RESUMEN
BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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Hemorragia Cerebral , Inhibidores del Factor Xa , Factor Xa , Hematoma , Proteínas Recombinantes , Humanos , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Anciano , Masculino , Femenino , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamente , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/efectos adversos , Factor Xa/uso terapéutico , Factor Xa/efectos adversos , Hematoma/inducido químicamente , Hematoma/tratamiento farmacológico , Anciano de 80 o más Años , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Enfermedad AgudaRESUMEN
BACKGROUND AND PURPOSE: In October 2020, the European Academy of Neurology (EAN) consensus statement for management of patients with neurological diseases during the coronavirus disease 2019 (COVID-19) pandemic was published. Due to important changes and developments that have happened since then, the need has arisen to critically reassess the original recommendations and address new challenges. METHODS: In step 1, the original items were critically reviewed by the EAN COVID-19 Task Force. In addition, new recommendations were defined. In step 2, an online survey with the recommendations forged in step 1 was sent to the Managing Groups of all Scientific and Coordinating Panels of EAN. In step 3, the final set of recommendations was made. RESULTS: In step 1, out of the original 36 recommendations, 18 were judged still relevant. They were edited to reflect the advances in knowledge and practice. In addition, 21 new recommendations were formulated to address the new knowledge and challenges. In step 2, out of the 39 recommendations sent for the survey, nine were approved as they were, whilst suggestions for improvement were given for the rest. In step 3, the recommendations were further edited, and some new items were formed to accommodate the participants' suggestions, resulting in a final set of 41 recommendations. CONCLUSION: This revision of the 2020 EAN Statement provides updated comprehensive and structured guidance on good clinical practice in people with neurological disease faced with SARS-CoV-2 infection. It now covers the issues from the more recent domains of COVID-19-related care, vaccine complications and post-COVID-19 conditions.
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BACKGROUND AND PURPOSE: The COVID-19 pandemic has significantly impacted health systems worldwide. Here, we assessed the pandemic's impact on clinical service, curricular training, and financial burden from a neurological viewpoint during the enforced lockdown periods and the assumed recovery by 2023. METHODS: An online 18-item survey was conducted by the European Academy of Neurology (EAN) NeuroCOVID-19 Task Force among the EAN community. The survey was online between February and March 2023. Questions related to general, demographic, clinical, work, education, and economic aspects. RESULTS: We collected 430 responses from 79 countries. Most health care professionals were aged 35-44 years, with >15 years of work experience. The key findings of their observations were as follows. (i) Clinical services were cut back in all neurological subspecialties during the most restrictive COVID-19 lockdown period. The most affected neurological subspecialties were services for patients with dementia, and neuromuscular and movement disorders. The levels of reduction and the pace of recovery were distinct for acute emergencies and in- and outpatient care. Recovery was slow for sleep medicine, autonomic nervous system disorders, neurorehabilitation, and dementia care. (ii) Student and residency rotations and grand rounds were reorganized, and congresses were converted into a virtual format. Conferences are partly maintained in a hybrid format. (iii) Affordability of neurological care and medication shortage are emerging issues. CONCLUSIONS: Recovery of neurological services up to spring 2023 has been incomplete following substantial disruption of neurological care, medical education, and health economics in the wake of the COVID-19 pandemic. The continued limitations for the delivery of neurological care threaten brain health and call for action on a global scale.
