Safety and efficacy of reperfusion therapies in acute ischemic stroke related to left ventricular thrombus: A retrospective cohort study.

BACKGROUND: Left ventricular thrombus (LVT) is a source of cardiogenic embolic stroke. Conflicting data exist in the literature regarding the utilization of intravenous thrombolysis (IVT) at the acute phase of stroke in presence of LVT. We sought to assess the efficacy and safety of reperfusion therapies (IVT and/or thrombectomy) in patients with LVT. METHODS: We retrospectively analyzed patients with acute ischemic stroke and proven LVT and divided them in two groups: an intervention group with patients treated by reperfusion therapies and a control group with untreated patients. RESULTS: Between 2009 and 2021, 3890 patients were treated by reperfusion therapies in the Lyon stroke center, 33 of whom (0.9%) had LVT. We identified 27 control patients. There were more embolic recurrences at six months in the intervention group than in the control group (nine recurrences versus three, P=0.03, OR=13.56, 95% CI [1.5;195]). Only two early embolic recurrences (< 24h) occurred, both in the IVT group. There was a 4.8-fold decrease in the median NIHSS score between baseline and 24h follow-up in the intervention group (P<0.0001), and the two groups exhibited similar six-month mortality. At stroke onset, cardiopathy was known in 70% of patients, while LVT was known in 30%. CONCLUSION: Acute reperfusion therapies seem to be effective in the context of stroke in patients with LVT. However, further studies are needed to support the hypothesis that stroke recurrence might be related to the use of IVT.

Comparison of magnetic resonance angiography techniques to brain digital subtraction arteriography in the setting of mechanical thrombectomy: A non-inferiority study.

INTRODUCTION: We performed a non-inferiority study comparing magnetic resonance angiography (MRA) techniques including contrast-enhanced (CE) and time-of-flight (TOF) with brain digital subtraction arteriography (DSA) in localizing occlusion sites in acute ischemic stroke (AIS) with a prespecified inferiority margin taking into account thrombus migration. MATERIALS AND METHODS: HIBISCUS-STROKE (CoHort of Patients to Identify Biological and Imaging markerS of CardiovascUlar Outcomes in Stroke) includes large-vessel-occlusion (LVO) AIS treated with mechanical thrombectomy (MT) following brain magnetic resonance imaging (MRI) including both CE-MRA and TOF-MRA. Locations of arterial occlusions were assessed independently for both MRA techniques and compared to brain DSA findings. Number of patients needed was 48 patients to exclude a difference of more than 20%. Discrepancy factors were assessed using univariate general linear models analysis. RESULTS: The study included 151 patients with a mean age of 67.6±15.9years. In all included patients, TOF-MRA and CE-MRA detected arterial occlusions, which were confirmed by brain DSA. For CE-MRA, 38 (25.17%) patients had discordant findings compared with brain DSA and 50 patients (33.11%) with TOF-MRA. The discordance factors were identical for both MRA techniques namely, tandem occlusions (OR=1.29, P=0.004 for CE-MRA and OR=1.61, P<0.001 for TOF-MRA), proximal internal carotid artery occlusions (OR=1.30, P=0.002 for CE-MRA and OR=1.47, P<0.001 for TOF-MRA) and time from MRI to MT (OR=1.01, P=0.01 for CE-MRA and OR=1.01, P=0.02 for TOF-MRA). CONCLUSION: Both MRA techniques are inferior to brain DSA in localizing arterial occlusions in LVO-AIS patients despite addressing the migratory nature of the thrombus.

Patients' productivity losses and informal care costs related to ischemic stroke: a French population-based study.

