Acute Diffusion-weighted Imaging Lesion Research Articles

Predictors of Early Neurological Improvement and Its Relationship to Thrombolysis Treatment and Long-Term Outcome in the WAKE-UP Study

Introduction: The aims of this study were to evaluate the relationship of clinical and imaging baseline factors and treatment on the occurrence of early neurological improvement (ENI) in the WAKE-UP trial of MRI-guided intravenous thrombolysis in unknown onset stroke and to examine the association of ENI with long-term favorable outcome in patients treated with intravenous thrombolysis. Methods: We analyzed data from all patients with at least moderate stroke severity, reflected by an initial National Institutes of Health Stroke Scale (NIHSS) score ≥4 randomized in the WAKE-UP trial. ENI was defined as a decrease in NIHSS of ≥8 or a decline to zero or 1 at 24 h after initial presentation to the hospital. Favorable outcome was defined as a modified Rankin Scale score of 0–1 at 90 days. We performed group comparison and multivariable analysis of baseline factors associated with ENI and performed mediation analysis to evaluate the effect of ENI on the relationship between intravenous thrombolysis and favorable outcome. Results: ENI occurred in 93 out of 384 patients (24.2%) and was more likely to occur in patients who received treatment with alteplase (62.4% vs. 46.0%, p = 0.009), had smaller acute diffusion-weighted imaging lesion volume (5.51 mL vs. 10.9 mL, p ≤ 0.001), and less often large-vessel occlusion on initial MRI (7/93 [12.1%] versus 40/291 [29.9%], p = 0.014). In multivariable analysis, treatment with alteplase (OR 1.97, 95% confidence interval [CI] 0.954–1.100), lower baseline stroke volume (OR 0.965, 95% CI: 0.932–0.994), and shorter time from symptom recognition to treatment (OR 0.994, 95% CI: 0.989–0.999) were independently associated with ENI. Patients with ENI had higher rates of favorable outcome at 90-day follow-up (80.6% vs. 31.3%, p ≤ 0.001). The occurrence of ENI significantly mediated the association of treatment with a good outcome, with ENI at 24 h explaining 39.4% (12.9–96%) of the treatment effect. Conclusion: Intravenous alteplase increases the odds of ENI in patients with at least moderate stroke severity, especially when given early. In patients with large-vessel occlusion, ENI is rarely observed without thrombectomy. ENI represents a good surrogate early marker of treatment effect as more than a third of good outcome at 90 days is explained by ENI at 24 h.

Incidental DWI Lesions in Patients with Recent Small Subcortical Infarctions

ObjectivesIncidental acute ischemic lesions distinct from the primary neurological insult are identified on diffusion-weighted imaging (DWI) in a number of conditions where cerebral microvascular pathology plays a central role. Another major manifestation of cerebral small vessel disease (CSVD) is ischemic stroke named as recent small subcortical infarction (RSSI). In this study, we sought to identify the prevalence and predictors of incidental DWI lesions in patients with RSSI. Materials and MethodsWe retrospectively analyzed a consecutive series of acute ischemic stroke patients with DWI evidence of acute lesions solely localized to perforator artery territories. Images were evaluated for the presence of additional acute or subacute subcortical DWI lesions, apart from the symptomatic lesion. Clinical features including vascular risk factor burden, together with imaging markers of chronic CSVD, were compared among patients with and without incidental acute or subacute lesions. ResultsAmong 396 patients with no alternate stroke etiology additional incidental subcortical DWI bright lesions were identified in 74 (19%) cases. These lesions were primarily localized in the corona radiata, or centrum semiovale. Patients with incidental DWI lesions were more likely to have a history of hypertension, a higher white matter hyperintensities burden in the periventricular and subcortical region, higher perivascular spaces burden in the basal ganglia, multiple cerebral microbleeds, and multiple chronic lacunes. Presence of multiple chronic lacunes (OR 5.98, 95% CI 3.18-11.24) and ≥2 vascular risk factors (OR 2.03, 95% CI 1.05-3.91) stood out as features significantly associated with incidental DWI lesions in multivariate analysis. ConclusionsOur study shows that acute or subacute ischemic lesions can be incidentally detected in approximately one-fifth of patients with RSSI. This observation suggests that the course of CSVD might be more active, temporally and spatially, in a distinct subgroup of RSSI patients, specifically those with a higher chronic lacune and vascular risk factor burden.

