Charlotte Rosso

Leukoaraiosis Is a Risk Factor for Symptomatic Intracerebral Hemorrhage After Thrombolysis for Acute Stroke

Background and Purpose— The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke. Methods— In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3). Results— The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59; P=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9; P=0.03). Conclusions— LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.

Risk for symptomatic intracerebral hemorrhage after thrombolysis assessed by diffusion-weighted magnetic resonance imaging†

The risk for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment has not been evaluated in large studies using diffusion‐weighted imaging (DWI). Here, we investigated the relation between pretreatment DWI lesion size and the risk for sICH after thrombolysis.

Intensive Versus Subcutaneous Insulin in Patients With Hyperacute Stroke Results From the Randomized INSULINFARCT Trial

Background and Purpose— Intensive insulin therapy (IIT) has not yet proven its efficacy on stroke prognosis or in the reduction of MRI infarct growth. The INSULINFARCT study aims at determining in patients with hyperacute stroke whether IIT, with a better control of poststroke hyperglycemia, would reduce subsequent MRI infarct growth than usual care with subcutaneous insulin. Methods— One hundred eighty patients with MRI-proven ischemic stroke and with National Institutes of Health Stroke Scale from 5 to 25 at admission (<6 hours) were randomized to receive IIT or usual subcutaneous insulin for 24 hours. Admission hyperglycemia was not required for recruitment. Control MRI and 3-month follow-up (with functional outcome and serious adverse events) were planned. The primary objective was to detect a difference in the proportion of patients with mean capillary glucose test <7 mmol/L during 24 hours. The secondary objective was to investigate whether IIT would reduce infarct growth. The analysis was planned in intention-to-treat. Patients with >3 missing capillary glucose test were excluded (n=4). Results— The proportion of patients with mean capillary glucose test <7 mmol/L in the first 24 hours was higher in the IIT group (95.4% [83 of 87] versus 67.4% [60 of 89]; P<0.0001). The infarct growth was lower in the subcutaneous insulin group (median, 10.8 cm3; 95% CI, 6.5–22.4 versus 27.9 cm3; 14.6–40.7; 60% of increase; P=0.04). The 3-month functional outcome (45.6% [41 of 90] versus 45.6% [41 of 90]), death (15.6% [14 of 90] versus 10% [9 of 90]), and serious adverse events (38.9% [35 of 90] versus 35.6% [32 of 90]) were similar in the subcutaneous insulin and IIT group. Conclusion— The IIT regimen improved glucose control in the first 24 hours of stroke but was associated with larger infarct growths. IIT cannot be recommended in hyperacute ischemic stroke. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique Identifier: NCT00472381.

Prediction of Infarct Growth Based on Apparent Diffusion Coefficients: Penumbral Assessment without Intravenous Contrast Material

PURPOSE To compare predicted and final infarct lesion volumes determined by processing apparent diffusion coefficient (ADC) maps derived at admission diffusion-weighted (DW) magnetic resonance (MR) imaging in patients with acute stroke and to verify that predicted areas of infarct growth reflect at-risk penumbral regions based on recanalization status. MATERIALS AND METHODS The French legislation waived the requirement for informed patient consent for the described research, which was based on patient medical files. However, patients and/or their relatives were informed that they could decline to participate in the research. Authors tested a semiautomated proprietary image analysis procedure in 98 patients with middle cerebral artery (MCA) stroke by modeling infarct growth on DW imaging-derived ADC maps. Predicted infarct growth (PIG) areas and predicted infarct volumes were correlated with final observed data. In addition, the effect of MCA recanalization on the correlation between predicted and observed infarct growth volumes was qualitatively assessed. RESULTS Predicted and final infarct volumes (rho = 0.828; 95% confidence interval [CI]: 0.753, 0.882; P < .0001) and infarct growth volumes (rho = 0.506; 95% CI: 0.342, 0.640; P < .0001) were significantly correlated. Visual comparative examination revealed satisfactory qualitative consistency between predicted and follow-up lesion masks. In patients without MCA recanalization, PIG did not differ significantly from final observed infarct growth (median PIG obtained with 0.93 ADC ratio cutoff [PIG(ratio)] of 27.1 cm(3) vs median infarct growth of 19.8 cm(3), P = .17). MCA recanalization revealed an overestimation of PIG (median PIG(ratio) of 24.8 cm(3) vs median infarct growth of 12 cm(3), P = .005), suggesting that the PIG area was part of ischemic penumbra. CONCLUSION Data show the feasibility of identifying at-risk ischemic tissue in patients with acute MCA stroke by using semiautomated analysis of ADC maps derived at DW imaging, without intravenous contrast material-enhanced perfusion-weighted imaging.

