Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. METHODS: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. RESULTS: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). CONCLUSION: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Determinants and Clinical Relevance of Iodine Contrast Extravasation after Endovascular Thrombectomy: A Dual-Energy CT Study.

BACKGROUND AND PURPOSE: Iodine contrast extravasation (ICE) is common in patients with acute ischemic stroke (AIS) after endovascular-thrombectomy (EVT). The aim of our study was to evaluate the incidence of ICE assessed by dual-energy CT (DECT), its determinants, and associations with clinical outcome. MATERIALS AND METHODS: We retrospectively examined imaging parameters and clinical factors from consecutive patients with AIS treated with EVT who had a DECT 24 hours thereafter, identified at a single academic center. Associations between ICE, clinical, imaging, and procedural parameters, as well as clinical outcome were explored by using univariable and multivariable models. RESULTS: A total of 197 consecutive patients were included (period 2019-2020), of which 53 (27%) demonstrated ICE that was pure ICE in 30/53 (57%) and mixed with intracranial hemorrhage (ICH) in 23/53 (43%). Low initial-ASPECTS, high per-procedural-contrast volume injected, and high admission-glycemia were independently associated with ICE (respectively, OR = 0.43, 95% CI, 0.16-1.13, P = .047; OR = 1.02, 95% CI, 1.00-1.04, P = .003; OR = 8.92, 95% CI, 0.63-125.77, P = .043). ICE was independently associated with ICH (P = .047), but not with poorer clinical outcome (6-month mRS >2, P = .223). Univariate analysis demonstrated that low ADC, higher ischemic volume, ICA occlusion, mass effect, longer procedure duration, combined thrombectomy technique, higher number of device passes, and lower recanalization rate were associated with ICE (respectively, P = .002; <.001; .002; <.001; .002; 0.011; <0.001; 0.015). CONCLUSIONS: ICE evaluated with DECT is a relatively frequent finding after EVT, present in almost one-third of patients. Lower admission ASPECTS, higher glycemia, and high contrast volume injected per procedure were associated with ICE. We also found an association between ICE and ICH, confirming blood-brain barrier alteration as a major determinant of ICH.

Factors associated with delayed revascularization in patients with ischemic stroke: a prospective study in one French region.

BACKGROUND AND IMPORTANCE: Optimizing the care pathway of stroke is crucial for the revascularization of ischemic stroke. OBJECTIVES: to identify factors associated with (1) a time interval over 4 h between the symptom onset and cerebral imaging in suspected stroke patients and (2) the absence of revascularization in patients with ischemic stroke. DESIGN, SETTINGS AND PARTICIPANTS: Patients over 18 years old with a suspected stroke admitted in 22 emergency rooms or stroke units in one French region between 1 March 2019 and 30 April 2019 were prospectively included by filling a dedicated form. OUTCOME MEASURES AND ANALYSIS: Factors associated with the previously mentioned outcome measures were identified using logistic regression models. MAIN RESULTS: In total 991 patients were included; 537 patients (64% of 845 with available time intervals) were admitted more than 4 h after symptom onset. Three predictors were identified: not calling emergency medical services (EMS) [odds-ratio (OR) 5.2; 95% confidence interval (3.4-8.1)], a preexisting autonomy loss [2.0 (1.3-2.9)] and atypical clinical presentation [2.0 (1.3-3.1)]. A total of 385 patients had an ischemic stroke of whom 93 underwent a revascularization procedure (24%). The same three predictors were associated with the absence of revascularization procedure, added to an initial admission in a hospital without stroke unit [3.1 (1.1-8.6)]. CONCLUSION: This study shows that efforts to organize the care chain for stroke need to be intensified in the region to reduce treatment time intervals, which could include information campaigns focused on the impact of EMS call and the clinical presentation recognition.