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COVID-19 , Demencia , Neurología , Humanos , Pandemias , SARS-CoV-2 , Control de Enfermedades Transmisibles , Neurología/educaciónRESUMEN
BACKGROUND: The COVID-19 pandemic has made its mark on world history forever causing millions of deaths, and straining health systems, economies, and societies worldwide. The European Academy of Neurology (EAN) reacted promptly. A special NeuroCOVID-19 Task Force was set up at the beginning of the pandemic to promote knowledge, research, international collaborations, and raise awareness about the prevention and treatment of COVID-19-related neurological issues. METHODS: Activities carried out during and after the pandemic by the EAN NeuroCOVID-19 Task Force are described. The main aim was to review all these initiatives in detail as an overarching lesson from the past to improve the present and be better prepared in case of future pandemics. RESULTS: During the pandemic, the Task Force was engaged in several initiatives: the creation of the EAN NEuro-covid ReGistrY (ENERGY); the launch of several surveys (neurological manifestations of COVID-19 infection; the pandemic's impact on patients with chronic neurological diseases; the pandemic's impact of restrictions for clinical practice, curricular training, and health economics); the publication of position papers regarding the management of patients with neurological diseases during the pandemic, and vaccination hesitancy among people with chronic neurological disorders; and the creation of a dedicated "COVID-19 Breaking News" section in EANpages. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force was immediately engaged in various activities to participate in the fight against COVID-19. The Task Force's concerted strategy may serve as a foundation for upcoming global neurological emergencies.
RESUMEN
Background and purpose:
The management of central retinal artery occlusion (CRAO) has long been conservative therapy with limited efficacy carried out in ophthalmology departments together with etiological investigations lacking a standardised protocol. However, CRAO is analogous to ischemic central nervous system stroke and is associated with increased stroke risk, thus, systemic thrombolysis treatment and multidisciplinary management can be beneficial. Since May 2022, at Semmelweis University CRAO patients diagnosed within 4.5 hours are given intravenous thrombolysis therapy and undergo etiologic workup based on current stroke protocols. Here we report our experience with the multidisciplinary, protocol-based management of CRAO in comparison with former non-protocol based ophthalmological conservative treatment.
. Methods:We reviewed CRAO patients’ data treated conservatively and with paracentesis within 6 hours at the Department of Ophthalmology between 2013 and 2022 including changes in visual acuity, neurological and cardiovascular findings compared to those in the thrombolysis project.
. Results:Of the 78 patients receiving non-protocol care, visual improvement was seen in 37% with natural course, 47% with conservative treatment and 47% with paracentesis. Four patients had significant carotid stenosis (2 underwent endarterectomy), 1 carotid dissection, 6 cardioembolism and 1 giant cell arteritis. Of the 4 patients within 4,5 hours, 3 gave their consent to the clinical trial and were treated with thrombolysis and underwent a full etiological assessment.
2 patients had improved visual acuity, 2 patients had significant carotid stenosis and underwent endarterectomy, 1 patient was started on anticoagulation for newly diagnosed atrial fibrillation.
CRAO patients presenting within 4,5 hours are rare and more patients are needed in our study to establish the efficacy of thrombolysis. However uniform protocollized evaluation helps identifying embolic sources thus, avoiding further and potentially more serious thromboembolic events.
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Estenosis Carotídea , Accidente Cerebrovascular Isquémico , Oclusión de la Arteria Retiniana , Accidente Cerebrovascular , Humanos , Terapia Trombolítica/métodos , Estenosis Carotídea/complicaciones , Estenosis Carotídea/terapia , Oclusión de la Arteria Retiniana/tratamiento farmacológico , Oclusión de la Arteria Retiniana/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Tratamiento ConservadorRESUMEN
BACKGROUND AND PURPOSE: We characterized autonomic pilomotor and sudomotor skin function in early Parkinson's disease (PD) longitudinally. METHODS: We enrolled PD patients (Hoehn and Yahr 1-2) and healthy controls from movement disorder centers in Germany, Hungary, and the United States. We evaluated axon-reflex responses in adrenergic sympathetic pilomotor nerves and in cholinergic sudomotor nerves and assessed sympathetic skin response (SSR), predominantly parasympathetic neurocardiac function via heart rate variability, and disease-related symptoms at baseline, after 2 weeks, and after 1 and 2 years. CLINICALTRIALS: gov: NCT03043768. RESULTS: We included 38 participants: 26 PD (60% females, aged 62.4 ± 7.4 years, mean ± SD) and 12 controls (75% females, aged 59.5 ± 5.8 years). Pilomotor function was reduced in PD compared to controls at baseline when quantified via spatial axon-reflex spread (78 [43-143], median [interquartile range] mm2 vs. 175 [68-200] mm2 , p = 0.01) or erect hair follicle count in the axon-reflex region (8 [6-10] vs. 11 [6-16], p = 0.008) and showed reliability absent any changes from baseline to Week 2 (p = not significant [ns]). Between-group differences increased over the course of 2 years (p < 0.05), although no decline was observed within groups (p = ns). Pilomotor impairment in PD correlated with motor symptoms (rho = -0.59, p = 0.017) and was not lateralized (p = ns). Sudomotor axon-reflex and neurocardiac function did not differ between groups (p = ns), but SSR was reduced in PD (p = 0.0001). CONCLUSIONS: Impairment of adrenergic sympathetic pilomotor function and SSR in evolving PD is not paralleled by changes to cholinergic sudomotor function and parasympathetic neurocardiac function, suggesting a sympathetic pathophysiology. A pilomotor axon-reflex test might be useful to monitor PD-related pathology.
