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.

Narcolepsies, update in 2023.

Narcolepsy type 1 (NT1) and type 2 (NT2), also known as narcolepsy with and without cataplexy, are sleep disorders that benefited from major scientific advances over the last two decades. NT1 is caused by the loss of hypothalamic neurons producing orexin/hypocretin, a neurotransmitter regulating sleep and wake, which can be measured in the cerebrospinal fluid (CSF). A low CSF level of hypocretin-1/orexin-A is a highly specific and sensitive biomarker, sufficient to diagnose NT1. Orexin-deficiency is responsible for the main NT1 symptoms: sleepiness, cataplexy, disrupted nocturnal sleep, sleep-related hallucinations, and sleep paralysis. In the absence of a lumbar puncture, the diagnosis is based on neurophysiological tests (nocturnal and diurnal) and the presence of the pathognomonic symptom cataplexy. In the revised version of the International Classification of sleep Disorders, 3rd edition (ICSD-3-TR), a sleep onset rapid eye movement sleep (REM) period (SOREMP) (i.e. rapid occurrence of REM sleep) during the previous polysomnography may replace the diurnal multiple sleep latency test, when clear-cut cataplexy is present. A nocturnal SOREMP is very specific but not sensitive enough, and the diagnosis of cataplexy is usually based on clinical interview. It is thus of crucial importance to define typical versus atypical cataplectic attacks, and a list of clinical features and related degrees of certainty is proposed in this paper (expert opinion). The time frame of at least three months of evolution of sleepiness to diagnose NT1 was removed in the ICSD-3-TR, when clear-cut cataplexy or orexin-deficiency are established. However, it was kept for NT2 diagnosis, a less well-characterized disorder with unknown clinical course and absence of biolo biomarkers; sleep deprivation, shift working and substances intake being major differential diagnoses. Treatment of narcolepsy is nowadays only symptomatic, but the upcoming arrival of non-peptide orexin receptor-2 agonists should be a revolution in the management of these rare sleep diseases.

Nocturnal agitation: From sleep state dissociation to sleep-related dissociative state.

Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate identification of its etiology is critical for appropriate therapeutic intervention. In children and young adults, distinguishing between non-rapid eye movement (NREM) sleep parasomnias and psychogenic non-parasomniac manifestations, a condition known as sleep-related dissociative disorder (SRDD), can be challenging. This review aims to summarize current clinical, neurophysiological, and epidemiological knowledge on NREM parasomnia and SRDD, and to present the pathophysiological hypotheses underlying these nocturnal manifestations. Sleepwalking, sleep terror and confusional arousals are the three main presentations of NREM parasomnias and share common clinical characteristics. Parasomniac episodes generally occur 30minutes to three hours after sleep-onset, they are usually short, lasting no more than few minutes and involve non-stereotyped, clumsy behaviors with frequent amnesia. The prevalence of NREM parasomnia decreases from 15-30% in children to 2-4% in adults. Parasomniac episodes are incomplete awakening from the deepest NREM sleep and are characterized by a dissociated brain activity, with a wake-like activation in motor and limbic structures and a preserved sleep in the fronto-parietal regions. SRDD is a less known condition characterized by dramatic, often very long episodes with frequent aggressive and potentially dangerous behaviors. SRDD episodes frequently occur in quiet wakefulness before falling asleep. These dissociative manifestations are frequently observed in the context of psychological trauma. The pathophysiology of SRDD is poorly understood but could involve transient changes in brain connectivity due to labile sleep-wake boundaries in predisposed individuals. We hypothesize that SRDD and NREM parasomnia are forms of sleep-related dissociative states favored by a sleep-wake state dissociation during sleep-onset and awakening process, respectively.

Evaluation of hypersomnolence: From symptoms to diagnosis, a multidimensional approach.

Hypersomnolence is a major public health issue given its high frequency, its impact on academic/occupational functioning and on accidentology, as well as its heavy socio-economic burden. The positive and aetiological diagnosis is crucial, as it determines the therapeutic strategy. It must consider the following aspects: i) hypersomnolence is a complex concept referring to symptoms as varied as excessive daytime sleepiness, excessive need for sleep, sleep inertia, or drowsiness, all of which warrant specific dedicated investigations; ii) the boundary between physiological and abnormal hypersomnolence is blurred, since most symptoms can be encountered in the general population to varying degrees without being considered as pathological, meaning that their severity, frequency, context of occurrence and related impairment need to be carefully assessed; iii) investigation of hypersomnolence relies on scales/questionnaires as well as behavioural and neurophysiological tests, which measure one or more dimensions, keeping in mind the possible discrepancy between objective and subjective assessment; iv) aetiological reasoning is driven by knowledge of the main sleep regulation mechanisms, epidemiology, and associated symptoms. The need to assess hypersomnolence is growing, both for its management, and for assessing the efficacy of treatments. The landscape of tools available for investigating hypersomnolence is constantly evolving, in parallel with research into sleep physiology and technical advances. These investigations face the challenges of reconciling subjective perception and objective data, making tools accessible to as many people as possible and predicting the risk of accidents.

