Association of Early Adulthood 25-Year Blood Pressure Trajectories With Cerebral Lesions and Brain Structure in Midlife.

Importance: Midlife elevated blood pressure (BP) is an important risk factor associated with brain structure and function. Little is known about trajectories of BP that modulate this risk. Objective: To identify BP trajectory patterns from young adulthood to midlife that are associated with brain structure in midlife. Design, Setting, and Participants: This cohort study used data of US adults from Coronary Artery Risk Development in Young Adults (CARDIA), a prospective longitudinal study of Black and White men and women (baseline age 18 to 30 years) examined up to 8 times over 30 years (1985-1986 to 2015-2016). There were 885 participants who underwent brain magnetic resonance imaging (MRI) in the 25th or 30th year examinations. Analyses were conducted November 2019 to December 2020. Exposures: Using group-based trajectory modeling, 5 25-year BP trajectories for 3 BP traits were identified in the total CARDIA cohort of participants with 3 or more BP measures, which were then applied to analyses of the subset of 853 participants in the Brain MRI substudy. Mean arterial pressure (MAP) was examined as an integrative measure of systolic and diastolic BP. With linear regression, the associations of the BP trajectories with brain structures were examined, adjusting sequentially for demographics, cardiovascular risk factors, and antihypertensive medication use. Main Outcomes and Measures: Brain MRI outcomes include total brain, total gray matter, normal-looking and abnormal white matter volumes, gray matter cerebral blood flow, and white matter fractional anisotropy. Results: Brain MRI analyses were conducted on 853 participants (mean [SD] age, 50.3 [3.6] years; 399 [46.8%] men; 354 [41.5%] Black and 499 [58.5%] White individuals). The MAP trajectory distribution was 187 individuals (21.1%) with low-stable, 385 (43.5%) with moderate-gradual, 71 (8.0%) with moderate-increasing, 204 (23.1%) with elevated-stable, and 38 (4.3%) with elevated-increasing. Compared with the MAP low-stable trajectory group, individuals in the moderate-increasing and elevated-increasing groups were more likely to have higher abnormal white matter volume (moderate: ß, 0.52; 95% CI, 0.23 to 0.82; elevated: ß, 0.57; 95% CI, 0.19 to 0.95). Those in the MAP elevated-increasing group had lower gray matter cerebral blood flow (ß, -0.42; 95% CI, -0.79 to -0.05) after adjusting for sociodemographics and cardiovascular risk factors. After adjustment for antihypertensive medication use, the difference was consistent for abnormal white matter volume, but results were no longer significant for gray matter cerebral blood flow. Conclusions and Relevance: Among young adults with moderate to high levels of BP, a gradual increase in BP to middle-age may increase the risk in diffuse small vessel disease and lower brain perfusion.

Training in Neurology: Resident Perception of the Utility and Applicability of Global Neurology Morning Reports.

Interest in global health is increasing among neurology residents. However, funding, time, and, recently, COVID-19 travel restrictions remain barriers to widespread participation. To meet this need, we instituted virtual global neurology morning reports with the objectives of (1) improving knowledge about neurologic diseases common in sub-Saharan Africa and (2) developing clinical reasoning skills through consideration of diagnostic and therapeutic limitations in resource-limited settings. Interactive case-based sessions were presented from Zambia via videoconference by a Johns Hopkins faculty member or Zambian neurology trainee. An anonymous cross-sectional survey was conducted among Johns Hopkins neurology residents. Of eligible participants, 69% (n = 30) completed the survey, 66% of whom were female, and 33% reported prior in-person global health experience. Although most participants did not anticipate a career in global health, the majority (85%) reported that exposure to global health was important. All but 1 participant (96%) reported satisfaction with the global neurology morning reports, with 100% reporting that they were useful to their clinical knowledge and 86% reporting that they were useful to their clinical practice. All respondents felt that morning reports should continue, and 69% ranked the educational value of the experience in the top quartile of the residency curriculum. Resident satisfaction with and perceived utility of global neurology morning reports were high, although the majority did not plan to pursue global neurology opportunities as part of their career. Remote learning opportunities may increase interest in global health among neurology residents.

Haptoglobin is associated with increased early perihematoma edema progression in spontaneous intracranial hemorrhage.

INTRODUCTION: Perihematomal edema in intracranial hemorrhage is influenced by free hemoglobin clearance and inflammation. Serum Haptoglobin (Hp) binds free hemoglobin, affecting heme clearance and free radical production. Of the three Hp phenotypes, Hp 1-1 has the greatest effect on free hemoglobin clearance. AIM: To determine if individuals with Hp 1-1 phenotype have different rates of early perihematomal edema formation as compared to those with Hp 2-1 and Hp 2-2. METHODS: We determined Hp phenotype, intracranial hemorrhage volume, and rate of early change in perihematomal volume in participants from three prospectively collected intracranial hemorrhage cohorts. The association of Hp phenotypes 1-1, 2-1, 2-2, with early change in perihematomal volume, while controlling for key clinical characteristics was analyzed using a multivariate model. FINDINGS: One-hundred and sixty-six participants were included: 73 (44%) female, 41 ( 25%) African Americans, 34 (20%) diabetics, 133 (80%) with hypertension, and 75 (45%) active smokers. There were 15 subjects with Hp phenotype 1-1, 86 with 2-1, and 65 with 2-2. In fully adjusted analysis, Hp 1-1 had a significantly increased estimated mean rate of early change in perihematomal volume at 1.15 (95% confidence interval 0.58-1.71) as compared to all other Hp 2-1 or Hp 2-2 containing phenotypes (0.30, 95% confidence interval 0.06-0.54; 0.29 95% CI 0.02-0.56). Neither mortality nor discharge mRS differed between Hp phenotypes. CONCLUSION: Haptoglobin phenotype is associated with early change in perihematomal volume. Hp 1-1 phenotype had significantly increased mean rate of early change in perihematomal volume within the first 96 h, suggesting that haptoglobin phenotype may be a key player in understanding the multiphasic progression of perihematomal volume in spontaneous intracerebral hemorrhage. A larger prospective observational study is warranted.

The Medical Management of Cerebral Edema: Past, Present, and Future Therapies.

Cerebral edema is commonly associated with cerebral pathology, and the clinical manifestation is largely related to the underlying lesioned tissue. Brain edema usually amplifies the dysfunction of the lesioned tissue and the burden of cerebral edema correlates with increased morbidity and mortality across diseases. Our modern-day approach to the medical management of cerebral edema has largely revolved around, an increasingly artificial distinction between cytotoxic and vasogenic cerebral edema. These nontargeted interventions such as hyperosmolar agents and sedation have been the mainstay in clinical practice and offer noneloquent solutions to a dire problem. Our current understanding of the underlying molecular mechanisms driving cerebral edema is becoming much more advanced, with differences being identified across diseases and populations. As our understanding of the underlying molecular mechanisms in neuronal injury continues to expand, so too is the list of targeted therapies in the pipeline. Here we present a brief review of the molecular mechanisms driving cerebral edema and a current overview of our understanding of the molecular targets being investigated.