Acute Diffusivity Biomarkers for Prediction of Motor and Language Outcome in Mild-to-Severe Stroke Patients.

Background and Purpose- Early severity of stroke symptoms-especially in mild-to-severe stroke patients-are imperfect predictors of long-term motor and aphasia outcome. Motor function and language processing heavily rely on the preservation of important white matter fasciculi in the brain. Axial diffusivity (AD) from the diffusion tensor imaging model has repeatedly shown to accurately reflect acute axonal damage and is thus optimal to probe the integrity of important white matter bundles and their relationship with long-term outcome. Our aim was to investigate the independent prognostic value of the AD of white matter tracts in the motor and language network evaluated at 24 hours poststroke for motor and aphasia outcome at 3 months poststroke. Methods- Seventeen (motor cohort) and 28 (aphasia cohort) thrombolyzed patients with initial mild-to-severe stroke underwent a diffusion tensor imaging sequence at 24 hours poststroke. Motor and language outcome were evaluated at 3 months poststroke with a composite motor score and the aphasia handicap scale. We first used stepwise regression to determine which classic (age, initial motor or aphasia severity, and lesion volume) and imaging (ratio of affected/unaffected AD of motor and language fasciculi) factors were related to outcome. Second, to determine the specificity of our a priori choices of fasciculi, we performed voxel-based analyses to determine if the same, additional, or altogether new regions were associated with long-term outcome. Results- The ratio of AD in the corticospinal tract was the sole predictor of long-term motor outcome, and the ratio of AD in the arcuate fasciculus-along with age and initial aphasia severity-was an independent predictor of 3-month aphasia outcome. White matter regions overlapping with these fasciculi naturally emerged in the corresponding voxel-based analyses. Conclusions- AD of the corticospinal tract and arcuate fasciculus are effective biomarkers of long-term motor and aphasia outcome, respectively.

Aphasia outcome: the interactions between initial severity, lesion size and location.

OBJECTIVES: The outcome of aphasia at 3 months is variable in patients with moderate/severe stroke. The aim was to predict 3-month aphasia outcome using prediction models including initial severity in addition to the interaction between lesion size and location at the acute phase. METHODS: Patients with post-stroke aphasia (assessed by the Aphasia Rapid Test at day 7-ART D7) and MRI performed at day 1 were enrolled (n = 73). Good outcome at 3-months was defined by an Aphasia Handicap Score of 0-2. Each infarct lesion was overlapped with an area of interest in the left temporo-parietal region to compute an intersection index (proportion of the critical region damaged by the infarct). We tested ART D7, age, lesion volume, and intersection index as well as a combined variable lesion volume*intersection in a univariate analysis. Then, we performed a multivariate analysis to investigate which variables were independent predictors of good outcome. RESULTS: ART at D7, infarct volume, and the intersection index were univariate predictors of good outcome. In the multivariate analysis, ART D7 and "volume ≥ 50 ml or intersection index ≥ 20%" correctly classified 89% of the patients (p < 0.0001). When added to the model, the interaction between both variables was significant indicating that the impact of the size or site variable depends on the initial severity of aphasia. CONCLUSION: In patients with initially severe aphasia, large infarct size or critical damage in left temporoparietal junction is associated with poor language outcome at 3 months.

Efficacy of Endovascular Therapy in Acute Ischemic Stroke Depends on Age and Clinical Severity.

