RESUMEN
BACKGROUND: Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG), necessitating ventilation. Achieving a safe and timely diagnosis of myasthenic crisis with atypical, isolated presentation is a considerable challenge particularly in elderly patients, where myasthenia gravis can present with isolated dysarthria in rare instances, giving a clinical impression of lacunar stroke. CASE PRESENTATION: We present a compelling case of a 73-year-old Caucasian female presenting with abrupt onset of isolated dysarthria. Despite initial treatment for a presumed lacunar stroke, subsequent evaluations led to her diagnosis of a myasthenic crisis. Within 72 h of admission, the patient developed dysphagia and shortness of breath, requiring supplemental oxygen. The case highlights the sequential progression of events from the atypical presentation of isolated dysarthria and its course to the management of a myasthenic crisis. CONCLUSION: Our reported case focuses on the discussion of myasthenia that mimicked a lacunar stroke and was finally diagnosed at a critical time of medical crisis. This case highlights the imperative notion that isolated dysarthria in elderly individuals warrants vigilant monitoring for possible myasthenia gravis, given the low incidence of lacunar stroke presenting with only dysarthria.
Asunto(s)
Disartria , Miastenia Gravis , Accidente Vascular Cerebral Lacunar , Humanos , Miastenia Gravis/diagnóstico , Miastenia Gravis/complicaciones , Anciano , Disartria/etiología , Femenino , Diagnóstico Diferencial , Accidente Vascular Cerebral Lacunar/diagnóstico , Accidente Vascular Cerebral Lacunar/complicaciones , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos de Deglución/etiología , Trastornos de Deglución/diagnóstico , Disnea/etiologíaRESUMEN
BACKGROUND: Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. METHODS: We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757â 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and ß-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18â 381), cerebral microbleed (3556 cases, 22â 306 controls), white matter perivascular space (9317 cases, 29â 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29â 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29â 708 controls), and lacunar stroke (6030 cases, 248â 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. RESULTS: We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (ß=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (ß=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (ß=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). CONCLUSIONS: Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.
Asunto(s)
Antihipertensivos , Presión Sanguínea , Enfermedades de los Pequeños Vasos Cerebrales , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/tratamiento farmacológico , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Femenino , Masculino , Accidente Vascular Cerebral Lacunar/genética , Accidente Vascular Cerebral Lacunar/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Persona de Mediana EdadRESUMEN
OBJECTIVES: Observational studies have suggested that SARS-CoV-2 infection may increase the burden of cerebral small vessel disease (CSVD). This study aims to explore the causal correlation between COVID-19 and the imaging markers of CSVD using Mendelian randomization (MR) methods. METHODS: Summary-level genome-wide association study (GWAS) statistics for COVID-19 susceptibility, hospitalization, and severity were utilized as proxies for exposure. Large-scale meta-analysis GWAS data on three neuroimaging markers of white matter hyperintensity, lacunar stroke, and brain microbleeds, were employed as outcomes. Our primary MR analysis employed the inverse variance weighted (IVW) approach, supplemented by MR-Egger, weighted median, and MR-PRESSO methods. We also conducted multivariable MR analysis to address confounding bias and validate the robustness of the established causal estimates. Comprehensive sensitivity analyses included Cochran's Q test, Egger-intercept analysis, MR-PRESSO, and leave-one-out analysis. RESULTS: The MR analysis revealed a significant causal correlation between the severity of COVID-19 and an increased risk of lacunar stroke, as demonstrated by the IVW method (ORivw = 1.08, 95% CI: 1.03-1.16, pivw = 0.005, FDR = 0.047). Nevertheless, no causal correlations were observed between COVID-19 susceptibility or hospitalization and any CSVD imaging markers. The robustness and stability of these findings were further confirmed by multivariable MR analysis and comprehensive sensitivity analyses. DISCUSSION: This study provides compelling evidence of a potential causal effect of severe COVID-19 on the incidence of lacunar stroke, which may bring fresh insights into the understanding of the comorbidity between COVID-19 and CSVD.
Asunto(s)
COVID-19 , Enfermedades de los Pequeños Vasos Cerebrales , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Humanos , COVID-19/diagnóstico por imagen , COVID-19/complicaciones , Análisis de la Aleatorización Mendeliana/métodos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Neuroimagen/métodos , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/genética , Accidente Vascular Cerebral Lacunar/epidemiologíaRESUMEN
A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.
