between deficits in naming and areas of focal atrophy in primary progressive aphasia (a neurodegenerative disease that specifically affects language processing). We tested patients, across multiple input modalities, on traditional naming tasks (picture naming) and more complex tasks (sentence completion with a name, naming in response to a question) and obtained high resolution MRI. Across most tasks, error rates were correlated with atrophy in the left middle and posterior inferior temporal gyrus. Overall, this result converges with prior literature suggesting that this region plays a major role in modality independent lexical processing.
Subject(s)
Aphasia, Primary Progressive/pathology , Brain/pathology , Aged , Female , Humans , Image Interpretation, Computer-Assisted , Language , Magnetic Resonance Imaging , MaleABSTRACT
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) can occur in patients following acute ischaemic stroke in the form of hemorrhagic transformation, and results in significant long-term morbidity and mortality. Anticoagulation theoretically increases risk. We evaluated stroke patients with an indication for anticoagulation to determine the factors associated with hemorrhagic transformation. METHODS: Three-hundred and forty-five patients with ICD-9 codes indicating: (i) acute ischaemic stroke; and (ii) an indication for anticoagulation were screened. One-hundred and twenty-three met inclusion criteria. Data were collected retrospectively. Neuroimaging was reviewed for infarct volume and evidence of ICH. Hemorrhages were classified as: hemorrhagic conversion (petechiae) versus intracerebral hematoma (a space occupying lesion); symptomatic versus asymptomatic. Using multivariable logistic regression, we determined the hypothesized factors associated with intracerebral bleeding. RESULTS: Age [odds ratio (OR)â =â 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (ORâ =â 1.10 per 10â ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; ORâ =â 1.95, 95% CI 1.04-3.66) were predictors of hemorrhagic transformation. Ninety- nine out of 123 patients were anticoagulated. Hemorrhage rates of patients on and off anticoagulation did not differ (25.3% vs. 20.8%; Pâ =â 0.79); however, all intracerebral hematomas (nâ =â 7) and symptomatic bleeds (nâ =â 8) occurred in the anticoagulated group. CONCLUSIONS: The risk of hemorrhagic transformation in patients with acute ischaemic stroke and an indication for anticoagulation is multifactorial, and most closely associated with an individual's age, infarct volume and eGFR.
Subject(s)
Anticoagulants/therapeutic use , Brain Ischemia/drug therapy , Cerebral Hemorrhage/drug therapy , Disease Progression , Stroke/drug therapy , Adult , Aged , Aged, 80 and over , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , Cerebral Hemorrhage/diagnosis , Cerebral Hemorrhage/epidemiology , Cohort Studies , Female , Follow-Up Studies , Humans , International Classification of Diseases/trends , Male , Middle Aged , Retrospective Studies , Stroke/diagnosis , Stroke/epidemiologyABSTRACT
The study of subjects with acquired brain damage in a specific location is important in exploring human brain function. Description of lesion locations within and across subjects is a crucial methodological component that usually involves the distinction of normal from damaged tissue (lesion segmentation) in relation to lesion locations in terms of a standard anatomical reference space (lesion mapping). Our study provides an atlas-based, computer-aided methodology for classification of hyperintense regions on diffusion-weighted images of the brain, representing either ischemic lesions or susceptibility artifacts. We applied a leave-one-out method of cross-validation that computed probabilistic atlases of true lesions and artifacts, based on training data. Our approach accurately classifies lesions and artifacts, but leaves a significant number of regions unclassified, due to the relatively small number of training samples. An initial segmentation step based on a larger sample of data sets is required to automate discrimination of lesions and artifacts.
ABSTRACT
This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA--nonfluent/agrammatic, semantic, and logopenic--were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as "imaging-supported" if the expected pattern of atrophy is found and "with definite pathology" if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.