BACKGROUND AND PURPOSE: Large societal costs of stroke should not be ignored. We aimed to estimate patients' productivity losses and informal care costs during the first year after ischemic stroke. METHODS: A cross-sectional survey was performed within the STROKE69 regional population-based cohort study. At 1 year post-stroke, each patient and the corresponding main informal caregiver received questionnaires followed by a telephone interview if necessary. Time losses were valued using the human capital approach and proxy good method for patients with and without a professional activity, respectively. RESULTS: Among the 222 patients with ischemic stroke (58% men; mean age 68 years; and 86% with a modified Rankin Scale (mRS) score of <3 at 3 months), 54%, 32%, and 25% received informal, formal, and both cares, respectively. Among the 108 main informal caregivers, 63% were women, 74% lived with the patient, and 57% were retired or unemployed. The mean cost of productivity losses was estimated at €7589 ± €12 305 per patient in the first post-stroke year with 5.4%, 71.2%, and 23.4% of these being attributed to presenteeism, absenteeism, and leisure time, respectively. Informal care was given at an average of 25 h/week. The annual mean estimated total cost of informal care was €10 635 per caregiver. CONCLUSIONS: Informal care and productivity losses of patients with ischemic stroke during the first post-stroke year represent a significant economic burden for society comparable to direct costs. These costs should be included in economic evaluations with the adoption of a societal perspective to avoid underestimating the societal stroke economic burden.

Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

Short and long-term impact of four sets of actions on acute ischemic stroke management in Rhône County, a population based before-and-after prospective study.

BACKGROUND: Optimizing access to recanalization therapies in acute ischemic stroke patients is crucial. Our aim was to measure the short and long term effectiveness, at the acute phase and 1 year after stroke, of four sets of actions implemented in the Rhône County. METHODS: The four multilevel actions were 1) increase in stroke units bed capacity and development of endovascular therapy; 2) improvement in knowledge and skills of healthcare providers involved in acute stroke management using a bottom-up approach; 3) development and implementation of new organizations (transportation routes, pre-notification, coordination by the emergency call center physician dispatcher); and 4) launch of regional public awareness campaigns in addition to national campaigns. A before-and-after study was conducted with two identical population-based cohort studies in 2006-7 and 2015-16 in all adult ischemic stroke patients admitted to any emergency department or stroke unit of the Rhône County. The primary outcome criterion was in-hospital management times, and the main secondary outcome criteria were access to reperfusion therapy (either intravenous thrombolysis or endovascular treatment) and pre-hospital management times in the short term, and 12-month prognosis measured by the modified Rankin Scale (mRS) in the long term. RESULTS: Between 2015-16 and 2006-7 periods ischemic stroke patients increased from 696 to 717, access to reperfusion therapy increased from 9 to 23% (p < 0.0001), calls to emergency call-center from 40 to 68% (p < 0.0001), first admission in stroke unit from 8 to 30% (p < 0.0001), and MRI within 24 h from 18 to 42% (p < 0.0001). Onset-to-reperfusion time significantly decreased from 3h16mn [2 h54-4 h05] to 2h35mn [2 h05-3 h19] (p < 0.0001), mainly related to a decrease in delay from admission to imaging. A significant decrease of disability was observed, as patients with mild disability (mRS [0-2]) at 12 months increased from 48 to 61% (p < 0.0001). Pre-hospital times, however, did not change significantly. CONCLUSIONS: We observed significant improvement in access to reperfusion therapy, mainly through a strong decrease of in-hospital management times, and in 12-month disability after the implementation of four sets of actions between 2006 and 2016 in the Rhône County. Reducing pre-hospital times remains a challenge.

Acute telestroke in France: A systematic review.

