Reducing the global burden of cerebral venous thrombosis: An international research agenda.

BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.

World Stroke Organization Brain & hEart globAl iniTiative Program.

INTRODUCTION: The World Stroke Organization (WSO) Brain & Heart Task Force developed the Brain & hEart globAl iniTiative (BEAT), a pilot feasibility implementation program to establish clinical collaborations between cardiologists and stroke physicians who work at large healthcare facilities. METHODS: The WSO BEAT pilot project focused on atrial fibrillation (AF) and patent foramen ovale (PFO) detection and management, and poststroke cardiovascular complications known as the stroke-heart syndrome. The program included 10 sites from 8 countries: Brazil, China, Egypt, Germany, Japan, Mexico, Romania, and the USA The primary composite feasibility outcome was the achievement of the following 3 implementation metrics (1) developing site-specific clinical pathways for the diagnosis and management of AF, PFO, and the stroke-heart syndrome; (2) establishing regular Neurocardiology rounds (e.g., monthly); and (3) incorporating a cardiologist to the stroke team. The secondary objectives were (1) to identify implementation challenges to guide a larger program and (2) to describe qualitative improvements. RESULTS: The WSO BEAT pilot feasibility program achieved the prespecified primary composite outcome in 9 of 10 (90%) sites. The most common challenges were the limited access to specific medications (e.g., direct oral anticoagulants) and diagnostic (e.g., prolonged cardiac monitoring) or therapeutic (e.g., PFO closure devices) technologies. The most relevant qualitative improvement was the achievement of a more homogeneous diagnostic and therapeutic approach. CONCLUSION: The WSO BEAT pilot program suggests that developing neurocardiology collaborations is feasible. The long-term sustainability of the WSO BEAT program and its impact on quality of stroke care and clinical outcomes needs to be tested in a larger and longer duration program.

The Neuropsychiatric Side of Cerebral Venous Thrombosis: A Case of Delirium and Catatonia.

We report a patient with cerebral venous thrombosis who initially presented with psychosis and who then progressed to delirium and catatonia within a few days. Upon treatment and resolution of the thrombosis, she presented complete remission of the psychiatric disturbances. This case highlights a specific neuropsychiatric presentation of cerebral venous thrombosis involving psychosis, catatonia, and delirium, which, to our best knowledge, has not been reported in the neurological or psychiatric literature. However, it reminds us of mental status and behavioral abnormalities which are not infrequent features of cerebral venous thrombosis. This leads to a discussion regarding the psychopathology, etiology, and pathophysiology of the case.

Predictors of Mortality and Functional Outcome in Pregnancy and Puerperium-Related Cerebral Venous Thrombosis.

INTRODUCTION: Cerebral venous thrombosis (CVT) associated with pregnancy and puerperium has long been recognized, with poor information in terms of functional outcomes. Our objective was to analyze risk factors, clinical, imaging, and laboratory variables to predict functional outcome and death in this population. METHODS: CVT registries from three referral centers from Pakistan, Turkey, and Mexico, recruiting prospective cases, were combined for CVT associated with pregnancy or puerperium. Datasets and variables were standardized. Demographic characteristics, presentation, risk factors, and functional outcomes in pregnancy/puerperium-related CVT were analyzed. Binary logistic regression was used to assess predictors of outcome. The main outcome was modified Rankin score >2 at 30 days and mortality at 30 days. RESULTS: Five hundred fifty-three cases (median age 28 years [IQR 23-34]) of CVT associated with pregnancy and puerperium were included; 439 cases (79.4%) happened in the puerperium and 20.6% during pregnancy (53.5% occurred during the first trimester). Anemia (36.7%) and dehydration (22.9%) were the commonest obstetric risk factors identified. Predictors of poor outcome (mRS >2) were encephalopathy (OR 12.8, p < 0.001), cases from Mexican origin (OR 3.1, p = 0.004), fever/puerperal infection (OR 2.7, p = 0.02), and anemia (OR 2.2, p = 0.01). Cases from Mexican origin (OR 12.0, p = 0.003) and Encephalopathy (OR 7.7, p < 0.001), presented with the highest mortality association in the final adjusted model. DISCUSSION/CONCLUSION: In CVT associated with pregnancy and puerperium, encephalopathy, fever/puerperal infection, and anemia are associated with bad functional outcomes, meanwhile encephalopathy and cases from Mexican origin with higher mortality in the acute (30-days) of CVT onset. Anemia and infection are potential reversible predictors of poor outcome that clinicians should be aware of in order to prevent poor outcomes in these patients.

