Sharmila Sagnier

Early Fiber Number Ratio Is a Surrogate of Corticospinal Tract Integrity and Predicts Motor Recovery After Stroke

Background and Purpose— The contribution of imaging metrics to predict poststroke motor recovery needs to be clarified. We tested the added value of early diffusion tensor imaging (DTI) of the corticospinal tract toward predicting long-term motor recovery. Methods— One hundred seventeen patients were prospectively assessed at 24 to 72 hours and 1 year after ischemic stroke with diffusion tensor imaging and motor scores (Fugl-Meyer). The initial fiber number ratio (iFNr) and final fiber number ratio were computed as the number of streamlines along the affected corticospinal tract normalized to the unaffected side and were compared with each other. The prediction of motor recovery (&Dgr;Fugl-Meyer) was first modeled using initial Fugl-Meyer and iFNr. Multivariate ordinal logistic regression models were also used to study the association of iFNr, initial Fugl-Meyer, age, and stroke volume with Fugl-Meyer at 1 year. Results— The iFNr correlated with the final fiber number ratio at 1 year (r=0.70; P<0.0001). The initial Fugl-Meyer strongly predicted motor recovery (≈73% of initial impairment) for all patients except those with initial severe stroke (Fugl-Meyer<50). For these severe patients (n=26), initial Fugl-Meyer was not correlated with motor recovery (R2=0.13; p=ns), whereas iFNr showed strong correlation (R2=0.56; P<0.0001). In multivariate analysis, the iFNr was an independent predictor of motor outcome (&bgr;=2.601; 95% confidence interval=0.304–5.110; P=0.031), improving prediction compared with using only initial Fugl-Meyer, age, and stroke volume (P=0.026). Conclusions— Early measurement of FNr at 24 to 72 hours poststroke is a surrogate marker of corticospinal tract integrity and provides independent prediction of motor outcome at 1 year especially for patients with severe initial impairment.

Stroke Location Is an Independent Predictor of Cognitive Outcome

Background and Purpose— On top of functional outcome, accurate prediction of cognitive outcome for stroke patients is an unmet need with major implications for clinical management. We investigated whether stroke location may contribute independent prognostic value to multifactorial predictive models of functional and cognitive outcomes. Methods— Four hundred twenty-eight consecutive patients with ischemic stroke were prospectively assessed with magnetic resonance imaging at 24 to 72 hours and at 3 months for functional outcome using the modified Rankin Scale and cognitive outcome using the Montreal Cognitive Assessment (MoCA). Statistical maps of functional and cognitive eloquent regions were derived from the first 215 patients (development sample) using voxel-based lesion-symptom mapping. We used multivariate logistic regression models to study the influence of stroke location (number of eloquent voxels from voxel-based lesion-symptom mapping maps), age, initial National Institutes of Health Stroke Scale and stroke volume on modified Rankin Scale and MoCA. The second part of our cohort was used as an independent replication sample. Results— In univariate analyses, stroke location, age, initial National Institutes of Health Stroke Scale, and stroke volume were all predictive of poor modified Rankin Scale and MoCA. In multivariable analyses, stroke location remained the strongest independent predictor of MoCA and significantly improved the prediction compared with using only age, initial National Institutes of Health Stroke Scale, and stroke volume (area under the curve increased from 0.697–0.771; difference=0.073; 95% confidence interval, 0.008–0.155). In contrast, stroke location did not persist as independent predictor of modified Rankin Scale that was mainly driven by initial National Institutes of Health Stroke Scale (area under the curve going from 0.840 to 0.835). Similar results were obtained in the replication sample. Conclusions— Stroke location is an independent predictor of cognitive outcome (MoCA) at 3 months post stroke.

Thalamic alterations remote to infarct appear as focal iron accumulation and impact clinical outcome.