BACKGROUND: Acute telestroke is the use of telemedicine to improve acute stroke care. It has demonstrated to be a safe and effective medical practice. Since 2011, acute telestroke has been promoted by the Ministry of Health in France, and in 2018 many regions were in the process or completion of implementing telestroke. The objective of this study was to describe acute telestroke implementation in France. METHODS: A systematic review was conducted using PubMed and ScienceDirect databases. Articles and abstracts in English and French, published between January 1st, 2000 to April 30th, 2018 were used. Studies conducted in France and that had presented an outcome evaluation of a regional acute telestroke activity were included. No meta-analysis was conducted. RESULTS: A total of 24 studies (14 in French, 10 in English) were included, with 13 published articles (7 indexed on PubMed) and 11 abstracts. Among the 13 published articles, there were seven observational retrospective studies, one quasi-experimental before-after study, one experimental randomised controlled trial, and four medico-economic studies. All telestroke network models of care were drip-and-ship with hub and spoke organisation. The case-control studies did not show a difference with or without telemedicine. The territorial thrombolysis rate was measured in two regions, with an increase in Franche-Comté from 0.2% (2004) to 9.9% (2015), and a relative increase of 76% in Nord-Pas-de-Calais between 2009-2010 and 2012. CONCLUSION: Implementation of acute telestroke in France had a positive clinical and public health impact but the evaluation remained limited and needs to be supported.

Multifocal arterial wall contrast - enhancement in ischemic stroke: A mirror of systemic inflammatory response in acute stroke.

PURPOSE: Intracranial plaque gadolinium enhancement revealed by high-resolution MRI imaging (HR MRI) is considered as a marker of plaque inflammation, a contributing factor of plaque unstability. The aim of the present study was to assess the distribution of gadolinium enhancement in intracranial atherosclerosis. METHODS: Single center analysis of ischemic stroke patients with intracranial atherosclerotic stenosis of M1 or M2 segments of middle cerebral artery, or terminal internal carotid artery (ICA) based on CT-angio or MR-angio. High-resolution MRI imaging (HRMRI) was performed within 6 first weeks following the index event, with 3DT2 BB (black-blood) and 3D T1 BB MR sequences pre and post-contrast administration. RESULTS: We identified 8 patients with 14 plaques, 4 were deemed non-culprit and 10 culprit. All culprit plaques (10/10 plaques) and 3 out of 4 non-culprit plaques showed a gadolinium enhancement. CONCLUSION: At the acute/subacute stage of stroke, a gadolinium enhancement may affect multiple asymptomatic intracranial plaques and may reflect a global inflammatory state.

Health policy for telestroke in France: A retrospective description from 2003 to 2016.

INTRODUCTION: Stroke is a public health priority in France. The use of telemedicine for stroke known as telestroke, is a safe and effective practice improving access to acute stroke care including thrombolysis. Telestroke is currently being implemented in France. The objective was to describe the public health policy supporting telestroke implementation in France. METHODS: An external ex-post evaluation of telestroke policy in France was conducted through a retrospective descriptive study from 2003 to 31st December 2016. Process, content, and actors of the health policy were described at a national level. The logical framework of the telestroke policy was described. The stages model of public policy from the 'Institut National de Santé Publique du Quebec' was used. RESULTS: Agenda setting was produced from 2003 to 2007. Policy formulation lasted from 2008 to 2009 with official reports on telemedicine, telehealth and stroke. The decision-making stage included the national stroke plan, the national telemedicine implementation strategy and an administrative document in 2012 that described the organization of telestroke implementation. Implementation in 2011 was initiated with dedicated funding and methodological resources. No dedicated evaluation of policy for telestroke was defined. CONCLUSIONS: Using a health policy model allowed to describe the policies supporting telestroke implementation in France and to highlight the need for better evaluation.

Measurement of the potential geographic accessibility from call to definitive care for patient with acute stroke.

