RESUMEN
BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Hemorrágico/complicaciones , Imagen de Difusión Tensora , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Hemorragia Cerebral/complicaciones , Imagen por Resonancia Magnética/métodos , Hematoma/complicaciones , Coagulación Sanguínea , Hemoglobinas , FibrinaRESUMEN
Moyamoya disease, a cerebrovascular disease leading to strokes in children and young adults, is characterized by progressive occlusion of the distal internal carotid arteries and the formation of collateral vessels. Altered genes play a prominent role in the aetiology of moyamoya disease, but a causative gene is not identified in the majority of cases. Exome sequencing data from 151 individuals from 84 unsolved families were analysed to identify further genes for moyamoya disease, then candidate genes assessed in additional cases (150 probands). Two families had the same rare variant in ANO1, which encodes a calcium-activated chloride channel, anoctamin-1. Haplotype analyses found the families were related, and ANO1 p.Met658Val segregated with moyamoya disease in the family with an LOD score of 3.3. Six additional ANO1 rare variants were identified in moyamoya disease families. The ANO1 rare variants were assessed using patch-clamp recordings, and the majority of variants, including ANO1 p.Met658Val, displayed increased sensitivity to intracellular Ca2+. Patients harbouring these gain-of-function ANO1 variants had classic features of moyamoya disease, but also had aneurysm, stenosis and/or occlusion in the posterior circulation. Our studies support that ANO1 gain-of-function pathogenic variants predispose to moyamoya disease and are associated with unique involvement of the posterior circulation.
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Anoctamina-1 , Enfermedad de Moyamoya , Niño , Humanos , Adulto Joven , Anoctamina-1/genética , Canales de Cloruro/genética , Enfermedad de Moyamoya/genética , Proteínas de Neoplasias/genéticaRESUMEN
BACKGROUND: Data from the early pandemic revealed that 0.62% of children hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had an acute arterial ischemic stroke (AIS). In a larger cohort from June 2020 to December 2020, we sought to determine whether our initial point estimate was stable as the pandemic continued and to understand radiographic and laboratory data that may clarify mechanisms of pediatric AIS in the setting of SARS-CoV-2. METHODS: We surveyed international sites with pediatric stroke expertise to determine numbers of hospitalized SARS-CoV-2 patients <18 years, numbers of incident AIS cases among children (29 days to <18 years), frequency of SARS-CoV-2 testing for children with AIS, and numbers of childhood AIS cases positive for SARS-CoV-2 June 1 to December 31, 2020. Two stroke neurologists with 1 neuroradiologist determined whether SARS-CoV-2 was the main stroke risk factor, contributory, or incidental. RESULTS: Sixty-one centers from 21 countries provided AIS data. Forty-eight centers (78.7%) provided SARS-CoV-2 hospitalization data. SARS-CoV-2 testing was performed in 335/373 acute AIS cases (89.8%) compared with 99/166 (59.6%) in March to May 2020, P<0.0001. Twenty-three of 335 AIS cases tested (6.9%) were positive for SARS-CoV-2 compared with 6/99 tested (6.1%) in March to May 2020, P=0.78. Of the 22 of 23 AIS cases with SARS-CoV-2 in whom we could collect additional data, SARS-CoV-2 was the main stroke risk factor in 6 (3 with arteritis/vasculitis, 3 with focal cerebral arteriopathy), a contributory factor in 13, and incidental in 3. Elevated inflammatory markers were common, occurring in 17 (77.3%). From centers with SARS-CoV-2 hospitalization data, of 7231 pediatric patients hospitalized with SARS-CoV-2, 23 had AIS (0.32%) compared with 6/971 (0.62%) from March to May 2020, P=0.14. CONCLUSIONS: The risk of AIS among children hospitalized with SARS-CoV-2 appeared stable compared with our earlier estimate. Among children in whom SARS-CoV-2 was considered the main stroke risk factor, inflammatory arteriopathies were the stroke mechanism.
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COVID-19 , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , COVID-19/epidemiología , Prueba de COVID-19 , Niño , Humanos , Accidente Cerebrovascular Isquémico/epidemiología , Pandemias , Prevalencia , SARS-CoV-2 , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiologíaRESUMEN
INTRODUCTION: Medical and socioeconomic factors may impact decisions to change the goals of care for patients with intracerebral hemorrhage (ICH) to comfort measures only. METHODS: We reviewed prospectively collected data on patients with ICH, including baseline patient demographics, Glasgow Coma Scale (GCS), National Institute of Health Stroke Scale (NIHSS), and ICH score. We conducted multivariable logistic regression analysis to identify predictors of change to comfort measures only status. RESULTS: Of 198 patients included in the analysis, 39 (19.7%) were made comfort measures only. Age, gender, insurance status, substance use, and medical comorbidities were similar between groups. Race was significantly different between the comfort measures only (black 15.4%, white 51.3%, other 33.3%) and noncomfort measures only groups (black 39.6%, white 45.9%, other 14.5%; Pâ¯=â¯.003). Patients changed to comfort measures only had higher mean income based on zip code ($59,264 versus $49,916; Pâ¯=â¯.021), higher median NIHSS (23 versus 16; Pâ¯=â¯.0001), higher ICH score (2.7 versus 1.5; P < .0001), lower median GCS (7 versus 13; P < .0001). Following multivariable analysis, factors associated with comfort measures only were GCS odds ratio (OR) 0.77, 95% confidence interval (CI) 0.68-0.86, P < .0001), intraventricular hemorrhage (IVH) volume (OR 1.03, 95% CI 1.01-1.06, Pâ¯=â¯.002), and black race (OR 0.24, 95% CI 0.07-0.82, Pâ¯=â¯.022). Mortality, poor outcome, and hospital length of stay were not significantly different between black and white patients. CONCLUSIONS: Lower GCS score, higher IVH volume, and race were independent predictors of comfort measures only. Black patients were 76% less likely to withdraw life support than white patients. There were no significant differences in mortality between black and white patients. Providers should be aware of potential racial disparities.
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Negro o Afroamericano , Hemorragia Cerebral/etnología , Hemorragia Cerebral/terapia , Toma de Decisiones Clínicas , Disparidades en Atención de Salud/etnología , Cuidados para Prolongación de la Vida , Población Blanca , Privación de Tratamiento , Anciano , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidad , Femenino , Escala de Coma de Glasgow , Mortalidad Hospitalaria/etnología , Humanos , Renta , Masculino , Persona de Mediana Edad , Comodidad del Paciente , Características de la Residencia , Factores de Riesgo , Texas/epidemiologíaRESUMEN
OBJECTIVE: To test the hypothesis that de novo genetic variants are responsible for moyamoya disease (MMD) in children with unaffected relatives, we performed exome sequencing of 28 affected children and their unaffected parents. METHODS: Exome sequencing was performed on 28 trios of affected patients with MMD and unaffected parents. RESULTS: We identified 3 novel rare de novo RNF213 variants, 1 in the RING domain and 2 in a highly conserved region distal to the RING domain (4,114-4,120). These de novo cases of MMD present at a young age with aggressive MMD and uniquely have additional occlusive vascular lesions, including renal artery stenosis. Two previously reported cases had de novo variants in the same limited region and presented young with aggressive MMD, and 1 case had narrowing of the inferior abdominal aorta. CONCLUSIONS: These results indicate a novel syndrome associated with RNF213 rare variants defined by de novo mutations disrupting highly conserved amino acids in the RING domain and a discrete region distal to the RING domain delimited by amino acids 4,114 to 4,120 leading to onset of severe MMD before 3 years of age and occlusion of other arteries, including the abdominal aorta, renal, iliac, and femoral arteries.