Cerebral Vasculopathies Research Articles

Early elevations in arterial pressure: a contributor to rapid depressive symptom emergence in female Zucker rats with metabolic disease?

One of the growing challenges to public health and clinical outcomes is the emergence of cognitive impairments, particularly depressive symptom severity, because of chronic elevations in metabolic disease and cerebrovascular disease risk. To more clearly delineate these relationships and to assess the potential for sexual dimorphism, we used lean (LZR) and obese Zucker rats (OZR) of increasing age to determine relationships between internal carotid artery (ICA) hemodynamics, cerebral vasculopathies, and the emergence of depressive symptoms. Male OZR exhibited progressive elevations in perfusion pressure within the ICA, which were paralleled by endothelial dysfunction, increased cerebral arterial myogenic activation, and reduced cerebral cortex microvessel density. In contrast, female OZR exhibited a greater degree of ICA hypertension than male OZR but maintained normal endothelial function, myogenic activation, and microvessel density to an older age range than did males. Although both male and female OZR exhibited significant and progressive elevations in depressive symptom severity, these were significantly worse in females. Finally, plasma cortisol concentration was elevated higher and at a younger age in female OZR as compared with males, and this difference was maintained to final animal usage at ∼17 wk of age. These results suggest that an increased severity of blood pressure waves may penetrate the cerebral circulation more deeply in female OZR than in males, which may predispose the females to a more severe emergence of depressive symptoms with chronic metabolic disease, whereas males may be more predisposed to more direct cerebral vasculopathies (e.g., stroke, transient ischemic attack).NEW & NOTEWORTHY We provide novel insight that the superior maintenance of cerebrovascular endothelial function in female versus male rats with chronic metabolic disease buffers myogenic activation of cerebral resistance arteries/arterioles despite worsening hypertension. As hypertension development is earlier and more severe in females, potentially due to an elevated stress response, the blunted myogenic activation allows greater arterial pressure wave penetrance into the cerebral microcirculation and is associated with accelerated emergence/severity of depressive symptoms in obese female rats.

Imaging Review of Pediatric Monogenic CNS Vasculopathy with Genetic Correlation.

Monogenic cerebral vasculopathy is a rare but progressively recognizable cause of pediatric cerebral vasculopathy manifesting as early as fetal life. These monogenic cerebral vasculopathies can be silent or manifest variably as fetal or neonatal distress, neurologic deficit, developmental delay, cerebral palsy, seizures, or stroke. The radiologic findings can be nonspecific, but the presence of disease-specific cerebral and extracerebral imaging features can point to a diagnosis and guide genetic testing, allowing targeted treatment. The authors review the existing literature describing the frequently encountered and rare monogenic cerebral vascular disorders affecting young patients and describe the relevant pathogenesis, with an attempt to categorize them based on the defective step in vascular homeostasis and/or signaling pathways and characteristic cerebrovascular imaging findings. The authors also highlight the role of imaging and a dedicated imaging protocol in identification of distinct cerebral and extracerebral findings crucial in the diagnostic algorithm and selection of genetic testing. Early and precise recognition of these entities allows timely intervention, preventing or delaying complications and thereby improving quality of life. It is also imperative to identify the specific pathogenic variant and pattern of inheritance for satisfactory genetic counseling and care of at-risk family members. Last, the authors present an image-based approach to these young-onset monogenic cerebral vasculopathies that is guided by the size and predominant radiologic characteristics of the affected vessel with reasonable overlap. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