See Duering and Schmidt (doi:10.1093/awx135) for a scientific commentary on this article.Thalamic alterations have been observed in infarcts initially sparing the thalamus but interrupting thalamo-cortical or cortico-thalamic projections. We aimed at extending this knowledge by demonstrating with in vivo imaging sensitive to iron accumulation, one marker of neurodegeneration, that (i) secondary thalamic alterations are focally located in specific thalamic nuclei depending on the initial infarct location; and (ii) such secondary alterations can contribute independently to the long-term outcome. To tackle this issue, 172 patients with an infarct initially sparing the thalamus were prospectively evaluated clinically and with magnetic resonance imaging to quantify iron through R2* map at 24-72 h and at 1-year follow-up. An asymmetry index was used to compare R2* within the thalamus ipsilateral versus contralateral to infarct and we focused on the 95th percentile of R2* as a metric of high iron content. Spatial distribution within the thalamus was analysed on an average R2* map from the entire cohort. The asymmetry index of the 95th percentile within individual nuclei (medio-dorsal, pulvinar, lateral group) were compared according to the initial infarct location in simple and multiple regression analyses and using voxel-based lesion-symptom mapping. Associations between the asymmetry index of the 95th percentile and functional, cognitive and emotional outcome were calculated in multiple regression models. We showed that R2* was not modified at 24-72 h but showed heterogeneous increase at 1 year mainly within the medio-dorsal and pulvinar nuclei. The asymmetry index of the 95th percentile within the medio-dorsal nucleus was significantly associated with infarcts involving anterior areas (frontal P = 0.05, temporal P = 0.02, lenticular P = 0.01) while the asymmetry index of the 95th percentile within the pulvinar nucleus was significantly associated with infarcts involving posterior areas (parietal P = 0.046, temporal P < 0.001) independently of age, gender and infarct volume, which was confirmed by voxel-based lesion-symptom mapping. The asymmetry index of the 95th percentile within the entire thalamus at 1 year was independently associated with poor functional outcome (P = 0.04), poor cognitive outcome (P = 0.03), post-stroke anxiety (P = 0.04) and post-stroke depression (P = 0.02). We have therefore identified that iron accumulates within the thalamus ipsilateral to infarct after a delay with a focal distribution that is strongly linked to the initial infarct location (in relation with the pattern of connectivity between thalamic nuclei and cortical areas or deep nuclei), which independently contributes to functional, cognitive and emotional outcome.

Proportion of single-chain recombinant tissue plasminogen activator and outcome after stroke

Objective: To determine whether the ratio single chain (sc)/(sc + 2 chain [tc]) recombinant tissue plasminogen activator (rtPA) influences outcomes in patients with cerebral ischemia. Methods: We prospectively included consecutive patients treated with IV rtPA for cerebral ischemia in 13 stroke centers and determined the sc/(sc + tc) ratio in the treatment administered to each patient. We evaluated the outcome with the modified Rankin Scale (mRS) at 3 months (prespecified analysis) and occurrence of epileptic seizures (post hoc analysis). We registered Outcome of Patients Treated by IV Rt-PA for Cerebral Ischaemia According to the Ratio Sc-tPA/Tc-tPA (OPHELIE) under ClinicalTrials.gov identifier no. NCT01614080. Results: We recruited 1,004 patients (515 men, median age 75 years, median onset-to-needle time 170 minutes, median NIH Stroke Scale score 10). We found no statistical association between sc/(sc + tc) ratios and handicap (mRS > 1), dependency (mRS > 2), or death at 3 months. Patients with symptomatic intracerebral hemorrhages had lower ratios (median 69% vs 72%, adjusted p = 0.003). The sc/(sc + tc) rtPA ratio did not differ between patients with and without seizures, but patients with early seizures were more likely to have received a sc/(sc + tc) rtPA ratio >80.5% (odds ratio 3.61; 95% confidence interval 1.26–10.34). Conclusions: The sc/(sc + tc) rtPA ratio does not influence outcomes in patients with cerebral ischemia. The capacity of rtPA to modulate NMDA receptor signaling might be associated with early seizures, but we observed this effect only in patients with a ratio of sc/(sc + tc) rtPA >80.5% in a post hoc analysis.

Interest of Antiplatelet Drug Testing after an Acute Ischemic Stroke

Background: Stroke occurrence despite chronic antiplatelet drug (APD) treatment is frequent. We aimed at evaluating the relevance of platelet aggregation testing in the identification of stroke etiology in this context. Methods: Patients admitted for a suspected acute ischemic stroke, while under APD (aspirin and/or clopidogrel), were prospectively included. The efficacy of the APD was evaluated using a Multiplate™ assay. Resistance was confirmed using light transmission aggregometry. A standardized diagnostic work-up was performed to identify stroke mechanism according to the TOAST and the ASCO classifications. We evaluated the influence of APD functional status on stroke severity and identified potential determinants of resistance. Results: APD resistance was observed in 53 of the 287 patients (18.5%). No difference in stroke mechanism depending on APD efficacy was observed. Patients sensitive to APD had less severe initial stroke severity (mean National Institutes of Health Stroke Scale 3.9 ± 5.6 vs. 7.2 ± 6.8; p < 0.01). Main determinants for APD resistance were a worse control of the diabetes and higher baseline levels of inflammation (mean CRP 26.4 ± 56.0 vs. 9.3 ± 21.0; p < 0.01). Conclusions: Platelet function testing does not provide orientation concerning stroke mechanism in patients who were previously on APDs. However, the high frequency of APD resistance and its association with inflammation and stroke severity are confirmed.