Quantitative analysis of thrombus migration before mechanical thrombectomy: Determinants and relationship with procedural and clinical outcomes.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke (AIS) and a large vessel occlusion (LVO), thrombus migration (T-Mig) is a common phenomenon before mechanical thrombectomy (MT), revealed by pre-treatment imaging. Previous works have used qualitative scales to define T-Mig. The aim of this study was to evaluate the determinants and impact of quantitatively assessed T-Mig on procedural characteristics and clinical outcome. METHODS: Consecutive patients with AIS due to LVO treated by MT at a reference academic hospital were analysed. Distance between vessel origin and beginning of the thrombus on MRI (3D-time-of-flight and/or contrast-enhanced magnetic-resonance-angiography) and digital-substracted-angiography (DSA) were measured in millimeters using a curve tool. Thrombus migration was defined quantitatively as ∆TD calculated as the difference between pre-MT-DSA and MRI thrombus location. ∆TD was rated as significant if above 5mm. RESULTS: A total of 267 patients were included (mean age 70±12 years; 46% females) were analyzed. Amongst them, 65 (24.3%) experienced any degree of T-Mig. T-Mig was found to be associated with iv-tPA administration prior to thrombectomy (ß-estimate 2.52; 95% CI [1.25-3.79]; p<0.001), fewer device passes during thrombectomy (1.22±1.31 vs 1.66±0.99; p<0.05), and shorter pre-treatment thrombi (ß-estimate -0.1millimeter; 95% CI [-0.27-0.07]; p<0.05). There was no association between T-Mig and a favourable outcome (defined by a 0-to-2 modified-Rankin-Scale at 3months, adjusted OR: 2.16 [0.93 - 5.02]; p=0.06) CONCLUSION: Thrombus migration happens in almost a fourth of our study sample, and its quantitative extent was associated with iv-tPA administration prior to MT, but not with clinical outcome.

Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials.

BACKGROUND: A larger therapeutic window for stroke treatment requires a significant change in the organization of emergency services, avoiding the increase in number of imaging exams and indirectly the time to treatment. OBJECTIVE: To highlight the relation between faster clinical evaluation and stroke over-suspicion and consequently excessive imaging acquisition. To identify predictors of ischemic stroke and stroke mimics (SM), aiming for better patient selection for comprehensive neuroimaging and reperfusion therapies. METHODS: Retrospective, cohort, observational, single-center study that reviewed all consecutive files of patients presenting with acute neurological symptoms who underwent CT scan or MRI from July 1, 2016 to July 1, 2017. RESULTS: 736 patient files were reviewed. 385 patients (52.3%) presented with confirmed acute ischemic infarct, 93 (12.6%) had another brain lesion mimicking acute ischemia, and 258 (35.1%) had normal imaging. Acute stroke was more frequent in elderly patients with atrial fibrillation, arterial hypertension, or dysarthria or right motor impairment. Stroke mimic was associated with female patients with low vascular risk factors, low NIHSS, and patients with decreased level of consciousness or symptoms suggestive of posterior circulation. DISCUSSION: 47.7% of all patients seen at the stroke unit did not have acute stroke lesions. Clinical assessment data have been used to provide indicators of acute stroke and stroke mimic patients, and symptoms corresponding to acute stroke and stroke mimic seem to be similar in the literature. CONCLUSION: Considering that the number of patients admitted for stroke treatment will increase even further with a larger therapeutic window for mechanical thrombectomy and for thrombolysis, a diagnostic decision-making algorithm for stroke patients is required in order to reinforce the suspicion of stroke indicating an urgent MRI.

Stroke-mimics in stroke-units. Evaluation after changes imposed by randomized trials / Imitadores de AVC em unidades de AVC. Avaliação após alterações impostas por ensaios randomizados

