Magnetic Resonance Perfusion Imaging: A new method for localizing regions of brain dysfunction associated with specific lexical impairments?

We investigated correlations between lexical impairments and regional infarction versus hypoperfusion in hyperacute stroke (within 24 hours of onset). Seven patients with hyperacute dominant hemisphere stroke underwent a battery of lexical tasks, and investigational MRI techniques of Diffusion-Weighted Imaging (DWI) and Magnetic Resonance Perfusion Imaging (MRPI). Lexical performance was a function of regional hypoperfusion (on MRPI) rather than region of (probably) completed infarct (on DWI). Strong correlations were found between: accuracy in auditory word comprehension and volume of left temporal and parietal hypoperfusion, and accuracy of naming and left parietal hypoperfusion. Frequent errors in repetition were associated with left temporal and/or left frontal hypoperfusion, but the volume of infarct in these areas was not significantly correlated with the rate of repetition errors. Results of this preliminary study indicate that MRPI is a promising tool for investigating the regions of hypoperfused (dysfunctional, but not infarcted) brain tissue associated with specific language impairments in hyperacute stroke.     

Neural substrates of the cognitive processes underlying reading: Evidence from magnetic resonance perfusion imaging in hyperacute stroke

Although it is widely agreed that reading aloud entails multiple cognitive processes, there is little evidence for localisation of these processes. We investigated regions of brain dysfunction associated with impairment of each process. Forty patients were studied within 24 hours of onset of dominant hemisphere stroke, using: (1) a battery of tasks to identify impaired processes underlying reading, and (2) magnetic resonance perfusion imaging (MRPI) and diffusion-weighted imaging (DWI). Impairment of each component of reading, except motor speech, was highly correlated with one or more regions of hypoperfusion identified by MRPI, but not with areas of infarct on DWI.     

The neglected role of the right hemisphere in spatial representation of words for reading

Background: Previous studies have indicated that focal brain damage can result in different types of “neglect dyslexia” (reading errors specific to the side of printed material contralateral to the side of brain damage).Aims: To identify the sites of lesions (or dysfunctional brain tissue) responsible for distinct types of neglect dyslexia, to inform a functional neuroanatomical model of brain regions involved in early stages of reading.Methods & Procedures: A battery of tests of hemispatial neglect and reading designed to distinguish neglect dyslexia in different reference frames (viewer-centred, stimulus-centred, and object-centred) was administered to 95 patients within 48 hours of onset of nondominant hemisphere stroke. Magnetic resonance diffusion and perfusion imaging was obtained on the same day as testing. Associations between each type of neglect dyslexia and areas of hypoperfusion and/or infarct were evaluated using chi-squared tests.Outcomes & Results: Viewer-centred neglect dyslexia was associated with hypoperfusion and/or infarct in right angular and supramarginal gyri and visual association cortex (“dorsal stream”). Stimulus-centred neglect dyslexia was associated with hypoperfusion and/or infarct of right superior temporal cortex (“ventral stream”). Object-centred neglect dyslexia was observed only with hypoperfusion and/or infarct of non-dominant superior temporal cortex in left-handed individuals.Conclusions: The identified associations provide evidence that different regions of cortex are critical for spatial attention to, or processing of, representations of words with distinct coordinate frames in the reading task.     

Combined diffusion and perfusion MRI with correlation to single-photon emission CT in acute ischemic stroke. Ischemic penumbra predicts infarct growth.