Admission Brain Cortical Volume

Background and Purpose— Several markers of poststroke cognitive impairment have been reported. The role of brain cortical volume remains uncertain. The aim of this study was to evaluate the influence of brain cortical volume on cognitive outcomes using a voxel-based morphometry approach in subjects without prestroke dementia. Methods— Ischemic stroke patients were prospectively recruited 24 to 72 hours post stroke (M0). Cognition was evaluated at M0, 3 months, and 1 year (M12) using the Montreal Cognitive Assessment, the Isaacs set test, and the Zazzo’s cancellation task. A 3-T brain magnetic resonance imaging was performed at M0. Grey matter (GM) was segmented using Statistical Parametric Mapping 12 software. Association between global GM volume and cognitive score slopes between M0 and M12 was evaluated using a linear mixed model. Correlations between focal GM volumes and changes in cognitive performance were evaluated using Statistical Parametric Mapping 12. Results— Two-hundred forty-eight patients were included (mean age 65±SD 14 years old, 66% men). Global GM volume was significantly associated with changes in Montreal Cognitive Assessment scores (&bgr;=0.01; P=0.04) and in the number of errors on the Zazzo’s cancellation task (&bgr;=−0.02; P=0.04) independently of other clinical/radiological confounders. Subjects with lower GM volumes in the left fronto-temporo-insular cortex were more vulnerable to transient Montreal Cognitive Assessment and Isaacs set test impairment. Subjects with lower GM volumes in right temporo-insular cortex, together with basal ganglia, were more vulnerable to transient cognitive impairment on the Zazzo’s cancellation task. Conclusions— Smaller cortical volumes in fronto-temporo-insular areas measured 24 to 72 hours post stroke are associated with cognitive vulnerability in the subacute stroke phase.

Immune-Thrombotic Thrombocytopenic Purpura is a Rare Cause of Ischemic Stroke in Young Adults: Case Reports and Literature Review

INTRODUCTION Immune thrombotic thrombocytopenic purpura (i-TTP), related to acquired ADAMTS-13 dysfunction, can lead to various neurological symptoms including ischemic stroke. To date the clinical, radiological, and biological characteristics of patients having a stroke as the inaugural manifestation of i-TTP are largely unknown. METHODS Probable immune-TTP was defined by a low ADAMTS-13 activity associated with the presence of ADAMTS-13 inhibitors and/or favorable clinicobiological response under immunological treatments. The clinical, radiological, biological data and outcome under treatment are described in a cohort of 17 patients coming from 3 local cases and a literature review. RESULTS Fourteen of the 17 patients were female and the mean age was 41 years. None of the patients had the classical pentad of TTP. Only 41% had a combination of thrombocythemia and hemolysis. Stroke was multifocal in 35% and included large artery strokes. No adverse event was observed following intravenous thrombolysis. Refractory and relapsing forms were observed in 47%. DISCUSSION The clinical, radiological, and biological presentation of patients with stroke as the inaugural presentation of i-TTP is heterogeneous. This diagnosis should be discussed in every young adult with ischemic stroke of undetermined source.

Clinical Predictors of Stroke Mimics in Patients Treated with Recombinant Tissue Plasminogen Activator according to a Normal Multimodal Computed Tomography Imaging

