RESUMEN
While pre-exposure prophylaxis (PrEP) has demonstrated efficacy in preventing HIV transmission, disparities in access persist in the United States, especially among Hispanic/Latinx sexual minority men (SMM). Language barriers and differences in how Latinx SMM obtain information may impact access to PrEP and HIV prevention. This study used data from the 2021 American Men's Internet Survey (AMIS) to examine differences in communication networks and PrEP use among Latinx SMM by primary language (Spanish vs. English). We examined the associations between Latinx SMM's individual- and meso-level communication networks and PrEP-related outcomes using modified Poisson regression with robust variances. Spanish-speaking Latinx SMM in the study were less likely to test for HIV, be aware of PrEP, and use daily PrEP, compared to English-speaking participants. Sexuality disclosure to a healthcare provider was positively associated with PrEP uptake among all participants and predicted STI testing over the past 12 months among English-speaking Latinx SMM. Findings highlight disparities in PrEP awareness and uptake among Latinx SMM, especially among those whose primary language is Spanish. Addressing these disparities through targeted interventions, including improved communication with healthcare providers, may help facilitate PrEP access and use in this population.
Asunto(s)
Infecciones por VIH , Hispánicos o Latinos , Lenguaje , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Humanos , Masculino , Hispánicos o Latinos/estadística & datos numéricos , Hispánicos o Latinos/psicología , Profilaxis Pre-Exposición/estadística & datos numéricos , Adulto , Infecciones por VIH/prevención & control , Infecciones por VIH/etnología , Minorías Sexuales y de Género/estadística & datos numéricos , Minorías Sexuales y de Género/psicología , Estados Unidos , Adulto Joven , Persona de Mediana Edad , Adolescente , Encuestas y Cuestionarios , Barreras de Comunicación , Comunicación , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/etnología , Aceptación de la Atención de Salud/psicología , Conocimientos, Actitudes y Práctica en SaludRESUMEN
PURPOSE OF REVIEW: Although pre-exposure prophylaxis (PrEP) is effective for reducing risk of HIV transmission, stigma persists as a barrier to HIV prevention. Digital technologies present opportunities to access hard-to-reach populations and increase the efficiency of established interventions. This review examines current digital interventions addressing stigma to improve PrEP-related outcomes. RECENT FINDINGS: Digital technologies are increasingly used for HIV prevention and include a wide range of formats. Recent interventions focused on stigma and PrEP tend to engage mobile phone-related technology and focus on younger populations with particular attention to men who have sex with men and transgender women. Digital interventions that address stigma are promising for improving PrEP-related outcomes. No single technology currently demonstrates consistent superiority. Limited access to PrEP and heightened stigma in under-resourced countries present challenges for interventions supporting diverse communities. Further research should examine how digital interventions can reduce stigma beyond the individual level to enhance PrEP use and explore opportunities to improve and integrate approaches to stigma measurement.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Personas Transgénero , Masculino , Humanos , Femenino , Homosexualidad Masculina , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Estigma SocialRESUMEN
Spinal cord injury (SCI) affects millions of people worldwide. Neural progenitor cell (NPC) transplantation is a promising treatment for regenerating lost spinal cord tissue and restoring neurological function after SCI. We conducted a literature search and found that less than a quarter of experimental rodent cell and tissue transplantation studies have investigated anatomical outcomes at longer than 4 months post-transplantation. This is a critical topic to investigate, given that stem and progenitor cell therapies would need to remain in place throughout the lifetime of an individual. We sought to determine how commonly assessed anatomical outcomes evolve between early and far chronic time-points post-NPC transplantation. At either 8 weeks or 26 weeks following transplantation of NPCs into sites of cervical SCI, we evaluated graft neuronal density, astroglial cell density, graft axon outgrowth, and regeneration of host axon populations into grafts in male and female mice. We found that graft neuronal density does not change over time, but the numbers of graft-associated astrocytes and glial fibrillary acidic protein intensity is significantly increased in the far chronic phase compared with the early chronic time-point. In addition, graft axon outgrowth was significantly decreased at 26 weeks post-transplantation compared with 8 weeks post-transplantation. In contrast, corticospinal axon regeneration into grafts was not diminished over time, but rather increased significantly from early to far chronic periods. Interestingly, we found that graft neuronal density is significantly influenced by sex of the host animal, suggesting that sex-dependent processes may shape graft composition over time. Collectively, these results demonstrate that NPC transplants are dynamic and that commonly assessed outcome measures associated with graft efficacy evolve over the weeks to months post-transplantation into the spinal cord.