BACKGROUND AND PURPOSE: More effective imaging methods are needed to overcome the limitations of CT in the investigation of treatments for acute ischemic stroke. Diffusion-weighted MRI (DWI) is sensitive in detecting infarcted brain tissue, whereas perfusion-weighted MRI (PWI) can detect brain perfusion in the same imaging session. Combining these methods may help in identifying the ischemic penumbra, which is an important concept in the hemodynamics of acute stroke. The purpose of this study was to determine whether combined DWI and PWI in acute (<24 hours) ischemic stroke can predict infarct growth and final size. METHODS: Forty-six patients with acute ischemic stroke underwent DWI and PWI on days 1, 2, and 8. No patient received thrombolysis. Twenty-three patients underwent single-photon emission CT in the acute phase. Lesion volumes were measured from DWI, SPECT, and maps of relative cerebral blood flow calculated from PWI. RESULTS: The mean volume of infarcted tissue detected by DWI increased from 46.1 to 75.6 cm(3) between days 1 and 2 (P<0.001; n=46) and to 78.5 cm(3) after 1 week (P<0.001; n=42). The perfusion-diffusion mismatch correlated with infarct growth (r=0. 699, P<0.001). The volume of hypoperfusion on the initial PWI correlated with final infarct size (r=0.827, P<0.001). The hypoperfusion volumes detected by PWI and SPECT correlated significantly (r=0.824, P<0.001). CONCLUSIONS: Combined DWI and PWI can predict infarct enlargement in acute stroke. PWI can detect hypoperfused brain tissue in good agreement with SPECT in acute stroke.     

Reversible focal ischemic injury demonstrated by diffusion-weighted magnetic resonance imaging in rats.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging (DWI) can quantitatively display focal brain abnormalities within minutes after the onset of ischemia. We performed the present study to determine the effects of 1 and 2 hours of temporary ischemia on DWI. METHODS: We examined DWI and T2-weighted magnetic resonance images (T2WI) during and after 1 and 2 hours of temporary middle cerebral artery occlusion in rats (n = 10 for each group). In a subgroup of four animals from each group, we employed perfusion magnetic resonance imaging to monitor cerebral perfusion. Neurological outcome and infarct size after survival for 24 hours were compared between the groups and correlated with DWI and T2WI studies. RESULTS: Perfusion studies qualitatively documented hypoperfusion and reperfusion during and after temporary occlusion. Lesion size on DWI during reperfusion was significantly less than that during ischemia for 1 (55% decline, p less than 0.02) but not 2 hours of occlusion. The DWI signal intensity ratio (intensity compared with that in the contralateral homologous area) just before withdrawal of the occluder was significantly less in regions where the hyperintensity disappeared after withdrawal than in regions with persistent hyperintensity (p less than 0.002). The T2WI studies revealed few or no abnormalities, except after 2 hours of occlusion. The neurological outcome was significantly better in the 1-hour than in the 2-hour group (p less than 0.05). Postmortem infarct volume was significantly smaller in the 1-hour group than in the 2-hour group (p less than 0.05). The postwithdrawal DWI accurately predicted infarct size (R = 0.96, p less than 0.0001). CONCLUSIONS: The present study indicates that DWI can rapidly display not only irreversible but also reversible ischemic brain damage and enhances the importance of DWI as a diagnostic modality for stroke.     

Reperfusion of specific cortical areas is associated with improvement in distinct forms of hemispatial neglect

ObjectiveTo test the hypothesis that restoring blood flow to specific right cortical regions in acute stroke results in improvement in distinct forms of hemispatial neglect distinguished by reference frame: viewer-centered versus stimulus-centered neglect.MethodsTwenty five patients with acute right stroke were evaluated at Day 1 and Day 3–5 with a battery of neglect tests and Diffusion- and Perfusion-Weighted MR Imaging. Multivariate linear regression analysis revealed Brodmann areas (BAs) where reperfusion predicted degree of improvement in scores on each type of neglect, independently of reperfusion of other areas, total change in the volume of infarct or hypoperfusion, and age.ResultsReperfusion of dorsal frontoparietal cortex (including BAs 40, 46, and 4) independently predicted improvement in viewer-centered neglect, such as detecting stimuli on left in line cancellation and scene copying (r = .951; p < .0001). Reperfusion of a more ventral temporo-occipital cortex, including right BAs 37, 38, 21 and 18, independently contributed to improvement in stimulus-centered neglect, such as detecting left gaps in circles (r = .926; p < .0001). Reperfusion of right midfusiform gyrus (temporal occipital cortex), change in total volume of ischemia, change in volume of hypoperfusion and age predicted degree of improvement in reading (reduction in “neglect dyslexic” errors; r = .915; p < .0001). Results demonstrate that reperfusing specific cortical regions yields improvement in different types of neglect.     