Stroke Among SARS-CoV-2 Vaccine Recipients in Mexico: A Nationwide Descriptive Study.

BACKGROUND AND OBJECTIVES: Information on stroke among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines remains scarce. We report stroke incidence as an adverse event following immunization (AEFI) among recipients of 79,399,446 doses of 6 different SARS-CoV-2 vaccines (BNT162b2, ChAdOx1 nCov-19, Gam-COVID-Vac, CoronaVac, Ad5-nCoV, and Ad26.COV2-S) between December 24, 2020, and August 31, 2021, in Mexico. METHODS: This retrospective descriptive study analyzed stroke incidence per million doses among hospitalized adult patients (≥18 years) during an 8-month interval. According to the World Health Organization, AEFIs were defined as clinical events occurring within 30 days after immunization and categorized as either nonserious or serious, depending on severity, treatment, and hospital admission requirements. Acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and cerebral venous thrombosis (CVT) cases were collected through a passive epidemiologic surveillance system in which local health providers report potential AEFI to the Mexican General Board of Epidemiology. Data were captured with standardized case report formats by an ad hoc committee appointed by the Mexican Ministry of Health to evaluate potential neurologic AEFI against SARS-COV-2. RESULTS: We included 56 patients (31 female patients [55.5%]) for an overall incidence of 0.71 cases per 1,000,000 administered doses (95% CI 0.54-0.92). Median age was 65 years (interquartile range [IQR] 55-76 years); median time from vaccination to stroke (of any subtype) was 2 days (IQR 1-5 days). In 27 (48.2%) patients, the event was diagnosed within the first 24 hours after immunization. The most frequent subtype was AIS in 43 patients (75%; 0.54 per 1,000,000 doses, 95% CI 0.40-0.73), followed by ICH in 9 (16.1%; 0.11 per 1,000,000 doses, 95% CI 0.06-0.22) and SAH and CVT, each with 2 cases (3.6%; 0.03 per 1,000,000 doses, 95% CI 0.01-0.09). Overall, the most common risk factors were hypertension in 33 (58.9%) patients and diabetes in 22 (39.3%). Median hospital length of stay was 6 days (IQR 4-13 days). At discharge, functional outcome was good (modified Rankin Scale score 0-2) in 41.1% of patients; in-hospital mortality rate was 21.4%. DISCUSSION: Stroke is an exceedingly rare AEFI against SARS-CoV-2. Preexisting stroke risk factors were identified in most patients. Further research is needed to evaluate causal associations between SARS-COV-2 vaccines and stroke.

Agenesis of the right internal carotid artery and aqueductal stenosis in a child with hydrocephalus, the role of endoscopic third ventriculostomy: a case report.

Agenesis of the internal carotid artery (aICA) is a rare congenital vascular condition that can affect one or both sides of the patient. Most patients remain asymptomatic, but ischemic/hemorrhagic stroke, intracranial aneurysm, and other neurologic findings can occur. CT scan can demonstrate the absence of the bony carotid canal and helps to differentiate a complete aICA from aplasia or hypoplasia. The association of aICA and aqueductal stenosis (AS) has never been reported in the literature. We report the case of a 9-year-old with agenesis of the right ICA associated with AS and hydrocephalus, which was treated successfully with an endoscopic third ventriculostomy (ETV). We review the literature looking for the association of the clinical findings and the evolution of the patient.

Barriers to Optimal Acute Management of Stroke: Perspective of a Stroke Center in Mexico City.