BACKGROUND AND PURPOSE: Efficacy of endovascular treatment (EVT) for ischemic stroke because of large vessel occlusion may depend on patients' age and stroke severity; we, therefore, developed a prognosis score based on these variables and examined whether EVT efficacy differs between patients with good, intermediate, or poor prognostic score. METHODS: A total of 4079 patients with an acute ischemic stroke were identified from the Paris Stroke Consortium registry. We developed the stroke checkerboard (SC) score (SC score=1 point per decade ≥50 years of age and 2 points per 5 points on the National Institutes of Health Stroke Scale) to predict spontaneous outcome. The primary outcome was the adjusted common odds ratio for an improvement in the modified Rankin Scale at 90 days after EVT, in patients with low, intermediate, or high SC scores. To rule out potential selection biases, a nested case-control analysis, with individual matching for all major prognostic factors, was also performed, to compare patients with large vessel occlusion in the anterior circulation treated or not with EVT. RESULTS: In patients untreated with EVT, SC scores <8 were predictive of good outcomes (modified Rankin Scale score, 0-2; area under the curve, 0.87), whereas SC scores >12 were predictive of poor outcomes (modified Rankin Scale score, 4-6; area under the curve, 0.88). In the overall population, there was an interaction between EVT and prognosis group (P<0.001). EVT was associated with improved outcome in patients with SC scores >12 (common odds ratio, 1.70; 95% confidence interval, 1.13-2.56) and SC scores 8 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.69) but not in patients with SC scores <8 (odds ratio, 0.72; 95% confidence interval, 0.56-0.93). Similar results were obtained in the case-control analysis among 449 patients treated with EVT and 449 matched patients untreated with EVT. CONCLUSIONS: In patients stratified with the SC score, EVT was associated with improved functional outcome in older and more severe patients but not in younger and less severe patients.

Mechanical Thrombectomy in Perioperative Strokes: A Case-Control Study.

BACKGROUND AND PURPOSE: Perioperative strokes (POS) are rare but serious complications for which mechanical thrombectomy could be beneficial. We aimed to compare the technical results and patients outcomes in a population of POS versus non-POS (nPOS) treated by mechanical thrombectomy. METHODS: From 2010 to 2017, 25 patients with POS (ie, acute ischemic stroke occurring during or within 30 days after a procedure) who underwent mechanical thrombectomy (POS group) were enrolled and paired with 50 consecutive patients with nPOS (control group), based on the occlusion's site, National Institute of Health Stroke Scale, and age. RESULTS: Respectively, mean age was 68.3±16.6 versus 67.2±16.6 years (P=0.70), and median National Institute of Health Stroke Scale score at admission was 20 (interquartile range, 15-25) versus 19 (interquartile range, 17-25; P=0.79). Good clinical outcome (modified Rankin Scale score of 0-2 at 3 months) was achieved by 33.3% (POS) versus 56.5% (nPOS) of patients (P=0.055). Successful reperfusion (modified Thrombolysis In Cerebral Infarction score of ≥2b) was obtained in 76% (POS) versus 86% (nPOS) of cases (P=0.22). Mortality at 3 months was 33.3% in the POS group versus 4.2% (nPOS) (P=0.002). The rate of major procedural complications was 4% (POS) versus 6% (nPOS); none were lethal. Average time from symptoms' onset to reperfusion was 4.9 hours (±2.0) in POS versus 5.2 hours (±2.6). CONCLUSIONS: Successful reperfusion seems accessible in POS within a reasonable amount of time and with a good level of safety. However, favorable outcome was achieved with a lower rate than in nPOS, owing to a higher mortality rate.

Axial Diffusivity of the Corona Radiata at 24 Hours Post-Stroke: A New Biomarker for Motor and Global Outcome.

Fractional anisotropy (FA) is an effective marker of motor outcome at the chronic stage of stroke yet proves to be less efficient at early time points. This study aims to determine which diffusion metric in which location is the best marker of long-term stroke outcome after thrombolysis with diffusion tensor imaging (DTI) at 24 hours post-stroke. Twenty-eight thrombolyzed patients underwent DTI at 24 hours post-stroke onset. Ipsilesional and contralesional FA, mean (MD), axial (AD), and radial (RD) diffusivities values were calculated in different Regions-of-Interest (ROIs): (1) the white matter underlying the precentral gyrus (M1), (2) the corona radiata (CoRad), (3) the posterior limb of the internal capsule (PLIC) and (4) the cerebral peduncles (CP). NIHSS scores were acquired at admission, day 1, and day 7; modified Rankin Scores (mRS) at 3 months. Significant decreases were found in FA, MD, and AD of the ipsilesional CoRad and M1. MD and AD were also significantly lower in the PLIC. The ratio of ipsi and contralesional AD of the CoRad (CoRad-rAD) was the strongest diffusion parameter correlated with motor NIHSS scores on day 7 and with the mRS at 3 months. A Receiver-Operator Curve analysis yielded a model for the CoRad-rAD to predict good outcome based on upper limb NIHSS motor scores and mRS with high specificity and sensitivity. FA values were not correlated with clinical outcome. In conclusion, axial diffusivity of the CoRad from clinical DTI at 24 hours post-stroke is the most appropriate diffusion metric for quantifying stroke damage to predict outcome, suggesting the importance of early axonal damage.

Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial.

BACKGROUND: Recently, the concept of 'clinically relevant penumbra' was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. METHODS: We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. FINDINGS: Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10(-6) mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. CONCLUSION: These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. TRIAL REGISTRATION: ClinicalTrials.gov NCT00472381.

Lipoprotein-associated phospholipase A2 during the hyperacute stage of ischemic and hemorrhagic strokes.

BACKGROUND: The objectives of the study were to compare lipoprotein-associated phospholipase A2 (Lp-PLA2) levels in a prospective cohort including both ischemic and hemorrhagic strokes at the hyperacute phase, and to investigate if these levels were associated with stroke severity. MATERIALS AND METHODS: Lp-PLA2 mass and activity were measured during the first 6 hours of symptom onset before any therapeutic intervention. The Lp-PLA2 level was analyzed by comparing the mass and activities in ischemic strokes and spontaneous intracerebral hemorrhages (ICH). Correlations between Lp-PLA2 levels and clinical scores as well as stroke volumes were made. The temporal evolution of Lp-PLA2 during the first week was analyzed in ischemic stroke patients. RESULTS: Lp-PLA2 mass was higher in ICH than in ischemic stroke (P = .001). Lp-PLA2 activity at admission correlated with initial and follow-up stroke volume in ICH (P = .003 and P = .004, respectively) but not in ischemic stroke. None of the measurements correlated with clinical severity for either diagnosis. Lp-PLA2 mass decreased during the first week after the use of statins in ischemic stroke, whereas the activity remained stable. CONCLUSIONS: Lp-PLA2 mass is higher in ICH compared with ischemic stroke during the hyperacute stage. Lp-PLA2 activity is associated with stroke volume in ICH but not in ischemic stroke. This suggests that Lp-PLA2 mass and activity could provide different information in the hyperacute stage of stroke.

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 cm(3); 95% CI, 6.5-22.4 versus 27.9 cm(3); 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. CONCLUSIONS: 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.

The hemodynamic status within 24 h after intravenous thrombolysis predicts infarct growth in acute ischemic stroke.

A rapid and complete recanalization of the occluded artery is the ideal goal when intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is administrated to patients with acute ischemic stroke, i.e., limiting the ongoing ischemia to achieve a better outcome. We explored the effect of complete versus partial recanalization of the occluded intracranial artery after IV thrombolysis on the infarct growth and evaluated the functional impact. Using diffusion-weighted (DWI) volumetric measurements before rt-PA administration (DWI(1)) and 24 h later (DWI(2)), we calculated the infarct growth in 36 consecutive patients with ischemic stroke treated with IV rt-PA, with the formula DWI(2)/DWI(1). Recanalization of the affected artery was assessed by transcranial Doppler (TCD) and magnetic resonance angiography (MRA) within 24 h of stroke onset. Three patients were eliminated from the analysis; 33 patients were fully analyzed (men: n = 23; mean (SD) age: 72.4 ± 16 years; time from stroke onset to rt-PA: 179 ± 54 min; mean NIHSS score at admission: 17). Patients achieving full recanalization by TCD had a smaller infarct growth, compared to those who had a partial or persistent occlusion after thrombolysis: 1.86 versus 2.91 (P = 0.017). This difference was not significant using MRA criteria: 2.01 versus 2.69 (P = 0.193). In the regression analysis, complete recanalization by TCD was an independent predictor of infarct growth (P = 0.045). Thus, complete recanalization measured by TCD within 24 h of IV thrombolysis was independently associated with smaller infarct growth.