Subject(s)
Aphasia, Primary Progressive/classification , Aphasia, Primary Progressive/pathology , Atrophy/pathology , Brain/pathology , Dementia/pathology , Humans , Neuropsychological TestsABSTRACT
Accumulating evidence indicates action naming may rely more on frontal-subcortical circuits, and noun naming may rely more on temporal cortex. Therefore, noun versus action fluency might distinguish frontal and subcortical dementias from cortical dementias primarily affecting temporal and/or parietal cortex such as Alzheimer's disease (AD). We hypothesized patients with subcortical dementia, e.g., normal pressure hydrocephalus (NPH) and patients with dementias predominantly affecting frontal cortex, e.g., behavioral variant frontotemporal dementia (bv-FTD) and progressive nonfluent aphasia (PNFA) have more difficulty on action fluency versus noun fluency (e.g., animal naming). Patients with AD, who have temporo parietal cortical dysfunction, should have more difficulty on noun versus verb fluency. A total of 234 participants, including healthy controls (n = 20) and patients diagnosed with NPH (n =144), AD (n = 33), bv-FTD (n = 22) or PNFA (n =15) were administered animal fluency, action fluency, and letter fluency tasks, and the Mini-Mental State Examination (MMSE, to control for dementia severity). NPH and bv-FTD/PNFA patients had significantly higher MMSE scores and animal fluency than AD patients (after adjusting for age), but their action fluency tended to be lower than in AD. Only NPH and bvFTD/PNFA patients showed significantly lower action verb than animal fluency. Results provide novel evidence that action naming relies more on frontal-subcortical circuits while noun naming relies more on temporoparietal cortex, indicating action verb fluency may be more sensitive than noun fluency, particularly for detecting frontal-subcortical dysfunction.
Subject(s)
Alzheimer Disease/physiopathology , Dementia/physiopathology , Frontotemporal Dementia/physiopathology , Language , Psychomotor Performance/physiology , Animals , Female , Humans , Male , Middle Aged , Nerve Net/physiopathology , Neuropsychological Tests , Verbal Behavior/physiologyABSTRACT
The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.
Subject(s)
Affect , Behavior , Brain Tissue Transplantation/ethics , Cell Transplantation/ethics , Central Nervous System Diseases/surgery , Clinical Trials as Topic/ethics , Cognition , Informed Consent , Biomedical Research/ethics , Brain Tissue Transplantation/adverse effects , Cell Transplantation/adverse effects , Ethics, Research , Humans , Neuropsychological Tests , Research Subjects , Surveys and Questionnaires , Therapeutic Human Experimentation/ethicsABSTRACT
BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis (CCD), the decrease in blood flow and metabolism in the cerebellar hemisphere contralateral to a supratentorial stroke, is frequently reported on positron-emission tomography (PET) and single-photon emission CT (SPECT) but is rarely described with MR perfusion techniques. This study was undertaken to determine the frequency of CCD observed in acute stroke by retrospective review of a research data base of patients with acute stroke evaluated by diffusion-weighted (DWI) and dynamic contrast susceptibility perfusion MR imaging (PWI). MATERIALS AND METHODS: PWI scans of 301 consecutive patients with acute stroke and positive DWI abnormality from a research data base were reviewed. Contralateral cerebellar hypoperfusion was identified by inspection of time-to-peak (TTP) maps for asymmetry with an absence of cerebellar abnormalities on T2-weighted scans, DWI, or disease of the vertebrobasilar system on MR angiography. In a subset of the cases, quantitative analysis of perfusion scans was performed using an arterial input function and singular value decomposition (SVD) to generate cerebral blood flow (CBF) maps. RESULTS: A total of 47 of 301 cases (15.61%) met the criteria of CCD by asymmetry of cerebellar perfusion on TTP maps. On quantitative analysis, there was corresponding reduction of CBF by 22.75 +/- 10.94% (range, 7.45% to 52.13%) of the unaffected cerebellar hemisphere). CONCLUSIONS: MR perfusion techniques can be used to detect CCD, though the frequency presented in this series is lower than that commonly reported in the PET/SPECT literature. Nevertheless, with its role in acute stroke and noninvasive nature, MR perfusion may be a viable alternative to PET or SPECT to study the phenomenon and clinical consequences of supratentorial stroke with CCD.