Detection of the ischemic penumbra using pH-weighted MRI.

The classic definition of the ischemic penumbra is a hypoperfused region in which metabolism is impaired, but still sufficient to maintain cellular polarization. Perfusion- and diffusion-weighted MRI (PWI, DWI) can identify regions of reduced perfusion and cellular depolarization, respectively, but it often remains unclear whether a PWI-DWI mismatch corresponds to benign oligemia or a true penumbra. We hypothesized that pH-weighted MRI (pHWI) can subdivide the PWI-DWI mismatch into these regions. Twenty-one rats underwent permanent middle cerebral artery occlusion and ischemic evolution over the first 3.5 h post-occlusion was studied using multiparametric MRI. End point was the stroke area defined by T(2)-hyperintensity at 24 h. In the acute phase, areas of reduced pH were always larger than or equal to DWI deficits and smaller than or equal to PWI deficits. Group analysis showed that pHWI deficits during this phase coincided with the resulting infarct area at endpoint. Final infarcts were smaller than PWI deficits (range 65% to 90%, depending on the severity of the occlusion) and much larger than acute DWI deficits. These data suggest that the outer boundary of the hypoperfused area showing a decrease in pH without DWI abnormality may correspond to the outer boundary of the ischemic penumbra, while the hypoperfused region at normal pH may correspond to benign oligemia. These first results show that pHWI can provide information complementary to PWI and DWI in the delineation of ischemic tissue.     

ApoE polymorphism and acute stroke: a study with diffusion- and perfusion-weighted MRI and MR angiography

OBJECTIVES: We examined whether the apolipoprotein E (ApoE) allele epsilon4 influences imaging findings in stroke as assessed by diffusion- (DWI) and perfusion-weighted (PWI) magnetic resonance imaging, and MR angiography (MRA). METHODS: Eight ApoE epsilon4 carriers and 15 non-carriers with acute ischemic stroke in the anterior circulation underwent DWI, PWI, and MRA within 24 h of stroke. DWI and PWI were repeated a week later. The apparent diffusion coefficient, relative cerebral volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time were measured in three subregions on day one. RESULTS: In the ischemic core and the area of infarct growth, rCBV values were significantly higher in the epsilon4 carriers compared with the non-carriers. Based on the MRA findings, collateral blood flow was better in the epsilon4 carriers than in the non-carriers. Under the comparable severity of hypoperfusion, the hypoperfused area proceeded to infarction later or did not proceed to infarction at all in the non-carriers. CONCLUSION: These preliminary data suggest that in the ApoE allele epsilon4 carriers the threshold for the brain tissue to survive hypoperfusion versus to proceed to infarction seems to be different from that of the non-carriers.     

Relationship between severity of MR perfusion deficit and DWI lesion evolution

OBJECTIVE: To assess whether a quantitative analysis of the severity of the early perfusion deficit on MRI in acute ischemic stroke predicts the evolution of the perfusion/diffusion mismatch and to determine thresholds of hypoperfusion that can distinguish between critical and noncritical hypoperfusion. METHODS: Patients with acute ischemic stroke were studied in whom perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI MRI) were performed within 7 hours of symptom onset and again after 4 to 7 days. Patients with early important decreases in points on the NIH Stroke Scale were excluded. Maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were created. These hemodynamic parameters were correlated with the degree of recruitment of the baseline PWI lesion by the DWI lesion. RESULTS: Twelve patients had an initial PWI > DWI mismatch of >20%. A linear relationship was observed between the initial MTT and the degree of recruitment of the baseline PWI lesion by the DWI lesion at follow-up (R(2) = 0.9, p < 0.001). Higher CBV values were associated with higher degrees of recruitment (rho = 0.732, p < 0.007). The volume of MTT of >4 (R(2) = 0.86, p < 0.001) or >6 seconds (R(2) = 0.85, p < 0.001) predicted final infarct size. CONCLUSION: Among patients who have had an acute stroke with PWI > DWI, who do not have dramatic early clinical improvement, the degree of expansion of the initial DWI lesion correlates with the severity of the initial perfusion deficit as measured by the mean transit time and the cerebral blood volume.     