BACKGROUND: The World Health Organization refers to stroke, the second most frequent cause of death in the world, in terms of pandemic. Present treatments are only effective within precise time windows. Only 10% of thrombolysis patients are eligible. Late assessment of the patient resulting from admission and lack of knowledge of the symptoms is the main explanation of lack of eligibility. METHODS: The aim is the measurement of the time of access to treatment facilities for stroke victims, using ambulances (firemen ambulances or EMS ambulances) and private car. The method proposed analyses the potential geographic accessibility of stroke care infrastructure in different scenarios. The study allows better considering of the issues inherent to an area: difficult weather conditions, traffic congestion and failure to respect the distance limits of emergency transport. RESULTS: Depending on the scenario, access times vary considerably within the same commune. For example, between the first and the second scenario for cities in the north of Rhône county, there is a 10 min difference to the nearest Primary Stroke Center (PSC). For the first scenario, 90% of the population is 20 min away of the PSC and 96% for the second scenario. Likewise, depending on the modal vector (fire brigade or emergency medical service), overall accessibility from the emergency call to admission to a Comprehensive Stroke Center (CSC) can vary by as much as 15 min. CONCLUSIONS: The setting up of the various scenarios and modal comparison based on the calculation of overall accessibility makes this a new method for calculating potential access to care facilities. It is important to take into account the specific pathological features and the availability of care facilities for modelling. This method is innovative and recommendable for measuring accessibility in the field of health care. This study makes possible to highlight the patients' extension of care delays. Thus, this can impact the improvement of patient care and rethink the healthcare organization. Stroke is addressed here but it is applicable to other pathologies.

Cerebrovascular events as presenting manifestations of Myeloproliferative Neoplasm.

AIM: To determine the incidence and main characteristics of cerebrovascular events as the presenting manifestations of myeloproliferative neoplasm (MPN). METHODS: The Hematology in Lyon (HEMILY) registry is a prospective database (763 patients) of all cases of MPN diagnosed since 2005 in the Rhône-Alpes district of France. The MPN cases were divided into four groups: polycythemia vera (PV); essential thrombocythemia (ET); myelofibrosis (MF); and atypical MPN. The ischemic stroke subtype was classified according to TOAST criteria. RESULTS: A stroke history revealed MPN in 35 (4.3%) patients: 22 (63%) had an ischemic stroke; eight (23%) had a transient ischemic attack; four (11%) had cerebral venous thrombosis; and one (3%) had hemorrhagic stroke. All patients had hemoglobin and/or platelet count abnormalities. In addition, 12 (34%) patients had PV, 21 (60%) had ET, one (3%) had MF and one (3%) had atypical/unclassified MPN. The JAK2 V617F mutation was found in 83% of patients. In 18 (51%) patients, an additional mechanism of stroke was present (atherosclerosis in 10 patients, atrial fibrillation in one patient and dissection in another). The median NIHSS score at entry was 2, and the median modified Rankin Scale score at 3 months was 0. Compared with the general MPN population, stroke-MPN patients presented with significantly higher levels of hemoglobin (P<0.001) and were more frequently positive for the JAK2 V617F mutation (P=0.044). CONCLUSION: Stroke revealing MPN is rare. However, careful attention should still be paid to blood counts even in patients with obvious stroke etiologies, as early diagnosis permits prompt treatment and decreases the risk of recurrence, thus limiting morbidity and mortality.

Safety of early initiation of rivaroxaban or dabigatran after thrombolysis in acute ischemic stroke.

The introduction of direct oral anticoagulants (DOA) in the early stage of cerebral infarction after thrombolysis may reduce the recurrence rate but raises safety concern. We sought to study the feasibility and safety of the introduction of rivaroxaban or dabigatran in this context. Thirty-four consecutive patients admitted for ischemic stroke related to non-valvular atrial fibrillation in whom DOA were given within the first two weeks following intravenous rt-PA were studied. A clinical and radiological monitoring protocol was established to ensure the safety of the prescription. None of the patients experienced symptomatic hemorrhagic transformation or a symptomatic recurrent ischemic event after early rivaroxaban or dabigatran introduction.

[Cerebral infarction after ovarian hyperstimulation in the era of thrombolysis]. / Infarctus cérébraux secondaires à une hyperstimulation ovarienne à l'ère de la thrombolyse.