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Enfermedades del Sistema Nervioso Autónomo , Enfermedad de Parkinson , Femenino , Humanos , Masculino , Enfermedad de Parkinson/diagnóstico , Reproducibilidad de los Resultados , Piel/patología , Sistema Nervioso Autónomo , Enfermedades del Sistema Nervioso Autónomo/etiología , AdrenérgicosRESUMEN
Background and purpose:
In our collaborative project, called MRI First!, every patient arriving with neurological symptoms of acute stroke and without contraindications was examined by MRI. Our aim was to detect the symptomatic lesions, to obtain appropriate information about the brain parenchyma and to analyse parenchymal perfusion and brain vasculature.
. Methods:The examinations were conducted on a Philips Ingenia 1.5 Tesla scanner with the following protocol: DWI-ADC, FLAIR, T2 FFE/SWI, PWI, and contrast-enhanced MRA. 415 patients were examined between January 2020 and May 2021. 179 patients arrived within-, and 136 patients after 4.5 hours symptoms onset time, while 100 patients had “wake-up” stroke.
. Results:Within the 4.5 hours group, 81 cases had acute ischemic lesion, 48 of them received reperfusion therapy. Acute ischemic lesion was found in 64 patients in the wake-up stroke group and in 64 in the 4.5-24 hours group. In these groups 10 and 12 patients obtained reperfusion therapy, respectively. Further 117 cases were considered as stroke mimics, in which cases unnecessary intravenous thrombolysis was avoidable.
. Conclusion:MRI is accepted as a sensitive diagnostic modality providing detailed information regarding the brain parenchyma, its perfusion and vasculature. Nonetheless, its worldwide utilization in acute stroke is low and further information should be collected on which patient groups would gain the most benefit from acute MR imaging. Our continuous work is aimed at that goal.
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Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Imagen por Resonancia Magnética/métodos , Encéfalo/patología , Isquemia Encefálica/diagnóstico , Imagen de Difusión por Resonancia MagnéticaRESUMEN
BACKGROUND: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial. METHODS: Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours. RESULTS: Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38-93) minutes for doctor consent, 55 (37-95) minutes for 2-stage patient, 69 (43-110) minutes for 2-stage relative, 75 (48-124) minutes for 1-stage patient, and 90 (56-155) minutes for 1-stage relative consents (P<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5-2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5-3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03-0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up. CONCLUSIONS: The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.