RELATIONSHIPS BETWEEN CEREBRAL VASCULOPATHIES AND MICROINFARCTS IN COMMUNITY-BASED OLDER ADULTS

Abstract Cerebral microinfarcts are associated with cognitive impairment and dementia. Less is known about the relationships of various vasculopathies (arteriolosclerosis and cerebral amyloid angiopathy (CAA) with microinfarcts. This case-control study examined the associations of the vasculopathies with microinfarcts in 842 older adults in the Adult Changes in Thought (ACT) autopsy data. Arteriolosclerosis was assessed by histological examination using the H&E stain; CAA was assessed using the Congo red histochemical stains; and microinfarcts was ascertained by blinded board-certified neuropathologists. Multivariable-adjusted logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the presence of cerebral microinfarcts associated with the two cerebral vasculopathies. Cerebral microinfarcts were present in 417 (49.5%) participants. Mild, moderate, and severe arteriolosclerosis was present in 13.2%, 43.9%, 29.7% of participants with microinfarcts, and 28.9%, 40.0%, and 12.5% of participants without microinfarcts, respectively. ORs (95% CIs) for microinfarcts associated with moderate and severe arteriolosclerosis were 2.15 (1.45-3.17) and 4.59 (2.88-7.33), respectively. Mild, moderate, and severe CAA was present in 18.0%, 17.5%, and 3.6% of participants with microinfarcts, and 18.1%, 16.5%, and 2.4% of participants without microinfarcts, respectively. ORs (95% CIs) for microinfarcts associated with moderate and severe CAA were 0.97 (0.65-1.44) and 1.37 (0.59-3.21), respectively. Cerebral microinfarcts were common in older adults and were associated with a higher prevalence of arteriolosclerosis, but not with CAA. Our study underscores the need for additional studies to better understand this complex relationship to develop interventions for primary prevention of cognitive impairment.

Short Lingual Frenulum as a Risk Factor for Cerebral Vasculopathies

Introduction: Tongue is the first functioning organ in the embryonic era. Its developmental alterations can result in malfunctions with damage in distant districts. Craniocervical anatomy suggests that tongue dysfunction may be involved in the damage to the arteriovenous encephalic flow. Objective: To evaluate the possible relationship between short frenulum and cerebral vasal problems. Method: We conducted an epidemiological research comparing the presence of vascular problems in families where the visited subject had short frenulum (which is a genetically transmitted pathology) and families where the visited subject did not have abnormality of the frenulum. Results: The presence of short tongue frenulum was correlated with the presence of episodes of vascular damage in about 80% of cases, while in families not affected by this tongue alteration the percentage of damage was between 10 and 13%. Conclusions: The enormous influence that the presence of an altered tongue frenulum seems to have on the future possibility of developing vascular problems should induce a more careful assessment of the presence of an incorrect-sized frenulum.

A Transcriptomic Comparative Study of Cranial Vasculature.

In genetic studies of cerebrovascular diseases, the optimal vessels to use as controls remain unclear. Our goal is to compare the transcriptomic profiles among 3 different types of control vessels: superficial temporal artery (STA), middle cerebral arteries (MCA), and arteries from the circle of Willis obtained from autopsies (AU). We examined the transcriptomic profiles of STA, MCA, and AU using RNAseq. We also investigated the effects of using these control groups on the results of the comparisons between aneurysms and the control arteries. Our study showed that when comparing pathological cerebral arteries to control groups, all control groups presented similar responses in the activation of immunological processes, the regulation of intracellular signaling pathways, and extracellular matrix productions, despite their intrinsic biological differences. When compared to STA, AU exhibited upregulation of stress and apoptosis genes, whereas MCA showed upregulation of genes associated with tRNA/rRNA processing. Moreover, our results suggest that the matched case-control study design, which involves control STA samples collected from the same subjects of matched aneurysm samples in our study, can improve the identification of non-inherited disease-associated genes. Given the challenges associated with obtaining fresh intracranial arteries from healthy individuals, our study suggests that using MCA, AU, or paired STA samples as controls are feasible strategies for future large-scale studies investigating cerebral vasculopathies. However, the intrinsic differences of each type of control should be taken into consideration when interpreting the results. With the limitations of each control type, it may be most optimal to use multiple tissues as controls.

Relationships between Cerebral Vasculopathies and Microinfarcts in a Community-Based Cohort of Older Adults.