Subject(s)
Cerebellar Diseases/pathology , Cerebellum/pathology , Magnetic Resonance Imaging/methods , Stroke/pathology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Cerebellar Diseases/etiology , Cerebellum/blood supply , Cerebrovascular Circulation , Humans , Magnetic Resonance Angiography , Middle Aged , Prognosis , Retrospective Studies , Stroke/complications , Young AdultABSTRACT
INTRODUCTION: Unilateral neglect after acute right hemispheric stroke significantly impedes poststroke recovery. We studied patients with right hemispheric stroke to determine whether increasing age was associated with more frequent or more severe neglect. METHODS: Eight neglect tests within 5 days of symptom onset (and within 24 hours of admission) were administered to 204 subjects with acute right hemispheric stroke. Size of infarct was measured, and neglect tests were scored as percent error. "Any neglect" was defined by an elevated neglect test score, standardized relative to a group of normal controls. RESULTS: When tested for neglect soon after acute stroke admission, 69.6% of subjects older than 65 years had "any neglect" (defined by comparison to a group of normal controls), compared with 49.4% of subjects aged 65 years and younger (p = 0.008). For every additional 10 years of age, patients were 1.83 times as likely to have neglect, even after adjusting for diffusion-weighted imaging (DWI) infarct volume and NIH Stroke Scale (NIHSS) score (95% CI 1.38-2.43). In addition, DWI volume and NIHSS independently predicted neglect. Score on virtually all of the neglect tests worsened as an effect of age. Percentage error on a line cancellation task was 3.8% higher for every additional 10 years of age, after adjustment for DWI volume and NIHSS (p = 0.006). Similar results were found for other neglect tests. CONCLUSIONS: Increasing age in patients with acute right hemispheric stroke significantly increases the odds of unilateral neglect as well as severity of neglect, independently of size of the stroke or NIH Stroke Scale score. The reason for this finding in older patients may be because they have more brain atrophy and may be less able to compensate for cerebral infarction, or because they tend to have more cardioembolic strokes, which may be more cortically based.
Subject(s)
Functional Laterality/physiology , Perceptual Disorders/etiology , Stroke/complications , Adult , Age Factors , Aged , Aged, 80 and over , Brain Infarction/etiology , Brain Infarction/pathology , Female , Humans , Male , Middle Aged , Regression Analysis , Severity of Illness Index , Stroke/pathologyABSTRACT
BACKGROUND AND PURPOSE: Diffusion-perfusion mismatch has been used to estimate salvageable tissue and predict potential for recovery in acute stroke. Location of the salvageable tissue may be as important as volume or percentage in predicting potential for recovery of specific functions. Impaired naming, a common and disabling deficit after left hemisphere stroke, is often associated with tissue dysfunction of left Brodmann area (BA) 37, posterior inferior temporal cortex. We tested the hypothesis that the presence of diffusion-perfusion mismatch within left BA 37 predicts probability and extent of short-term improvement of naming. METHODS: One hundred five patients with acute left hemisphere ischemic stroke had diffusion-weighted imaging, perfusion-weighted imaging, a test of picture naming, and other language tests at admission and 2 to 4 days later. Linear regression was used to determine whether diffusion-perfusion mismatch in any BA in language cortex, total volume of mismatch, or diffusion or perfusion abnormality predicted degree of improvement in naming by days 3 to 5. RESULTS: The presence of >20% diffusion-perfusion mismatch in left BA 37 and total volumes of diffusion and perfusion abnormality at day 1 each independently predicted degree of improvement in naming. Mismatch in this area did not predict the degree of improvement in other language tests or the NIH Stroke Scale in this study. CONCLUSIONS/RELEVANCE: Diffusion-perfusion mismatch in left Brodmann area 37 was strongly associated with acute improvement in naming, independently of volume or percentage of total mismatch or diffusion or perfusion abnormality. These data indicate that mismatch in a particular area is a marker of salvageable tissue and an important predictor of potential for recovery of functions that depend on that area. Location of mismatch before treatment may help to predict potential benefits of reperfusion.