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Accidente Cerebrovascular , Ácido Tranexámico , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/terapia , Humanos , Consentimiento Informado , Modelos Logísticos , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
Parkinson's disease (PD) is a chronic, progressive neurodegenerative condition; characterized with the degeneration of the nigrostriatal dopaminergic pathway and neuroinflammation. During PD progression, microglia, the resident immune cells in the central nervous system (CNS) display altered activity, but their role in maintaining PD development has remained unclear to date. The purinergic P2Y12-receptor (P2Y12R), which is expressed on the microglia in the CNS has been shown to regulate microglial activity and responses; however, the function of the P2Y12R in PD is unknown. Here we show that MPTP-induced PD symptoms in mice are associated with marked neuroinflammatory changes and P2Y12R contribute to the activation of microglia and progression of the disease. Surprisingly, while pharmacological or genetic targeting of the P2Y12R augments acute mortality in MPTP-treated mice, these interventions protect against the neurodegenerative cell loss and the development of neuroinflammation in vivo. Pharmacological inhibition of receptors during disease development reverses the symptoms of PD and halts disease progression. We found that P2Y12R regulates ROCK and p38 MAPK activity and control cytokine production. Our principal finding is that the receptor has a dualistic role in PD: functional P2Y12Rs are essential to initiate a protective inflammatory response, since the lack of the receptor leads to reduced survival; however, at later stages of neurodegeneration, P2Y12Rs are apparently responsible for maintaining the activated state of microglia and stimulating pro-inflammatory cytokine response. Understanding protective and detrimental P2Y12R-mediated actions in the CNS may reveal novel approaches to control neuroinflammation and modify disease progression in PD.
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Trastornos Parkinsonianos/metabolismo , Receptores Purinérgicos P2Y12/metabolismo , Animales , Encéfalo/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Dopamina/metabolismo , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Antagonistas del Receptor Purinérgico P2Y/farmacología , Receptores Purinérgicos P2Y12/genética , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Quinasas Asociadas a rho/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Health risks associated with SARS-CoV-2 infection are undisputed. Moreover, the capability of vaccination to prevent symptomatic, severe, and fatal COVID-19 is recognized. There is also early evidence that vaccination can reduce the chance for long COVID-19. Nonetheless, the willingness to get vaccinated and receive booster shots remains subpar among people with neurologic disorders. Vaccine scepticism not only jeopardizes collective efforts to end the COVID-19 pandemic but puts individual lives at risk, as some chronic neurologic diseases are associated with a higher risk for an unfavorable COVID-19 course. METHODS: In this position paper, the NeuroCOVID-19 Task Force of the European Academy of Neurology (EAN) summarizes the current knowledge on the prognosis of COVID-19 among patients with neurologic disease, elucidates potential barriers to vaccination coverage, and formulates strategies to overcome vaccination hesitancy. A survey among the Task Force members on the phenomenon of vaccination hesitancy among people with neurologic disease supports the lines of argumentation. RESULTS: The study revealed that people with multiple sclerosis and other nervous system autoimmune disorders are most skeptical of SARS-CoV-2 vaccination. The prevailing concerns included the chance of worsening the pre-existing neurological condition, vaccination-related adverse events, and drug interaction. CONCLUSIONS: The EAN NeuroCOVID-19 Task Force reinforces the key role of neurologists as advocates of COVID-19 vaccination. Neurologists need to argue in the interest of their patients about the overwhelming individual and global benefits of COVID-19 vaccination. Moreover, they need to keep on eye on this vulnerable patient group, its concerns, and the emergence of potential safety signals.
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Vacunas contra la COVID-19 , COVID-19 , Enfermedades del Sistema Nervioso , Vacilación a la Vacunación , COVID-19/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Humanos , Pandemias , SARS-CoV-2 , Vacunación/psicología , Síndrome Post Agudo de COVID-19RESUMEN
BACKGROUND AND PURPOSE: Despite the increasing number of reports on the spectrum of neurological manifestations of COVID-19 (neuro-COVID), few studies have assessed short- and long-term outcome of the disease. METHODS: This is a cohort study enrolling adult patients with neuro-COVID seen in neurological consultation. Data were collected prospectively or retrospectively in the European Academy of Neurology NEuro-covid ReGistrY ((ENERGY). The outcome at discharge was measured using the modified Rankin Scale and defined as 'stable/improved' if the modified Rankin Scale score was equal to or lower than the pre-morbid score, 'worse' if the score was higher than the pre-morbid score. Status at 6 months was also recorded. Demographic and clinical variables were assessed as predictors of outcome at discharge and 6 months. RESULTS: From July 2020 to March 2021, 971 patients from 19 countries were included. 810 (83.4%) were hospitalized. 432 (53.3%) were discharged with worse functional status. Older age, stupor/coma, stroke and intensive care unit (ICU) admission were predictors of worse outcome at discharge. 132 (16.3%) died in hospital. Older age, cancer, cardiovascular complications, refractory shock, stupor/coma and ICU admission were associated with death. 262 were followed for 6 months. Acute stroke or ataxia, ICU admission and degree of functional impairment at discharge were predictors of worse outcome. 65/221 hospitalized patients (29.4%) and 10/32 non-hospitalized patients (24.4%) experienced persisting neurological symptoms/signs. 10/262 patients (3.8%) developed new neurological complaints during the 6 months of follow-up. CONCLUSIONS: Neuro-COVID is a severe disease associated with worse functional status at discharge, particularly in older subjects and those with comorbidities and acute complications of infection.