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Células-Madre Neurales , Traumatismos de la Médula Espinal , Ratones , Masculino , Femenino , Humanos , Animales , Axones/fisiología , Regeneración Nerviosa/fisiología , Células-Madre Neurales/trasplante , Médula Espinal , Neuronas , Trasplante de Células Madre/métodosRESUMEN
Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery of motor and sensory functions after SCI, is poorly understood. We transplanted developmentally-restricted spinal cord NPCs, isolated from E11.5-E13.5 mouse embryos, into sites of adult mouse SCI and analyzed graft axon outgrowth, cellular composition, host axon regeneration, and behavior. Earlier-stage grafts exhibited greater axon outgrowth, enrichment for ventral spinal cord interneurons and Group-Z spinal interneurons, and enhanced host 5-HT+ axon regeneration. Later-stage grafts were enriched for late-born dorsal horn interneuronal subtypes and Group-N spinal interneurons, supported more extensive host CGRP+ axon ingrowth, and exacerbated thermal hypersensitivity. Locomotor function was not affected by any type of NPC graft. These findings showcase the role of spinal cord graft cellular composition in determining anatomical and functional outcomes following SCI.
Asunto(s)
Células-Madre Neurales , Traumatismos de la Médula Espinal , Ratones , Animales , Axones/fisiología , Regeneración Nerviosa , Células-Madre Neurales/fisiología , Neuronas/fisiología , Traumatismos de la Médula Espinal/terapiaRESUMEN
Children with sickle cell disease (SCD) demonstrate cerebral hemodynamic stress and are at high risk of strokes. We hypothesized that curative hematopoietic stem cell transplant (HSCT) normalizes cerebral hemodynamics in children with SCD compared with pre-transplant baseline. Whole-brain cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were measured by magnetic resonance imaging 1 to 3 months before and 12 to 24 months after HSCT in 10 children with SCD. Three children had prior overt strokes, 5 children had prior silent strokes, and 1 child had abnormal transcranial Doppler ultrasound velocities. CBF and OEF of HSCT recipients were compared with non-SCD control participants and with SCD participants receiving chronic red blood cell transfusion therapy (CRTT) before and after a scheduled transfusion. Seven participants received matched sibling donor HSCT, and 3 participants received 8 out of 8 matched unrelated donor HSCT. All received reduced-intensity preparation and maintained engraftment, free of hemolytic anemia and SCD symptoms. Pre-transplant, CBF (93.5 mL/100 g/min) and OEF (36.8%) were elevated compared with non-SCD control participants, declining significantly 1 to 2 years after HSCT (CBF, 72.7 mL/100 g per minute; P = .004; OEF, 27.0%; P = .002), with post-HSCT CBF and OEF similar to non-SCD control participants. Furthermore, HSCT recipients demonstrated greater reduction in CBF (-19.4 mL/100 g/min) and OEF (-8.1%) after HSCT than children with SCD receiving CRTT after a scheduled transfusion (CBF, -0.9 mL/100 g/min; P = .024; OEF, -3.3%; P = .001). Curative HSCT normalizes whole-brain hemodynamics in children with SCD. This restoration of cerebral oxygen reserve may explain stroke protection after HSCT in this high-risk patient population.
Asunto(s)
Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Accidente Cerebrovascular , Humanos , Niño , Anemia de Células Falciformes/terapia , Accidente Cerebrovascular/prevención & control , Hemodinámica , Oxígeno , Circulación CerebrovascularRESUMEN
Non-ketotic hyperglycemia (NKH) is associated with a spectrum of symptoms and radiographic findings due to poorly-controlled diabetes mellitus. These lesions, which predominantly affect the parieto-occipital cortex, are commonly missed by neurologists and neuroradiologists due to their subtle hypointense appearance on T2-based imaging. We report four atypical cases of this syndrome to highlight its subtle, protean presentation in order to aid timely diagnosis. Based on our institutional case series, we describe four cases of NKH with atypical presentation and lesion burden affecting the anterior cortex. We review the clinical presentations, laboratory abnormalities, neuroimaging, and corresponding electroencephalography. Four patients with atypical NKH were characterized in our series. Presenting symptoms ranged from rhythmic hand-tapping to generalized tonic-clonic status epilepticus. Laboratory values were notable for marked hyperglycemia (range: 447 - 627 mg/dL), mild pseudo-hyponatremia (range: 127 - 136 mmol/L), and elevated hemoglobin A1C levels (range: 10.9 - 16.1%). All patients were found to have the classically described pattern of T2-based hypointensity; three with atypical distributions involving the "anterior" cortex. These lesions corresponded to the electrographic nidus of seizure burden. During follow-up, both seizures and T2-based hypointensity resolved within weeks of serum glucose normalization. Our series of four NKH patients with atypical findings of T2-based signal abnormalities expands the clinico-radiographic phenotype revealing a more protean distribution than previously described. Knowledge of these atypical imaging features will aid both the neurologist and radiologist in timely diagnosis and care of these patients.