Dysphasia is associated with diffusion-weighted MRI abnormalities in patients with transient neurological symptoms

BackgroundThe clinical characteristics of diffusion-weighted imaging (DWI) abnormalities after transient neurological symptoms are of great significance for the early diagnosis and urgent intervention of transient ischemic attack (TIA). This study was aimed to investigate the clinical characteristics associated with acute DWI lesions in transient neurological symptoms.MethodsWe retrospectively recruited 302 patients with transient neurological symptoms. According to DWI findings, they were divided into DWI positive and DWI negative group. The clinical characteristics and the TIA-related scores such as ABCD2, ABCD3, ABCD3I, Dawson score, and the Diagnosis of TIA (DOT) score were compared between the two groups. Logistic regression analysis and receiver operating characteristic curves were used to identify the independent factors and compare the predictive value of different TIA scores for acute DWI lesions.ResultsA total of 302 patients were enrolled in this study. The mean age was 61.8 years, and 67.2% were male. We found 89 (29.5%) patients with DWI positivity. Logistic regression analysis showed the characteristic associated with DWI lesions was dysphasia (OR 2.226, 95% CI 1.220–4.062). The area under the curve for Dawson score and the DOT score was 0.610 (95% CI 0.543–0.678) and 0.625 (95% CI 0.559–0.691), respectively.ConclusionWe found that DWI lesions were detected in 29.5% of patients with transient neurological symptoms and were associated with dysphasia. Dawson score and DOT score could have a higher predictability of DWI lesions in patients with transient neurological symptoms.

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial.

Background and Purpose- Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods- FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results- FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions- In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.

Incidence and Predictors of Acute Ischemic Lesions on Brain Magnetic Resonance Imaging in Patients With a Clinical Diagnosis of Transient Ischemic Attack in China.

Background: The associations between the clinical characteristics and diffusion-weighted imaging (DWI) positivity in patients with a clinical diagnosis of transient ischemic attack (TIA) are still poorly understood. The purpose of our study was to determine the incidence of TIA related acute infarction by DWI, and to determine the underlying predictors of DWI positivity in TIA patients.Methods: Between Jan 2017 and Dec 2018, we retrospectively enrolled 430 patients with a clinical diagnosis of TIA who underwent DWI. Patients were divided into those with acute ischemic lesions (DWI positive group) and those without (DWI negative group). The clinical characteristics, laboratory data, and imaging parameters were compared between the two groups.Results: A total of 430 time-based TIA patients (mean age, 61.4 ± 13.0) were enrolled in this study. About 126 (29.3%) of TIA patients had a DWI positive lesion in our series. Comparing TIA patients with positive DWI to those with negative DWI, acute lesions were more likely to be more male, have higher hyperlipidemia and a smoking history, more speech abnormalities and increased motor weakness; and higher systolic and diastolic blood pressure, homocysteine, fasting blood glucose, and the scores of ABCD2, ABCD3, ABCD3-I, and Dawson. Several independent predictors of DWI positivity were identified with logistic regression analysis: motor weakness (odds ratio 4.861, P = 0.021), speech abnormalities (odds ratio 4.029, P = 0.024), and ABCD3-I (odds ratio 13.141, P = 0.001). ABCD3-I showed the greatest area under the ROC curve, with a sensitivity of 85.7% and specificity of 72.4%.Conclusion: In patients with a clinical diagnosis of TIA, 29.3% demonstrated acute DWI lesions on brain magnetic resonance imaging (MRI). They were associated with motor weakness, speech abnormalities and higher ABCD3-I score at admission.

Small cortical grey matter lesions show no persistent infarction in transient ischaemic attack? A prospective cohort study

ObjectivesTo find determining factors for persistent infarction signs in patients with transient ischaemic attack (TIA), herein initial diffusion lesion size, visibility on apparent diffusion coefficient (ADC) or fluid-attenuated inversion recovery...

White matter hyperintensity volume predicts persistent cognitive impairment in transient ischemic attack and minor stroke.