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COVID-19 , Neurología , Accidente Cerebrovascular , Estupor , Adulto , Anciano , COVID-19/complicaciones , Estudios de Cohortes , Coma , Humanos , Unidades de Cuidados Intensivos , Estudios Retrospectivos , SARS-CoV-2 , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: Individuals with ischemic stroke or transient ischemic attack (TIA) have a high early risk of ischemic stroke despite dual antiplatelet therapy. The risk of ischemic stroke, and associated disability, represents a significant unmet clinical need. Genetic variants resulting in reduced factor XI levels are associated with reduced risk for ischemic stroke but are not associated with increased intracranial bleeding. Milvexian is an oral small-molecule inhibitor of FXIa that binds activated factor XI with high affinity and selectivity and may reduce the risk of stroke when added to antiplatelet drugs without significant bleeding. We aimed to evaluate the dose-response relationship of milvexian in participants treated with dual antiplatelets. METHODS: We began a phase II, double-blinded, randomized, placebo-controlled trial at 367 sites in 2019. Participants (N = 2366) with ischemic stroke (National Institutes of Health Stroke Scale score ≤7) or high-risk TIA (ABCD2 score ≥6) were randomized to 1 of 5 doses of milvexian or placebo for 90 days. Participants also received clopidogrel 75 mg daily for the first 21 days and aspirin 100 mg for 90 days. The efficacy endpoint was the composite of ischemic stroke or incident infarct on magnetic resonance imaging. Major bleeding, defined as type 3 or 5 bleeding according to the Bleeding Academic Research Consortium, was the safety endpoint. Participant follow-up will end in 2022. CONCLUSION: The AXIOMATIC-SSP trial will evaluate the dose-response of milvexian for ischemic stroke occurrence in participants with ischemic stroke or TIA.
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Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Tromboembolia , Aspirina/efectos adversos , Clopidogrel/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Factor XIa , Fibrinolíticos/efectos adversos , Hemorragia , Humanos , Ataque Isquémico Transitorio/diagnóstico por imagen , Ataque Isquémico Transitorio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevención Secundaria , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Tromboembolia/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS: We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS: A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001). CONCLUSIONS: Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .).
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Aspirina/uso terapéutico , Inhibidores del Factor Xa/uso terapéutico , Embolia Intracraneal/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/prevención & control , Anciano , Aspirina/efectos adversos , Isquemia Encefálica/prevención & control , Inhibidores del Factor Xa/efectos adversos , Femenino , Hemorragia/inducido químicamente , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Rivaroxabán/efectos adversos , Prevención Secundaria/métodos , Accidente Cerebrovascular/etiologíaRESUMEN
Coronavirus disease 2019 (COVID-19), a multi-organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID-19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID-19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long-term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID-19 Task Force intends to raise awareness of the potential impact of COVID-19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.
