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BACKGROUND AND PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that causes vascular malformations in a variety of organs and tissues, including brain AVMs. Because brain AVMs have the potential to cause disabling or fatal intracranial hemorrhage, detection of these lesions before rupture is the goal of screening MR imaging/MRA examinations in patients with HHT. Prior studies have demonstrated superior sensitivity for HHT-related brain AVMs by using postcontrast MR imaging sequences as compared with MRA alone. We now present data regarding the incremental benefit of including arterial spin-labeling (ASL) perfusion sequences as part of MR imaging/MRA screening in patients with this condition. MATERIALS AND METHODS: We retrospectively analyzed 831 patients at the UCSF Hereditary Hemorrhagic Telangiectasia Center of Excellence. Of these, 42 patients had complete MR imaging/MRA, ASL perfusion scans, and criterion-standard DSA data. Two neuroradiologists reviewed imaging studies and a third provided adjudication when needed. RESULTS: Eight patients had no brain AVMs detected on DSA. The remaining 34 patients had 57 brain AVMs on DSA. Of the 57 identified AVMs, 51 (89.5%) were detected on ASL and 43 (75.4%) were detected on conventional MR imaging/MRA sequences (P = .049), with 8 lesions detected on ASL perfusion but not on conventional MR imaging. CONCLUSIONS: ASL provides increased sensitivity for brain AVMs in patients with HHT. Inclusion of ASL should be considered as part of comprehensive MR imaging/MRA screening protocols for institutions taking care of patients with HHT.
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Malformações Arteriovenosas Intracranianas , Angiografia por Ressonância Magnética , Marcadores de Spin , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagem , Telangiectasia Hemorrágica Hereditária/complicações , Feminino , Masculino , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/complicações , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Angiografia por Ressonância Magnética/métodos , Idoso , Sensibilidade e Especificidade , Imageamento por Ressonância Magnética/métodos , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening. We aimed to confirm whether brain VMs can form de novo in patients with HHT. METHODS: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review. RESULTS: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation. CONCLUSIONS: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted.
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Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagem , Masculino , Feminino , Criança , Adolescente , Estudos Longitudinais , Encéfalo/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/complicações , Adulto , Pré-Escolar , Adulto JovemRESUMO
Climate change adversely affects the well-being of humans and the entire planet. A planetary health framework recognizes that sustaining a healthy planet is essential to achieving individual, community, and global health. Radiology contributes to the climate crisis by generating greenhouse gas (GHG) emissions during the production and use of medical imaging equipment and supplies. To promote planetary health, strategies that mitigate and adapt to climate change in radiology are needed. Mitigation strategies to reduce GHG emissions include switching to renewable energy sources, refurbishing rather than replacing imaging scanners, and powering down unused scanners. Radiology departments must also build resiliency to the now unavoidable impacts of the climate crisis. Adaptation strategies include education, upgrading building infrastructure, and developing departmental sustainability dashboards to track progress in achieving sustainability goals. Shifting practices to catalyze these necessary changes in radiology requires a coordinated approach. This includes partnering with key stakeholders, providing effective communication, and prioritizing high-impact interventions. This article reviews the intersection of planetary health and radiology. Its goals are to emphasize why we should care about sustainability, showcase actions we can take to mitigate our impact, and prepare us to adapt to the effects of climate change. © RSNA, 2024 Supplemental material is available for this article. See also the article by Ibrahim et al in this issue. See also the article by Lenkinski and Rofsky in this issue.