Diffusion- and perfusion-weighted brain magnetic resonance imaging in patients with neurologic complications after cardiac surgery

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.     

FLAIR Vascular Hyperintensities in Acute ICA and MCA Infarction: A Marker for Mismatch and Stroke Severity?

Background: Vascular hyperintensities of brain-supplying arteries on stroke FLAIR MRI are common and represent slow flow or stasis. FLAIR vascular hyperintensities (FVH) are discussed as an independent marker for cerebral hypoperfusion, but the impact on infarct size and clinical outcome in acute stroke patients is controversial. This study evaluates the association of FVH with infarct morphology, clinical stroke severity and infarct growth in patients with symptomatic internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion. Methods: MR images of 84 patients [median age 73 years (IQR 65-80), 56.0% male, median NIHSS 7 (IQR 3-13)] with acute stroke due to symptomatic ICA or MCA occlusion or stenosis were reviewed. Vessel occlusions were identified by MRA time of flight and graded with the TIMI score. Diffusion and perfusion deficit volumes on admission and FLAIR lesion volumes on discharge were assessed. The presence and number of FVH were evaluated according to MCA-ASPECT areas, and associations with MR volumes, morphology of infarction, recanalization status, presence of white matter disease and hemorrhagical transformation as well as with stroke severity (NIHSS), stroke etiology and thrombolysis rate were analyzed. Results: FVH were detectable in 75 (89.3%) patients. The median number of FVH was 4 (IQR 2-7). Patients with FVH >4 presented with more severe strokes due to NIHSS (p = 0.021), had larger initial DWI lesions (p = 0.008), perfusion deficits (p = 0.001) and mismatch volumes/ratios (p = 0.005). The final infarct volume was larger (p = 0.005), and hemorrhagic transformation was more frequent (p = 0.029) in these patients. Conclusions: The presence of FVH indicates larger ischemic areas in brain parenchyma predominantly caused by proximal anterior circulation vessel occlusion. A high count of FVH might be a further surrogate marker for initial ischemic mismatch and stroke severity.     

Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial

BACKGROUND: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). METHODS: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. FINDINGS: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. INTERPRETATION: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.     

Correlation between diffusion- and perfusion-weighted MRI and neurological deficit measured by the Scandinavian Stroke Scale and Barthel Index in hyperacute subcortical stroke (< or = 6 hours)

OBJECTIVE: We used combined diffusion-weighted (DWI) and perfusion-weighted (PWI) MRI to characterize hyperacute infarctions within 6 h of symptom onset with special reference to subcortical infarctions, and investigated the relation between perfusion-diffusion mismatch volume and functional outcome. MATERIAL AND METHODS: Twenty-two patients presenting with symptoms of acute stroke underwent DWI and PWI within 6 h of symptom onset, and follow-up MRI 30 days later. Twelve of these had a subcortical infarction on acute DWI. Lesion volumes were measured by acute DWI and PWI as well as chronic T(2)-weighted MRI (T2WI). Clinical severity was measured by the Scandinavian Stroke Scale (SSS) and the Barthel Index (BI). RESULTS: In the 12 patients with subcortical infarctions, PWI and especially DWI correlated strongly with acute and chronic neurological SSS score, as well as with final infarct volume. Furthermore, a hyperacute PWI/DWI mismatch in this subgroup predicted lesion growth. There was a weaker correlation between acute DWI/PWI and neurological score among all 22 patients, and patients with a PWI/DWI mismatch larger than 100 ml had a significantly larger lesion growth and a poorer outcome than patients with a smaller mismatch. CONCLUSIONS: Subcortical infarctions may represent a sizeable subgroup of acute stroke patients. Also subcortical infarctions may have a PWI/DWI mismatch and therefore may respond to neuroprotective/thrombolytic therapy. Hyperacute DWI may reflect the acute clinical status and predict the outcome in patients with subcortical infarction.     

Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome

BACKGROUND: The prognostic value of the biochemical changes seen with proton MR spectroscopy (1H MRS) in ischemic stroke was examined. Acute diffusion-weighted imaging (DWI) was used to identify regions of ischemia for 1H MRS voxel localization. METHODS: Nineteen patients had 36 1H MRS studies, 13 patients acutely (mean, 11.1 hours), 10 subacutely (mean, 3.9 days), and 13 at outcome (mean, 82 days). Single-voxel, long-echo, timepoint-resolved spectroscopy was used to obtain lactate, n-acetylaspartate (NAA), choline, and creatine levels from the infarct core. Outcome measures were final infarct volume and clinical assessment scales (Canadian Neurological Scale, Barthel Index, and Rankin Scale). RESULTS: Acute lactate/choline ratio correlated more strongly with clinical outcome scores (r = 0.76 to 0.83; p < 0.01) and final infarct size (r = 0. 96; p < 0.01) than acute DWI lesion volume or acute NAA/choline ratio. Combination of acute lactate/choline ratio with acute DWI lesion volume improved prediction of all outcome scores (R2 = 0.80 to 0.90). The predictive effect of acute lactate/choline ratio was independent of acute DWI lesion volume (p < 0.001). In subacute and chronic infarction, both lactate/choline and NAA/choline ratios continued to correlate with outcome (p < 0.05). At the chronic stage, persistent lactate/choline ratio elevation strongly correlated with outcome measures (r = 0.71 to 0.87). CONCLUSION: Lactate/choline ratio measured in the acute infarct core by 1H MRS improves the prediction of stroke outcome and provides prognostic information complementary to DWI. Lactate/choline ratio could be used as an additional marker to select patients for acute and chronic therapies.     

Where (in the brain) do semantic errors come from?

Background

Semantic errors result from the disruption of access either to semantics or to lexical representations. One way to determine the origins of these errors is to evaluate comprehension of words that elicit semantic errors in naming. We hypothesized that in acute stroke there are different brain regions where dysfunction results in semantic errors in both naming and comprehension versus those with semantic errors in oral naming alone.

Methods

A consecutive series of 196 patients with acute left hemispheric stroke who met inclusion criteria were evaluated with oral naming and spoken word/picture verification tasks and magnetic resonance imaging within 48 h of stroke onset. We evaluated the relationship between tissue dysfunction in 10 pre-specified Brodmann's areas (BA) and the production of coordinate semantic errors resulting from (1) semantic deficits or (2) lexical access deficits.

Results

Semantic errors arising from semantic deficits were most associated with tissue dysfunction/infarct of left BA 22. Semantic errors resulting from lexical access deficits were associated with hypoperfusion/infarct of left BA 37.

Conclusion

Our study shows that semantic errors arising from damage to distinct cognitive processes reflect dysfunction of different brain regions.     

Differential patterns of evolution in acute middle cerebral artery infarction with perfusion-diffusion mismatch: atherosclerotic vs. cardioembolic occlusion