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Epilepsia , Hiperglucemia , Electroencefalografía , Epilepsia/complicaciones , Glucosa , Hemoglobina Glucada , Humanos , Hiperglucemia/complicaciones , Cetosas , Fenotipo , Convulsiones/diagnósticoRESUMEN
BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is a common finding in patients presenting to the emergency department with acute neurological symptoms. Noncontrast head computed tomography (NCCT) is the primary modality for assessment and detection of ICH in the acute setting. RAPID ICH software aims to automatically detect ICH on NCCT and was previously shown to have high accuracy when applied to a curated test data set. Here, we measured the test performance characteristics of RAPID ICH software in detecting ICH on NCCT performed in patients undergoing emergency stroke evaluation at a tertiary academic comprehensive stroke center. MATERIALS AND METHODS: This retrospective study assessed consecutive patients over a 6-month period who presented with acute neurological symptoms suspicious for stroke and underwent NCCT with RAPID ICH postprocessing. RAPID ICH detection was compared with the interpretation of a reference standard comprising a board-certified or board-eligible neuroradiologist, or in cases of discrepancy, adjudicated by a consensus panel of 3 neuroradiologists. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of RAPID ICH for ICH detection were determined. RESULTS: Three hundred seven NCCT scans were included in the study. RAPID ICH correctly identified 34 of 37 cases with ICH and 228 of 270 without ICH. RAPID ICH had a sensitivity of 91.9% (78.1%-98.3%), specificity of 84.4% (79.6%-88.6%), NPV of 98.7% (96.3%-99.6%), PPV of 44.7% (37.6%-52.1%), and overall accuracy of 85.3% (80.9%-89.1%). CONCLUSIONS: In a real-world scenario, RAPID ICH software demonstrated high NPV but low PPV for the presence of ICH when evaluating possible stroke patients.
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Hemorragias Intracraneales , Accidente Cerebrovascular , Humanos , Hemorragias Intracraneales/diagnóstico por imagen , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Individuals with sickle cell anemia have heightened risk of stroke and cognitive dysfunction. Given its high prevalence globally, whether sickle cell trait (SCT) is a risk factor for neurological injury has been of interest; however, data have been limited. We hypothesized that young, healthy adults with SCT would show normal cerebrovascular structure and hemodynamic function. METHODS: As a case-control study, young adults with (N=25, cases) and without SCT (N=24, controls) underwent brain magnetic resonance imaging to quantify brain volume, microstructural integrity (fractional anisotropy), silent cerebral infarcts (SCI), intracranial stenosis, and aneurysms. Pseudocontinuous arterial spin labeling and asymmetric spin echo sequences measured cerebral blood flow and oxygen extraction fraction, respectively, from which cerebral metabolic oxygen demand was calculated. Imaging metrics were compared between SCT cases and controls. SCI volume was correlated with baseline characteristics. RESULTS: Compared with controls, adults with SCT demonstrated similar normalized brain volumes (SCT 0.80 versus control 0.81, P=0.41), white matter fractional anisotropy (SCT 0.41 versus control 0.43, P=0.37), cerebral blood flow (SCT 62.04 versus control, 61.16 mL/min/100 g, P=0.67), oxygen extraction fraction (SCT 0.27 versus control 0.27, P=0.31), and cerebral metabolic oxygen demand (SCT 2.71 versus control 2.70 mL/min/100 g, P=0.96). One per cohort had an intracranial aneurysm. None had intracranial stenosis. The SCT cases and controls showed similar prevalence and volume of SCIs; however, in the subset of participants with SCIs, the SCT cases had greater SCI volume versus controls (0.29 versus 0.07 mL, P=0.008). Of baseline characteristics, creatinine was mildly elevated in the SCT cohort (0.9 versus 0.8 mg/dL, P=0.053) and correlated with SCI volume (ρ=0.49, P=0.032). In the SCT cohort, SCI distribution was similar to that of young adults with sickle cell anemia. CONCLUSIONS: Adults with SCT showed normal cerebrovascular structure and hemodynamic function. These findings suggest that healthy individuals with SCT are unlikely to be at increased risk for early or accelerated ischemic brain injury.
