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Background: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes., Methods: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions., Results: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P <0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P =0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P =0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P =0.291)., Conclusions: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke., Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719., Competing Interests: Disclosures Dr Oishi is a consultant for Corporate-M and AnatomyWorks. This arrangement is being managed by Johns Hopkins University in accordance with its conflict-of-interest policies. Dr Hillis receives compensation as the editor-in-chief of Stroke and from Elsevier as an associate editor of PracticeUpdate Neurology, grant support from the National Institutes of Health, salary from the Johns Hopkins University School of Medicine, and funding from the National Institute on Deafness and Other Communication Disorders. Disclosures provided by Dr Hillis in compliance with the annual Journal Editor Disclosure Questionnaire of the American Heart Association are available at https://www.ahajournals.org/editor-coi-disclosures. The other authors report no conflicts.

Although pretreatment radiographic biomarkers are well established for hemorrhagic transformation (HT) following successful mechanical thrombectomy (MT) in large vessel occlusion (LVO) strokes, they are yet to be explored for medium vessel occlusion (MeVO) acute ischemic strokes. We aim to investigate pretreatment imaging biomarkers representative of collateral status, namely the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index, and their association with HT in successfully recanalized MeVOs. A prospectively collected registry of acute ischemic stroke patients with MeVOs successfully recanalized with MT between 2019 and 2023 was retrospectively reviewed. A multivariate logistic regression for HT of any subtype was derived by combining significant univariate predictors into a forward stepwise regression with minimization of Akaike information criterion. Of 60 MeVO patients successfully recanalized with MT, HT occurred in 28.3% of patients. Independent factors for HT included: diabetes mellitus history (p = 0.0005), CBV index (p = 0.0071), and proximal versus distal occlusion location (p = 0.0062). A multivariate model with these factors had strong diagnostic performance for predicting HT (area under curve [AUC] 0.93, p < 0.001). Lower CBV indexes, distal occlusion location, and diabetes history are significantly associated with HT in MeVOs successfully recanalized with MT. Of note, HIR was not found to be significantly associated with HT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Purpose: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients., Methods: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value ≤.05., Results: Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes., Conclusions: Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients., (© 2023 American Society of Neuroimaging.)

STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes., Competing Interests: Disclosures Dr Samaniego reports compensation from Rapid Medical for consultant services; compensation from Medtronic for consultant services; compensation from iSchemaView for consultant services; compensation from MicroVention, Inc, for consultant services; and compensation from Cerenovus for consultant services. Dr Boltze reports compensation from Targed Biopharmaceuticals B.V. for consultant services; employment by the University of Warwick; and compensation from Astrocyte Pharmaceuticals for consultant services. Dr Lyden reports compensation from the NIH Clinical Center for other services; compensation from Apex Innovations for consultant services; and employment by the University of Southern California. Dr Hill reports grants from Medtronic; compensation from Brainsgate, Ltd, for consultant services; grants from Boehringer Ingelheim; grants from Medtronic; grants from NoNO, Inc; a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle NVI; grants from Medtronic; grants from the Canadian Institutes of Health Research; grants from MicroVention, Inc; and employment by the University of Calgary. Dr Campbell reports employment by the University of Melbourne. Dr Nguyen reports compensation from Brainomix for consultant services and compensation from Idorsia for other services. Dr Silva reports compensation from Boehringer Ingelheim for consultant services; employment by UNIFESP; compensation from Bayer for consultant services; compensation from iSchemaView for consultant services; employment by Sociedade Beneficente Israelita Brasileira Albert Einstein; and compensation from Pfizer for other services. Dr Sheth reports stock holdings in Verve Therapeutics; compensation from Rhaeos for consultant services; compensation from Sense for data and safety monitoring services; compensation from Astrocyte for consultant services; compensation from Cerevasc for consultant services; grants from Hyperfine; employment by Yale School of Medicine; a patent pending for Stroke wearables licensed to Alva Health; stock holdings in AbbVie; grants from Biogen; compensation from CSL Behring for consultant services; and compensation from ZOLL Medical Corporation for data and safety monitoring services. Dr Fisher reports compensation from Simcere USA for consultant services; employment by Beth Israel Deaconess Medical Center; compensation from Lumosa for consultant services; and employment by Beth Israel Deaconess Medical Center. Dr Hillis reports employment by the Johns Hopkins University School of Medicine; compensation from Elsevier Publishing for other services; compensation from the National Institute on Deafness and Other Communication Disorders for other services; and compensation from the American Heart Association for other services. Dr Carone reports stock options in Brainomix, Ltd, and employment by Brainomix, Ltd. Dr Deljkich reports employment by Imperative Care, Inc. Dr Albers reports compensation from Genentech for consultant services; stock holdings in iSchemaView; and compensation from iSchemaView for consultant services. Dr Heit reports compensation from Medtronic for consultant services; compensation from iSchemaView for consultant services; and compensation from MicroVention, Inc, for consultant services. The other authors report no conflicts.