Spatial regularization of SVM for the detection of diffusion alterations associated with stroke outcome.

In this paper, we propose a new method to detect differences at the group level in brain images based on spatially regularized support vector machines (SVM). We propose to spatially regularize the SVM using a graph Laplacian. This provides a flexible approach to model different types of proximity between voxels. We propose a proximity graph which accounts for tissue types. An efficient computation of the Gram matrix is provided. Then, significant differences between two populations are detected using statistical tests on the outputs of the SVM. The method was first tested on synthetic examples. It was then applied to 72 stroke patients to detect brain areas associated with motor outcome at 90 days, based on diffusion-weighted images acquired at the acute stage (median delay one day). The proposed method showed that poor motor outcome is associated to changes in the corticospinal bundle and white matter tracts originating from the premotor cortex. Standard mass univariate analyses failed to detect any difference on the same population.

Reliability of the ECASS Radiological Classification of Postthrombolysis Brain Haemorrhage: A Comparison of CT and Three MRI Sequences

Background: Postthrombolysis brain haemorrhagic transformations (HT) are often categorized with the CT-based classification of the European Cooperative Acute Stroke Study (ECASS). However, little is known about the reliability of this classification and its extension to MRI. Our objective was to compare the inter- and intraobserver reliability of this classification on CT and 3 MRI sequences. Methods: Forty-three patients with postthrombolysis HT on CT or at least 1 of the 3 MRI sequences: fluid-attenuation inversion recovery (FLAIR), diffusion-weighted imaging (DWI), and T2* gradient recalled echo (T2*GRE) were selected. Twelve control patients without any bleeding were added to avoid a bias based on a pure HT-positive cohort. Each series of images were independently classified with the ECASS method by 6 blinded observers. Inter- and intraobserver reproducibility was categorized from poor to excellent depending on ĸ values. Results: The inter- and intraobserver overall concordance of the classification was good for T2*GRE, DWI and CT (ĸ > 0.6) and moderate for FLAIR (ĸ < 0.6). The interobserver concordance for parenchymal haematomas was excellent for T2*GRE (ĸ > 0.8) and moderate for CT, FLAIR and DWI. Conclusion: The T2*GRE sequence is the most reproducible method to categorize postthrombolysis HT and has an excellent reliability for the severe parenchymal haematoma category, suggesting that this sequence should be used to assess HT in thrombolytic therapy trials.

Neurological sequelae after cerebral anoxia

Primary objective: Cardiac arrest can cause neurological impairment. The aim of this study is to confirm the disability and the predominant part of executive and behavioural impairments after cardiac arrest. Research design: A retrospective study is proposed. Methods and procedures: All consecutive patients admitted to the Department of Rehabilitation for Neurological Impairments following cerebral anoxia after cardiac arrest between 1995–2007 were included. Clinical and neuropsychological assessment was proposed. Main outcomes and results: Thirty patients, 19 men, were examined. Ages ranged from 16–58 (mean = 39.5). Fourteen patients presented with severe disability and 16 patients presented with moderate disability. In the first group (severe disability) no patients were autonomous for daily life activities. They presented with dysexecutive syndrome and behavioural disorders associated with amnesia syndrome; 64% of them presented with motor disorders. In the second group, patients with moderate disability were autonomous in daily life but not for the complex activities or functioning. They had no motor impairment but suffered from executive and memory impairments. Behavioural changes were noted. Medical history or demographic data did not differ between the two groups. Conclusion: The study confirms the predominant part of executive, memory and behavioural impairments after cardiac arrest. This retrospective study cannot provide prognosis factors and further prognosis studies are needed.