BACKGROUND: An acute perfusion-diffusion mismatch is known to be the strongest predictor of infarct growth. However, the differential patterns of clinical and radiological evolution according to stroke mechanism are unknown. METHODS: The study retrospectively reviewed consecutive patients who had 1) acute middle cerebral artery (MCA) territory infarction, 2) diffusion- and perfusion-weighted imaging (DWI and PWI) and MR angiography within 24 h of onset, and follow-up DWI 5 days later, 3) stenosis (>/=50%) or occlusion of MCA on baseline imaging, 4) a baseline PWI-DWI mismatch >20%, and 5) either atherosclerotic MCA disease (MCAD) or cardioembolism (CE). National Institutes of Health Stroke Scale (NIHSS) scores and infarct volume at baseline and 5 days were obtained. RESULTS: Of 90 patients, 52 had MCAD and 38 had CE. At baseline, CE group had more severe stroke (median NIHSS, 9 vs. 5; p=0.001) and larger infarct volume (median 8.32 cc vs. 3.0 cc; p=0.034) than MCAD group. During the 1-week period, CE group had larger infarct volume growth (median 12.85 cc vs. 3.02 cc; p=0.004) than MCAD group, although clinical improvement based on NIHSS (baseline minus 5-day) tended to be higher for CE than MCAD group (median 3 vs. 1; p=0.08). The correlation between infarct volume and NIHSS score was stronger in CE (r=0.841) compared to MCAD (r=0.582) group at 5-day. CONCLUSIONS: Substantial differences in the clinico-radiological evolution of acute ischemic stroke exist according to stroke mechanism. These data emphasize the importance of the stroke mechanism in the design of MRI-based acute stroke trials.     

Cerebral blood flow in patients with various symptoms of hemispatial neglect following ischemic stroke

BACKGROUND AND PURPOSE: The most common cause of hemispatial neglect (HN) is cerebral infarction. It can be induced by lesions in many different regions of the right hemisphere. The purpose of this article was to determine the prevalence of post-stroke HN, its clinical picture, and neuroanatomical correlates. MATERIAL AND METHODS: Forty-six stroke patients with a focal right-hemisphere lesion were studied. Neglect in visual domain, assessed with a battery of drawing, line bisection and shape cancellation tests, was observed in 20 cases. The single-photon emission-computed tomography (SPECT) images of the brain were obtained with 740 MBq (20 mCi) of Tc-99m-labeled ECD on a triple-headed gamma camera. RESULTS: The most sensitive measure of HN was the cancellation test, which all neglect patients performed poorly. Twelve patients, classified as mildly impaired, showed no significant rightward deviation on line bisection, but they showed left visual neglect on the cancellation test. Reverse dissociation was not noted. Performance on a clock-drawing test revealed HN only in two patients, who showed also evidence of HN on other tests. Thereby, some of the tests seem to be more difficult or more sensitive to impairment. The critical area of perfusion abnormalities in all neglect patients were frontal lobe and striatum on the right. In severe HN, SPECT images evidenced the most extensive hypoperfusion throughout the perisylvian region and subcortical structures of the right hemisphere. Although parietal cortex was affected in patients with moderate to severe HN, it was spared in the rest. CONCLUSIONS: HN was a relatively common symptom of vascular right-hemisphere damage (43% of the patient population). HN was a complex disturbance in terms of its clinical manifestation and neuroimaging correlates. Our findings challenge the classical notion that damage to the parietal cortex is critically associated with HN. Instead, our results support the model attributing hemispatial neglect to a defect in a cortico-striato-thalamo-cortical loop. Also, the present study highlights the usefulness of cerebral blood flow SPECT imaging as a diagnostic aid in the post-stroke deficits of cognition following right-hemisphere damage.     

Dynamic functional cerebral blood volume responses to normobaric hyperoxia in acute ischemic stroke

Studies suggest that neuroprotective effects of normobaric oxygen (NBO) therapy in acute stroke are partly mediated by hemodynamic alterations. We investigated cerebral hemodynamic effects of repeated NBO exposures. Serial magnetic resonance imaging (MRI) was performed in Wistar rats subjected to focal ischemic stroke. Normobaric oxygen-induced functional cerebral blood volume (fCBV) responses were analyzed. All rats had diffusion-weighted MRI (DWI) lesions within larger perfusion deficits, with DWI lesion expansion after 3 hours. Functional cerebral blood volume responses to NBO were spatially and temporally heterogeneous. Contralateral healthy tissue responded consistently with vasoconstriction that increased with time. No significant responses were evident in the acute DWI lesion. In hypoperfused regions surrounding the acute DWI lesion, tissue that remained viable until the end of the experiment showed relative preservation of mean fCBV at early time points, with some rats showing increased fCBV (vasodilation); however, these regions later exhibited significantly decreased fCBV (vasoconstriction). Tissue that became DWI abnormal by study-end initially showed marginal fCBV changes that later became moderate fCBV reductions. Our results suggest that a reverse-steal hemodynamic effect may occur in peripheral ischemic zones during NBO treatment of focal stroke. In addition, CBV responses to NBO challenge may have potential as an imaging marker to distinguish ischemic core from salvageable tissues.     