Background Temporary and permanent cognitive changes following transient ischemic attack/minor stroke have been described previously. It is unknown if persisting cognitive deficits in these patients are correlated with acute infarction identified using magnetic resonance imaging. Aims We tested the hypothesis that persistent cognitive impairment after transient ischemic attack/minor stroke can be predicted by the volume of diffusion-weighted imaging lesions. Methods Acute transient ischemic attack/minor stroke (NIH stroke scale score ≤ 3) patients were prospectively recruited within 72 h of onset. Patients underwent Montreal cognitive assessment and magnetic resonance imaging, including diffusion-weighted imaging and Fluid-Attenuated Inverse Recovery sequences, at baseline, days 7 and 30. Cognitive testing was repeated at day 90. Diffusion-weighted imaging lesion and Fluid-Attenuated Inverse Recovery chronic white matter hyperintensity volumes were measured planimetrically. Cognitive impairment was defined a priori as Montreal cognitive assessment score < 26. Results One hundred fifteen patients were imaged at a median (inter-quartile range) of 24.0 (16.6) h after onset. Acute ischemic lesions were present in 91 (79%) patients. Cognitive impairment rates were similar in patients with (47/91, 52%) and without diffusion-weighted imaging lesions (13/24, 54%; p = 0.83). Although linear regression indicated no relationship between acute diffusion-weighted imaging lesion volume and day 30 Montreal cognitive assessment scores (β = -0.163, [-2.243, 0.334], p = 0.144), white matter hyperintensity volumes at baseline were predictive of persistent cognitive deficits after 30 days (β = 2.24, [1.956, 45.369], p = 0.005). Conclusions In most transient ischemic attack/minor stroke patients who suffer acute cognitive impairment post event, deficits are temporary. Deficits after 30 days of onset are correlated with chronic white matter hyperintensity, suggesting subclinical cognitive impairment and/or impaired ability to compensate for the effects of acute ischemic infarcts.

Fluid-Attenuated Inversion Recovery Vascular Hyperintensity Topography, Novel Imaging Marker for Revascularization in Middle Cerebral Artery Occlusion.

In acute arterial occlusion, fluid-attenuated inversion recovery vascular hyperintensity (FVH) has been linked to slow flow in leptomeningeal collaterals and cerebral hypoperfusion, but the impact on clinical outcome is still controversial. In this study, we aimed to investigate the association between FVH topography or FVH-Alberta Stroke Program Early CT Score (ASPECTS) pattern and outcome in acute M1-middle cerebral artery occlusion patients with endovascular treatment. We included acute M1-middle cerebral artery occlusion patients treated with endovascular therapy (ET). All patients had diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery before ET. Distal FVH-ASPECTS was evaluated according to distal middle cerebral artery-ASPECT area (M1-M6) and acute DWI lesion was also reviewed. The presence of FVH inside and outside DWI-positive lesions was separately analyzed. Clinical outcome after ET was analyzed with respect to different distal FVH-ASPECTS topography. Among 101 patients who met inclusion criteria for the study, mean age was 66.2±17.8 years and median National Institutes of Health Stroke Scale was 17.0 (interquartile range, 12.0-21.0). FVH-ASPECTS measured outside of the DWI lesion was significantly higher in patients with good outcome (modified Rankin Scale [mRS] score of 0-2; 8.0 versus 4.0, P<0.001). Logistic regression demonstrated that FVH-ASPECTS outside of the DWI lesion was independently associated with clinical outcome of these patients (odds ratio, 1.3; 95% confidence interval, 1.06-1.68; P=0.013). FVH-ASPECTS inside the DWI lesion was associated with hemorrhagic transformation (odds ratio, 1.3; 95% confidence interval, 1.04-1.51; P=0.019). Higher FVH-ASPECTS measured outside the DWI lesion is associated with good clinical outcomes in patients undergoing ET. FVH-ASPECTS measured inside the DWI lesion was predictive of hemorrhagic transformation. The FVH pattern, not number, can serve as an imaging selection marker for ET in acute middle cerebral artery occlusion.

Frequency and predictors of acute ischaemic lesions on brain magnetic resonance imaging in young patients with a clinical diagnosis of transient ischaemic attack.

Acute lesions in patients with transient ischaemic attack (TIA) are important as they are associated with increased risk for recurrence. Characteristics associated with acute lesions in young TIA patients were therefore investigated. The sifap1 study prospectively recruited a multinational European cohort (n = 5023) of patients aged 18-55 years with acute cerebrovascular event. The detection of acute ischaemic lesions was based on diffusion-weighted imaging (DWI). The frequency of DWI lesions was assessed in 829 TIA patients who met the criteria of symptom duration <24 h and their association with demographic, clinical and imaging variables was analysed. The median age was 46 years (interquartile range 40-51 years); 45% of the patients were female. In 121 patients (15%) ≥1 acute DWI lesion was detected. In 92 patients, DWI lesions were found in the anterior circulation, mostly located in cortical-subcortical areas (n = 63). Factors associated with DWI lesions in multiple regression analysis were left hemispheric presenting symptoms [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.27-2.91], dysarthria (OR 2.17, 95% CI 1.38-3.43) and old brain infarctions on MRI (territories of the middle and posterior cerebral artery: OR 2.43, 95% CI 1.42-4.15; OR 2.41, 95% CI 1.02-5.69, respectively). In young patients with a clinical TIA 15% demonstrated acute DWI lesions on brain MRI, with an event pattern highly suggestive of an embolic origin. Except for the association with previous infarctions there was no clear clinical predictor for acute ischaemic lesions, which indicates the need to obtain MRI in young individuals with TIA.