Asunto(s)
Ageusia , Tegmento Pontino , Accidente Vascular Cerebral Lacunar , Humanos , Femenino , Anciano , Ageusia/etiología , Ageusia/fisiopatología , Tegmento Pontino/patología , Tegmento Pontino/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/patología , Accidente Vascular Cerebral Lacunar/complicaciones , Accidente Vascular Cerebral Lacunar/etiología , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Imagen por Resonancia MagnéticaAsunto(s)
Accidente Vascular Cerebral Lacunar , Humanos , Proyectos Piloto , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Venas Cerebrales/fisiopatología , Circulación Cerebrovascular/fisiologíaRESUMEN
BACKGROUND: Recent studies, using diffusion tensor image analysis along the perivascular space (DTI-ALPS), suggest impaired perivascular space (PVS) function in cerebral small vessel disease, but they were cross-sectional, making inferences on causality difficult. We determined associations between impaired PVS, measured using DTI-ALPS and PVS volume, and cognition and incident dementia. METHODS: In patients with lacunar stroke and confluent white matter hyperintensities, without dementia at baseline, recruited prospectively in a single center, magnetic resonance imaging was performed annually for 3 years, and cognitive assessments, including global, memory, executive function, and processing speed, were performed annually for 5 years. We determined associations between DTI-ALPS and PVS volume with cerebral small vessel disease imaging markers (white matter hyperintensity volume, lacunes, and microbleeds) at baseline and with changes in imaging markers. We determined whether DTI-ALPS and PVS volume at baseline and change over 3 years predicted incident dementia. Analyses were controlled for conventional diffusion tensor image metrics using 2 markers (median mean diffusivity [MD] and peak width of skeletonized MD) and adjusted for age, sex, and vascular risk factors. RESULTS: A total of 120 patients, mean age 70.0 years and 65.0% male, were included. DTI-ALPS declined over 3 years, while no change in PVS volume was found. Neither DTI-ALPS nor PVS volume was associated with cerebral small vessel disease imaging marker progression. Baseline DTI-ALPS was associated with changes in global cognition (ß=0.142, P=0.032), executive function (ß=0.287, P=0.027), and long-term memory (ß=0.228, P=0.027). Higher DTI-ALPS at baseline predicted a lower risk of dementia (hazard ratio, 0.328 [0.183-0.588]; P<0.001), and this remained significant after including median MD as a covariate (hazard ratio, 0.290 [0.139-0.602]; P<0.001). Change in DTI-ALPS predicted dementia conversion (hazard ratio, 0.630 [0.428-0.964]; P=0.048), but when peak width of skeletonized MD and median MD were entered as covariates, the association was not significant. There was no association between baseline PVS volume, or PVS change over 3 years, and conversion to dementia. CONCLUSIONS: DTI-ALPS predicts future dementia risk in patients with lacunar strokes and confluent white matter hyperintensities. However, the weakening of the association between change in DTI-ALPS and incident dementia after controlling for peak width of skeletonized MD and median MD suggests part of the signal may represent conventional diffusion tensor image metrics. PVS volume is not a predictor of future dementia risk.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Trastornos del Conocimiento , Demencia , Accidente Vascular Cerebral Lacunar , Sustancia Blanca , Humanos , Masculino , Anciano , Femenino , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Cognición , Trastornos del Conocimiento/etiología , Imagen por Resonancia Magnética/efectos adversos , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/epidemiología , Accidente Vascular Cerebral Lacunar/complicaciones , Demencia/diagnóstico por imagen , Demencia/epidemiología , Demencia/complicaciones , Sustancia Blanca/patologíaRESUMEN
BACKGROUND: The importance of thromboembolism in the pathogenesis of lacunar stroke (LS), resulting from cerebral small vessel disease (cSVD), is debated, and although antiplatelets are widely used in secondary prevention after LS, there is limited trial evidence from well-subtyped patients to support this approach. We sought to evaluate whether altered anticoagulation plays a causal role in LS and cSVD using 2-sample Mendelian randomization. METHODS: From a recent genome-wide association study (n=81â 190), we used 119 genetic variants associated with venous thrombosis at genome-wide significance (P<5*10-8) and with a linkage disequilibrium r2<0.001 as instrumental variables. We also used genetic associations with stroke from the GIGASTROKE consortium (62â 100 ischemic stroke cases: 10â 804 cardioembolic stroke, 6399 large-artery stroke, and 6811 LS). In view of the lower specificity