Subject(s)
Brain Ischemia/physiopathology , Diffusion Magnetic Resonance Imaging/methods , Recovery of Function , Reperfusion Injury/physiopathology , Stroke/physiopathology , Adult , Aged , Aged, 80 and over , Aphasia/physiopathology , Brain Ischemia/diagnosis , Brain Ischemia/pathology , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Recovery of Function/physiology , Reperfusion Injury/diagnosis , Reperfusion Injury/pathology , Stroke/diagnosis , Stroke/pathology , Temporal Lobe/pathology , Temporal Lobe/physiologyABSTRACT
BACKGROUND: Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. METHODS: An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. RESULTS: While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. CONCLUSIONS: Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.
Subject(s)
Brain Diseases/therapy , Cell- and Tissue-Based Therapy/ethics , Clinical Trials as Topic/ethics , Neurology/ethics , Neurology/standards , Animals , Biomedical Research/ethics , Biomedical Research/standards , Biomedical Research/trends , Cell- and Tissue-Based Therapy/methods , Cell- and Tissue-Based Therapy/standards , Clinical Trials Data Monitoring Committees/standards , Clinical Trials Data Monitoring Committees/trends , Clinical Trials as Topic/standards , Ethics Committees, Research/standards , Ethics Committees, Research/trends , Humans , Neurology/trends , Risk Assessment , Stem Cell Transplantation/ethics , Stem Cell Transplantation/methods , Stem Cell Transplantation/standards , Time Factors , United States , United States Food and Drug Administration/standards , United States Food and Drug Administration/trendsABSTRACT
We review the literature on current knowledge of the role of unilateral spatial neglect as an independent predictor of poor functional outcome after right brain injury, the neural mechanisms and neural substrates that are responsible for the manifestation of neglect behaviors, and the available rehabilitation techniques for neglect amelioration. We focus on the neuroimaging correlates of these rehabilitation techniques and rehabilitation amelioration, their mode of action and their potential to make a difference in functional outcomes, by assessing their potential to improve patients' performance in activities of daily living. We recognize that there is no consensus on efficacious treatments for neglect rehabilitation, and acknowledge that the lack of complete clarity of the neural substrates and mechanisms underlying neglect phenomena may hinder the development of efficacious rehabilitation techniques. We discuss current opinions on the neural mechanisms of hemispatial neglect and delved into the neural substrates of neglect based on functional and structural imaging. We explore the role of damage or dysfunction within specific right hemisphere structures in generating certain neglect subtypes and discussed how such knowledge may guide treatments for the rehabilitation of unilateral neglect. From this foundation, we proceed to explore the available rehabilitation techniques for neglect amelioration and how neuroimaging may guide the choice of therapies for different forms of unilateral neglect. We discuss cognitive rehabilitation approaches which form the bedrock of most traditional rehabilitation programs and follow with a description of other available, but less well utilized methods of neglect rehabilitation, including sensory stimulation, sensorimotor adaptation to visual perturbations by prism adaptation, and pharmacological agents (mainly dopamine agonists) that might augment rehabilitation. We also discuss the efficacy of these techniques in neglect rehabilitation and compare the potential of these diverse techniques to ameliorate not only the different symptoms of neglect, but also the different subtypes of neglect. Finally, we make suggestions about future research that could enhance the rehabilitation of neglect.
Subject(s)
Perceptual Disorders/diagnosis , Perceptual Disorders/rehabilitation , Diagnostic Imaging , Humans , Outcome Assessment, Health Care , Perceptual Disorders/physiopathology , Recovery of Function/physiologyABSTRACT
Several studies have demonstrated reorganization of cognitive and motor function caused by stroke. This study examined the influence of hypoperfused brain regions, in addition to the area of the infarct itself, on reorganization of the cognitive processes underlying word generation in stroke patients. In addition, we also sought to determine the influence of hypoperfusion on the blood oxygen level dependent/(BOLD) effect. Subjects with left and right subacute or chronic subcortical strokes, along with normal controls, were imaged while performing a verbal fluency task (word generation). The study population included six normal subject and six stroke patients with subcortical infarcts and cortical hypoperfusion in the middle cerebral artery territory who had recovered or improved markedly in word fluency. While normal subjects displayed a left-lateralized fronto-temporo-parietal and bilateral cingulo-striatal-thalamic-cerebellar network, the activation pattern of stroke patients was determined both by the hypoperfused regions and infarcted areas of the brain. Specifically, patients showed diminished BOLD effect in the cortical regions that were hypoperfused, even though their infarcts were subcortical, and showed increased BOLD effect in the homologous regions of the normal hemisphere. This finding raises the possibility that cortical hypoperfusion in the absence of infarct can cause shift of language functions to the opposite, intact hemisphere. However, reduced BOLD effect in the task relative to rest was found in hypoperfused regions in two patients, raising the possibility that regional function persisted, even though vascular reactivity was impaired. Results illustrate the complexities of functional imaging studies of recovery in patients with vascular lesions.