Abstract A larger therapeutic window for stroke treatment requires a significant change in the organization of emergency services, avoiding the increase in number of imaging exams and indirectly the time to treatment. Objective: To highlight the relation between faster clinical evaluation and stroke over-suspicion and consequently excessive imaging acquisition. To identify predictors of ischemic stroke and stroke mimics (SM), aiming for better patient selection for comprehensive neuroimaging and reperfusion therapies. Methods: Retrospective, cohort, observational, single-center study that reviewed all consecutive files of patients presenting with acute neurological symptoms who underwent CT scan or MRI from July 1, 2016 to July 1, 2017. Results: 736 patient files were reviewed. 385 patients (52.3%) presented with confirmed acute ischemic infarct, 93 (12.6%) had another brain lesion mimicking acute ischemia, and 258 (35.1%) had normal imaging. Acute stroke was more frequent in elderly patients with atrial fibrillation, arterial hypertension, or dysarthria or right motor impairment. Stroke mimic was associated with female patients with low vascular risk factors, low NIHSS, and patients with decreased level of consciousness or symptoms suggestive of posterior circulation. Discussion: 47.7% of all patients seen at the stroke unit did not have acute stroke lesions. Clinical assessment data have been used to provide indicators of acute stroke and stroke mimic patients, and symptoms corresponding to acute stroke and stroke mimic seem to be similar in the literature. Conclusion: Considering that the number of patients admitted for stroke treatment will increase even further with a larger therapeutic window for mechanical thrombectomy and for thrombolysis, a diagnostic decision-making algorithm for stroke patients is required in order to reinforce the suspicion of stroke indicating an urgent MRI.

Resumo Uma janela terapêutica maior para o tratamento do AVC exige uma mudança significativa na organização dos serviços de emergência, para evitar o aumento do número de exames de imagem e indiretamente o tempo de tratamento. Objetivo: destacar a relação entre avaliação clínica mais rápida e suspeita de acidente vascular cerebral e, consequentemente, aquisição de imagem excessiva, e identificar preditores de acidente vascular cerebral isquêmico e imitações de acidente vascular cerebral (SM), visando uma melhor seleção de pacientes para terapias abrangentes de neuroimagem e reperfusão. Métodos: estudo observacional de coorte retrospectivo, em centro único, que revisou todos os arquivos consecutivos de pacientes com sintomas neurológicos agudos submetidos à tomografia computadorizada ou ressonância magnética de 1 de julho de 2016 a 1 de julho de 2017. Resultados: Foram revisados 736 prontuários. 385 pacientes (52,3%) apresentaram infarto isquêmico agudo confirmado, 93 (12,6%) apresentaram outra lesão cerebral imitando isquemia aguda e 258 (35,1%) apresentaram imagem normal. O AVC agudo foi mais frequente em pacientes idosos com fibrilação atrial, hipertensão arterial, ou disartria ou comprometimento motor direito. A imitação de acidente vascular cerebral foi associada a pacientes do sexo feminino com baixos fatores de risco vascular, NIHSS baixo e pacientes com diminuição do nível de consciência ou sintomas sugestivos de circulação posterior. Discussão: 47,7% de todos os pacientes atendidos na unidade de AVC não apresentaram lesões agudas de AVC. Conclusão: Considerando que o número de pacientes admitidos para tratamento de AVC aumentará ainda mais com uma janela terapêutica maior para trombectomia e trombólise IV, é necessário um algoritmo de tomada de decisão diagnóstica para pacientes com AVC, a fim de reforçar a suspeita de AVC indicando uma imagem cerebral urgente.

Early Sitting in Ischemic Stroke Patients (SEVEL): A Randomized Controlled Trial.

BACKGROUND: Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients. OBJECTIVE: As early mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome. METHODS: This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score [0-2] at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure. RESULTS: One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin [0-2] score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms. CONCLUSION: Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke outcome with a realized 37% power. However, enrollment was sufficient to rule out effect sizes greater than 25% with 80% power, indicating that early sitting is unlikely to have an extreme effect in either direction on stroke outcome. Additionally, we were not able to provide a blinded assessment of the primary outcome. Taking these limitations into account, our results may help guide the development of more effective acute stroke rehabilitation strategies, and the design of future acute stroke trials involving out of bed activities and other mobilization regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT01573299.

Functional Outcome of Hemorrhagic Transformation after Thrombolysis for Ischemic Stroke: A Prospective Study.