Cerebral microinfarcts are associated with cognitive impairment and dementia. Small vessel diseases such as cerebral arteriolosclerosis and cerebral amyloid angiography (CAA) have been found to be associated with microinfarcts. Less is known about the associations of these vasculopathies with the presence, numbers, and location of microinfarcts. These associations were examined in the clinical and autopsy data of 842 participants in the Adult Changes in Thought (ACT) study. Both vasculopathies were categorized by severity (none, mild, moderate, and severe) and region (cortical and subcortical). Odds ratios (OR) and 95% CIs for microinfarcts associated with arteriolosclerosis and CAA adjusted for possible modifying covariates such as age at death, sex, blood pressure, APOE genotype, Braak, and CERAD were estimated. 417 (49.5%) had microinfarcts (cortical, 301; subcortical, 249), 708 (84.1%) had cerebral arteriolosclerosis, 320 (38%) had CAA, and 284 (34%) had both. Ors (95% CI) for any microinfarct were 2.16 (1.46-3.18) and 4.63 (2.90-7.40) for those with moderate (n = 183) and severe (n = 124) arteriolosclerosis, respectively. Respective Ors (95% CI) for the number of microinfarcts were 2.25 (1.54-3.30) and 4.91 (3.18-7.60). Similar associations were observed for cortical and subcortical microinfarcts. Ors (95% Cis) for the number of microinfarcts associated with mild (n = 75), moderate (n = 73), and severe (n = 15) amyloid angiopathy were 0.95 (0.66-1.35), 1.04 (0.71-1.52), and 2.05 (0.94-4.45), respectively. Respective Ors (95% Cis) for cortical microinfarcts were 1.05 (0.71-1.56), 1.50 (0.99-2.27), and 1.69 (0.73-3.91). Respective Ors (95% Cis) for subcortical microinfarcts were 0.84 (0.55-1.28), 0.72 (0.46-1.14), and 0.92 (0.37-2.28). These findings suggest a significant association of cerebral arteriolosclerosis with the presence, number, and location (cortical and subcortical) of microinfarcts, and a weak and non-significant association of CAA with each microinfarct, highlighting the need for future research to better understand the role of small vessel diseases in the pathogenesis of cerebral microinfarcts.

Transcriptomic atlas and interaction networks of brain cells in mouse CNS demyelination and remyelination

Demyelination is a hallmark of multiple sclerosis, leukoencephalopathies, cerebral vasculopathies, and several neurodegenerative diseases. The cuprizone mouse model is widely used to simulate demyelination and remyelination occurring in these diseases. Here, we present a high-resolution single-nucleus RNA sequencing (snRNA-seq) analysis of gene expression changes across all brain cells in this model. We define demyelination-associated oligodendrocytes (DOLs) and remyelination-associated MAFBhi microglia, as well as astrocytes and vascular cells with signatures of altered metabolism, oxidative stress, and interferon response. Furthermore, snRNA-seq provides insights into how brain cell types connect and interact, defining complex circuitries that impact demyelination and remyelination. As an explicative example, perturbation of microglia caused by TREM2 deficiency indirectly impairs the induction of DOLs. Altogether, this study provides a rich resource for future studies investigating mechanisms underlying demyelinating diseases.

Abstract 35: Changes In Sickle Cell Vasculopathy After Hematopoietic Stem Cell Transplantation

Introduction: Cerebral vasculopathies (stenoses and aneurysms) are a major cause of stroke and disability in adults and children with sickle cell disease (SCD). HSCT has been shown to prevent or improve large vessel intracranial stenosis in children when compared to standard care (Verlhac 2020). We sought to determine the impact of HSCT on the development and progression of cerebral vasculopathies in adults with SCD. Methods: The study population included patients with SCD (HbSS, HbSC, and HbS/beta-thalassemia) that were enrolled in NIH studies (14-H-0077, 09-H-0225, 03-H-0170) and underwent HSCT from 2004-19 and received pre- and post-transplant MRI/MRA studies. MRA images were reviewed by two independent readers and scored for stenoses in eight intracranial arteries, Moyamoya collateralization, and presence and progression of intracranial aneurysms. Changes in vasculopathy were compared before and after transplantation. Results: Eighty-seven patients were included in the study, mean age 32.2 yrs. and 58% male. Median follow-up period was 3.3 yrs. (range: 0.5-17 yrs.), and 28% had evidence of vasculopathy at transplant; 17% with stenotic vasculopathy and 13% with aneurysm(s). None of the patients without vasculopathy developed stenoses or aneurysms after HSCT. MRA stenoses scores improved after HSCT in 62% of patients with vasculopathy, with a median change of 1.0 (range: 1-6; p=0.01). All intracranial aneurysms identified at transplant remained unchanged in follow-up. Conclusions: Hematopoietic stem cell transplantation improved or prevented the development of vasculopathy in adults with sickle cell disease.