Background: Stroke is a leading cause of death and disability worldwide, particularly in low- and middle-income countries. We aimed to identify the main barriers to optimal acute management of stroke in a referral center. Methods: Demographic data was collected from patients assessed with acute stroke in the emergency department of the Instituto Nacional de Neurología y Neurocirugía (INNN) from January to June 2019. Additionally, a telephone interview was conducted with patients/primary caregiver to know which they considered the main reason for the delay in arrival at INNN since the onset of stroke. Results: 116 patients were assessed [age 65 ± 15 years, 67 (57.8%) men]. Patients consulted other facilities prior to arrival at INNN in 59 (50.9%) cases (range of hospitals visited 1-4), 83 (71.6%) arrived in a private car, with prenotification in only 4 (3.4%) of the total sample. The mean onset-to-door time was 17 h (45 min-10 days). Telephone interviews were done in 61 patients/primary caregivers, stating that they consider the multiple evaluations in other facilities [n = 26/61 (42.6%)] as the main reason for delay in arrival at the ED, followed by ignorance of stroke symptoms and treatment urgency [n = 21/61 (34.4%)]. Conclusion: In this small, retrospective, single center study, the main prehospital barrier to optimal acute management of stroke in a developing country is multiple medical evaluations prior to the patient's transport to a specialized stroke hospital, who mostly arrived in a private car and without prenotification. These barriers can be overcome by strengthening public education and improving patient transfer networks and telemedicine.

Foix-Chavany-Marie Syndrome as a Manifestation of Unilateral Opercular Stroke.

INTRODUCTION: Foix-Chavany-Marie syndrome (FCMS) is a type of pseudobulbar palsy that affects facio-pharyngo-glosso-masticatory muscles. MATERIALS AND METHODS: A 62-year-old man was admitted to the emergency department after 9 hours of acute dysarthria and dysphagia. MRI showed restricted diffusion in the right operculum on diffusion-weighted imaging (DWI). No thrombolytic therapy was given. The patient had a history of mechanical aortic valve replacement under anticoagulation with a vitamin K antagonist. Work-up demonstrated suboptimal levels of INR. Due to severe dysphagia during hospitalization, a percutaneous endoscopic gastrostomy (PEG) was performed. RESULTS: The patient was discharged 5 days later, with a modified Rankin scale (mRs) score of 3, and secondary stroke prevention. He had achieved an excellent functional outcome (mRs 1) at 6-month follow-up. CONCLUSION: Our patient had a satisfactory recovery due to prompt diagnosis, secondary stroke prevention, and compliance with treatment. LEARNING POINTS: In the presence of acute dysarthria and dysphagia, Foix-Chavany-Marie syndrome (FCMS) should be considered.FCMS may occur in the presence of unilateral opercular stroke.Swallowing and speech therapy play an essential role in rehabilitation after the acute setting.

Risk factors for ischemic antiphospholipid syndrome: A case-control study.

OBJECTIVE: The objective of this study was to identify clinical and laboratory risk factors for ischemic stroke (IS) in primary antiphospholipid syndrome (APS) patients. MATERIALS AND METHODS: We performed a case-control study with consecutive primary APS patients divided into two groups, those who presented with IS, vs. those with no history of stroke. Demographics, vascular risk factors, therapeutic approaches, laboratory, imaging and functional outcomes were recorded. RESULTS: Fifty-three confirmed primary APS patients with IS and sixty-six non-stroke primary APS controls were recruited. Most patients were female (65.5 %), with a median age of 33 years. The main vascular risk factors for primary APS-associated stroke were hypertension (11.3 %), diabetes (11.3 %) and hypercholesterolemia (9.4 %). Among patients with stroke, median NIHSS score was 6; 15.1 % of these patients presented a recurrent stroke, and 88.8 % had a good functional outcome at the final follow-up. Positive lupus anticoagulant (OR = 6.1, 95 %CI 2.7-13.5), anti-ß2 glycoprotein IgG (OR = 3.6, 95 %CI 1.7-7.9), and anticardiolipin IgG (OR = 2.8, 95 %CI 1.3-5.9) were more prevalent in non-stroke primary APS, with a triple-positive antibody presence in 46.4 % of controls vs. 22.2 % of patients with stroke (OR = 3.0, 95 %CI 1.3-6.7). At the time of the index event (arterial or venous), 14 known primary APS patients were using vitamin K antagonists, but only 35.7 % of them had achieved therapeutic INR. CONCLUSION: Patients with primary APS and IS have similar vascular risk factors and lower antibody positivity than those with extracranial thrombosis.

Bilateral Decompressive Craniectomy in Malignant Cerebral Venous Thrombosis.