Subject(s)
Brain Mapping , Cerebral Cortex/pathology , Functional Laterality/physiology , Infarction, Middle Cerebral Artery/pathology , Verbal Behavior/physiology , Adult , Case-Control Studies , Cerebral Cortex/blood supply , Cerebrovascular Circulation/physiology , Female , Humans , Infarction, Middle Cerebral Artery/physiopathology , Magnetic Resonance Imaging , Male , Middle Aged , Oxygen/blood , Oxygen/metabolism , Recovery of Function , Reference ValuesSubject(s)
Cognition Disorders/drug therapy , Cognition Disorders/therapy , Plasma Exchange/methods , Prednisone/therapeutic use , Thyroiditis, Autoimmune/drug therapy , Thyroiditis, Autoimmune/therapy , Administration, Oral , Combined Modality Therapy/methods , Female , Humans , Middle Aged , Prednisone/administration & dosageABSTRACT
We carried out baseline and short-term follow-up MRI, including perfusion-weighted imaging (PWI) and tests of neurologic and cognitive function on 15 consecutive patients with large-vessel ischemic stroke who showed a persistent large perfusion-diffusion mismatch at enrollment up to seven days after the onset of symptoms. Of these, ten underwent induced blood pressure elevation with phenylephrine and oral medications (in eight) or intravenous fluids (in two) with the goal of improving perfusion; five had no such treatment. Significant functional improvement was defined by a reduction of 3 or more points on the NIH stroke scale (NIHSS). Significant improvement in perfusion was defined by a reduction in the volume of hypoperfused brain by 30 cc on PWI using time-to-peak (TTP) maps, without enlargement of the infarct. There was a strong, statistically significant association between improved function and improved perfusion: six (75%) of eight patients who improved in function, but none of the seven who did not, showed a reduction in volume of hypoperfused brain. All six patients who met the perfusion goal, and only two (22%) of nine who did not showed significant functional improvement (Fisher's exact: P < 0.01). There were no differences between patients who improved functionally and those who did not with respect to age, initial volume of abnormality on DWI or PWI, initial NIHSS, or changes on DWI. These findings indicate that reduction in volume of hypoperfused brain on PWI is a marker of response to treatment to improve perfusion even in subacute stroke and that partial reperfusion of regions of salvageable but dysfunctional tissue is a mechanism of improved function associated with induced blood pressure elevation.
Subject(s)
Brain Ischemia/complications , Cognition Disorders/etiology , Magnetic Resonance Angiography , Stroke/diagnosis , Stroke/therapy , Adult , Aged , Aged, 80 and over , Brain/blood supply , Cardiotonic Agents/therapeutic use , Endpoint Determination , Female , Fluid Therapy , Follow-Up Studies , Humans , Male , Middle Aged , Phenylephrine/therapeutic use , Prognosis , Prospective Studies , Sensitivity and Specificity , Severity of Illness Index , Treatment OutcomeABSTRACT
BACKGROUND: Small, unrandomized studies have indicated that pharmacologically induced blood pressure elevation may improve function in ischemic stroke, presumably by improving blood flow to ischemic, but noninfarcted tissue (which may be indicated by diffusion-perfusion mismatch on MRI). We conducted a pilot, randomized trial to evaluate effects of pharmacologically induced blood pressure elevation on function and perfusion in acute stroke. METHODS: Consecutive series of patients with large diffusion-perfusion mismatch were randomly assigned to induced blood pressure elevation ('treated' patients, n = 9) or conventional management ('untreated' patients, n = 6). RESULTS: There were no significant differences between groups at baseline. NIH Stroke Scale (NIHSS) scores were lower (better) in treated versus untreated patients at day 3 (mean 5.6 vs. 12.3; p = 0.01) and week 6-8 (mean 2.8 vs. 9.7; p < 0.04). Treated (but not untreated) patients showed significant improvement from day 1 to day 3 in NIHSS score (from mean 10.2 to 5.6; p < 0.002), cognitive score (from mean 58.7 to 27.9% errors; p < 0.002), and volume of hypoperfused tissue (mean 132 to 58 ml; p < 0.02). High Pearson correlations between the mean arterial pressure (MAP) and accuracy on daily cognitive tests indicated that functional changes were due to changes in MAP. CONCLUSION: Results warrant a full-scale, double-blind clinical trial to evaluate the efficacy and risk of induced blood pressure elevation in selective patients with acute/subacute stroke.