Abstract WP96: Quantitative Imaging Markers On Vessel Wall Magnetic Resonance Imaging Correlate With Disease Activity And Treatment Response In Cerebral Vasculopathies

Introduction: Little is known about the utility of vessel wall magnetic resonance imaging (VWMRI) in assessing treatment response in various inflammatory and non-inflammatory intracranial vasculopathies, and if there is any correlation of vessel wall enhancement (VWE) with disease activity. We aimed to quantitatively investigate the differences in VWE patterns on follow-up VWMRI in patients with primary CNS vasculitis (PCNSV), secondary CNS vasculitis (SCNSV) and intracranial atherosclerotic disease (ICAD). Methods: VWMRI scans of patients with a confirmed diagnosis of either PCNSV, SCNSV or ICAD presenting to our tertiary care center between January 2015 and January 2021 were reviewed. Inclusion criteria were age greater than 18 years and at least 2 VWMRI scans available, including one from time of first clinical presentation with active disease. For each patient, 20 arterial segments were evaluated on VWMRI for the presence of VWE and the total number of enhancing arterial segments were reported. Percent concentricity, median number of enhancing arterial segments (MEAS) and percent change in MEAS was calculated and compared across all 3 diagnoses. Results: A total of 28 patients met study inclusion criteria (median age 47, 43% male) and had a diagnosis of either PCNSV (n=6), SCNSV (n=7) or ICAD (n=15). Median time to follow-up VWMRI was 22, 20 & 11 weeks for PCNSV, SCNSV & ICAD respectively. On initial VWMRI, the MEAS was 7 for each PCNSV & SCNSV and 6 for ICAD. Higher percent concentricity of VWE was seen more with PCNSV (92.3%) and SCNSV (71.4%) compared to ICAD (22.2%). All (100%) patients with PCNSV and 2 (33%) patients with SCNSV were treated with immunosuppression whereas 3 (50%) patients with SCNSV were treated with antimicrobials. All patients with PCNSV and SCNSV improved clinically whereas those with ICAD progressed or remained stable. The MEAS on follow up VWMRI decreased with treatment in patients with PCNSV (43% decrease) and SCNSV (14% decrease) but increased in those with ICAD (16% increase) and correlated clinically with disease activity and treatment response. Conclusion: Percent concentricity and MEAS on VWMRI may be useful non-invasive markers to monitor disease activity & treatment response in patients with intracranial vasculopathies.

Natural History of Pediatric Patients with Sickle Cell Disease and Concurrent Cerebral Vasculopathies: Report of 62 Cases from a Single Institution

Natural History of Pediatric Patients with Sickle Cell Disease and Concurrent Cerebral Vasculopathies: Report of 62 Cases from a Single Institution

Nursing Assistance To The Patient With Acute Myocardial Infarction; Nursing Implications

Nursing Assistance To The Patient With Acute Myocardial Infarction; Nursing Implications

Nursing Assistance To The Patient With Acute Myocardial Infarction; Nursing Implications

Nursing Assistance To The Patient With Acute Myocardial Infarction; Nursing Implications

Epilepsy in NF1: Epidemiologic, Genetic, and Clinical Features. A Monocentric Retrospective Study in a Cohort of 784 Patients.