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.

Are there socio-economic inequities in access to reperfusion therapy: The stroke 69 cohort.

BACKGROUND AND PURPOSE: Low socio-economic status of individuals has been reported to be associated with a higher incidence of stroke and influence the diagnosis after revascularization. However, whether it is associated with poorer acute stroke management is less clear. To determine whether social deprivation was associated with a poorer access to reperfusion therapy, either intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) in a population-based cohort. METHODS: Over a 14-month period, all consecutive adult patients admitted to any emergency department or a comprehensive or primary stroke center (CSC/PSC) of the Rhône county with a confirmed ischemic stroke were included. The socioeconomic status of each patient was measured using the European Deprivation Index (EDI). The association between EDI and access to reperfusion therapy was assessed in univariate and multivariate logistic regression analyses. RESULTS: Among the 1226 consecutive IS patients, 316 (25%) were admitted directly in a PSC or CSC, 241 (19.7%) received a reperfusion therapy; 155 IVT alone, 20 EVT alone, and 66 both therapies. Median age was 79 years, 1030 patients had an EDI level of 1 to 4, and 196 an EDI of 5 (the most deprived group). The most deprived patients (EDI level 5) did not have a poorer access to reperfusion therapy compared to all other patients in univariate (OR 1.22, 95%CI [0.85; 1.77]) nor in multivariate analyses (adjOR 0.97, 95%CI [0.57; 1.66]). CONCLUSIONS: We did not find any significant association between socioeconomic deprivation and access to reperfusion therapy. This suggests that the implementation of EVT was not associated with increased access inequities.

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.

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.

Tandem Carotid Lesions in Acute Ischemic Stroke: Mechanisms, Therapeutic Challenges, and Future Directions.

Approximately 15% of patients undergoing endovascular thrombectomy for anterior circulation acute ischemic stroke have a tandem lesion, defined as a severe stenosis or occlusion of the cervical internal carotid artery ipsilateral to its intracranial occlusion. Patients with tandem lesions have worse outcomes than patients with isolated intracranial occlusions, but the optimal management of their carotid lesions during endovascular thrombectomy remains controversial. The main options commonly used in current practice include acute stent placement in the carotid lesion versus thrombectomy alone without definitive revascularization of the carotid artery. While treatment decisions for these patients are often complex and strategies vary according to clinical, anatomic, and technical considerations, only results from randomized trials comparing these approaches are likely to strengthen current recommendations and optimize patient care.

Academic and professional paths of narcoleptic patients: the Narcowork study.

OBJECTIVE/BACKGROUND: To study educational and professional pathways of narcoleptic patients and examine demographic, disease-related and environmental factors associated with a better academic and professional prognosis. PATIENTS/METHODS: In sum, 69 narcoleptic patients (51 narcolepsy type 1 and 18 narcolepsy type 2, age 42.5 ± 18.2 years) were enrolled in this pilot monocentric cross-sectional study with a comparison group (80 age- and sex-matched controls) between October 2017 and July 2018 in Lyon Center for Sleep Medicine. They completed questionnaires about their academic and professional trajectories and specific scales of quality of life (EuroQol quality of life scale EQ-5D-3L), depression (beck depression inventory, BDI), sleepiness (Epworth Sleepiness Scale, ESS) and narcoleptic symptoms severity (narcolepsy severity scale, NSS). RESULTS: No difference in grade repetition or final obtained diploma was observed between patients and controls, but patients evaluated their academic curricula as more difficult (45.5% vs 16.9%, p = 0.0007), complained for more attentional deficits (75% vs 22.1%, p < 0.0001), and had needed more educational reorientation (28.6% vs 9.9%, p = 0.01). Even if no difference was observed in occupational category and professional status, patients expressed significantly less satisfaction about their work. Patients had more signs of depression [OR severe depression = 4.4 (1.6-12.6), p = 0.02] and their quality of life was significantly decreased (67.3 ± 18.4 vs 80.6 ± 13.2, p = 0.0007) as compared to controls. Multivariate analysis showed that a more favorable professional career was associated with a better quality of life. CONCLUSIONS: Educational and professional pathways do not seem to be significantly impaired in narcoleptic patients, but their experience and quality of life are affected. These findings may allow to reassure patients and should lead to a more comprehensive management of the disease. CLINICAL TRIAL REGISTRATION: Narcowork, https://clinicaltrials.gov/ct2/show/NCT03173378, N° NCT03173378.