for LS with the CT-based phenotyping mainly used in GIGASTROKE, we also used data from patients with magnetic resonance imaging-confirmed LS (n=3199). We also investigated associations with more chronic magnetic resonance imaging features of cSVD, namely, white matter hyperintensities (n=37â 355) and diffusion tensor imaging metrics (n=36â 533). RESULTS: Mendelian randomization analyses showed that genetic predisposition to venous thrombosis was associated with an increased odds of any ischemic stroke (odds ratio [OR], 1.19 [95% CI, 1.13-1.26]), cardioembolic stroke (OR, 1.32 [95% CI, 1.21-1.45]), and large-artery stroke (OR, 1.41 [95% CI, 1.26-1.57]) but not with LS (OR, 1.07 [95% CI, 0.99-1.17]) in GIGASTROKE. Similar results were found for magnetic resonance imaging-confirmed LS (OR, 0.94 [95% CI, 0.81-1.09]). Genetically predicted risk of venous thrombosis was not associated with imaging markers of cSVD. CONCLUSIONS: These findings suggest that altered thrombosis plays a role in the risk of cardioembolic and large-artery stroke but is not a causal risk factor for LS or imaging markers of cSVD. This raises the possibility that antithrombotic medication may be less effective in cSVD and underscores the necessity for further trials in well-subtyped cohorts with LS to evaluate the efficacy of different antithrombotic regimens in LS.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Accidente Cerebrovascular Embólico , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Trombosis , Trombosis de la Vena , Humanos , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Imagen de Difusión Tensora , Accidente Cerebrovascular Embólico/complicaciones , Fibrinolíticos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/complicaciones , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/genética , Accidente Vascular Cerebral Lacunar/complicaciones , Trombosis/complicaciones , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/epidemiología , Trombosis de la Vena/genéticaAsunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/genética , Aspirina/uso terapéutico , Accidente Vascular Cerebral Lacunar/terapia , Estudio de Asociación del Genoma CompletoRESUMEN
A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.
Asunto(s)
Isquemia Encefálica , Enfermedades de los Pequeños Vasos Cerebrales , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Humanos , Isquemia Encefálica/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Lípidos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Accidente Cerebrovascular/prevención & control , Accidente Vascular Cerebral Lacunar/terapiaRESUMEN
Ischemic stroke is the most common stroke, caused by occlusion of cerebral vessels and leading causes of disability. Erythropoietin (EPO) has non-hematopoietic effects as a neuroprotectant after ischemic event. This study aimed to learn the serum level of EPO in acute ischemic stroke. This cross-sectional study of ischemic stroke patients with onset < 24 h and consecutive sampling was used to collect the data from medical records review, physical examinations, head CT, 24-h EPO, 24-h and seventh-day NIHSS. A total of 47 patients consisting of 59.6% women, with a median age of 53 years old (21-70). The median 24 h EPO level was 808.6 pg/mL (134.2-2988.9). The relationship between 24 h-EPO and 24-h NIHSS were not significant (r = 0.101; p = 0.250), nor to 7th day NIHSS (r = - 0.0174; p = 0.121) and to delta NIHSS (r = 0.186; p = 0.106). The relationship of blood collection time (hour) and EPO was significant (r = - 0.260; p = 0.039). There was a statistically significant difference between serum EPO levels in ischemic stroke patients with lacunar stroke compared to non-lacunar stroke (288.5 vs. 855.4 ng/mL; p = 0.021). There was a relationship between the time of collection of blood and the level of EPO and also there was difference EPO level in lacunar stroke subtype compared with non-lacunar. The relationship between EPO and NIHSS lost significance after analysis. There is a need for a future study comparing each stroke risk factor and the same blood collection time.
Asunto(s)
Isquemia Encefálica , Eritropoyetina , Accidente Cerebrovascular Isquémico , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios TransversalesAsunto(s)
Trastornos de Deglución , Parálisis Facial , Accidente Vascular Cerebral Lacunar , Humanos , Accidente Vascular Cerebral Lacunar/complicaciones , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Parálisis Facial/etiología , Trastornos de Deglución/etiología , Disartria/etiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts. METHODS: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates. RESULTS: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient ß = 0.020; SE = 0.009; p = 0.03). DISCUSSION: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.