Enlarged perivascular spaces and small diffusion-weighted lesions in intracerebral hemorrhage.

To examine the association between enlarged perivascular spaces (EPVS) and the prevalence and extent of small acute diffusion-weighted imaging (DWI) lesions (SA-DWIL) in patients with spontaneous supratentorial intracerebral hemorrhage (ICH). We conducted a retrospective review of a consecutive cohort of 201 patients with spontaneous supratentorial ICH who had brain MRI with DWI within 1 month of ICH onset. We compared the clinical and imaging characteristics, including EPVS, of patients with and without SA-DWIL. We used univariate and multivariate logistic regression analyses to determine the variables associated with SA-DWIL. Small acute DWI lesions were detected in 27.9% (n = 56) of patients. Intraventricular and subarachnoid extension of ICH (p ≤ 0.001), high centrum semiovale (CSO)-EPVS (p < 0.001), high basal ganglia-EPVS (p = 0.007), overall extent of white matter hyperintensity (p = 0.018), initial ICH volume (p < 0.001), and mean change in mean arterial blood pressure (δ MAP = MAP at admission - the lowest MAP before MRI scan) (p = 0.027) were associated with SA-DWIL on univariate analyses. On multivariate logistic regression analyses, larger ICH volume (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.01-1.06; p = 0.006) and high CSO-EPVS (OR 12.56; 95% CI 4.40-35.85; p < 0.001) were independently associated with the presence of SA-DWIL. In our cohort, high EPVS, in particular CSO-EPVS, and larger hematoma volume emerged as independent predictors for SA-DWIL after ICH. Our findings might provide a new explanation for the pathophysiologic mechanisms predisposing to SA-DWIL after ICH.

Acute diffusion-weighted imaging lesion patterns predict progressive small subcortical infarct in the perforator territory of the middle cerebral artery.

Single small subcortical infarct (SSSI) is generally considered to have a fair outcome. However, early neurological deterioration (END), a relatively unfavorable clinical course occurring during the acute phase of infarction, is not uncommon. The aim of this study was to investigate the relationship between lesion patterns detected by diffusion-weighted imaging (DWI) and the presence of END in patients with acute SSSI in the perforator territory of the middle cerebral artery (MCA). Three hundred twelve patients with acute SSSI in the perforator territory of MCA were prospectively recruited from Jinling Hospital between January 2010 and May 2013. Acute DWI lesion patterns were classified as proximal SSSI (pSSSI) or distal SSSI (dSSSI) patterns, according to the relationship between lesion location and the parent artery. Neurological deficits were evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and continued over the following 72 h 1-3 times a day. END was defined as an increase in NIHSS score ≥ 2 points during the first 72 h after admission. Of the total 312 patients, the pSSSI pattern was found in 139 (44.55%) patients and the dSSSI pattern in 173 (55.45%) patients. Statistical analysis suggested that the indicators for small-artery disease (hypertension and leukoaraiosis) and atherosclerosis (diabetes mellitus and cerebral atherosclerosis) significantly differed according to lesion patterns (P < 0.05). During hospitalization, 88 (28.21%) patients experienced END. Univariate analysis revealed that female sex (P = 0.004), pSSSI pattern (P < 0.001), initial NIHSS (P = 0.001), lesion diameter (P = 0.005), ipsilateral large-artery stenosis (P = 0.008), and concomitant intracranial atherosclerotic stenosis (P = 0.021) were significantly associated with END. After adjusting for confounding factors, pSSSI pattern was an independent predictor of END (OR 1.871, 95% CI 1.095-3.198, P = 0.022). In the further subgroup analysis of patients with different etiologies, pSSSI pattern was found to be independently associated with END in patients with large-artery atherosclerosis (OR 3.593, 95% CI 1.268-11.057, P = 0.026) and in patients with small-artery disease (OR 2.523, 95% CI 1.121-5.676, P = 0.025), but not in patients with cardioembolism (OR 0.854, 95% CI 0.147-4.953, P = 0.861). pSSSI pattern was closely related to END in acute SSSI caused by large-artery atherosclerosis and small-artery disease in the perforator territory of the MCA.