Simple SummaryNeurofibromatosis type 1 is a relatively frequent neurocutaneous and tumor predisposition syndrome, which has been associated with a variety of neurological manifestations, including an increased incidence of seizures. Epilepsy in NF1 has been investigated over time by a number of studies, but most of these works were performed on small samples and often suffered from selection biases. Our study aimed to provide additional epidemiologic, clinical, and molecular data to the literature by retrospectively analyzing a large cohort of consecutive unselected patients affected with NF1. Such data may provide a better insight into the matter to other authors and clinicians alike.An increased lifetime risk of epilepsy has been reported in neurofibromatosis type 1 (NF1) patients, ranging between 4% and 14%. To further analyze the correlation between NF1 and epilepsy, we retrospectively reviewed the epidemiologic, clinical, radiological, and molecular data of 784 unselected patients diagnosed with NF1 and referred to the neurofibromatosis outpatient clinics at the University Hospital of Padua. A crude prevalence of epilepsy of 4.7% was observed. In about 70% of cases, seizures arose in the context of neuroradiological findings, with the main predisposing factors being cerebral vasculopathies and hydrocephalus. In the absence of structural abnormalities, the prevalence of epilepsy was found to be 1.27%, which is approximately equal to the total prevalence in the general population. NF1 patients with seizures exhibit a higher incidence of intellectual disability and/or developmental delay, as well as of isolated learning disabilities. The comparison of causative NF1 mutations between the two groups did not reveal a specific genotype–phenotype correlation. Our data refine the current knowledge on epileptological manifestations in NF1 patients, arguing against the hypothesis that specific mechanisms, inherent to neurofibromin cellular function, might determine an increased risk of epilepsy in this condition.

Moyamoya Disease Associated with Graves’ Disease and Down Syndrome: A Case Report and Literature Review

BackgroundMoyamoya vessels are cerebral vasculopathies characterized by net-like collateral vessel formation at the cerebral basal area and stenosis of the terminal internal carotid artery, proximal middle cerebral artery, and anterior cerebral artery. A diagnosis of Moyamoya disease depends on the bilateral presence of Moyamoya vessels. Moyamoya disease associated with Graves' disease has rarely been reported to be a cause of ischemic events due to hyperthyroidism. However, there are extremely rare cases of Moyamoya disease with concurrent Graves' disease and Down syndrome. We aimed to report such a case, and to compare these cases’ clinical features, pathogenesis, and treatment effects to those of the cases of concurrent Moyamoya disease and Graves' disease alone. MethodsWe performed an English literature search using the PubMed database and the keywords Moyamoya, quasi-Moyamoya, Graves’ disease, thyrotoxicosis, Down syndrome, and trisomy 21. ResultsOnly five cases of Moyamoya disease with Graves' disease and Down syndrome have been reported, including our own. Four patients were female (80%), and all underwent antithyroid therapy and experienced ischemic episodes, including transient ischemic attacks. At the time of their vascular accident, two patients were in a thyrotoxic state; only our patient was in a euthyroid state. The mean age was 15.6 years (standard deviation: 6.1), which was younger than the mean age of 31.4 years (standard deviation: 13) in patients with Moyamoya disease and Graves' disease alone. Down syndrome is commonly associated with abnormal vascular networks due to increased endostatin concentrations or immunological abnormalities such as those that occur in Graves' disease. Graves' disease accelerates the progression of Moyamoya disease and ischemic attacks due to atherosclerosis, enhances sympathetic nervous system activity and immunological changes. As compared to Moyamoya disease patients, patients with concurrent Graves' disease only and Moyamoya disease patients with concurrent Graves' disease and Down syndrome may experience accelerated disease progression or more frequent ischemic attacks. ConclusionEarly imaging follow-ups and strict control of thyroid function are necessary in such cases; if ischemic attacks have already occurred, revascularization surgery may be effective.