Asunto(s)
Anemia de Células Falciformes , Rasgo Drepanocítico , Sustancia Blanca , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/epidemiología , Estudios de Casos y Controles , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Constricción Patológica/complicaciones , Humanos , Imagen por Resonancia Magnética/métodos , Oxígeno/metabolismo , Rasgo Drepanocítico/diagnóstico por imagen , Estrés Fisiológico , Adulto JovenRESUMEN
Symmetric, progressive, necrotizing lesions in the brainstem are a defining feature of Leigh syndrome (LS). A mechanistic understanding of the pathogenesis of these lesions has been elusive. Here, we report that leukocyte proliferation is causally involved in the pathogenesis of LS. Depleting leukocytes with a colony-stimulating factor 1 receptor inhibitor disrupted disease progression, including suppression of CNS lesion formation and a substantial extension of survival. Leukocyte depletion rescued diverse symptoms, including seizures, respiratory center function, hyperlactemia, and neurologic sequelae. These data reveal a mechanistic explanation for the beneficial effects of mTOR inhibition. More importantly, these findings dramatically alter our understanding of the pathogenesis of LS, demonstrating that immune involvement is causal in disease. This work has important implications for the mechanisms of mitochondrial disease and may lead to novel therapeutic strategies.
Asunto(s)
Enfermedad de Leigh , Animales , Modelos Animales de Enfermedad , Complejo I de Transporte de Electrón , Enfermedad de Leigh/genética , Leucocitos/metabolismo , Ratones , Ratones NoqueadosRESUMEN
OBJECTIVE: To determine the patient- and tissue-based relationships between cerebral hemodynamic and oxygen metabolic stress, microstructural injury, and infarct location in adults with sickle cell disease (SCD). METHODS: Control participants and patients with SCD underwent brain MRI to quantify cerebral blood flow (CBF), oxygen extraction fraction (OEF), mean diffusivity (MD), and fractional anisotropy (FA) within normal-appearing white matter (NAWM) and infarcts on fluid-attenuated inversion recovery. Multivariable linear regression examined the patient- and voxel-based associations between hemodynamic and metabolic stress (defined as elevated CBF and OEF, respectively), white matter microstructure, and infarct location. RESULTS: Of 83 control participants and patients with SCD, adults with SCD demonstrated increased CBF (50.9 vs 38.8 mL/min/100 g, p < 0.001), increased OEF (0.35 vs 0.25, p < 0.001), increased MD (0.76 vs 0.72 × 10-3 mm2s-1, p = 0.005), and decreased FA (0.40 vs 0.42, p = 0.021) within NAWM compared to controls. In multivariable analysis, increased OEF (ß = 0.19, p = 0.035), but not CBF (ß = 0.00, p = 0.340), independently predicted increased MD in the SCD cohort; neither were predictors in controls. On voxel-wise regression, the SCD cohort demonstrated widespread OEF elevation, encompassing deep white matter regions of elevated MD and reduced FA, which spatially extended beyond high-density infarct locations from the SCD cohort. CONCLUSION: Elevated OEF, a putative index of cerebral oxygen metabolic stress, may provide a metric of ischemic vulnerability that could enable individualization of therapeutic strategies in SCD. The patient- and tissue-based relationships between elevated OEF, elevated MD, and cerebral infarcts suggest that oxygen metabolic stress may underlie microstructural injury prior to the development of cerebral infarcts in SCD.
Asunto(s)
Anemia de Células Falciformes , Sustancia Blanca , Adulto , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico por imagen , Infarto Cerebral , Circulación Cerebrovascular , Humanos , Imagen por Resonancia Magnética , Oxígeno , Consumo de Oxígeno , Estrés Fisiológico , Sustancia Blanca/diagnóstico por imagenRESUMEN
Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P < .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.