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COVID-19 , Neurología , Humanos , Pandemias , SARS-CoV-2 , VacunaciónRESUMEN
BACKGROUND: Recent advances in therapeutic options may prevent deterioration related to Huntington's disease (HD), even at the pre-symptomatic stage. Be that as it may, a well-characterized patient population is essential for screening and monitoring outcome. Accordingly, the aim of this study was to describe the characteristics of a Hungarian subpopulation of HD patients and mutation carriers diagnosed at the University of Szeged. METHODS: We conducted a search for International Classification of Diseases (ICD) code G10H0 in the local medical database for the period of 1 January 1998 to 31 December 2018. RESULTS: We identified 90 HD cases (male: 45, female: 45) and 34 asymptomatic carriers (male: 15, female: 19). The median age of onset was 45 years (range: 16-79). There were 3 cases of juvenile onset (3.3%), and 7 of late disease onset (7.8%). The median repeat length was 43 (range: 36-70) for the pathological and 19 for the non-pathological alleles (range: 9-35). 17.5% of the pathological alleles were in the decreased penetrance range, while 7% of non-pathological alleles were intermediate. CONCLUSIONS: The genetic and clinical features of the population examined in the present study were in line with the previous Hungarian study, as well as with international literature. The exceptions were the higher ratio of reduced penetrance and intermediate alleles.
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Enfermedad de Huntington/epidemiología , Enfermedad de Huntington/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Femenino , Humanos , Hungría , Proteína Huntingtina/genética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: New guidelines recommend thrombectomy up to 24 h in selected patients; however, the workload and benefit of extending time window are not known. We conducted a prospective single-centre study to determine the caseload, imaging and interventional need of extended time window. METHODS: All consecutive ischemic stroke patients within 24 h from onset in an 11-month period were included. Thrombectomy eligibility in the 0-6 h time window was based on current guidelines; in the 6-24 h time window, it was based on a combination of DEFUSE 3 and DAWN study criteria using MRI to identify target mismatch. Clinical outcome in treated patients was assessed at 3 months. RESULTS: Within 24 h of onset, 437 patients were admitted. In the 0-6 h time window, 238 patients (54.5%) arrived of whom 221 (92.9%) underwent CTA or MRA, 82 (34.5%) had large vessel occlusion (LVO), 30 (12.6%) had thrombectomy and 11 (36.6%) became independent (mRS ≤ 2). In the extended 6-24 h time window, 199 patients (45.5%) arrived of whom 127 (63.8%) underwent CTA or MRA, 44 (22.1%) had LVO, 8 (4%) had thrombectomy and 4 (50%) became independent. CONCLUSION: Extending the time window from 6 to 24 h results in a 26.7% increase in patients receiving thrombectomy and a 36.4% increase of independent clinical outcome in treated patients at the price of a significantly increased burden of clinical and imaging screening due to the similar caseload but a smaller proportion of treatment eligible patients in the extended as compared with the standard time window.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Humanos , Estudios Prospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía , Resultado del TratamientoRESUMEN
In aging societies, the morbidity and mortality of dementia is increasing at a significant rate, thereby imposing burden on healthcare, economy and the society as well. Patients' and caregivers' quality of life and life expectancy are greatly determined by the early diagnosis and the initiation of available symptomatic treatments. Cholinesterase inhibitors and memantine have been the cornerstones of Alzheimer's therapy for approximately two decades and over the years, more and more experience has been gained on their use in non-Alzheimer's dementias too. The aim of our work was to provide a comprehensive summary about the use of cholinesterase inhibitors and memantine for the treatment of Alzheimer's and non-Alzheimers's dementias.