Biomarkers of stroke recovery: consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable

The most difficult clinical questions in stroke rehabilitation are “What is this patient’s potential for recovery?” and “What is the best rehabilitation strategy for this person, given her/his clinical profile?” Without answers to these questions, clinicians struggle to make decisions regarding the content and focus of therapy, and researchers design studies that inadvertently mix participants who have a high likelihood of responding with those who do not. Developing and implementing biomarkers that distinguish patient subgroups will help address these issues and unravel the factors important to the recovery process. The goal of the present paper is to provide a consensus statement regarding the current state of the evidence for stroke recovery biomarkers. Biomarkers of motor, somatosensory, cognitive and language domains across the recovery timeline post-stroke are considered; with focus on brain structure and function, and exclusion of blood markers and genetics. We provide evidence for biomarkers that are considered ready to be included in clinical trials, as well as others that are promising but not ready and so represent a developmental priority. We conclude with an example that illustrates the utility of biomarkers in recovery and rehabilitation research, demonstrating how the inclusion of a biomarker may enhance future clinical trials. In this way, we propose a way forward for when and where we can include biomarkers to advance the efficacy of the practice of, and research into, rehabilitation and recovery after stroke.

Diffusion-weighted MRI in acute stroke within the first 6 hours: 1.5 or 3.0 Tesla?

Objectives: To compare the sensitivity and specificity of 1.5-T and 3.0-T diffusion-weighted MRI (DWI) to detect hyperacute ischemic stroke lesions. Methods: We blindly reviewed the DWI of 135 acute stroke patients and 34 controls performed at 1.5 T (n = 108) or 3.0 T (n = 61). The stroke patients all had subsequently proved carotid territory ischemic stroke and were imaged within the first 6 hours after stroke onset. Four readers (2 neuroradiologists and 2 stroke neurologists) blinded to clinical data and magnetic field strength recorded the presence of ischemic lesions on DWI and apparent diffusion coefficient (ADC) maps if necessary. Sensitivity, specificity, and false-negative rates were computed. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and DWI contrasts were calculated at both field strengths. Results: The accuracy of DWI in stroke diagnosis was superior at 1.5 T (98.8%) than at 3.0 T (90.9%, p = 0.03). The sensitivity decreased from 99.1% at 1.5 T to 92.5% at 3.0 T (p = 0.06) and the specificity from 97.8% to 84.1% (p = 0.002). ADC map readings did not improve accuracy, sensitivity, or specificity. The false-negative rate was 0.6% at 1.5 T and 6.1% at 3.0 T. Type of readers, stroke severity, and type of the coil did not affect diagnosis value. SNR and CNR were significantly higher at 3 T (p < 0.0001) but DWI contrast was lower (p = 0.04). Conclusions: Blind reading by 4 experts of a large series of images shows that 1.5-T diffusion-weighted MRI (DWI) is better than 3.0-T DWI for the imaging of hyperacute stroke during the therapeutic window of thrombolysis.

Glucose and Acute Stroke Evidence for an Interlude

Hyperglycemia (HG), a common phenomenon in all types of acute strokes, is increasingly considered as a potential therapeutic target in ischemic stroke because there is now strong evidence that high glucose levels are independent predictors of larger infarct size, poor clinical outcome, and higher risk of mortality.1 In the past few years this has led many acute stroke centers to initiate intensive insulin therapy (IIT) policies often modeled on intensive care unit practices. Unfortunately, the initial enthusiasm for IIT in the intensive care unit has disappeared because currently available evidence-based data fail to identify any clinical benefit at the time of continuing to outline the high risk of hypoglycemia.2 Furthermore, in the neurocritical care setting, the increased frequency of hypoglycemia may result in higher mortality.3 Finally, the UK Glucose Insulin in Stroke Trial (GIST-UK) failed to demonstrate any benefit from IIT in 933 patients with stroke.4 Five other small randomized trials were not powered to demonstrate a clinical benefit, but all showed that IIT induced a high risk of hypoglycemia in patients with acute stroke.5–10 It may be time for an interlude. As highlighted by others, there is a need for safer methods of improving glucose control before launching large randomized trials.1,11 We will also argue here that the proper design of large trials may require further experimental work and proof-of-concept human studies, which in turn may benefit from some results obtained in the past decade. It should be stressed that HG is a complex phenomenon in acute stroke and may result from known diabetes or undiagnosed diabetes, metabolic syndrome, acquired insulin resistance, stress response, and lesion size or its location. Furthermore, despite many theories, the mechanism of HG toxicity in acute stroke remains to be clearly elucidated. ### Correlation Between HG and Stroke Outcome in Large Clinical Series #### Admission HG in Ischemic Stroke A 2001 …