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Mudança Climática , Saúde Global , Humanos , Gases de Efeito Estufa , Radiologia , Serviço Hospitalar de Radiologia/organização & administraçãoRESUMO
BACKGROUND: Heterogeneity in the severity of cerebral cavernous malformations (CCMs) disease, including brain bleedings and thrombosis that cause neurological disabilities in patients, suggests that environmental, genetic, or biological factors act as disease modifiers. Still, the underlying mechanisms are not entirely understood. Here, we report that mild hypoxia accelerates CCM disease by promoting angiogenesis, neuroinflammation, and vascular thrombosis in the brains of CCM mouse models. METHODS: We used genetic studies, RNA sequencing, spatial transcriptome, micro-computed tomography, fluorescence-activated cell sorting, multiplex immunofluorescence, coculture studies, and imaging techniques to reveal that sustained mild hypoxia via the CX3CR1-CX3CL1 (CX3C motif chemokine receptor 1/chemokine [CX3C motif] ligand 1) signaling pathway influences cell-specific neuroinflammatory interactions, contributing to heterogeneity in CCM severity. RESULTS: Histological and expression profiles of CCM neurovascular lesions (Slco1c1-iCreERT2;Pdcd10fl/fl; Pdcd10BECKO) in male and female mice found that sustained mild hypoxia (12% O2, 7 days) accelerates CCM disease. Our findings indicate that a small reduction in oxygen levels can significantly increase angiogenesis, neuroinflammation, and thrombosis in CCM disease by enhancing the interactions between endothelium, astrocytes, and immune cells. Our study indicates that the interactions between CX3CR1 and CX3CL1 are crucial in the maturation of CCM lesions and propensity to CCM immunothrombosis. In particular, this pathway regulates the recruitment and activation of microglia and other immune cells in CCM lesions, which leads to lesion growth and thrombosis. We found that human CX3CR1 variants are linked to lower lesion burden in familial CCMs, proving it is a genetic modifier in human disease and a potential marker for aggressiveness. Moreover, monoclonal blocking antibody against CX3CL1 or reducing 1 copy of the Cx3cr1 gene significantly reduces hypoxia-induced CCM immunothrombosis. CONCLUSIONS: Our study reveals that interactions between CX3CR1 and CX3CL1 can modify CCM neuropathology when lesions are accelerated by environmental hypoxia. Moreover, a hypoxic environment or hypoxia signaling caused by CCM disease influences the balance between neuroinflammation and neuroprotection mediated by CX3CR1-CX3CL1 signaling. These results establish CX3CR1 as a genetic marker for patient stratification and a potential predictor of CCM aggressiveness.
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Receptor 1 de Quimiocina CX3C , Quimiocina CX3CL1 , Modelos Animais de Doenças , Hemangioma Cavernoso do Sistema Nervoso Central , Transdução de Sinais , Animais , Feminino , Humanos , Masculino , Camundongos , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/genética , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Hemangioma Cavernoso do Sistema Nervoso Central/genética , Hemangioma Cavernoso do Sistema Nervoso Central/metabolismo , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Hipóxia/metabolismo , Hipóxia/complicações , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Patológica/metabolismo , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/genéticaRESUMO
OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. METHODS: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. RESULTS: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. CONCLUSIONS: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment.
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Angiografia Cerebral , Malformações Arteriovenosas Intracranianas , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagem , Telangiectasia Hemorrágica Hereditária/epidemiologia , Criança , Masculino , Feminino , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/cirurgia , Pré-Escolar , Adolescente , LactenteRESUMO
Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.
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Malformações Arteriovenosas , Células Endoteliais , Humanos , Animais , Camundongos , Encéfalo , Hemorragia/complicações , Colágeno Tipo IRESUMO
Cerebral cavernous malformations (CCMs) are vascular lesions characterized by a porous endothelium. The lack of a sufficient endothelial barrier can result in microbleeds and frank intracerebral hemorrhage. A primary mechanism for lesion development is a sequence variant in at least 1 of the 3 CCM genes (CCM1, CCM2, and CCM3), which influence various signaling pathways that lead to the CCM phenotype. A common downstream process associated with CCM gene loss of function involves overactivation of RhoA and its effector Rho-associated kinase (ROCK). In this study, we review RhoA/ROCK-related mechanisms involved in CCM pathophysiology as potential therapeutic targets. Literature searches were conducted in PubMed using combinations of search terms related to RhoA/ROCK and CCMs. In endothelial cells, CCM1, CCM2, and CCM3 proteins normally associate to form the CCM protein complex, which regulates the functions of a wide variety of protein targets (e.g., MAP3K3, SMURF1, SOK-1, and ICAP-1) that directly or indirectly increase RhoA/ROCK activity. Loss of CCM complex function and increased RhoA/ROCK activity can lead to the formation of stress fibers that contribute to endothelial junction instability. Other RhoA/ROCK-mediated pathophysiologic outcomes include a shift to a senescence-associated secretory phenotype (primarily mediated by ROCK2), which is characterized by endothelial cell migration, cell cycle arrest, extracellular matrix degradation, leukocyte chemotaxis, and inflammation. ROCK represents a potential therapeutic target, and direct (fasudil, NRL-1049) and indirect (statins) ROCK inhibitors have demonstrated various levels of efficacy in reducing lesion burden in preclinical models of CCM. Current (atorvastatin) and planned (NRL-1049) clinical studies will determine the efficacy of ROCK inhibitors for CCM in humans, for which no US Food and Drug Administration-approved or EU-approved pharmacologic treatment exists.