Asunto(s)
Anemia de Células Falciformes , Hidroxiurea/administración & dosificación , Imagen por Resonancia Magnética , Fármacos Neuroprotectores/administración & dosificación , Estrés Fisiológico/efectos de los fármacos , Accidente Cerebrovascular , Adolescente , Adulto , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Niño , Femenino , Humanos , Masculino , Consumo de Oxígeno/efectos de los fármacos , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/prevención & controlRESUMEN
OBJECTIVE: Computed tomographic angiography (CTA) is increasingly utilized to evaluate for traumatic cerebrovascular injury (TCVI). The purpose of this study was to determine the yield, management effect, and risk of stroke or poor outcome of a positive CTA in a large cohort of trauma patients. PATIENTS AND METHODS: A retrospective analysis was performed on 1290 consecutive trauma patients that underwent head and/or neck CTA at our level I trauma center from 2006 to 2015. Clinical variables assessed include mechanism of injury, neurological status, CTA findings, subsequent imaging results, patient management, and clinical outcomes. RESULTS: Among 1290 patients who underwent CTA, 200 (15.5%) were positive for TCVI, higher in blunt than penetrating trauma patients. In a generalized linear model, factors that increased likelihood of positive CTA included multiple cervical fractures, fractures with foraminal involvement, gunshot injury, Glasgow Coma Scale ≤ 13, and focal neurological deficit. Excluding cases with these factors lowered the positive rate to 4.3%. Of the 200 CTA-positives, 99 were treated for TCVI and 9 (4.5%) developed a subsequent stroke as compared to 5 (0.5%) in CTA-negative patients (odds ratio 10.2, Fisher exact test, pâ¯<â¯0.001). Risk of death or nursing facility discharge location was also higher in CTA-positive patients, correcting for age and presenting GCS (pâ¯<â¯0.01). CONCLUSION: CTA had a modest yield in identifying TCVI in this cohort. When positive, CTA influenced management and predicted an increased risk of subsequent stroke and poor outcome.
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Angiografía Cerebral , Traumatismos Cerebrovasculares/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adulto , Anciano , Anciano de 80 o más Años , Angiografía de Substracción Digital/métodos , Angiografía Cerebral/métodos , Femenino , Escala de Coma de Glasgow , Humanos , Masculino , Persona de Mediana Edad , Traumatismos del Cuello/complicaciones , Factores de Riesgo , Accidente Cerebrovascular/etiología , Centros Traumatológicos , Heridas no Penetrantes/complicacionesRESUMEN
OBJECTIVE: To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD. METHODS: Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps. RESULTS: Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort. CONCLUSIONS: Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.
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Anemia de Células Falciformes/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador , Imagen por Resonancia Magnética , Oxígeno/metabolismo , Accidente Cerebrovascular/diagnóstico por imagen , Adolescente , Anemia de Células Falciformes/metabolismo , Anemia de Células Falciformes/terapia , Encéfalo/metabolismo , Circulación Cerebrovascular , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Consumo de Oxígeno , Accidente Cerebrovascular/metabolismo , Adulto JovenRESUMEN
Blood transfusions are the mainstay of stroke prevention in pediatric sickle cell anemia (SCA), but the physiology conferring this benefit is unclear. Cerebral blood flow (CBF) and oxygen extraction fraction (OEF) are elevated in SCA, likely compensating for reduced arterial oxygen content (CaO2). We hypothesized that exchange transfusions would decrease CBF and OEF by increasing CaO2, thereby relieving cerebral oxygen metabolic stress. Twenty-one children with SCA receiving chronic transfusion therapy (CTT) underwent magnetic resonance imaging before and after exchange transfusions. Arterial spin labeling and asymmetric spin echo sequences measured CBF and OEF, respectively, which were compared pre- and posttransfusion. Volumes of tissue with OEF above successive thresholds (36%, 38%, and 40%), as a metric of regional metabolic stress, were compared pre- and posttransfusion. Transfusions increased hemoglobin (Hb; from 9.1 to 10.3 g/dL; P < .001) and decreased Hb S (from 39.7% to 24.3%; P < .001). Transfusions reduced CBF (from 88 to 82.4 mL/100 g per minute; P = .004) and OEF (from 34.4% to 31.2%; P < .001). At all thresholds, transfusions reduced the volume of peak OEF found in the deep white matter, a location at high infarct risk in SCA (P < .001). Reduction of elevated CBF and OEF, both globally and regionally, suggests that CTT mitigates infarct risk in pediatric SCA by relieving cerebral metabolic stress at patient- and tissue-specific levels.