Clinical usefulness of the visibility of the transcerebral veins at 3T on T2*-weighted sequence in acute stroke patients.

OBJECTIVES: The objective of this work was to investigate the clinical usefulness of the visibility of the transcerebral veins (VTV) in acute ischemic stroke patients at 3T. METHODS: Sixty consecutive carotid artery territory stroke patients were included retrospectively. Two readers categorized the VTV on T2*-weighted sequence at 3T for each hemisphere, and asymmetry of this sign was assessed between each hemisphere by an asymmetry index (AI) using a three-item scale. The VTV and AI were correlated with clinical and radiological covariates. Particular interest was focused on patients for whom initial diffusion-weighted imaging alone was inconclusive. RESULTS: VTV were detected in the stroke hemisphere in 58.3% (n = 35) and in the contralateral side in 10% (n = 6, p<0.0001). Asymmetry of the VTV between ischemic and contralateral hemispheres was present in 53.3% (n = 32). Intracranial artery occlusion, final infarct volume and symptomatic hemorrhagic transformation were correlated with a higher AI at baseline (ρ = 0.563, ρ = 0.291, and ρ = 0.285, p<0.05, respectively). Three hyperacute stroke patients with subtle DWI high signal intensity at admission demonstrated VTV. CONCLUSIONS: The pathological value of the VTV seems to reside in its asymmetry between hemispheres, as it was correlated with important clinical parameters. This study also suggests that the VTV could be a supportive finding in stroke diagnosis, especially when DWI is unreliable.

[Quality assurance indicators for risk management in the follow-up of medical care received by acute ischemic stroke patients]. / Des indicateurs de qualité et de gestion des risques pour suivre la prise en charge hospitalière des accidents vasculaires cérébraux.

Although recommendations for diagnosis and treatment of stroke are available, the aim of this study was to identify indicators of quality and risk management for acute ischemic stroke hospital patients. We conducted a descriptive study of stroke patients who were diagnosed less than 12 hours before admission to the Pitié-Salpêtrière hospital's neurology and stroke unit. Data were collected using a literature review and from existing recommendation. During the study period (August 2003 through April 2005) 310 eligible patients were identified. In 87.5% of the cases, patients suffered from a cerebral infarction and in 10.3% from an intracranial haemorrhage. The initial deficit was mild to severe. The average time between the first symptoms and admission in the stroke unit was 212 +/- 130 minutes. Forty percent of patients who underwent a thrombolysis did so within the first 3 hours. The average length of stay in the stroke unit was 17.5 days. Thirty-one percent of the patients were discharged to go home, 47% to a rehabilitation unit and 8% died. Ten indicators of quality and risk management are proposed, taking in account the events before admission, hospital care, side effects, duration of stay, discharge location and the handicap.

[Medical and social characteristics and treatment plans for brain-damaged patients hospitalized]. / Caractéistiques médicales et sociales et trajectoires de soins des patients cérébro-lésés hospitalisés.

The study objective was to better understand the clinical and social characteristics, and the treatment plans, of brain-damaged patients who were hospitalized longer than one month in acute care units. A 6-month descriptive prospective epidemiological study of 90 patients was carried out. The average length of stay (LOS) was 84 +/- 73 days. Patients were severely disabled: 17.83% of patients showed a Glasgow Outcome Scale (GOS) 2, 70% a GOS 3 and 12.2%, a GOS > or =4. Two-thirds of the patients had social difficulties that influenced their LOS (68.4 days when social difficulties <3, versus 157.4 days when > or =3). An average of 4 rehabilitation settings were solicited per patient. The actual rehabilitation setting matched the patient's and team's wishes in only 63.4% of the cases. Several proposals are discussed to improve overall management of care for brain-damaged patients: the need to establish a mobile steering team, to improve multidisciplinary approaches, and to create acute physical medicine and rehabilitation units.