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Enfermedad de Alzheimer , Memantina , Enfermedad de Alzheimer/tratamiento farmacológico , Cuidadores , Inhibidores de la Colinesterasa/uso terapéutico , Humanos , Memantina/uso terapéutico , Calidad de VidaRESUMEN
Background and Purpose- Blend, black hole, island signs, and hypodensities are reported to predict hematoma expansion in acute intracerebral hemorrhage. We explored the value of these noncontrast computed tomography signs in predicting hematoma expansion and functional outcome in our cohort of intracerebral hemorrhage. Methods- The TICH-2 (Tranexamic acid for IntraCerebral Hemorrhage-2) was a prospective randomized controlled trial exploring the efficacy and safety of tranexamic acid in acute intracerebral hemorrhage. Baseline and 24-hour computed tomography scans of trial participants were analyzed. Hematoma expansion was defined as an increase in hematoma volume of >33% or >6 mL on 24-hour computed tomography. Poor functional outcome was defined as modified Rankin Scale of 4 to 6 at day 90. Multivariable logistic regression was performed to identify predictors of hematoma expansion and poor functional outcome. Results- Of 2325 patients recruited, 2077 (89.3%) had valid baseline and 24-hour scans. Five hundred seventy patients (27.4%) had hematoma expansion while 1259 patients (54.6%) had poor functional outcome. The prevalence of noncontrast computed tomography signs was blend sign, 366 (16.1%); black hole sign, 414 (18.2%); island sign, 200 (8.8%); and hypodensities, 701 (30.2%). Blend sign (adjusted odds ratio [aOR] 1.53 [95% CI, 1.16-2.03]; P=0.003), black hole (aOR, 2.03 [1.34-3.08]; P=0.001), and hypodensities (aOR, 2.06 [1.48-2.89]; P<0.001) were independent predictors of hematoma expansion on multivariable analysis with adjustment for covariates. Black hole sign (aOR, 1.52 [1.10-2.11]; P=0.012), hypodensities (aOR, 1.37 [1.05-1.78]; P=0.019), and island sign (aOR, 2.59 [1.21-5.55]; P=0.014) were significant predictors of poor functional outcome. Tranexamic acid reduced the risk of hematoma expansion (aOR, 0.77 [0.63-0.94]; P=0.010), but there was no significant interaction between the presence of noncontrast computed tomography signs and benefit of tranexamic acid on hematoma expansion and functional outcome (P interaction all >0.05). Conclusions- Blend sign, black hole sign, and hypodensities predict hematoma expansion while black hole sign, hypodensities, and island signs predict poor functional outcome. Noncontrast computed tomography signs did not predict a better response to tranexamic acid. Clinical Trial Registration- URL: https://www.isrctn.com. Unique identifier: ISRCTN93732214.
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Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/fisiopatología , Hematoma/tratamiento farmacológico , Ácido Tranexámico/farmacología , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Cervical spine involvement may lead to severe complications in rheumatoid arthritis (RA). In the era of modern therapies, atlantoaxial subluxation (AAS) may be rare; however, it may still be detected in asymptomatic patients. The onset of myelopathy can occur at any time. Altogether 49 female RA patients were included. Among them, 15 were methotrexate treated, biologic free, while 34 patients received biologics. The patients had no cervical pain or any neurological symptoms. We assessed the first (C1) and second (C2) cervical vertebrae by 3 T magnetic resonance imaging (MRI). In addition to AAS, we also determined odontoid erosion or periodontal soft tissue thickening. We associated our MRI findings with clinical, laboratory parameters, and hand radiography. We detected anterior AAS and soft tissue thickening in one-quarter, while odontoid erosions in eight (16%) of RA patients. There were no significant differences among the therapeutic subgroups. No posterior or vertical AAS was seen. Anterior AAS was associated with higher degree of inflammation, soft tissue thickening was seen at younger age, while odontoid erosions were associated with van der Heijde-Sharp scores of the hand. None of the patients had any lesions requiring surgery. The presence of cervical involvement in RA patients with 10-11 years of disease duration is still an important and frequent phenomenon. Higher disease activity and erosive disease are associated with atlantoaxial involvement. 3 T MRI is a sensitive method to assess AAS, as well as soft tissue lesions and odontoid erosions.
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Artritis Reumatoide , Productos Biológicos , Humanos , Femenino , Estudios Transversales , Vértebras Cervicales/diagnóstico por imagen , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnóstico por imagen , Artritis Reumatoide/tratamiento farmacológico , Imagen por Resonancia Magnética , Productos Biológicos/uso terapéuticoRESUMEN
In the original article, the first author's given name and family name were interchanged as provided by the authors in the original manuscript.