Asunto(s)
Accidente Cerebrovascular Isquémico , Noma , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Anciano , Humanos , Estudios Transversales , Hematócrito , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
BACKGROUND AND OBJECTIVES: Risk of readmission after stroke differs by stroke (sub)type and etiology, with higher risks reported for hemorrhagic stroke and cardioembolic stroke. We examined the risk and cause of first readmission by stroke subtype over the years post incident stroke. METHODS: Atherosclerosis Risk in Communities (ARIC) study participants (n = 1,412) with first-ever stroke were followed up for all-cause readmission after incident stroke. Risk of first readmission was examined by stroke subtypes (cardioembolic, thrombotic/lacunar, and hemorrhagic [intracerebral and subarachnoid]) using Cox and Fine-Gray proportional hazards models, adjusting for sociodemographic and cardiometabolic risk factors. RESULTS: Among 1,412 participants (mean [SD] age 72.4 [9.3] years, 52.1% women, 35.3% Black), 1,143 hospitalizations occurred over 41,849 person-months. Overall, 81% of participants were hospitalized over a maximum of 26.6 years of follow-up (83% of participants with thrombotic/lacunar stroke, 77% of participants with cardioembolic stroke, and 78% of participants with hemorrhagic stroke). Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions. Over the entire follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (hazard ratio [HR] 0.82, 95% CI 0.71-0.95) and hemorrhagic stroke (HR 0.74, 95% CI 0.58-0.93) in adjusted Cox proportional hazards models. By contrast, there was no statistically significant difference among subtypes when adjusting for atrial fibrillation and competing risk of death. Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (HR 0.66, 95% CI 0.46-0.93) and during 1 month-1 year (HR 0.78, 95% CI 0.62-0.97), and hemorrhagic stroke was associated with lower risk during 1 month-1 year (HR 0.60, 95% CI 0.41-0.87). There was no significant difference between subtypes in readmission risk during later periods. DISCUSSION: Over 26 years of follow-up, 81% of stroke participants experienced a readmission. Cardiovascular and cerebrovascular diagnoses at readmission were most common across stroke subtypes. Though cardioembolic stroke has previously been reported to confer higher risk of readmission, in this study, the readmission risk was not statistically significantly different between stroke subtypes or over different periods when accounting for the competing risk of death.
Asunto(s)
Accidente Cerebrovascular Embólico , Accidente Cerebrovascular Hemorrágico , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Femenino , Humanos , Anciano , Masculino , Accidente Cerebrovascular/epidemiología , HospitalizaciónRESUMEN
OBJECTIVE: Genome-wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases, including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study, we performed targeted high-depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. METHODS: A total of 95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44, and PMF1/PMF1-BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and Rare Variant Influential Filtering Tool analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, chromatin immunoprecipitation followed by sequencing, and chromatin interaction analysis with paired-end tag databases. Multivariable Mendelian randomization assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at 1q22 could be causally related to ICH risk. RESULTS: Common and rare variant analyses prioritized variants in SEMA4A 5'-UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that 1q22 is spatially organized in a single chromatin loop, and that the genes therein belong to the same topologically associating domain. Chromatin immunoprecipitation followed by sequencing and chromatin interaction analysis with paired-end tag data analysis highlighted the presence of long-range interactions between the SEMA4A-promoter and PMF1-enhancer regions prioritized by association testing. Multivariable Mendelian randomization analyses demonstrated that PMF1 overexpression could be causally related to non-lobar ICH risk. INTERPRETATION: Altered promoter-enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and cerebral small vessel disease. ANN NEUROL 2024;95:325-337.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Semaforinas , Accidente Vascular Cerebral Lacunar , Humanos , Estudio de Asociación del Genoma Completo , Hemorragia Cerebral/genética , Hemorragia Cerebral/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/genética , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Accidente Vascular Cerebral Lacunar/complicaciones , Cromatina , Semaforinas/genéticaRESUMEN
INTRODUCTION: This study aims to assess the effect of enlarged perivascular spaces (EPVS) in patients using the methods of scale score and 3D volume quantification and to determine whether EPVS progression is related to the occurrence of silent lacunar infarction (SLI). METHOD: Three hundred sixty-seven elderly patients with EPVS were screened by MRI on the day of admission and 2 years later; 295 patients were included in the final study, among which 136 patients had EPVS with SLI (EL); and 159 patients had EPVS without SLI (EOL). Both scale score and 3D volume quantification method were used to evaluate EPVS. The 295 patients were divided into three groups based on EPVS progression state: Group 1 (no progression), Group 2 (0-50% EPVS progression), and Group 3 (≥ 50% EPVS progression). Multiple logistic regression analysis was used to analyze the risk of occurrence of SLI. RESULTS: The EPVS scores and ΔEPVS scores were not significantly different between the EL and EOL groups (p > 0.05). EPVS volumes and their progression were significantly higher in EL compared with EOL (p < 0.001). The incidence of SLI was increased in Groups 2 and 3 compared with those in Group 1, and the trend test showed statistically significant (p = 0.032). Multiple logistic regression analysis showed that the risk of occurrence of SLI was significantly increased in Group 2 (OR 2.24; p = 0.024) and Group 3 (OR 3.31; p = 0.037) versus that in Group 1. CONCLUSION: 3D volume quantification allows for a more sensitive assessment of EPVS changes, and the progression of EPVS volume may contribute to the occurrence of SLI.