Trial Design: Current protocols for treatment of acute ischemic stroke with intravenous thrombolytics, such as alteplase (tPA) and tenecteplase (tNK), recommend the completion of a routine non-contrast head CT at 24 hours post treatment to evaluate for hemorrhage prior to the initiation of antiplatelet therapy for secondary stroke prevention. This guideline was instituted because it had been part of the protocol in the NINDS multicenter randomized placebo-controlled trial that showed the benefit of IV thrombolytics within 3 hours of stroke onset. Recent observational studies indicate that the repeat (stability) head CT rarely alters clinical management, in the absence of neurological worsening or evidence of clinical signs of hemorrhagic conversion, such as seizures, severe headache, or novel acute deficits. A solitary CT carries with it a non-negligible dose of radiation with additive cost to the medical system at large., Methods: We aimed to identify, with a randomized, blinded outcome assessment trial, if a routine head CT at 24 hours, in the absence of clinical indication, negatively influences clinical outcomes. We enrolled 58 patients, and evaluated differences between groups with t-tests. We also evaluated differences between outcomes (90 day modified Rankin Scale, mRS and change in National Institutes of Health Stroke Scale, NIHSS) from pretreatment to discharge using multivariable logistic regression, including age, baseline NIHSS, and group as independent variables., Results: We found no added benefit of routine CT on either outcome measure., Conclusion: It is likely safe to forgo follow up imaging after thrombolysis in the absence of clinical decompensation., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In acute ischemic stroke, reported relationships between lesion metrics and behavior have largely focused on lesion volume and location. However, hypoperfusion has been shown to correlate with deficits in the acute stage. Hypoperfusion is typically identified using perfusion imaging in clinical settings, which requires contrast. Unfortunately, contrast is contraindicated for some individuals. An alternative method has been proposed to identify hypoperfusion using hyperintense vessels on fluid-attenuated inversion recovery (FLAIR) imaging. This study aimed to validate the clinical importance of considering hypoperfusion when accounting for behavior in acute stroke and demonstrate the clinical utility of scoring the presence of hyperintense vessels to quantify it. One hundred and fifty-three participants with acute ischemic stroke completed a battery of commonly-used neurological and behavioral measures. Clinical MRIs were used to determine lesion volume and to score the presence of hyperintense vessels seen on FLAIR images to estimate severity of hypoperfusion in six different vascular regions. National Institutes of Health Stroke Scale (NIHSS) scores, naming accuracy (left hemisphere strokes), and language content produced during picture description were examined in relation to lesion volume, hypoperfusion, and demographic variables using correlational analyses and multivariable linear regression. Results showed that lesion volume and hypoperfusion, in addition to demographic variables, were independently associated with performance on NIHSS, naming, and content production. Specifically, hypoperfusion in the frontal lobe independently correlated with NIHSS scores, while hypoperfusion in parietal areas independently correlated with naming accuracy and content production. These results correspond to previous reports associating hypoperfusion with function, confirming that hypoperfusion is an important consideration-beyond lesion volume-when accounting for behavior in acute ischemic stroke. Quantifying hypoperfusion using FLAIR hyperintense vessels can be an essential clinical tool when other methods of identifying hypoperfusion are unavailable or time prohibitive., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether right ventral stream and limbic structures (including posterior superior temporal gyrus [STG], STG, temporal pole, inferior frontal gyrus pars orbitalis, orbitofrontal cortex, amygdala, anterior cingulate, gyrus, and the sagittal stratum) are implicated in emotional prosody identification., Methods: Patients with MRI scans within 48 hours of unilateral right hemisphere ischemic stroke were enrolled. Participants were presented with 24 sentences with neutral semantic content spoken with happy, sad, angry, afraid, surprised, or bored prosody and chose which emotion the speaker was feeling based on tone of voice. Multivariable linear regression was used to identify individual predictors of emotional prosody identification accuracy from a model, including percent damage to proposed right hemisphere structures, age, education, and lesion volume across all emotions (overall emotion identification) and 6 individual emotions. Patterns of recovery were also examined at the chronic stage., Results: The overall emotion identification model was significant (adjusted r 2 = 0.52; p = 0.043); greater damage to right posterior STG ( p = 0.038) and older age ( p = 0.009) were individual predictors of impairment. The model for recognition of fear was also significant (adjusted r 2 = 0.77; p = 0.002), with greater damage to right amygdala ( p = 0.047), older age ( p < 0.001), and less education ( p = 0.005) as individual predictors. Over half of patients with chronic stroke had residual impairments., Conclusions: Right posterior STG in the right hemisphere ventral stream is critical for emotion identification in speech. Patients with stroke with damage to this area should be assessed for emotion identification impairment., (© 2019 American Academy of Neurology.)