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The global temperature has been increasing resulting in climate change. This negatively impacts planetary health that disproportionately affects the most vulnerable among us, especially children. Extreme weather events, such as hurricanes, tornadoes, wildfires, flooding, and heatwaves, are becoming more frequent and severe, posing a significant threat to our patients' health, safety, and security. Concurrently, shifts in environmental exposures, including air pollution, allergens, pathogenic vectors, and microplastics, further exacerbate the risks faced by children. In this paper, we provide an overview of pediatric illnesses that are becoming more prevalent and severe because of extreme weather events, global temperature increases, and shifts in environmental exposures. As members of pediatric health care teams, it is crucial for pediatric radiologists to be knowledgeable about the impacts of climate change on our patients, and continue to advocate for safe, healthier environments for our patients.
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Biodiversidade , Radiologia , Humanos , Criança , Plásticos , Temperatura , Mudança ClimáticaRESUMO
BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.
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Hemangioma Cavernoso do Sistema Nervoso Central , Acidente Vascular Cerebral , Adulto , Humanos , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemorragia , Estudos Prospectivos , Qualidade de Vida , Acidente Vascular Cerebral/terapia , Resultado do TratamentoRESUMO
BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (P=0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03652181.
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Hemangioma Cavernoso do Sistema Nervoso Central , Hemorragia , Humanos , Estudos Prospectivos , Hemorragia/etiologia , Hemorragia/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Hemangioma Cavernoso do Sistema Nervoso Central/patologia , Biomarcadores , Imageamento por Ressonância Magnética/métodos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicaçõesRESUMO
We are grateful to Eker et al. for their thoughtful analysis and response to our publication titled Comparing Characteristics and Treatment of Brain Vascular Malformations in Children and Adults with HHT [...].
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BACKGROUND: MR arthrography is an essential diagnostic tool to assess and guide management of labral, ligamentous, fibrocartilaginous, and capsular abnormalities in children. While fluoroscopy is traditionally used for intra-articular contrast administration, ultrasound offers advantages of portability and lack of ionizing radiation exposure for both the patient and proceduralist. OBJECTIVE: The purpose of this retrospective study is to quantify technical success and frequency of complications of ultrasound-guided arthrogram injections at our institution. MATERIALS AND METHODS: This retrospective analysis investigates the results of 217 ultrasound-guided arthrograms of the shoulder, elbow, and hip in patients aged 5-18 years. Successful injection of contrast into the target joint, clinical indication for MR arthrography, and complications were reviewed. RESULTS: Accurate ultrasound-guided intra-articular administration of contrast into the target joint was successful for 100% of shoulder cases (90/90), 97% of elbow cases (77/79), and 98% of hip cases (47/48). Leak of contrast outside the target joint occurred in 1.4% (3/217) of cases. No major side effects including excessive bleeding, paresthesia, allergic reactions, or infection occurred during or after the procedure. Additionally, no major vessel, nerve, or tendon complications were observed on MR images. CONCLUSION: Ultrasound guidance is a reliable, effective, and safe approach to arthrography in children.