BACKGROUND/AIMS: Hemorrhagic transformation (HT) is usually taken into account when symptomatic, but the role of asymptomatic HT is not well known. The aim of our study was to evaluate the link between HT after thrombolysis for ischemic stroke and functional outcome at 3 months, with particular emphasis on asymptomatic HT. METHODS: Our study was performed prospectively between June 2012 and June 2013 in the Stroke Unit of the University Hospital Center of Tours (France). All patients treated with intravenous thrombolysis were consecutively included. HT was classified on susceptibility-weighted imaging (SWI) with 3-tesla MRI at 7 ± 3 days after treatment. We evaluated functional outcome at 3 months using the modified Rankin Scale (mRS). Dependency was defined as an mRS score of ≥ 3. RESULTS: After 1 year, 128 patients had received thrombolytic therapy for ischemic stroke, of whom 90 patients underwent both 3-tesla MRI and SWI at day 7. Fifty-two had HT, including 8 symptomatic cases. At 3 months, 68% of those patients were dependent compared to 31% of patients without HT [OR 4.6 (1.9-11.4), p = 0.001]. In asymptomatic HT, the rate was 62% [OR 3.5 (1.4-8.9), p = 0.007], but did not reach significance after adjustment for stroke severity. DISCUSSION: Our study found no statistically significant effect of HT on outcome after adjustment for initial stroke severity. However, the innocuousness of HT is not certain, and only few studies have already highlighted the increased risk of dependency. Using 3-tesla MRI with SWI allows us to increase the detection rate of small hemorrhage. CONCLUSION: HT after thrombolysis is very frequent on SWI, but the initial stroke severity is an important predictor to assess the role of HT for patient outcome.

Quality of Life After Off-Label Thrombolysis for Ischemic Stroke in Elderly Patients.

INTRODUCTION: The use of intravenous thrombolysis with alteplase for ischemic stroke in Europe is restricted to subjects aged <80 years. Recent studies have reported the efficacy and safety of alteplase in older patients. However, data concerning the quality of life (QOL) of these elderly subjects are sparse. OBJECTIVES: The aim of this study was to compare the QOL of patients aged ≥80 years with that of patients aged <80 years at 3 months after thrombolysis. METHOD: This was a prospective study comprising French-speaking patients aged >18 years treated using thrombolytic therapy for ischemic stroke at the Hospital of Tours (Tours, France) between June 2012 and January 2013. QOL was assessed using the Stroke Impact Scale (SIS). The presence of mood disorders or cognitive impairments was also assessed. RESULTS: QOL was evaluated for 62 subjects among the 83 enrolled patients who received thrombolytic treatment; 21 patients were aged >80 years. Concerning scores on the SIS, using a multivariate analysis, only the memory and thinking score was significantly and negatively associated with the elderly population [odds ratio (OR) 0.036, 95% confidence interval (CI) 0.004-0.339; p = 0.004]. No significant difference was observed among all the other QOL scores. Neurological recovery and functional status did not differ between the two groups. CONCLUSION: QOL after intravenous thrombolysis in the elderly population was comparable to that of younger subjects. Despite its small sample size, this study showed promising results in favor of intravenous thrombolysis in the elderly population and highlighted the importance of systematic screening for post-stroke cognitive impairment, particularly in this population.

Diagnostic and therapeutic value of echocardiography during the acute phase of ischemic stroke.