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort.A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis.Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe.The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation.

Failure to recognize sarcasm can lead to important miscommunications. Few previous studies have identified brain lesions associated with impaired recognition of sarcasm. We tested the hypothesis that percent damage to specific white matter tracts, age, and education together predict accuracy in sarcasm recognition. Using multivariable linear regression, with age, education, and percent damage to each of eight white matter tracts as independent variables, and percent accuracy on sarcasm recognition as the dependent variable, we developed a model for predicting sarcasm recognition. Percent damage to the sagittal stratum had the greatest weight and was the only independent predictor of sarcasm recognition.

Objective: Awareness of motor functioning is most likely a complex process that requires integration of sensory-motor feedback to constantly update the system on the functioning of the limb during motor behavior. Using lesion mapping procedures and behavioral measures, the current study aimed to evaluate neural correlates of anosognosia for hemiplegia (AHP) in the acute stage (first 48 hr) of right hemisphere stroke., Method: Thirty-five individuals with right hemisphere stroke who presented to an urban medical center within 24 hr of symptom onset were included in the study. All 35 individuals had hemiplegia, and 8 of these individuals exhibited AHP., Results: Fisher's exact test statistical map of lesion-deficit association (range is between-log(p) 4 to 11) found maximal value of 10.9 located in pars orbitalis (Brodmann's Area 47; BA). In this selected location, 6 out of 8 patients with AHP had tissue abnormality, whereas none of the unaffected subjects had tissue abnormality in BA 47. Right BA 44/45 was also found to be lesioned more frequently in individuals with AHP (75%) than without AHP (11%)., Conclusions: The current study findings provide preliminary support for unique involvement of the right inferior frontal gyrus (IFG), pars orbitalis (BA 47) in AHP. The current data suggest that frontal operculum may play a key role in awareness of limb functioning., ((c) 2015 APA, all rights reserved).)

Background and Purpose: Early blood-brain barrier damage after acute ischemic stroke has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of blood-brain barrier damage evident on pre-tissue-type plasminogen activator MRI scans was related to the degree of post-tissue-type plasminogen activator ICH in patients with acute ischemic stroke., Methods: Analysis was performed on a database of patients with acute ischemic stroke provided by the Stroke Imaging Repository (STIR) and Virtual International Stroke Trials Archive (VISTA) Imaging Investigators. Patients with perfusion-weighted imaging lesions>10 mL and negative gradient-recalled echo imaging before intravenous tissue-type plasminogen activator were included. Postprocessing of the perfusion-weighted imaging source images was performed to estimate changes in blood-brain barrier permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up gradient-recalled echo images were reviewed for evidence of ICH and divided into 3 groups according to European Cooperative Acute Stroke Study (ECASS) criteria: no hemorrhage, hemorrhagic infarction, and parenchymal hematoma., Results: Seventy-five patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as hemorrhagic infarction and 9 were classified as parenchymal hematoma. The mean permeability (±SDs), expressed as an index of contrast leakage, was 17.0±8.8% in the no hemorrhage group, 19.4±4.0% in the hemorrhagic infarction group, and 24.6±4.5% in the parenchymal hematoma group. Permeability was significantly correlated with ICH grade in univariate (P=0.007) and multivariate (P=0.008) linear regression modeling., Conclusions: A perfusion-weighted imaging-derived index of blood-brain barrier damage measured before intravenous tissue-type plasminogen activator is given is associated with the severity of ICH after treatment in patients with acute ischemic stroke., (© 2014 American Heart Association, Inc.)