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Artrografia , Articulação do Ombro , Humanos , Criança , Artrografia/métodos , Estudos Retrospectivos , Meios de Contraste , Injeções Intra-Articulares , Articulação do Ombro/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Ultrassonografia de Intervenção/métodosRESUMO
This large, multinational, sex-based analysis among individuals with HHT showed that pulmonary AVM frequency, physical characteristics, presentation, complications and management do not generally significantly differ between males and females https://bit.ly/3TNLA6v.
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BACKGROUND: Rupture of brain arteriovenous malformations (bAVMs) carries potentially devastating consequences. For patients presenting with ruptured bAVMs, several clinical grading systems have been shown to predict long-term patient morbidity and may be taken into consideration when making clinical decisions. Unfortunately, use of these scoring systems is typically limited to their prognostic value and offer little to patients in therapeutic benefit. Tools are needed not only to predict prognosis for patients experiencing ruptured bAVMs but to gain insight into what characteristics predispose patients to poor long-term outcomes before they rupture. Our objective was to find clinical, morphologic, and demographic variables that correlate with unfavorable clinical grades on presentation in patients with ruptured bAVMs. METHODS: We retrospectively reviewed a cohort of patients with ruptured bAVMs. Linear regression models were used to test whether Glasgow Coma Scale (GCS) and Hunt-Hess scores on presentation(outcomes) were associated with patient and arteriovenous malformation (AVM) characteristics (predictors) individually. RESULTS: GCS and Hunt-Hess were assessed following bAVM rupture for 121 brain cases. The median age at rupture was 28.5 years, and 62 (51%) were female. Smoking history was associated with worse GCS; current and past smokers had GCS scores 1.33 points lower on average than nonsmokers (95% confidence interval [CI] -2.59 to -0.07, P = 0.039) and had worse Hunt-Hess scores (0.42, 95% CI 0.07-0.77, P = 0.019). Associated aneurysms were associated with worse GCS (-1.60, 95% CI -3.16 to -0.05, P = 0.043) and trended towards worse Hunt-Hess scores (0.42 points, 95% CI -0.01 to 0.86, P = 0.057). CONCLUSIONS: Patient smoking status and presence of an AVM associated aneurysm were shown to have modest correlations with unfavorable clinical grades (Hunt-Hess, GCS) on presentation, with unfavorable clinical grades being associated with long-term patient prognosis following bAVM rupture. Further investigation using AVM-specific grading scales and external data are needed to determine the utility of these and other variables in clinical practice for patients with bAVM.
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Background: Quantitative susceptibility mapping (QSM) and dynamic contrast enhanced quantitative perfusion (DCEQP) MRI sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cavernous angiomas. We assessed their prospective changes in cavernous angiomas with symptomatic hemorrhage (CASH) in a multisite trial readiness project ( clinicaltrials.gov NCT03652181 ). Methods: Patients with CASH in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of CASH lesion were acquired at baseline, and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined lesional symptomatic hemorrhage (SH) or asymptomatic change (AC). Sample size calculations for hypothesized therapeutic effects were conducted. Results: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (p= 0.019). Annual QSM increase by ≥ 6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with AC during the same epoch, and 3.82 times more frequently than clinical events. DCEQP change had lower sensitivity for SH and AC than QSM change, and greater variance. A trial with smallest sample size would detect a 30% difference in QSM annual change in 34 or 42 subjects (one and two-tailed, respectively), power 0.8, alpha 0.05. Conclusions: Assessment of QSM change is feasible and sensitive to recurrent bleeding in CASH. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the U.S. F.D.A. of QSM as a biomarker of drug effect in CASH.