Pencil beam scanning proton therapy for the treatment of craniopharyngioma complicated with radiation-induced cerebral vasculopathies: A dosimetric and linear energy transfer (LET) evaluation

Background and purposeThis study analyses the dosimetric and dose averaged Linear Energy transfer (LETd) correlation in paediatric craniopharyngioma (CP) patients with and without radiation-induced cerebral vasculopathies (RICVs) treated with pencil beam scanning (PBS) proton therapy (PT). Material and methodsWe reviewed a series of 16 CP patients treated with PT to a median dose of 54 Gy(RBE). Two (12.5%) index patients presented RICVs 14 and 24 months (median, 19) after PT. Organs at risks (OARs) as bilateral internal carotid arteries (ICAs) and circle of Willis were contoured based on CTs and MRIs pre- and post-PT. Dosimetry was reviewed and LETd distributions were calculated; LETd metric for PTVs and OARs were analysed. For a sub-cohort, dosimetric and LETd values robustness due to range uncertainties were computed. ResultsFor the two index patients, no correlation was observed between RICVs and OARs doses. However for those patients mean(maximum) LETd values in the affected OARs were up to 4.0 ± 0.4 (7.8 ± 0.1)keV/μm; those LETd values were significantly higher (p = 0.02) than the mean(maximum) LETd values for the rest of the cohort (mean: 3.1 ± 0.3, maximum: 4.8 ± 1.0 keV/μm). This was due to asymmetric field arrangement, thus resulting in marked asymmetric LETd distributions. For such arrangement, maximum LETd values variations in vascular structures due to range uncertainties were up to 1.2 keV/μm, whilst for the symmetric one they were up to 0.7 keV/μm. ConclusionsFor children with and without RICVs, quantitative analysis showed a significant correlation with LETd average/maximum values in vascular structures, whilst no correlation was found on dosimetric parameters.

Pediatric Hematologist/Oncologists' Beliefs about Hematopoietic Stem Cell Transplant for Children with Sickle Cell Disease: A Sickle Cell Transplant Advocacy and Research Alliance (STAR) Study

Background Hematopoietic stem cell transplantation (HSCT) provides a curative therapy for children severely affected by sickle cell disease (SCD). Rejection-free survival following a matched sibling donor (MSD) HSCT for these children is very high. As safer approaches are developed, using reduced intensity conditioning and improved graft versus host disease prophylaxis, there is rationale for extending MSD HSCT to less severely affected children to spare them increasing morbidity and early mortality in adulthood. Providers' perceptions may contribute to the slow adoption of MSD HSCT for less severe SCD. In this study we assess providers' perceptions about MSD HSCT for children with variable SCD severity and determine the influence of provider characteristics on HSCT attitudes. Methods Pediatric Hematologists/Oncologists (PHO) were eligible to participate in this IRB exempt study. An e-survey was distributed to all STAR members and ASH members who self-identified as PHO and posted on the American Society of Pediatric Hematology/Oncology Clinical Forum listserv. Analysis was performed to describe participant demographics and the proportion of participants who practice exclusively Pediatric Hematology with a focus on SCD (PSCD) vs. general PHO; we evaluated correlations between these characteristics and likelihood of HSCT referral for each scenario. Results Of the 203 respondents, 59% were female, and 69% were between the ages of 30 and 49 years. Spearman's rank correlation analysis did not reveal any significant relationship between respondent age and likelihood to refer to HSCT for any of the survey scenarios. Two-thirds self-identified as Caucasian, 19% Asian, 7% African American and 3% Hispanic. 35% of respondents practiced general PHO, 20% PSCD, 20% Pediatric Hematology, 15% Pediatric HSCT, and 4% Hemostasis. The majority (75%) of respondents were very or somewhat likely to order HLA typing for a child with HbSS/HbSβ⁰thalassemia who had full siblings, regardless of disease severity. Only 48% would refer a child with HbSS/HbSβ⁰thalassemia who had an HLA-MSD but never admitted to the hospital; referral likelihood differed significantly by practice focus [PHO: 23% very or somewhat likely vs. 54% of PSCD (p=0.002)]. Conversely, 99% of respondents were very or somewhat likely to refer a child who suffered an overt stroke, while 85% and 84% were very or somewhat likely to refer a child who had an abnormal TCD or silent infarct, respectively. 49% of respondents were very or somewhat likely to refer a child with HbSS/HbSβ⁰thalassemia if they had a history of suboptimal adherence to hydroxyurea; referral likelihood again differed by practice focus [PHO: 35% very or somewhat likely vs. 64% PSCD (p=0.021)]. Concern about transplant related mortality (TRM) was the predominant reason for not referring. For children with severe clinical phenotypes of HbSC and HbSβ+thalassemia, 78% of respondents were very or somewhat likely to refer, compared to only 23% who would refer asymptomatic children with SCD variants. PHO and PSCD did not differ in the likelihood to refer either group. 87% of respondents were very or somewhat likely to refer a child with β-thalassemia major for MSD HSCT, regardless of disease severity; no statistically significant difference was found between PHO and PSCD in referral likelihood. A significantly higher proportion of respondents would refer an asymptomatic child with β-thalassemia major (87%) than those who were very or somewhat likely to refer an asymptomatic child with HbSS/HbSβ⁰thalassemia (47%, p<0.00001) or other SCD variants (23%, p= 0.0005). Discussion HSCT is a curative therapy for people with SCD. There was almost complete agreement that a HSCT referral should be made for children with HbSS/HbSβ⁰thalassemia and cerebral vasculopathies who have an MSD, but attitudes varied for almost every other clinical scenario posed. PSCD providers were more likely to refer asymptomatic patients and those with questionable adherence to hydroxyurea compared to general PHOs. TRM was the most common reason for not referring an asymptomatic child for MSD HSCT. Yet, TRM is low in the setting of pediatric MSD HSCT for SCD. Additional education about the decreased quality of life in aging people with SCD and their lack of improvement in life expectancy is needed so that physician perception of HSCT changes and the number of young asymptomatic children with SCD referred for MSD HSCT increases. Disclosures Meier: CVS Caremark: Consultancy. Guilcher:Jazz Pharmaceuticals: Other: ASH 2017 meeting attendance.