INTRODUCTION: Despite the extremely favourable prognosis of patients with cerebral venous thrombosis (CVT), death occurs in 10-15% of patients. In severe cases of malignant CVT with supratentorial haemorrhagic lesions, cerebral oedema and brain herniation, decompressive surgery may be the only life-saving treatment. PATIENT AND METHODS: We present the case of a puerperal young woman with progressive headache, seizures and decreased alertness. Thrombosis of the entire superior sagittal sinus with bifrontal venous infarcts and midline shift was confirmed by magnetic resonance imaging with venography sequencing. Despite medical treatment with anticoagulation, progressive neurological deterioration was observed, so bilateral, frontal decompressive craniectomy was performed. RESULTS: At the 6-month follow-up, we observed partial functional recovery with a modified Rankin score of 3. DISCUSSION: Bilateral decompressive craniectomy may be a life-saving therapeutic option when medical therapy fails and there are clinical and radiological features of progression in both cerebral hemispheres. LEARNING POINTS: Malignant cerebral venous thrombosis presents with diffuse haemorrhagic lesions or cerebral oedema associated with brain herniation and rapid clinical deterioration.Decompressive surgery may be the only life-saving treatment in severe cases.Early and adequate intervention based on the characteristics of the lesions allowed preservation of life and improvement in long-term functionality.

[Characterisation of factors associated with carotid stenosis in a population at high risk]. / Caracterizacion de factores asociados con estenosis carotidea en una poblacion de alto riesgo.

INTRODUCTION: Moderate to severe stenosis is the less prevalent among the forms of carotid atherosclerotic disease), but it carries a high risk of ischaemic stroke. AIM: To characterise factors associated with moderate to severe carotid stenosis in a high-risk population. PATIENTS AND METHODS: We performed an analysis on traditional risk factors associated with carotid stenosis ≥50% in 533 patients who received Doppler ultrasound due to a history of stroke (34%) or who had = 2 of the risk factors: age ≥55 years (86%), hypertension (65%), dyslipidemia (52%), obesity (42%), diabetes (40%) or smoking (40%). RESULTS: The prevalence of carotid stenosis ≥50% was 7.1%, symptomatic (associated with stroke in congruent territory) in 5.6%, bilateral in 2.1% and bilateral symptomatic in 1.5%. A 36.8% of patients had moderate to severe load (≥4) of atherosclerotic plaques (25.9% moderate: 4-6 plaques, and 10.9% severe: ≥7 plaques). By multivariate analysis we identified the age ≥75 years, dyslipidemia, and smoking as factors independently associated with carotid stenosis ≥50%, and hypertension and smoking with symptomatic stenosis. The number of risk factors was strongly associated with the prevalence of carotid stenosis. Notably, neither diabetes nor obesity explained the degree of moderate to severe carotid stenosis. CONCLUSIONS: As forms of carotid atherosclerotic disease, moderate to severe stenosis is less frequent than a high burden of atherosclerotic plaques. Advanced age, smoking, dyslipidemia and hypertension are the main traditional risk factors associated with the degree of carotid stenosis.

TITLE: Caracterizacion de factores asociados con estenosis carotidea en una poblacion de alto riesgo.Introduccion. La estenosis moderada a grave es la forma de enfermedad carotidea aterosclerosa menos prevalente, pero que implica un alto riesgo de ictus isquemico. Objetivo. Caracterizar los factores asociados con la estenosis carotidea moderada a grave en una poblacion de alto riesgo. Pacientes y metodos. Realizamos un analisis de los factores de riesgo tradicionales asociados a estenosis carotidea >= 50% en 533 pacientes que recibieron evaluacion mediante ultrasonograma Doppler por historia de ictus (34%), o que contaban con al menos dos de los factores de riesgo: edad >= 55 años (86%), hipertension (65%), dislipidemia (52%), obesidad (42%), diabetes (40%) o tabaquismo (40%). Resultados. La prevalencia de estenosis carotidea >= 50% fue del 7,1%, sintomatica (asociada a ictus en territorio congruente) en el 5,6%, bilateral en el 2,1% y sintomatica bilateral en el 1,5%. Un 36,8% de los pacientes presento carga moderada a grave (>= 4) de placas de ateroma (25,9%, moderada: 4-6 placas; y 10,9%, grave: >= 7 placas). Mediante analisis multivariable se identifico la edad >= 75 años, la dislipidemia y el tabaquismo como factores asociados con estenosis >= 50%, y la hipertension arterial y el tabaquismo con estenosis sintomatica. El numero de factores de riesgo se asocio fuertemente con la prevalencia de estenosis carotidea. Notablemente, ni la diabetes ni la obesidad explicaron el grado de estenosis moderada a grave. Conclusiones. Como formas de enfermedad carotidea aterosclerosa, la frecuencia de estenosis moderada a grave es menor que una carga alta de placas de ateroma. La edad avanzada, el tabaquismo, la dislipidemia y la hipertension son los principales factores tradicionales que se asocian con el grado de estenosis carotidea.