A simple brain atrophy measure improves the prediction of malignant middle cerebral artery infarction by acute DWI lesion volume

In patients with malignant middle cerebral artery infarction (MMI) decompressive surgery within 48 h improves functional outcome. In this respect, early identification of patients at risk of developing MMI is crucial. While the acute diffusion weighted imaging (DWI) lesion volume was found to predict MMI with high predictive values, the potential impact of preexisting brain atrophy on the course of space-occupying middle cerebral artery (MCA) infarction and the development of MMI remains unclear. We tested the hypothesis that the combination of the acute DWI lesion volume with simple measures of brain atrophy improves the early prediction of MMI. Data from a prospective, multicenter, observational study, which included patients with acute middle cerebral artery main stem occlusion studied by MRI within 6 h of symptom onset, was analyzed retrospectively. The development of MMI was defined according to the European randomized controlled trials of decompressive surgery. Acute DWI lesion volume, as well as brain and cerebrospinal fluid volume (CSF) were delineated. The intercaudate distance (ICD) was assessed as a linear brain atrophy marker by measuring the hemi-ICD of the intact hemisphere to account for local brain swelling. Binary logistic regression analysis was used to identify significant predictors of MMI. Cut-off values were determined by Classification and Regression Trees analysis. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the resulting models were calculated. Twenty-one (18 %) of 116 patients developed a MMI. Malignant middle cerebral artery infarctions patients had higher National Institutes of Health Stroke Scale scores on admission and presented more often with combined occlusion of the internal carotid artery and MCA. There were no differences in brain and CSF volume between the two groups. Diffusion weighted imaging lesion volume was larger (p < 0.001), while hemi-ICD was smaller (p = 0.029) in MMI patients. Inclusion of hemi-ICD improved the prediction of MMI. Best cut-off values to predict the development of MMI were DWI lesion volume > 87 ml and hemi-ICD ≤ 9.4 mm. The addition of hemi-ICD to the decision tree strongly increased PPV (0.93 vs. 0.70) resulting in a reduction of false positive findings from 7/23 (30 %) to 1/15 (7 %), while there were only slight changes in specificity, sensitivity and NPV. The absolute number of correct classifications increased by 4 (3.4 %). The integration of hemi-ICD as a linear marker of brain atrophy, that can easily be assessed in an emergency setting, may improve the prediction of MMI by lesion volume based predictive models.

Is White Matter More Prone to Diffusion Lesion Reversal After Thrombolysis?

In acute ischemic stroke, white matter (WM) is considered more resistant to infarction than gray matter (GM). To test this hypothesis, we compared the fate of WM and GM voxels belonging to the acute diffusion-weighted imaging (DWI) lesion, expecting WM voxels to be more prone to reversal after thrombolysis. Reversible acute DWI (RAD) lesion was defined voxel-wise as an acute lesion on initial DWI (DWI1) with no visible lesion on 24-hour DWI (DWI2). Only patients with RAD lesions >10 mL and >10% of DWI1 from our previously reported cohort were eligible. The core was defined as voxels hyperintense on DWI1 and DWI2. Semiautomated segmentation of DWI1, core, and RAD lesions, normalization into standard space, and WM/GM segmentation allowed calculations of WM/GM proportions in each region of interest using a voxel-counting algorithm. Thirty patients were eligible (RAD lesion median volume [interquartile range], 23.3 mL [19.1-35.0 mL]; onset-to-treatment time, 134 minutes [105-185 minutes]). WM voxels fraction was greater in RAD lesions than in the core (59.4% [52.8%-68.9%] versus 49.6% [43.0%-57.5%]; P=0.011). The proportion of reversibility was greater for WM than for GM voxels (60.8% [25.5%-88.7%] versus 53.5% [21.1%-77.3%]; P=0.02). The percentage of RAD lesions increased with the proportion of WM present in the acute DWI lesion (P<0.0001; R=0.67). Acute DWI lesions predominantly involving WM may be more prone to reversal and, hence, to respond to therapy than their GM counterparts.