Yield of diagnostic imaging in atraumatic convexity subarachnoid hemorrhage

IntroductionAtraumatic convexity subarachnoid hemorrhage is a subtype of spontaneous subarachnoid hemorrhage that often presents a diagnostic challenge. Common etiologies include cerebral amyloid angiopathy, vasculopathies, and coagulopathy; however, aneurysm is rare....

EP-1958: LET evaluation for pediatric craniopharyngioma with cerebral vasculopathies after PBS proton therapy

EP-1958: LET evaluation for pediatric craniopharyngioma with cerebral vasculopathies after PBS proton therapy

Higher prevalence of spontaneous cerebral vasculopathy and cerebral infarcts in a mouse model of sickle cell disease

Stroke is a dramatic complication of sickle cell disease (SCD), which is associated with cerebral vasculopathies including moya moya, intravascular thrombi, cerebral hyperemia, and increased vessel tortuosity. The spontaneous occurrence of these pathologies in the sickle cell mouse model has not been described. Here, we studied Townes humanized sickle cell and age-matched control mice that were 13 months old. We used in vivo two-photon microscopy to assess blood flow dynamics, vascular topology, and evidence of cerebral vasculopathy. Results showed that compared to controls, sickle cell mice had significantly higher red blood cell (RBC) velocity (0.73 mm/s vs. 0.55 mm/s, p = 0.013), capillary vessel diameter (4.84 µM vs. 4.50 µM, p = 0.014), and RBC volume flux (0.015 nL/s vs. 0.010 nL/s, p = 0.021). Also, sickle cell mice had significantly more tortuous capillary vessels (p < 0.0001) and significantly shorter capillary vessel branches (p = 0.0065) compared to controls. Sickle cell mice also had significantly higher number of capillary occlusive events (3.4% vs. 1.9%, p < 0.0001) and RBC stalls (3.8% vs. 2.1%, p < 0.0001) in the cerebral capillary bed. In post-mortem immunohistochemical analyses, sickle cell mice had a 2.5-fold higher frequency of cortical microinfarcts compared to control mice. Our results suggest that aged Townes sickle cell mice spontaneously develop SCD-associated cerebral vasculopathy.

Clinical and Angiographic Aspects of Cerebral Thrombotic Vasculopathies : A Brazilian Single Center Experience (P4.376)

Clinical and Angiographic Aspects of Cerebral Thrombotic Vasculopathies : A Brazilian Single Center Experience (P4.376)