Asunto(s)
Accidente Vascular Cerebral Lacunar , Humanos , Anciano , Accidente Vascular Cerebral Lacunar/diagnóstico por imagen , Accidente Vascular Cerebral Lacunar/epidemiología , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a rare and complex disorder with variable clinical presentation and a typical magnetic resonance imaging (MRI) pattern of vasogenic edema with typical and atypical locations. It is often triggered by other diseases and drugs and the most prototypical association is with persistently elevated arterial pressure values. Among the potential cerebrovascular complications, intracranial bleeding has been described, but ischemic stroke is uncommonly reported. METHODS: We are presenting a case of a male patient with prolonged and sustained arterial hypertension acutely presenting with lacunar ischemic stroke involving the right corona radiata and composite MRI findings with the association of chronic small vessel disease (SVD) markers, acute symptomatic lacunar stroke, and atypical, central variant, posterior fossa dominant PRES. In the MRI follow-up, the white matter hyperintensities in T2-fluid attenuated inversion recovery (FLAIR sequences) due to PRES. DISCUSSION: The pathophysiology of PRES is not yet fully known, but the association with markedly increased values of arterial pressure is typical. In this context, ischemic stroke has not been considered in the clinical and neuroradiological manifestations of PRES and it has been only occasionally reported in the literature. In this case, the main hypothesis is that sustained hypertension may have triggered both manifestations, PRES, and ischemic stroke and the last one allowed to diagnose the first one. CONCLUSIONS: Atypical variants of PRES are not so rare and it may also occur in typical triggering situations. The association with ischemic stroke is even rarer and it may add some clues to the pathomechanisms of PRES.
Asunto(s)
Hipertensión , Accidente Cerebrovascular Isquémico , Síndrome de Leucoencefalopatía Posterior , Accidente Vascular Cerebral Lacunar , Sustancia Blanca , Humanos , Masculino , Síndrome de Leucoencefalopatía Posterior/complicaciones , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/complicaciones , Hipertensión/complicaciones , Imagen por Resonancia Magnética/métodos , Accidente Vascular Cerebral Lacunar/complicaciones , Accidente Vascular Cerebral Lacunar/diagnóstico por imagenRESUMEN
BACKGROUND: Despite previous research suggesting a potential association between cerebral small vessel disease (CSVD) and epilepsy, the precise causality and directionality between cerebral small vessel disease (CSVD) and epilepsy remain incompletely understood. We aimed to investigate the causal link between CSVD and epilepsy. METHOD: A bidirectional two-sample Mendelian randomization (MR) analysis was performed to evaluate the causal relationship between CSVD and epilepsy. The analysis included five dimensions of CSVD, namely small vessel ischemic stroke (SVS), intracerebral hemorrhage (ICH), white matter damage (including white matter hyperintensity [WMH], fractional anisotropy, and mean diffusivity), lacunar stroke, and cerebral microbleeds. We also incorporated epilepsy encompassing both focal epilepsy and generalized epilepsy. Inverse variance weighted (IVW) was used as the primary estimate while other four MR techniques were used to validate the results. Pleiotropic effects were controlled by adjusting vascular risk factors through multivariable MR. RESULT: The study found a significant association between SVS (odds ratio [OR] 1.117, PFDR = 0.022), fractional anisotropy (OR 0.961, PFDR = 0.005), mean diffusivity (OR 1.036, PFDR = 0.004), and lacunar stroke (OR 1.127, PFDR = 0.007) with an increased risk of epilepsy. The aforementioned correlations primarily occurred in focal epilepsy rather than generalized epilepsy on subgroup analysis and retained their significance in the multivariable MR analysis. CONCLUSION: Our study demonstrated that genetic susceptibility to CSVD independently elevates the risk of epilepsy, especially focal epilepsy. Diffusion tensor imaging may help screen patients at high risk for epilepsy in CSVD. Improved management of CSVD may be a significant approach in reducing the overall prevalence of epilepsy.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Epilepsias Parciales , Epilepsia Generalizada , Epilepsia , Accidente Vascular Cerebral Lacunar , Humanos , Imagen de Difusión Tensora , Análisis de la Aleatorización Mendeliana , Imagen por Resonancia Magnética/métodos , Enfermedades de los Pequeños Vasos Cerebrales/complicaciones , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/epidemiología , Epilepsia/diagnóstico por imagen , Epilepsia/epidemiología , Epilepsia/genéticaRESUMEN