Abstract T P35: Baseline Diffusion Weighted Imaging Lesion Volume Predicts Disappearance of Infarct on Fluid Attenuated Inverse Recovery Sequences Within 30 Days of TIA/Minor Stroke

Introduction: Evidence of infarction on MRI is predictive of early stroke recurrence after TIA/minor stroke. It has recently been reported that diffusion-weighted imaging (DWI) changes are not associated with evidence of infarction on Fluid Attenuated Inverse Recovery (FLAIR) sequences 90 days later in 30% of patients. We completed a serial MRI study to determine the time course of infarct resolution. We tested the hypothesis that acute DWI lesion volume predicts infarct disappearance by 30 days. Methods: Acute TIA/minor stroke patients (NIHSS≤3) were prospectively imaged at baseline, 7 and 30 days after symptom onset. Lesion volumes were measured planimetrically by a blinded rater at each time point on DWI and FLAIR sequences. Mean and relative (to contralateral tissue) Apparent Diffusion Coefficient ((r)ADC) values were also calculated. Results: Acute DWI lesions were found in 94/172 patients. Median time between symptom onset and baseline MRI was 20.9(19.3) h. DWI volume decreased from baseline (1.51 ml (4.36)) at 7 days (1.13 ml (2.96), P =0.001) and at 30 days (0.40 ml (0.97), P &lt;0.0001). DWI lesions at 7 days pseudo-normalized (infarct visible on FLAIR) in 3.4% and resolved without evidence of infarction in 8% of patients. Seventy-seven (82%) patients had persistent lesions on FLAIR at 30 days (FLAIR+). Baseline NIHSS scores were similar between FLAIR+ (1.40±1.21) and FLAIR– patients (1.18±1.19, P =0.64). Baseline rADC was similar in FLAIR+ (0.84(0.17)) and FLAIR– patients (0.89(0.21), P =0.155). Baseline DWI volumes were larger in FLAIR+ (2.08 ml (6.9)) than FLAIR– patients (0.69 ml (0.95), P =0.007). ROC analysis indicated that a baseline DWI volume &lt;2.04 ml predicted absence of FLAIR lesion at 30 days with a specificity of 100% and sensitivity of 50.6%. Good functional outcome (modified Rankin Score ≤2) at 90 days was similar in FLAIR+ (54/62, 87%) and FLAIR– patients (12/12, 100%, P =0.339). Conclusion: Acute DWI lesions are transient and not always associated with visible infarction on FLAIR, even as early as 7 days after symptom onset. Delaying MRI results in a failure to demonstrate evidence of infarction in the majority of patients, particularly those with DWI lesion volumes below 2 ml.

Diffusion‐weighted imaging and diagnosis of transient ischemic attack

ObjectiveMagnetic resonance (MR) diffusion-weighted imaging (DWI) is sensitive to small acute ischemic lesions and might help diagnose transient ischemic attack (TIA). Reclassification of patients with TIA and a DWI lesion as “stroke” is under consideration. We assessed DWI positivity in TIA and implications for reclassification as stroke.MethodsWe searched multiple sources, without language restriction, from January 1995 to July 2012. We used PRISMA guidelines, and included studies that provided data on patients presenting with suspected TIA who underwent MR DWI and reported the proportion with an acute DWI lesion. We performed univariate random effects meta-analysis to determine DWI positive rates and influencing factors.ResultsWe included 47 papers and 9,078 patients (range = 18–1,693). Diagnosis was by a stroke specialist in 26 of 47 studies (55%); all studies excluded TIA mimics. The pooled proportion of TIA patients with an acute DWI lesion was 34.3% (95% confidence interval [CI] = 30.5–38.4, range = 9–67%; I2 = 89.3%). Larger studies (n > 200) had lower DWI-positive rates (29%; 95% CI = 23.2–34.6) than smaller (n < 50) studies (40.1%; 95% CI = 33.5–46.6%; p = 0.035), but no other testable factors, including clinician speciality and time to scanning, reduced or explained the 7-fold DWI-positive variation.InterpretationThe commonest DWI finding in patients with definite TIA is a negative scan. Available data do not explain why ⅔ of patients with definite specialist-confirmed TIA have negative DWI findings. Until these factors are better understood, reclassifying DWI-positive TIAs as strokes is likely to increase variance in estimates of global stroke and TIA burden of disease. ANN NEUROL 2014;75:67–76

Ischemic Volumes and Early Neurologic Deterioration in Acute Brainstem Infarctions with Hemoglobin A1c

Aim: To investigate the association of hemoglobin A_1c (HbA_1c) with acute diffusion-weighted imaging lesion volumes (DIV) and early neurologic deterioration (END) in brainstem infarctions (BSIs). Methods: 152 patients with acute BSIs were included in this study. The relationship between HbA_1c and DIV quartiles was examined. Data considered potentially associated with HbA_1c and END after admission and patients' symptomatic changes prior to admission were collected. Results: There was a significant correlation between HbA_1c (%) and DIV (Spearman ρ = 0.201, p = 0.013). The median HbA_1c (%) values for successive DIV quartiles (lowest to highest quartile) were as follows: 5.90, 6.35, 6.25, and 7.50 (p = 0.033). The incidence of diabetes mellitus had a significant association with DIV quartiles (p = 0.042). HbA_1c was significantly associated with symptomatic progression prior to admission (p = 0.015). 29 patients developed END after admission. Age, HbA_1c, systolic blood pressure, and fibrinogen were significantly associated with END. On logistic regression analysis, HbA_1c and fibrinogen proved to be independent variables. Conclusions: HbA_1c may be a possible predictor for ischemic severity, early deterioration of acute BSIs, and short-term prognosis. Long-term good glycemic control is very important in BSIs. Further studies are warranted to confirm these results.