BACKGROUND: Echocardiography is routinely used to identify potential cardiac sources of embolism (CSE) in the acute phase of ischemic stroke (IS). We know that transoesophageal echography (TEE) is superior to detect CSE than transthoracic echography (TTE). However, the indications of each technique remain controversial. We aimed to evaluate the diagnostic yield (DY) and the therapeutic impact (TI) of echocardiography (both techniques combined) in IS and to analyze impact of clinical factors on these values. METHODS: We included consecutive IS patients over a period of 22 months. All patients underwent TTE, and selected patients (young or with a high suspicion of cardioembolic origin) then underwent TEE. DY (detection of CSE) and TI (introduction of oral anticoagulant, closure of patent foramen ovale and targeted cardiologic consultation) were systematically evaluated. RESULTS: We analyzed 300 patients (mean age 61 years). All patients underwent TTE and 127 patients underwent TTE and TEE. Echocardiography overall detected CSE in 22% of patients with a TI in 11% of all cases. The TI was higher in patients less than or equal to 55 years of age. In contrast to other studies, the DY and TI of echocardiography were not associated with vascular risk factors. CONCLUSIONS: Echocardiography, as currently practiced in our stroke unit, allows detection of CSE in one patient in five, and leads to change in therapy in half of these cases. Our results suggest that TTE should be used for all patients admitted for IS, and to limit the use of TEE to younger patients.

Contribution of corticospinal tract and functional connectivity in hand motor impairment after stroke.

BACKGROUND: Motor outcome after stroke is associated with reorganisation of cortical networks and corticospinal tract (CST) integrity. However, the relationships between motor severity, CST damage, and functional brain connectivity are not well understood. Here, the main objective was to study the effect of CST damage on the relationship between functional motor network connectivity and hand motor function in two groups of stroke patients: the severely (n=8) and the mildly impaired (n=14). METHODS: Twenty-two carotid stroke patients with motor deficits were studied with magnetic resonance imaging (MRI) at 3 weeks, at 3 and 6 months. Healthy subjects (n=28) were scanned once. The CST injury was assessed by fractional anisotropy values. Functional connectivity was studied from a whole-hand grip task fMRI in a cortical and cerebellar motor network. Functional connectivity indexes were computed between these regions at each time point. The relationship between hand motor strength, ipsilesional CST damage and functional connectivity from the primary motor cortex (M1) was investigated using global and partial correlations. FINDINGS: In mildly impaired patients, cortico-cortical connectivity was disturbed at three weeks but returned to a normal pattern after 3 months. Cortico-cerebellar connectivity was still decreased at 6 months. In severely impaired patients, the cortico-cortical connectivity tended to return to a normal pattern, but the cortico-cerebellar connectivity was totally abolished during the follow-up. In the entire group of patients, the hand motor strength was correlated to the ipsilesional functional connectivity from M1. Partial correlations revealed that these associations were not anymore significant when the impact of CST damage was removed, except for the ipsilesional M1-contralateral cerebellum connectivity. CONCLUSION: Functional brain connectivity changes can be observed, even in severely impaired patients with no recovery. Upper limb function is mainly explained by the CST damage and by the ipsilesional cortico-cerebellar connectivity.

Assessment of corticospinal tract (CST) damage in acute stroke patients: comparison of tract-specific analysis versus segmentation of a CST template.

PURPOSE: To compare two techniques to assess corticospinal tract (CST) damage in stroke patients: tract-specific analysis by probabilistic tractography and segmentation using a CST template. MATERIALS AND METHODS: We extracted fractional anisotropy (FA) values, the FA ratio, and mean diffusivity (MD) in 18 stroke patients and 21 healthy volunteers matched for age and sex. We compared the two methods in order to determine their ability to detect 1) differences between diffusion tensor imaging (DTI) parameters of healthy volunteers and stroke patients, 2) the correlation between DTI parameters and clinical scores, and 3) the correlation between DTI parameters and blood oxygen level-dependent (BOLD) signals in a fist-closure task. RESULTS: FA values were higher with the tractography approach than with the segmentation method, but differences between the ipsilesional CST and the homologous region in healthy subjects were detected using both methods. In patients, clinical scores were significantly correlated with FA values and FA ratios with both methods. The BOLD signal was positively correlated with FA values for CST with the segmentation but not with the tractography approach. CONCLUSION: CST damage in stroke patients can be assessed by either probabilistic tractography or segmentation of a CST template. Although each method has advantages and limitations, both are sensitive enough to detect differences among stroke patients and identify specific correlations with clinical scores.