Subject(s)
Blood Pressure/physiology , Cerebrovascular Circulation/physiology , Fludrocortisone/therapeutic use , Midodrine/therapeutic use , Phenylephrine/therapeutic use , Recovery of Function/physiology , Sodium Chloride/therapeutic use , Stroke/drug therapy , Stroke/physiopathology , Vasoconstrictor Agents/therapeutic use , Adult , Aged , Aged, 80 and over , Blood Pressure/drug effects , Cerebrovascular Circulation/drug effects , Drug Therapy, Combination , Female , Fludrocortisone/administration & dosage , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Midodrine/administration & dosage , Phenylephrine/administration & dosage , Pilot Projects , Recovery of Function/drug effects , Sodium Chloride/administration & dosage , Stroke/pathology , Time Factors , Vasoconstrictor Agents/administration & dosageABSTRACT
We have hypothesized that most cases of aphasia or hemispatial neglect due to acute, subcortical infarct can be accounted for by concurrent cortical hypoperfusion. To test this hypothesis, we demonstrate: (i) that pure subcortical infarctions are associated with cortical hypoperfusion in subjects with aphasia/neglect; (ii) that reversal of cortical hypoperfusion is associated with resolution of the aphasia; and (iii) that aphasia/neglect strongly predicts cortical ischaemia and/or hypoperfusion. We prospectively evaluated a consecutive series of 115 patients who presented within 24 h of onset or progression of stroke symptoms, with MRI sequences including diffusion weighted imaging (DWI) and perfusion weighted imaging (PWI), and detailed testing for aphasia or hemispatial neglect. The association between aphasia or neglect and cortical infarct (or dense ischaemia) on DWI and cortical hypoperfusion indicated by PWI, was evaluated with chi-squared analyses. Fisher exact tests were used for analyses with small samples. Cases of DWI lesion restricted to subcortical white matter and/or grey matter structures (n = 44) were examined for the presence of aphasia or neglect, and for the presence of cortical hypoperfusion. In addition, subjects who received intervention to restore perfusion were evaluated with DWI, PWI, and cognitive tests before and after intervention. Finally, the positive predictive value of the cognitive deficits for identifying cortical abnormalities on DWI and PWI were calculated from all patients. Of the subjects with only subcortical lesions on DWI in this study (n = 44), all those who had aphasia or neglect showed concurrent cortical hypoperfusion. Among the patients who received intervention that successfully restored cortical perfusion, 100% (six out of six) showed immediate resolution of aphasia. In the 115 patients, aphasia and neglect were much more strongly associated with cortical hypoperfusion (chi(2) = 57.3 for aphasia; chi(2) = 28.7 for neglect; d.f. = 1; P < 0.000001 for each), than with cortical infarct/ischaemia on DWI (chi(2) = 8.5 for aphasia; chi(2) = 9.7 for neglect; d.f. = 1; P < 0.005 for each). Aphasia showed a much higher positive predictive value for cortical abnormality on PWI (95%) than on DWI (62%), as did neglect (100% positive predictive value for PWI versus 74% for DWI). From these data we conclude that aphasia and neglect due to acute subcortical stroke can be largely explained by cortical hypoperfusion.