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Anemia de Células Falciformes , Circulación Cerebrovascular , Transfusión de Eritrocitos , Angiografía por Resonancia Magnética , Oxígeno/sangre , Adolescente , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/terapia , Velocidad del Flujo Sanguíneo , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Large-vessel vasculopathy (LVV) increases stroke risk in pediatric sickle cell disease beyond the baseline elevated stroke risk in this vulnerable population. The mechanisms underlying this added risk and its unique impact on the developing brain are not established. METHODS: We analyzed magnetic resonance imaging and angiography scans of 66 children with sickle cell disease and infarcts by infarct density heatmaps and Jacobian determinants, a metric utilized to delineate focal volume change, to investigate if infarct location, volume, frequency, and cerebral atrophy differed among hemispheres with and without LVV. RESULTS: Infarct density heatmaps demonstrated infarct "hot spots" within the deep white matter internal border zone region in both LVV and non-LVV hemispheres, but with greater infarct density and larger infarct volumes in LVV hemispheres (2.2 mL versus 0.25 mL, P < 0.001). Additional scattered cortical infarcts in the internal carotid artery territory occurred in LVV hemispheres, but were rare in non-LVV hemispheres. Jacobian determinants revealed greater atrophy in gray and white matter of the parietal lobes of LVV compared with non-LVV hemispheres. CONCLUSION: Large-vessel vasculopathy in sickle cell disease appears to increase ischemic vulnerability in the borderzone region, as demonstrated by the increased frequency and extent of infarction within deep white matter, and increased risk of focal atrophy. Scattered infarctions across the LVV-affected hemispheres suggest additional stroke etiologies of vasculopathy (i.e., thromboembolism) in addition to chronic hypoxia-ischemia.
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Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico por imagen , Angiografía Cerebral , Infarto Cerebral/complicaciones , Infarto Cerebral/diagnóstico por imagen , Imagen por Resonancia Magnética , Adolescente , Atrofia/complicaciones , Atrofia/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To describe the neurologic and neuroimaging manifestations associated with Cantú syndrome. METHODS: We evaluated 10 patients with genetically confirmed Cantú syndrome. All adult patients, and pediatric patients who were able to cooperate and complete the studies, underwent neuroimaging, including vascular imaging. A salient neurologic history and examination was obtained for all patients. RESULTS: We observed diffusely dilated and tortuous cerebral blood vessels in all patients who underwent vascular imaging. White matter changes were observed in all patients who completed an MRI brain study. Two patients had a persistent trigeminal artery. One patient had an occluded right middle cerebral artery. One patient had transient white matter changes suggestive of posterior reversible encephalopathic syndrome. Four patients had migraines with one patient having complicated migraines. Seizures were seen in early life but infrequent. The majority of patients had mild developmental delays and one patient had a diagnosis of autism. CONCLUSIONS: Cantú syndrome is associated with various neurologic manifestations, particularly cerebrovascular findings including dilated and tortuous cerebral vessels, white matter changes, and persistent fetal circulation. Involvement of the KATP SUR2/Kir6.1 subtype potentially plays an important role in the neurologic manifestations of Cantú syndrome.
Asunto(s)
Encéfalo/irrigación sanguínea , Cardiomegalia/diagnóstico por imagen , Cardiomegalia/diagnóstico , Hipertricosis/diagnóstico por imagen , Hipertricosis/diagnóstico , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/diagnóstico , Adolescente , Adulto , Encéfalo/patología , Cardiomegalia/patología , Niño , Preescolar , Femenino , Humanos , Hipertricosis/patología , Lactante , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Osteocondrodisplasias/patología , Tomografía Computarizada por Rayos X , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adulto JovenRESUMEN
Study Design Retrospective cohort. Objective To clarify the sensitivity of C3-C2 spinolaminar line test as a screening tool for the stenosis of C1 space available for the cord (SAC). Methods Spine clinic records from April 2005 to August 2011 were reviewed. The C1 SAC was measured on lateral radiographs, and the relative positions between a C1 posterior arch and the C3-C2 spinolaminar line were examined and considered "positive" when the C1 ring lay ventral to the line. Computed tomography (CT) scans and magnetic resonance imaging (MRI) were utilized to measure precise diameters of C1 and C2 SAC and to check the existence of spinal cord compression. Results Four hundred eighty-seven patients were included in this study. There were 246 men and 241 women, with an average age of 53 years (range: 18 to 86). The mean SAC at C1 on radiographs was 21.2 mm (range: 13.5 to 28.2). Twenty-one patients (4.3%) were positive for the spinolaminar line test; all of these patients had C1 SAC of 19.4 mm or less. Eight patients (1.6%) had C1 SAC smaller than C2 on CT examination; all of these patients had a positive spinolaminar test, with high sensitivity (100%) and specificity (97%). MRI analysis revealed that two of the eight patients with a smaller C1 SAC had spinal cord compression at the C1 level. Conclusion Although spinal cord compression at the level of atlas without instability is a rare condition, the spinolaminar line can be used as a screening of C1 stenosis.