Ischemic stroke is a very rare complication but classic ovarian hyperstimulation. We report the cases of three young women aged 35, 37 and 27 years. All three were victims of ischemic formed by proximal occlusion of the middle cerebral artery secondary to ovarian hyperstimulation. The first and the third had a proximal occlusion of the right middle cerebral artery occlusion and the second of the left middle cerebral artery. The last two have benefited from a patient intravenous thrombolysis. The first patient did not receive thrombolysis because it was out of time. Against by their evolution was different. The first has almost recovered its deficit, the second sequelae quite heavy after craniectomy and the third died despite her craniectomy.

[Sequential MRI imaging of progressive bilateral rostro-caudal medullary infarction]. / Infarctus bulbaire paramédian bilatéral d'évolution progressive: à propos de deux cas documentés en imagerie par résonance magnétique séquentielle.

Bilateral medial medullary infarction is exceptional. Initial symptoms can be misleading, even for a trained neurologist. We report two patients who presented progressive quadriplegia, anarthia and dysphagia. Sequential MRI showed progressive constitution of the characteristic "heart appearance" sign.

[Acquired amusia and musical anhedonia]. / Amusie acquise et anhédonie musicale.

Amusia is defined as an auditory agnosia, specifically related to music, resulting from a cerebral lesion or being of congenital origin. Amusia is rarely associated to musical anhedonia. We report the case of a 43-year-old patient who suffered in January 2012 from a right ischemic lesion affecting the superior temporal cortex, in particular lateral Heschl Gyrus and the posterior part of the Superior Temporal Gyrus (Brodmann areas 21 and 22). Neuropsychological tests revealed an amusia combined to musical anhedonia. The specificity of this case is based on the combination of both syndromes highlighting the relation between neural networks involved in the processing of musical information in both its perceptual and emotional components.

Effects of structural and functional cerebellar lesions on sensorimotor adaptation of saccades.

The cerebellum is critically involved in the adaptation mechanisms that maintain the accuracy of goal-directed acts such as saccadic eye movements. Two categories of saccades, each relying on different adaptation mechanisms, are defined: reactive (externally triggered) saccades and voluntary (internally triggered) saccades. The contribution of the medio-posterior part of the cerebellum to reactive saccades adaptation has been clearly demonstrated, but the evidence that other parts of the cerebellum are also involved is limited. Moreover, the cerebellar substrates of voluntary saccades adaptation have only been marginally investigated. Here, we addressed these two questions by investigating the adaptive capabilities of patients with cerebellar or pre-cerebellar stroke. We recruited three groups of patients presenting focal lesions located, respectively, in the supero-anterior cerebellum, the infero-posterior cerebellum and the lateral medulla (leading to a Wallenberg syndrome including motor dysfunctions similar to those resulting from lesion of the medio-posterior cerebellum). Adaptations of reactive saccades and of voluntary saccades were tested during separate sessions in all patients and in a group of healthy participants. The functional lesion of the medio-posterior cerebellum in Wallenberg syndrome strongly impaired the adaptation of both reactive and voluntary saccades. In contrast, patients with lesion in the supero-anterior part of the cerebellum presented a specific adaptation deficit of voluntary saccades. Finally, patients with an infero-posterior cerebellar lesion showed mild adaptation deficits. We conclude that the medio-posterior cerebellum is critical for the adaptation of both saccade categories, whereas the supero-anterior cerebellum is specifically involved in the adaptation of voluntary saccades.

[Subarachnoidal hemorrhage and multiple vascular cerebral abnormalities in ß-thalassemia major]. / Hémorragie sous-arachnoïdienne et anomalies vasculaires cérébrales multiples au cours d'une ß-thalassémie majeure.

ß-thalassemia is a genetic hemoglobinopathy, which can cause hypercoagulability, vessel wall damages and thromboembolic events. Spontaneous subarachnoidal hemorrhages are not commonly described in this affection. We report subarachnoidal hemorrhage, observed during the post-partum period in a 27-year-old woman suffering from ß-thalassemia major. Brain MRI revealed complex vascular abnormalities: intracranial carotid occlusion, carotid micro-aneurisms, abnormally developed deep perforators and cortical arteries.