Intravenous thrombolysis for acute ischaemic stroke in patients on direct oral anticoagulants.

BACKGROUND AND PURPOSE: Whereas intravenous thrombolysis (IVT) is allowed for acute ischaemic stroke in patients on vitamin K antagonists with international normalized ratio ≤1.7, there are no similar recommendations for patients on direct oral anticoagulants (DOACs), notably due to the lack of coagulation tests to assess the therapeutic effects. Although the literature is scarce, consisting of small case series and retrospective studies, considering the frequency of this situation the French Vascular Neurology Society and the French Study Group on Haemostasis and Thrombosis have worked on a joint position paper to provide a practical position regarding the emergency management of ischaemic stroke in patients on DOACs. METHOD: Based on a review of the literature, the authors wrote a first text that was submitted to a broad panel of members from the two societies. The text was then amended by the authors to address experts' comments and to reach a consensus. RESULTS: In patients with normal renal function and who stopped the DOAC for at least 48 h, the management should not differ from that in patients without oral anticoagulant. In patients who are still on DOACs, mechanical thrombectomy is encouraged preferentially when applicable in first line. Otherwise, when specific tests are available, values <50 ng/ml indicate that IVT is allowed. In the absence of specific tests, standard tests (thrombin time, prothrombin time and activated partial thromboplastin time) can be used for dabigatran and rivaroxaban, although interpretation of these tests may be less reliable. In some patients on dabigatran, idarucizumab may be used before IVT. CONCLUSIONS: In this expert opinion paper, it is suggested that IVT can be performed in patients selected according to the time elapsed since the drug was last taken, renal function, type of hospital where the patient is admitted and plasma concentration of DOAC.

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.

Pramipexole-responsive acute restless arms syndrome after surgery under general anesthesia: Case report and literature review.

We reported a case of acute restless arms syndrome occurring after colorectal surgery under general anaesthesia. This case was also compared with other cases of restless legs/arms syndromes occurring in a perioperative context through a literature review. As the restless legs syndrome, the restless arms syndrome can be exacerbated by perioperative procedures and improved with pramipexole from the first day of treatment. This case reinforces the idea that the restless arms syndrome seems to be subsumed along with the restless legs syndrome, and is a further argument to use the diagnosis term "restless limb syndrome" for the restlessness of any limb with clinical features similar to the restless legs syndrome.

Mechanical thrombectomy in acute ischemic stroke.

Recent randomized trials have demonstrated the efficacy of stent retriever thrombectomy, in association with intravenous thrombolysis, in acute ischemic stroke related to the occlusion of the distal internal carotid artery or the proximal middle cerebral artery within six hours of symptom onset. Mechanical thrombectomy should be performed as soon as possible after symptom onset. High age alone should not be considered as a contraindication for mechanical thrombectomy. Mechanical thrombectomy is recommended in acute ischemic stroke patients with large vessel occlusions and salvageable brain tissue if intravenous thrombolysis is contraindicated. Re-organization of stroke care systems is needed to provide rapid access to endovascular therapy equitably to all eligible patients.

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.

[Intravenous thrombolysis in ischemic stroke: Therapeutic perspectives]. / Thrombolyse intraveineuse des infarctus cérébraux: perspectives thérapeutiques.

New therapeutic strategies are under evaluation to improve the treatment of acute ischemic stroke (AIS). Approaches combining intravenous (IV) thrombolysis with recombinant tissue plasminogen activator (rt-PA) and antithrombotic agents are currently evaluated. The combination of IV rt-PA and aspirin showed a high rate of intracranial hemorrhage whereas the association of rt-PA and eptifibatide seems more promising. The results of recent studies evaluating the administration of eptifibatide or argatroban in conjunction with conventional IV thrombolysis with rt-PA are expected to clarify the safety and efficacy of these treatments. More fibrin-specific plasminogen activators, tenecteplase and desmoteplase, are also investigated. These fibrinolytic agents showed a favorable safety profile but their efficacy in AIS remains uncertain. While phase III studies, DIAS-3 and DIAS-4, evaluating IV desmoteplase up to nine hours after stroke onset did not meet the primary endpoint, the results of studies comparing IV tenecteplase and IV rt-PA are expected.

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.