Subject(s)
Aphasia/pathology , Cerebral Cortex/blood supply , Cerebral Cortex/pathology , Perceptual Disorders/pathology , Stroke/pathology , Adult , Aged , Brain/blood supply , Brain/pathology , Cerebral Infarction/pathology , Chi-Square Distribution , Female , Humans , Male , Middle Aged , Prospective StudiesABSTRACT
Based on earlier findings that the presence of word comprehension impairment (a deficit in the meaning of words, or lexical semantics) in acute stroke was strongly associated with the presence of hypoperfusion or infarct in Wernicke's area, we tested the hypothesis that the severity of word comprehension impairment was correlated with the magnitude of delay in perfusion of Wernicke's area on magnetic resonance perfusion-weighted imaging. Eighty patients were prospectively studied within 24 hours of onset or progression of acute left hemisphere stroke symptoms, with diffusion-weighted imaging, perfusion-weighted imaging, and detailed language tests. For 50 patients without infarct in Wernicke's area, we found a strong Pearson correlation between the rate of errors on a word comprehension test and the mean number of seconds of delay in time-to-peak concentration of contrast in Wernicke's area, relative to the homologous region on the right. These results add further evidence for the crucial role of Wernicke's area (Brodmann's area 22) in word comprehension and indicate that the magnitude of delay on PWI may be a gross indicator of tissue dysfunction.
Subject(s)
Aphasia, Wernicke/diagnosis , Memory Disorders/diagnosis , Stroke/diagnosis , Stroke/physiopathology , Temporal Lobe/blood supply , Temporal Lobe/physiopathology , Adult , Aged , Aphasia, Wernicke/etiology , Cerebrovascular Circulation , Disease Progression , Humans , Language Tests , Magnetic Resonance Angiography , Memory Disorders/etiology , Memory Disorders/physiopathology , Middle Aged , Predictive Value of Tests , Prospective Studies , Severity of Illness Index , Stroke/complications , Temporal Lobe/pathologyABSTRACT
BACKGROUND: Neurologic complications after cardiac surgery include stroke, encephalopathy, and persistent cognitive impairments. More precise neuroimaging of patients with these complications may lead to a better understanding of the etiology and treatment of these disorders. OBJECTIVE: To study the pattern of ischemic changes on diffusion- and perfusion-weighted magnetic resonance imaging (DWI, and MRPI, respectively) in patients with neurologic complications after cardiac surgery. METHODS: All records were reviewed of our patients undergoing cardiac surgery in the previous year who also underwent postoperative DWI or MRPI. Neurologic symptoms, vascular studies, and the pattern of ischemic changes were recorded. Acute ischemic lesions were classified as having a territorial, watershed, or lacunar pattern of infarction. Patients with multiple territorial infarcts in differing vascular distributions that were not explained by occlusive vascular lesions were classified as having multiple emboli. RESULTS: Fourteen patients underwent DWI and 4 underwent MRPI. Acute infarcts were found in 10 of 14 patients by DWI as compared with 5 of 12 patients by computed tomography. Eight patients presented with encephalopathy (associated with focal neurologic deficits in 4), 4 with focal deficits alone, and 2 with either fluctuating symptoms or transient ischemic attacks. Among patients with encephalopathy, 7 of 8 had patterns of infarction suggestive of multiple emboli, including 3 of 4 patients with no focal neurologic deficits. Several patients had combined watershed and multiple embolic patterns of ischemia. Findings of MRPI studies were abnormal in 2 of 4 patients, showing diffusion-perfusion mismatch; both patients had either fluctuating deficits or transient ischemic attacks, and their conditions improved with blood pressure manipulation. CONCLUSIONS: In patients with neurologic symptoms after cardiac surgery, DWI is more sensitive to ischemic change than computed tomographic scanning and can demonstrate patterns of infarction that may help us understand etiology. The most common pattern was multiple embolic infarcts. Preliminary experience with MRPI suggests that some patients have persistent diffusion-perfusion mismatch after surgery and may benefit from therapeutic intervention.