Early Detection of Underlying Cavernomas in Patients with Spontaneous Acute Intracerebral Hematomas.

BACKGROUND AND PURPOSE: Early identification of the etiology of spontaneous acute intracerebral hemorrhage is essential for appropriate management. This study aimed to develop an imaging model to identify cavernoma-related hematomas. MATERIALS AND METHODS: Patients 1-55 years of age with acute (≤7 days) spontaneous intracerebral hemorrhage were included. Two neuroradiologists reviewed CT and MR imaging data and assessed the characteristics of hematomas, including their shape (spherical/ovoid or not), their regular or irregular margins, and associated abnormalities including extralesional hemorrhage and peripheral rim enhancement. Imaging findings were correlated with etiology. The study population was randomly split to provide a training sample (50%) and a validation sample (50%). From the training sample, univariate and multivariate logistic regression was performed to identify factors predictive of cavernomas, and a decision tree was built. Its performance was assessed using the validation sample. RESULTS: Four hundred seventy-eight patients were included, of whom 85 had hemorrhagic cavernomas. In multivariate analysis, cavernoma-related hematomas were associated with spherical/ovoid shape (P < .001), regular margins (P = .009), absence of extralesional hemorrhage (P = .01), and absence of peripheral rim enhancement (P = .002). These criteria were included in the decision tree model. The validation sample (n = 239) had the following performance: diagnostic accuracy of 96.1% (95% CI, 92.2%-98.4%), sensitivity of 97.95% (95% CI, 95.8%-98.9%), specificity of 89.5% (95% CI, 75.2%-97.0%), positive predictive value of 97.7% (95% CI, 94.3%-99.1%), and negative predictive value of 94.4% (95% CI, 81.0%-98.5%). CONCLUSIONS: An imaging model including ovoid/spherical shape, regular margins, absence of extralesional hemorrhage, and absence of peripheral rim enhancement accurately identifies cavernoma-related acute spontaneous cerebral hematomas in young patients.

Role of the parietal cortex in predicting incoming actions.

Animal and human studies have shown that the parietal and the ventral premotor cortices constitute the neural substrate of the so-called mirror system. The word "mirror" originally referred to the discovery of neurons in non-human primates whose visual response echoes their motor response. This account proposes that action understanding and imitation depend on a mechanism which activates directly our own motor system as we observe the actions of other agents (Rizzolatti and Sinigaglia, 2010). Single unit recording experiments have also demonstrated that parietal neurons have predictive activity and discharge well ahead of a planned movement. Interestingly, patients with parietal damage can show impairments in their ability to imitate or understand an observed action, but they have also difficulties in monitoring early phases of their own movement planning, be it simple reaching movements or more complex object-directed actions. The fact that both deficits may co-occur after a parietal lesion raises the question whether this reflects the impairment of a common mechanism. To address this question we examined EEG activity in patients with selective lesions in the inferior parietal lobe (N=6) who were requested to watch passively a video showing an actor grasping a colored object. The object's color cued the subject that the actor was about to move. We recorded the Readiness Potential (RP), a marker of motor preparation which also arises when preparing to observe an action (Kilner et al., 2004). Parietal patients' performance was compared to that of neurologically normal subjects (n=9) and patients with a ventral premotor cortex lesion (N=4). We show that neurologically normal subjects and premotor patients exhibit a significant RP prior to the observed action, whereas no such RP is observed in parietal patients. Our results indicate that parietal cortex injury alters the ability to monitor the early planning phases not only of one's own actions but those of other agents as well. We speculate that parietal activity during action observation does not only or essentially reflect a mirroring process, as recently proposed by mirror neurons' account, but involve instead an anticipatory process which arises through prior learning and predictive mechanisms.