Functional imaging studies of healthy participants and previous lesion studies have provided evidence that empathy involves dissociable cognitive functions that rely on at least partially distinct neural networks that can be individually impaired by brain damage. These studies converge in support of the proposal that affective empathy--making inferences about how another person feels--engages at least the following areas: prefrontal cortex, orbitofrontal gyrus, anterior insula, anterior cingulate cortex, temporal pole, amygdala and temporoparietal junction. We hypothesized that right-sided lesions to any one of these structures, except temporoparietal junction, would cause impaired affective empathy (whereas bilateral damage to temporoparietal junction would be required to disrupt empathy). We studied 27 patients with acute right hemisphere ischaemic stroke and 24 neurologically intact inpatients on a test of affective empathy. Acute impairment of affective empathy was associated with infarcts in the hypothesized network, particularly temporal pole and anterior insula. All patients with impaired affective empathy were also impaired in comprehension of affective prosody, but many patients with impairments in prosodic comprehension had spared affective empathy. Patients with impaired affective empathy were older, but showed no difference in performance on tests of hemispatial neglect, volume of infarct or sex distribution compared with patients with intact affective empathy.

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) = 1.50 per 10-year increment, 95% confidence interval (CI) 1.07-2.08], infarct volume (OR = 1.10 per 10 ccs, 95% CI 1.06-1.18) and worsening category of renal impairment by estimated glomerular filtration rate (eGFR; OR = 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%; P = 0.79); however, all intracerebral hematomas (n = 7) and symptomatic bleeds (n = 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., (© 2013 The Author(s) European Journal of Neurology © 2013 EFNS.)

The role of the anterior temporal lobes in cognition and language has been much debated in the literature over the last few years. Most prevailing theories argue for an important role of the anterior temporal lobe as a semantic hub or a place for the representation of unique entities such as proper names of peoples and places. Lately, a few studies have investigated the role of the most anterior part of the left anterior temporal lobe, the left temporal pole in particular, and argued that the left anterior temporal pole is the area responsible for mapping meaning on to sound through evidence from tasks such as object naming. However, another recent study indicates that bilateral anterior temporal damage is required to cause a clinically significant semantic impairment. In the present study, we tested these hypotheses by evaluating patients with acute stroke before reorganization of structure-function relationships. We compared a group of 20 patients with acute stroke with anterior temporal pole damage to a group of 28 without anterior temporal pole damage matched for infarct volume. We calculated the average percent error in auditory comprehension and naming tasks as a function of infarct volume using a non-parametric regression method. We found that infarct volume was the only predictive variable in the production of semantic errors in both auditory comprehension and object naming tasks. This finding favours the hypothesis that left unilateral anterior temporal pole lesions, even acutely, are unlikely to cause significant deficits in mapping meaning to sound by themselves, although they contribute to networks underlying both naming and comprehension of objects. Therefore, the anterior temporal lobe may be a semantic hub for object meaning, but its role must be represented bilaterally and perhaps redundantly.