Combining Magnetic Resonance Imaging within Six-Hours of Symptom Onset with Clinical Follow-Up at 24 h Improves Prediction of ‘malignant’ Middle Cerebral Artery Infarction

A large diffusion-weighted imaging lesion ≤six-hours of symptom onset was found to predict the development of 'malignant' middle cerebral artery infarction with high specificity, positive predictive value, and negative predictive value, but sensitivity was low. We tested the hypothesis that sensitivity can be improved by adding information from clinical follow-up examination after 24 h. We analyzed data from a prospective, multicenter, observational cohort study of patients with acute ischemic stroke and middle cerebral artery occlusion studied by stroke magnetic resonance imaging ≤six-hours of symptom onset. We used the National Institutes of Health Stroke Scale to assess severity of symptoms after 24 h. We used the Classification and Regression Trees analysis to define the optimal thresholds of diffusion-weighted imaging lesion volume and the National Institutes of Health Stroke Scale after 24 h in patients developing 'malignant' middle cerebral artery infarction. We calculated sensitivity, specificity, positive predictive value, and negative predictive value for two simple predictive models based on acute diffusion-weighted imaging lesion volume alone and acute diffusion-weighted imaging lesion volume together with the National Institutes of Health Stroke Scale after 24 h. Of 135 patients, 27 (20%) developed a 'malignant' middle cerebral artery infarction. The Classification and Regression Trees analysis identified acute diffusion-weighted imaging lesion ≥78 ml and the National Institutes of Health Stroke Scale score after 24 h ≥22 as optimal cut-offs. Inclusion of the National Institutes of Health Stroke Scale score after 24 h in a simple two-step decision tree increased sensitivity from 0·59 to 0·79, while specificity, positive predictive value, and negative predictive value remained largely unchanged. Clinical follow-up examination after 24 h helps identify patients at risk of 'malignant' middle cerebral artery infarction that are missed by predictive algorithms based on early diffusion-weighted imaging lesion volume alone.

Very Low Cerebral Blood Volume Predicts Parenchymal Hematoma in Acute Ischemic Stroke

Parenchymal hematoma (PH) may worsen the outcome of patients with stroke. The aim of our study was to confirm the relationship between the volume of very low cerebral blood volume (CBV) and PH using a European multicenter database (I-KNOW). A secondary objective was to explore the impact of early reperfusion and recanalization. The volume of cerebral tissue with CBV≤2.5th percentile of the normal hemisphere was calculated within the acute diffusion-weighted imaging lesion. Hemorrhagic transformation was assessed on day 2 MRI according to the European Cooperative Acute Stroke Study II criteria. Recanalization and reperfusion were assessed on 3-hour follow-up MRI. Of the 110 patients, hemorrhagic transformation occurred in 59 patients, including 7 PH. In univariate analysis, the acute National Institutes of Health Stroke Scale score (P=0.002), acute diffusion-weighted imaging lesion volume (P=0.02), and thrombolysis (P=0.03), but not very low CBV (P=0.52), were associated with hemorrhagic transformation. The volume of very low CBV was the only predictor of PH (P=0.007). Early reperfusion and recanalization had no influence on either hemorrhagic transformation or PH. Very low CBV was the only independent predictor of PH in patients with acute stroke.

