Mathilde Poli

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.

Circadian sleep/wake rhythm abnormalities as a risk factor of a poststroke apathy

Background Poststroke apathy affects 19–55% of patients following stroke and has a negative impact on functional recovery, general health, and quality of life, as well as being a source of significant burden for caregivers. Aims A major clinical issue is the delayed diagnosis of post-stroke apathy, and so the aim of our study is to evaluate the relationship between early poststroke alterations of circadian rhythms of sleep/wake cycles and the occurrence of poststroke apathy. Methods Forty-six patients with a recent magnetic resonance imaging confirmed stroke were included. Main exclusion criteria were a mild to severe disability impeding home discharge from the hospital and the presence of apathy or dementia before stroke. Cerebrovascular lesions were evaluated by magnetic resonance imaging. At hospital discharge, an actigraph was used to measure patients global activity as well as parameters of circadian rhythmicity (relative amplitude, interdaily stability, intradaily variability) and sleep (sleep duration, sleep efficiency, fragmentation index) over seven-days. Apathy was assessed at hospital discharge as well as at three-months using the Apathy Inventory and the Lille Apathy Rating Scale. Results Of the 46 patients evaluated, 10 (22%) showed apathy three-months after stroke (median Apathy Inventory = 4·5). Before inclusion, these 10 subjects did not differ significantly from other patients concerning their sleep and, at inclusion, they did not differ concerning apathy, anxiety, depression, or cognitive and functional abilities. However, actigraphy measured at discharged identified significant alterations of sleep (P < 0·005). Future poststroke apathy patients exhibited a decrease in sleep efficiency (actual sleep time expressed as a percentage of time in bed) and an increase in the fragmentation index (degree of fragmentation during the sleep period) at three-months. No association was observed between poststroke apathy and the characteristics of cerebrovascular lesions (stroke location, extent of leucoencephalopathy, number of lacunes and microbleeds). Conclusion These results indicate that early poststroke alterations of sleep/wake circadian rhythms — easily evaluated by actigraphy — are associated with a higher risk of poststroke apathy at three-months. In terms of clinical outcomes, our results provide targets for very early identification of patients at risk to develop apathy after stroke and for assessing when to start specific therapy to optimize rehabilitation efficiency.

Left Atrial Appendage Closure in Patients with Atrial Fibrillation and Previous Intracerebral Hemorrhage

BACKGROUND Percutaneous left atrial appendage closure (LAAC) may be considered in patients with atrial fibrillation and contraindication for long-term anticoagulation. This study aimed to assess the safety and efficacy of LAAC followed by single antiplatelet therapy in patients with atrial fibrillation and previous spontaneous intracerebral hemorrhage (ICH). METHODS In this explorative, prospective, single-center study, consecutive patients who underwent LAAC because of previous spontaneous ICH over a period of 4 years were analyzed. Risks of ischemic strokes and hemorrhagic complications were estimated using the CHA2DS2-VASc and HAS-BLED scores, respectively. Single antiplatelet therapy was given for at least 6 months post implantation. Clinical follow-up included cardiological evaluations at 1, 3, 6, and 12 months, and neurological evaluations at 3 and 12 months. RESULTS A total of 46 patients underwent LAAC with a mean follow-up of 12 ± 7 months. The observed annual rate of ischemic stroke was 4.35% compared with an expected rate of 7.23% according to the mean risk of the population based on CHA2DS2-VASc score, which translated into a 40% risk reduction. The observed annual rate of major bleeding was 4.35% compared with an expected rate of 8.05% according to the mean risk of the population based on HAS-BLED score, which translated into a 46% risk reduction. CONCLUSIONS LAAC followed by single antiplatelet therapy is feasible as an alternative to oral anticoagulation in high-risk patients with previous ICH, with an acceptable periprocedural risk. Longer follow-up in a larger number of patients will be needed to establish the effectiveness of LAAC relative to direct oral anticoagulants.

Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later

Objective: To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. Design: Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. Setting: A university hospital acute stroke unit. Subjects: Thirty-four mild ischemic stroke patients. Interventions: None. Main measures: One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. Results: The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels (p = 0.041) and increases in activities of daily living (p = 0.011). Material support from friends and family was associated with increases in activities of daily living (p = 0.012). No effect was observed for support received from medical staff. Conclusions: Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.

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.

Atrial fibrillation is a major cause of stroke in apneic patients: a prospective study

OBJECTIVES Large prospective studies have established that sleep-disordered breathing (SDB) is associated with an increased incidence of cardiovascular and cerebrovascular diseases. Heterogeneous results have been published about SDB and ischaemic stroke mechanism. The aim of this study was to evaluate the relationship between poststroke apneic syndrome and stroke aetiologies according to the ASCO classification. METHODS A total of 134 patients with acute ischaemic cerebrovascular events were prospectively included. Patients with severe or infratentorial infarctions were excluded. Stroke risk factors and clinical characteristics were recorded in all patients. An overnight polygraphy was recorded (Embletta PDS). Apneic patients were defined if the polygraphy reported an apnea-hypopnea index ≥15. A standardized diagnosis workup, including serum biological investigation, evaluation of extra and intracranial arteries and heart morphology and function, was performed. Stroke mechanism was defined using ASCO and TOAST classifications. RESULTS A proportion of 42% (56 of 134) of the patients were diagnosed as having sleep apneas. Apneic patients were older (p < 0.001), had higher BMI (p = 0.02), and more were hypertensive (p < 0.001). Using ASCO classification, a major cardioembolic source of stroke, mainly atrial fibrillation, was more frequently observed in apneic patients (41.1% vs. 20.5%, p < 0.05), while no difference was observed when considering atherosclerosis or small-vessel disease mechanisms. Univariate analysis showed that cardioembolic stroke depends on sex, age, left atrial size and OSA; however, age remained the only significant factor in multivariate analysis. CONCLUSION This study confirms the high prevalence of sleep apneas in stroke-affected patients and identifies atrial fibrillation as a major source of stroke in this population. The strong correlation between age and SDB seems to drive the increased frequency of stroke related to atrial fibrillation in this population.

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.

Resting Heart Rate Predicts Depression and Cognition Early after Ischemic Stroke: A Pilot Study

BACKGROUND Early detection of poststroke depression (PSD) and cognitive impairment (PSCI) remains challenging. It is well documented that the function of autonomic nervous system is associated with depression and cognition. However, their relationship has never been investigated in the early poststroke phase. This pilot study aimed at determining whether resting heart rate (HR) parameters measured in early poststroke phase (1) are associated with early-phase measures of depression and cognition and (2) could be used as new tools for early objective prediction of PSD or PSCI, which could be applicable to patients unable to answer usual questionnaires. METHODS Fifty-four patients with first-ever ischemic stroke, without cardiac arrhythmia, were assessed for resting HR and heart rate variability (HRV) within the first week after stroke and for depression and cognition during the first week and at 3 months after stroke. RESULTS Multiple regression analyses controlled for age, gender, and stroke severity revealed that higher HR, lower HRV, and higher sympathovagal balance (low-frequency/high-frequency ratio of HRV) were associated with higher severity of depressive symptoms within the first week after stroke. Furthermore, higher sympathovagal balance in early phase predicted higher severity of depressive symptoms at the 3-month follow-up, whereas higher HR and lower HRV in early phase predicted lower global cognitive functioning at the 3-month follow-up. CONCLUSIONS Resting HR measurements obtained in early poststroke phase could serve as an objective tool, applicable to patients unable to complete questionnaires, to help in the early prediction of PSD and PSCI.