Oral reading is a complex skill involving the interaction of orthographic, phonological, and semantic processes. Functional imaging studies with nonimpaired adult readers have identified a widely distributed network of frontal, inferior parietal, posterior temporal, and occipital brain regions involved in the task. However, while functional imaging can identify cortical regions engaged in the process under examination, it cannot identify those brain regions essential for the task. The current study aimed to identify those neuroanatomical regions critical for successful oral reading by examining the relationship between word and nonword oral reading deficits and areas of tissue dysfunction in acute stroke. We evaluated 91 patients with left hemisphere ischemic stroke with a test of oral word and nonword reading, and magnetic resonance diffusion-weighted and perfusion-weighted imaging, within 24-48h of stroke onset. A voxel-wise statistical map showed that impairments in word and nonword reading were associated with a distributed network of brain regions, including the inferior and middle frontal gyri, the middle temporal gyrus, the supramarginal and angular gyri, and the middle occipital gyrus. In addition, lesions associated with word deficits were found to be distributed more frontally, while nonword deficits were associated with lesions distributed more posteriorly., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Functional imaging studies consistently find that older adults recruit bilateral brain regions in cognitive tasks that are strongly lateralized in younger adults, a characterization known as the Hemispheric Asymmetry Reduction in Older Adults model. While functional imaging displays what brain areas are active during tasks, it cannot demonstrate what brain regions are necessary for task performance. We used behavioral data from acute stroke patients to test the hypothesis that older adults need both hemispheres for a verbal working memory task that is predominantly left-lateralized in younger adults. Right-handed younger (age ⩽ 50, n = 7) and older adults (age > 50, n =21) with acute unilateral stroke, as well as younger (n =6) and older (n =13) transient ischemic attack (TIA) patients, performed a self-paced verbal item-recognition task. Older patients with stroke to either hemisphere had a higher frequency of deficits in the verbal working memory task compared to older TIA patients. Additionally, the deficits in older stroke patients were mainly in retrieval time while the deficits in younger stroke patients were mainly in accuracy. These data suggest that bihemispheric activity is necessary for older adults to successfully perform a verbal working memory task.

Background and Purpose: We aimed to determine if ischemia involving Broca area predicts Broca aphasia more reliably in acute or chronic stroke., Methods: We included consecutive right-hand-dominant patients with left hemisphere ischemic stroke (<48 hours from onset for acute stroke or >6 months after stroke for chronic stroke). MRI scans were analyzed for ischemic lesions or hypoperfusion in Broca area (Brodmann areas 44 and 45). Patients were scored on the Western Aphasia Battery to classify aphasia syndromes; chi(2) tests were used to identify significant associations., Results: The presence of infarct involving any part of Broca area and the presence of Broca or global aphasia was much stronger in acute (chi(2)=38.1; df1; P<0.0001) than in chronic stroke (chi(2)=0.54; df1; P=0.46; not significant). The association between infarct or hypoperfusion covering all of Broca area and the presence of Broca or global aphasia was much stronger in acute (chi(2)=35.8; df1; P<0.0001) than in chronic stroke (chi(2)=1.2; df1; p=0.27; not significant). In a subset of 20 patients studied longitudinally, the associations were significant only acutely, not chronically (chi(2)=20; df1; P<0.0001 vs. chi(2)=0; df1; p=1; not significant for ischemia involving part of Broca area, and chi(2)=16.4; df1; P<0.0001 vs chi(2)=3.2; df1; p=0.08; not significant for ischemia covering all of Broca area)., Conclusions: Broca aphasia is more reliably associated with infarct/ hypoperfusion of Broca area in acute stroke. Many chronic stroke patients with damage to part or all of Broca area had neither Broca nor global aphasia. Broca or global aphasia was sometimes present initially in these patients but resolved by 6 months. Our results indicate that the acute aphasia syndrome may allow the clinician to predict the compromised vascular territory, even when structural imaging shows only a small (or no) infarct.

We aimed to identify neuroanatomical regions associated with deficits to the graphemic buffer, a working memory component of the spelling system that holds the sequence of letter identities during production. We evaluated 331 patients with left hemisphere ischemic stroke with various spelling tests and magnetic resonance diffusion-weighted imaging and perfusion-weighted imaging, within 48 hours of stroke onset. A voxel-wise statistical map showed that ischemia in voxels in posterior and inferior frontal and parietal cortex, subcortical white matter underlying prefrontal cortex, lateral occipital gyrus, or caudate was associated with impairment in maintaining the sequence of letter identities while spelling.