The Relationship between Neurological Worsening and Lesion Patterns in Patients with Acute Middle Cerebral Artery Stenosis

Background: Intracranial atherosclerotic disease is one of the most common causes of ischemic stroke especially in Asians, Hispanics and blacks. Although middle cerebral artery (MCA) stenosis is increasingly being recognized with the advent of magnetic resonance angiography (MRA) or transcranial Doppler ultrasonography, few studies have focused on acute neurological worsening (NW) in patients with MCA stenosis. We investigated the relationship between NW and lesion patterns detected by diffusion-weighted imaging (DWI). Methods: We studied 44 consecutive patients out of a total of 2,863 consecutive patients who had symptomatic lesions in the territory of the MCA and in whom MRA and/or conventional angiography showed isolated MCA stenosis ≥50% in the MCA trunk. Acute DWI lesion patterns were classified as follows: (1) pial artery territory infarcts (PAI); (2) small cortical and/or subcortical infarcts (SCS); (3) deep penetrating artery territory infarcts (DPI); (4) cortical border zone infarcts (CBZ), and (5) internal border zone infarcts (IBZ). NW was defined as worsening by ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) during the first 7 days. Functional outcome was assessed by the modified Rankin Scale (mRS) at 3 months after stroke onset. Poor outcome was defined as ≥3 on the mRS. The severity of MCA stenosis on MRA was further categorized as 50-75% (moderate) and >75% or focal signal loss with the presence of distal MCA signal (severe). Results: There were 14 patients (31.8%) who showed NW and 16 patients (36.3%) who showed poor outcomes. Nine of the 14 patients with NW showed poor outcomes (64.2%). The most frequent lesions in the present study were SCS (n = 16, 36.3%), followed by IBZ (n = 12, 27.2%) and DPI (n = 11, 25.0%). Prevalence of IBZ was significantly higher in the group with NW compared to that without NW (p = 0.0081), while the prevalence of SCS, DPI, PAI and CBZ did not differ between the two groups. Logistic regression analysis showed significantly high age- and sex-adjusted odds ratios (ORs) for NW only for IBZ (OR 10.9, p = 0.0051). The degree of stenosis did not correlate with NW and lesion patterns. Conclusions: Only IBZ among various lesion patterns correlated strongly with NW. IBZ are considered to be more associated with hemodynamic compromise, while embolic pathogeneses contribute more to CBZ or SCS. Early interventional medical treatments such as thrombolytic or anti-platelet therapy or stenting should be considered in cases of IBZ in MCA stenosis.

Abstract TP439: Temporary Cognitive Impairment in Transient Ischemic Attack and Minor Stroke Patients is Predicted by Chronic White Matter Hyperintensity Volume

Background: Cognitive changes have been described in subacute TIA/minor stroke (TIA/MIS), but the temporal profile is unknown. We tested the hypothesis that TIA/MIS patients experience transient cognitive impairment, and that this can be predicted by Diffusion-Weighted Imaging (DWI) lesion volume. Methods: Acute TIA/MIS stroke (NIH stroke scale score ≤3) patients with no history of cognitive impairment were prospectively recruited within 72 h of onset. Patients underwent Montreal Cognitive Assessment (MoCA), Mini-Mental Status Examination (MMSE) and MRI, including DWI and Fluid-Attenuated Inverse Recovery (FLAIR) sequences, at baseline, days 7 and 30. DWI lesion and FLAIR chronic white matter hyperintensity (WMH) volumes were measured planimetrically. Results: Fifty patients (mean age 68 ±15.1 years) were imaged at a median (IQR) of 26.5 (28.5) h after onset. Cognitive impairment (scores ≤26) was detected more frequently with MoCA (31/50, 62%) than MMSE (13/50, 26%, p=0.009). Acute ischemic lesions (DWI) were present in 33 (66%) patients. Mean DWI volume at baseline was 4.5 ± 11.1ml. Patients with DWI lesions (22/33, 67%) had similar impairment rates as those without (9/17, 53%; p=0.34). Linear regression indicated no relationship between acute DWI lesion volume (log transformed) and baseline MoCA scores (β=0.028, 95% CI [-2.09, 2.44]). Impaired patients had larger WMH volumes (13.6 ± 21.9 ml) than unaffected patients (2.6 ± 3.2 ml, p=0.01). Log transformed WMH volumes were inversely predictive of baseline MoCA scores (β=-0.54, 95% CI [-7.84, -2.28]). Median MoCA scores improved over time (27(5) at day 7 and 28(5) at day 30). Patients with baseline impairment and an increase of ≥2 points on MoCA by day 30 were defined as reverters (N=20). DWI lesion frequency was similar in reverters and those with persisting impairment (75% vs 64%, p= 0.50), as was DWI (6.9 ±14.3 ml vs 1.2 ±1.9 ml; p= 0.113) and WMH lesion volume (17.0 ± 26.2 ml vs 8.1 ± 8.1 ml; p= 0.18). Conclusions: Most TIA/MIS patients have evidence of temporary acute cognitive impairment when assessed with MoCA. Deficits are correlated with chronic WMH, suggesting an unmasking of subclinical cognitive impairment. Temporary cognitive deficits should be considered in the management of TIA/MIS patients.