Association of ischemic lesion patterns on early diffusion-weighted imaging with TOAST stroke subtypes

BACKGROUND: Different topographic patterns in patients who experience an acute ischemic stroke may be related to specific stroke causes. OBJECTIVE: To determine if lesion patterns on early diffusion-weighted imaging (DWI) are associated with stroke subtypes determined by the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. DESIGN: Cross-sectional study. SETTING: General community hospital.Patients We studied 172 consecutive ischemic stroke patients with a symptomatic lesion on DWI performed within 24 hours of stroke onset. MAIN OUTCOME MEASURES: Lesion patterns on DWI were classified into single lesions (corticosubcortical, cortical, subcortical > or =15 mm, or subcortical <15 mm), scattered lesions in one vascular territory (small scattered lesions or confluent with additional lesions), and multiple lesions in multiple vascular territories (in the unilateral anterior circulation, in the posterior circulation, in bilateral anterior circulations, or in anterior and posterior circulations). RESULTS: We found an overall significant relationship between DWI lesion patterns and TOAST stroke subtypes (P<.001). Corticosubcortical single lesions (P =.01), multiple lesions in anterior and posterior circulations (P =.03), and multiple lesions in multiple cerebral circulations (P =.008) were associated with cardioembolism. Multiple lesions in the unilateral anterior circulation (P =.04) and small scattered lesions in one vascular territory (P =.06) were related to large-artery atherosclerosis. Nearly half (11/23) of the patients with a single subcortical lesion that was 15 mm or larger were classified as having cryptogenic strokes (P =.001), although 9 of these patients had a classic lacunar syndrome without cortical hypoperfusion. CONCLUSIONS: Early DWI lesion patterns are associated with specific stroke causes. Conventional 15-mm criteria for lacunes, however, may underestimate the diagnosis of small-vessel occlusion with DWI.     

Prior antiplatelet use and infarct volume in ischemic stroke

BACKGROUND: Conflicting data exist on the role of antiplatelet agents in reducing incident ischemic stroke magnitude, but most prior studies used clinically-assessed neurologic deficit as the index of stroke extent rather than more precise volumetric measurements of infarct size. We assessed the relation of premorbid antiplatelet use to initial diffusion-weighted MRI (DWI) lesion volumes among acute ischemic stroke patients. METHODS: Consecutive patients presenting within 24 h of ischemic stroke over an 18-month period were studied. DWI lesions were outlined using a semi-automated threshold technique. Subjects were categorized into two groups: antiplatelet (AP) or no antithrombotic (NA). The relationship between prestroke antithrombotic status and DWI infarct volumes was examined using multivariate quantile regression. RESULTS: One hundred sixty-six individuals met study criteria: 75 AP and 91 NA patients. Median DWI volume was lower in the AP group than in the NA group (1.5 cc vs. 5.4 cc, p=0.031). A multivariable model (adjusting for age, history of transient ischemic attack, admission temperature, admission blood pressure, admission serum glucose, stroke onset to imaging interval, stroke mechanism, premorbid statin and antihypertensive use) demonstrated smaller infarcts in the AP vs. NA group (adjusted volume difference: -1.3 cc, 95% CI=-0.09, -2.5, p=0.037). Prior statin use, no history of TIA, large vessel atherosclerosis and microvascular ischemic disease stroke mechanism were also independently associated with reduced infarct volume. CONCLUSIONS: Prior antiplatelet treatment is independently associated with reduced cerebral infarct volume among acute ischemic stroke patients. Premorbid statin use, TIA history and stroke mechanism also predict infarct volume in ischemic stroke.