Background and Purpose: Dysphagia is a common problem after stroke associated with significant morbidity and mortality. Except for patients with brain stem strokes, particularly lateral medullary strokes, it is difficult to predict which cases are likely to develop swallowing dysfunction based on their neuroimaging. Clear models of swallowing control and integration of cortico-bulbar input have not been defined and the role of subcortical structures is unclear. The purpose of this study was to identify supratentorial regions of interest (ROIs) that might be related to clinically important dysphagia in acute stroke patients, focusing on subcortical structures., Methods: We studied 29 acute supratentorial ischemic stroke cases admitted to our institution between 2001 and 2005 diagnoses with first ischemic stroke and without history of swallowing dysfunction. Subjects had MRI within 24 hours. Cases were defined as those subjects who were diagnosed as dysphagic after clinical evaluation by a speech language pathologist (SLP) and whose dysphagia was considered clinically significant, ie, requiring treatment by diet modification. Controls were defined as those patients who: (1) passed the stroke unit's dysphagia screening, (2) had a clinical evaluation by SLP that did not result in a diagnosis of dysphagia or diet modifications, or (3) had no documented evidence of dysphagia evaluation or treatment during hospitalization and were discharged on a regular diet. A trained technician, blinded to case-control status, examined 12 ROIs for dysfunctional tissue in diffusion and perfusion-weighted images. The odds ratio (OR) of dysphagia was calculated for each ROI. Logistic regression models were used to adjust for stroke severity (NIHSS) and volume., Results: Analysis of data on 14 cases and 15 controls demonstrated significant differences in the unadjusted odds of dysphagia for the following ROIs: (1) primary somatosensory, motor, and motor supplementary areas (PSSM; OR=10, P=0.009); (2) orbitofrontal cortex (OFC; OR=6.5, P=0.04); (3) putamen, caudate, basal ganglia (PCBG; OR=5.33, P=0.047); and (4) internal capsule (IC; OR=26; P=0.005). Nonsignificant differences were found in the insula and temporopolar cortex. Adjusted OR of dysphagia for subjects with strokes affecting the IC was 17.8 (P=0.03). Adjusted odds ratios for the PSSM, OFC, and PCBG were not statistically significant., Conclusions: Significantly increased odds of dysphagia were found in subjects with IC involvement. Other supratentorial areas that may be associated with dysphagia include the PSSM, OFC, and PCBG. Analysis of additional areas was limited by the number of subjects in our sample. Future studies with larger sample size are feasible and will contribute to the development of a full swallowing control model.

Hemispatial neglect is a common and disabling consequence of stroke. Previous reports examining the relationship between gender and the incidence of unilateral spatial neglect (USN) have included either a large numbers of patients with few neglect tests or small numbers of patients with multiple tests. To determine if USN was more common and/or severe in men or women, we examined a large group of patients (312 right-handed) within 24 hours of acute right hemisphere ischemic stroke. Multiple spatial neglect tasks were used to increase the sensitivity of neglect detection. No differences based upon gender were observed for the prevalence, severity, or a combined task measure of USN.

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.

Activation of the left midfusiform gyrus in response to reading words and pseudowords is such a reliable finding in functional imaging that this region has been called "the visual word form area" (VWFA). However, this label has recently been challenged, because activation in VWFA is also observed in other lexical tasks. We evaluated whether VWFA is necessary, sufficient, or specialized for reading by examining how frequently acute lesions in VWFA disrupt tasks that require access to written word forms versus other lexical tasks. We administered lexical tasks with spoken and written input and output, and identified damage or dysfunction of VWFA and other regions of interest (ROI) on diffusion- and perfusion-weighted imaging (DWI and PWI) in 80 patients within 24 h of onset of acute left ischemic stroke. Associations between abnormalities in each region of interest and impairment on lexical tasks were evaluated with chi-squared tests. Damage or dysfunction of VWFA was not significantly associated with impairment of written word comprehension or lexical decision, but was significantly associated with impairment on all tasks requiring lexical output: oral reading and oral naming (visual or tactile input), and written naming. We account for these results and results from functional imaging by proposing that the left midfusiform gyrus normally has two roles in reading: (1) computation of location- and modality-independent grapheme sequences from written word stimuli, and (2) a modality-independent stage of lexical processing that links modality-specific input and output representations. VWFA is not necessary for the former because the right homologue of VWFA can immediately assume this role.

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.

Functional imaging data collected during cognitive tasks show which brain regions are active during those tasks, but do not necessarily indicate which regions are essential for those tasks. Here, in a study of two cases of selectively impaired written naming of verbs after focal brain ischemia, we combined imaging and behavioral testing to unambiguously identify brain regions that are crucial for a specific cognitive process. We used magnetic resonance perfusion imaging to show that the selective impairment in each case was due to hypoperfusion (low blood flow) in left posterior inferior frontal gyrus (PIFG) and precentral gyrus (PrG); the impairment was immediately reversed when blood flow was restored to these regions, indicating that parts of the left frontal lobe are crucial for representing and processing verbs.