AIMS: It remains inconclusive regarding alcohol intake and stroke risk because determining risk factors depends on the specific pathogenesis of stroke. We used the variant rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) as an instrument to investigate the causal role of alcohol intake in cerebral small- and large-vessel diseases. METHODS: We studied 682 men (mean age, 70.0 years), without stroke, in a cross-sectional Mendelian randomization analysis. We assessed small-vessel diseases (SVDs), which comprised lacunar infarcts, white matter hyperintensities (WMHs), and cerebral microbleeds, and large intracranial artery stenosis (ICAS) on brain magnetic resonance imaging. RESULTS: The median (25%tiles, 75%tiles) alcohol consumption by ALDH2-rs671 inactive A allele (n=313 [45.9%]) and non-A allele (n=369 [54.1%]) carriers was 3.5 (0.0, 16.0) and 32.0 (12.9, 50.0) g/day, respectively. Non-A allele carriers had higher prevalent hypertension and lower low-density lipoprotein cholesterol concentrations than A allele carriers. In age-adjusted ordinal logistic regression for graded burden, odds ratios (95% confidence intervals) for total SVDs, lacunar infarcts, WMHs, cerebral microbleeds, and ICAS in non-Aallele carriers were 1.46 (1.09-1.94), 1.41 (0.95-2.08), 1.39 (1.05-1.85), 1.69 (1.06-2.69), and 0.70 (0.50-0.98), respectively, compared with A allele carriers. These associations attenuated to statistical non-significance after considering covariates and amount of alcohol intake. CONCLUSIONS: Our findings suggest a positive association of alcohol consumption with risk of cerebral SVDs and its inverse association with risk of large-vessel disease through intermediaries, such as hypertension or low-density lipoprotein cholesterol. These findings provide insight into potential causal mechanisms linking alcohol consumption with stroke risk.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Hipertensión , Accidente Vascular Cerebral Lacunar , Accidente Cerebrovascular , Masculino , Humanos , Anciano , Análisis de la Aleatorización Mendeliana , Estudios Transversales , Consumo de Bebidas Alcohólicas/efectos adversos , Aldehído Deshidrogenasa Mitocondrial/genética , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genética , LDL-Colesterol , Enfermedades de los Pequeños Vasos Cerebrales/genética , Hemorragia Cerebral/etiología , Hemorragia Cerebral/genéticaRESUMEN
INTRODUCTION: Hyperactivity immune responses to coronavirus disease 2019 (COVID-19) can lead to several manifestations in the human organ. One of the most affected organs is the respiratory system. Not only does it affect the respiratory system, but hyperactivity can also affect the neuromuscular and cerebrovascular systems, though it is scarce for both systems to be affected simultaneously. CASE PRESENTATION: We presented a mild COVID-19 patient with a history of progressive general weakness and dysphagia on day seventh day after patient was first diagnosed with COVID-19, which continued with diplopia and shortness of breath. The patient experienced respiratory failure type 1 and was admitted to an intensive care unit. A head CT scan showed multiple lacunar infarcts in the nucleus lentiform, while the electromyography (EMG) showed Guillain-Barré syndrome (GBS) with the subtype acute inflammatory demyelinating polyneuropathy (AIDP). The patient was reported to have successful therapy with intravenous immunoglobulin (IVIG) for five days and physical rehabilitation for three months. General weakness disappeared after the therapy, and the patient could do regular daily activities. CONCLUSIONS: Various neurological symptoms can manifest in COVID-19 patients. Acute progressive muscle weakness should be considered as an autoimmune and cerebrovascular disease induced by COVID-19. Early diagnosis and treatment can provide a better outcome for the patient.
Asunto(s)
COVID-19 , Síndrome de Guillain-Barré , Accidente Vascular Cerebral Lacunar , Humanos , COVID-19/complicaciones , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/diagnóstico , SARS-CoV-2 , Inmunoglobulinas IntravenosasRESUMEN
BACKGROUND: Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer's disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample. METHODS: Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43). RESULTS: We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (ß = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (ß = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition. CONCLUSION: The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.