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BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations. Individuals with HHT often identify low humidity and temperature as detrimental to epistaxis severity. We set out to assess the relationship between humidity and temperature on epistaxis severity in patients with HHT. METHODS: Retrospective cross-sectional study at an academic hospital with an HHT center between July 1, 2014 and January 1, 2022. The primary outcome of this study was ESS. Pearson correlation analyses and multiple linear regression analyses were performed to test the association between weather variables and epistaxis severity scre (ESS). Results were reported as coefficient and 95% confidence interval (CI). RESULTS: Four hundred twenty-nine patients were included in the analysis. Through a Pearson correlation analysis, neither humidity (regression coefficient = -0.01; 95% CI, -0.006 to 0.003; p = 0.50), daily low temperature (regression coefficient = 0.01; 95% CI, -0.011 to 0.016; p = 0.72), or daily high temperature (regression coefficient = 0.01; 95% CI, -0.004 to 0.013; p = 0.32) were significantly correlated with ESS. In a multiple linear regression analysis, adjusting for both daily low temperature and humidity, medications taken, demographics, and genotype, neither daily low temperature (regression coefficient = -0.02; 95% CI, -0.04 to 0.01; p = 0.14) nor humidity (regression coefficient = 0.01; 95% CI, -0.01 to 0.01; p = 0.64) were significantly associated with ESS. CONCLUSION: We have shown in a large clinical sample that neither humidity nor temperature were strongly correlated with HHT patient epistaxis severity.
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Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/epidemiologia , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/complicações , Estudos Retrospectivos , Epistaxe/epidemiologia , Epistaxe/etiologia , Estudos Transversais , TemperaturaRESUMO
Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disease characterized by the development of vascular malformations (VMs) in organs such as the brain and lungs, as well as telangiectases on mucosal surfaces. Prophylactic treatment of organ VMs may prevent potential complications, such as hemorrhage. However, brain VM treatment-surgical resection, embolization, and/or radiosurgery-is not recommended for all patients due to the associated risks. Given the scarcity of data regarding HHT-related brain VM presentation and treatment trends in pediatric patients, we aim to describe the clinical presentations and the patterns of treatment of HHT-related brain VMs in a pediatric cohort, and compare pediatric trends to those of adults. Demographic and clinical data were analyzed in 114 pediatric patients with HHT-related brain VMs and compared with a cohort of 253 adult patients enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. Our data demonstrated that a higher proportion of pediatric patients with HHT-related brain VMs were symptomatic at presentation (p = 0.004). Moreover, a higher proportion of pediatric patients presented with intracranial hemorrhage (p < 0.001) and seizure (p = 0.002) compared to adult patients. Surgical resection was the most common brain VM treatment modality in both children and adults. We conclude that pediatric patients may be more likely to present with symptoms and complications from brain VMs, supporting the case for screening for brain VMs in children with HHT.
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Aim: Neuroinflammation plays a key role in both the pathogenesis and the progression of cerebral cavernous malformations (CCM). Flutriciclamide ([18F]GE-180) is a translocator protein (TSPO) targeting positron emission tomography (PET) tracer, developed for imaging neuroinflammation. The objectives of this study were to describe characteristics of flutriciclamide uptake in different brain tissue regions in CCM patients compared to controls, and to evaluate flutriciclamide uptake and iron deposition within CCM lesions. Materials and methods: Five patients with CCM and six controls underwent a 60 or 90 min continuous PET/MRI scan following 315 ± 68.9 MBq flutriciclamide administration. Standardized uptake value (SUV) and standardized uptake value ratio (SUVr) were obtained using the striatum as a pseudo-reference. Quantitative susceptibility maps (QSM) were used to define the location of the vascular malformation and calculate the amount of iron deposition in each lesion. Results: Increased flutriciclamide uptake was observed in all CCM lesions. The temporal pole demonstrated the highest radiotracer uptake; the paracentral lobule, cuneus and hippocampus exhibited moderate uptake; while the striatum had the lowest uptake, with average SUVs of 0.66, 0.55, 0.63, 0.55, and 0.33 for patient with CCM and 0.57, 0.50, 0.48, 0.42, and 0.32 for controls, respectively. Regional SUVr showed similar trends. The average SUV and QSM values in CCM lesions were 0.58 ± 0.23 g/ml and 0.30 ± 0.10 ppm. SUVs and QSM were positively correlated in CCM lesions (r = 0.53, p = 0.03). Conclusion: The distribution of flutriciclamide ([18F]GE-180) in the human brain and CCM lesions demonstrated the potential of this TSPO PET tracer as a marker of neuroinflammation that may be relevant for characterizing CCM disease progression along with QSM.