BACKGROUND Multimodal computed tomography imaging (MCTI) is increasingly used for rapid assessment of acute stroke. We investigated characteristics and final diagnoses of patients treated with recombinant tissue plasminogen activator (rt-PA) while admission imaging was unremarkable. METHODS From our prospectively collected stroke database (2013-2016), we identified consecutive patients treated with rt-PA on the basis of an unremarkable brain MCTI and assessed with a 24-hour follow-up brain magnetic resonance imaging (MRI). Demographic data, medical history, score on the 15-item National Institute of Health Stroke Scale, and final diagnosis were considered. Absence of MRI infarction and alternate diagnosis defined stroke mimics (SMs). Univariable and multivariable logistic regression analyses identified factors predictive of SMs. RESULTS Sixty-eight (47.9%) SMs, 63 (44.4%) strokes, and 11 (7.7%) aborted strokes were found. SMs had more often aphasia (P = .003) and hemianopia (P = .0008), whereas upper limb weakness (ULW) (P = .03) and limb ataxia (P = .002) were more prevalent in strokes. Headache (adjusted odds ratio [Adj. OR], 3.89 [95% confidence interval {CI} 1.44-10.47]), relevant history of epilepsy, migraine, dementia or depression (Adj. OR 3.66 [95% CI 1.31-10.18]), unilateral sensory loss (Adj. OR 2.60 [95% CI 1.05-6.45]), and hemianopia (Adj. OR 4.94 [95% CI 1.46-16.77]) were independent predictors of SMs whereas ULW (Adj. OR 3.16 [95% CI 1.28-7.82]) and ataxia (Adj. OR 3.81 [95% CI 1.43-10.13]) predicted stroke. Sensitivity of hemianopia or aphasia for SMs was 52.9%, with specificity of 84.1%, positive predictive value of 78.3%, and negative predictive value of 62.4%. CONCLUSIONS Hemianopia and/or aphasia with normal MCTI suggest SMs. Diffusion-weighted MRI might be discussed before rt-PA administration in patients with such a clinical pattern.

Trendelenburg Positioning in Large Vessel Ischaemic Stroke: A Pre-Post Observational Study Using Propensity Score Matching

Background: Along with pharmacological and mechanical recanalization, improving cerebral perfusion through the recruitment of collateral vessels during the acute phase of ischaemic stroke (IS) is a clinical challenge. Our objective was to assess the effectiveness and safety of Trendelenburg positioning (TP), a procedure intended to increase cerebral blood flow, on the outcome of IS. Methods: Two cohorts of patients with an acute supratentorial IS related to a large artery occlusion were compared. In the first cohort (n = 119), we used standard positioning (0 to +30°); in the second cohort (n = 90), we used TP (0 to –15°). The primary outcome measure was the improvement of National Institutes of Health Stroke Scale (NIHSS) score between admission and day 2. Factors associated with an improvement ≥4 points of NIHSS score were assessed using multiple logistic regression and propensity score (PS) matching analyses. Results: TP was significantly associated with a greater improvement of NIHSS score within 48 h following stroke onset (4.0 ± 5.7 vs. 1.8 ± 5.9, p = 0.011) but also at discharge (p = 0.005). Multiple logistic regression analysis suggested that TP was an independent predictor of early neurological improvement (adjusted OR 1.81, 95% CI 1.00–3.27) in a model controlling recanalization and haemoglobin level. In addition, PS matching analysis confirmed the possible effectiveness of TP (unadjusted OR 1.99, 95% CI 1.04–3.82), especially in male subjects. The effect of TP was more pronounced in patients with admission mean arterial blood pressure ≥100 mm Hg, those exhibiting a good collateral vessel network on admission CT-angiography or experiencing an effective recanalization. Furthermore, TP was not associated with life-threatening complications. Conclusion: TP could be an effective and safe strategy in patients with large IS resulting from the proximal occlusion of a large vessel.

Contribution of routine cardiac biological markers to the etiological workup of ischemic stroke

Background: Optimization of the detection of atrial fibrillation following stroke is mandatory. Unfortunately, access to long‐term cardiac monitoring is limited in many centers. The aim of this study was to assess the potential usefulness of three routine biological markers, troponin, D‐dimers and BNP, measured in acute stroke phase in the selection of patients at risk of cardio‐embolic stroke. Methods: Troponin, D‐Dimers and BNP were measured within 48h after admission for ischemic stroke in 634 patients. Stroke mechanism was defined at the 3months follow‐up visit using ASCOD classification using a standardized work‐up. Association between clinical, radiological and biological markers and stroke mechanism was evaluated using logistic regression analyses. Results: 159 patients (25.1% of total study population) had a cardiac mechanism. On multivariate analysis, admission initial stroke severity (OR 1.04, 95 CI% 1.004–1.07, p<0.05) history of heart failure (OR 3.03, 95% CI 1.19–7.73, p<0.05), ECG abnormalities and high BNP value (OR 4.34, 95% CI 2.59–7.29, p<0.05) were associated with pure cardiac stroke mechanism. Conclusion: High BNP value measured within 48h after stroke admission is an independent predictor of cardiac stroke mechanism. Its measurement might be used to improve the selection of patients for whom further cardiologic investigations such as continuous long term ECG monitoring would be the most useful. BNP should be added to the standard admission‐work‐up for stroke patients.