Caracterización de factores asociados con estenosis carotídea en una población de alto riesgo / Characterisation of factors associated with carotid stenosis in a population at high risk

Introducción. La estenosis moderada a grave es la forma de enfermedad carotídea aterosclerosa menos prevalente, pero que implica un alto riesgo de ictus isquémico. Objetivo. Caracterizar los factores asociados con la estenosis carotídea moderada a grave en una población de alto riesgo. Pacientes y métodos. Realizamos un análisis de los factores de riesgo tradicionales asociados a estenosis carotídea ≥ 50% en 533 pacientes que recibieron evaluación mediante ultrasonograma Doppler por historia de ictus (34%), o que contaban con al menos dos de los factores de riesgo: edad ≥ 55 años (86%), hipertensión (65%), dislipidemia (52%), obesidad (42%), diabetes (40%) o tabaquismo (40%). Resultados. La prevalencia de estenosis carotídea ≥ 50% fue del 7,1%, sintomática (asociada a ictus en territorio congruente) en el 5,6%, bilateral en el 2,1% y sintomática bilateral en el 1,5%. Un 36,8% de los pacientes presentó carga moderada a grave (≥ 4) de placas de ateroma (25,9%, moderada: 4-6 placas; y 10,9%, grave: ≥ 7 placas). Mediante análisis multivariable se identificó la edad ≥ 75 años, la dislipidemia y el tabaquismo como factores asociados con estenosis ≥ 50%, y la hipertensión arterial y el tabaquismo con estenosis sintomática. El número de factores de riesgo se asoció fuertemente con la prevalencia de estenosis carotídea. Notablemente, ni la diabetes ni la obesidad explicaron el grado de estenosis moderada a grave. Conclusiones. Como formas de enfermedad carotídea aterosclerosa, la frecuencia de estenosis moderada a grave es menor que una carga alta de placas de ateroma. La edad avanzada, el tabaquismo, la dislipidemia y la hipertensión son los principales factores tradicionales que se asocian con el grado de estenosis carotídea (AU)

Introduction. Moderate to severe stenosis is the less prevalent among the forms of carotid atherosclerotic disease), but it carries a high risk of ischaemic stroke. Aim. To characterise factors associated with moderate to severe carotid stenosis in a high-risk population. Patients and methods. We performed an analysis on traditional risk factors associated with carotid stenosis ≥ 50% in 533 patients who received Doppler ultrasound due to a history of stroke (34%) or who had ≥ 2 of the risk factors: age ≥ 55 years (86%), hypertension (65%), dyslipidemia (52%), obesity (42%), diabetes (40%) or smoking (40%). Results. The prevalence of carotid stenosis ≥ 50% was 7.1%, symptomatic (associated with stroke in congruent territory) in 5.6%, bilateral in 2.1% and bilateral symptomatic in 1.5%. A 36.8% of patients had moderate to severe load (≥ 4)of atherosclerotic plaques (25.9% moderate: 4-6 plaques, and 10.9% severe: ≥ 7 plaques). By multivariate analysis we identified the age ≥ 75 years, dyslipidemia, and smoking as factors independently associated with carotid stenosis ≥ 50%, and hypertension and smoking with symptomatic stenosis. The number of risk factors was strongly associated with the prevalence of carotid stenosis. Notably, neither diabetes nor obesity explained the degree of moderate to severe carotid stenosis. Conclusions. As forms of carotid atherosclerotic disease, moderate to severe stenosis is less frequent than a high burden of atherosclerotic plaques. Advanced age, smoking, dyslipidemia and hypertension are the main traditional risk factors associated with the degree of carotid stenosis (AU)