Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in strok

An Unusual Cause of Vertebral Artery Dissection: Esophagogastroduodenoscopy

Brain-supplying arterial dissection is considered one of the most common vascular causes of stroke in younger patients. Dissections are usually preceded by trauma or mechanical stress; the vascular stressor may be trivial as this condition has been described in association with manipulation and stretching the neck. Here we describe a case of vertebral artery dissection and stroke following esophagogastroduodenoscopy. This case highlights a potentially serious complication that may occur after procedures that require hyperextension of the neck

Intraventricular Hemorrhage Severity as a Predictor of Outcome in Intracerebral Hemorrhage

Background/Objective: Intraventricular hemorrhage (IVH) extension after spontaneous supratentorial intracerebral hemorrhage (sICH) is an independent predictor of worse outcome. However, there is a paucity of data looking at the degree of IVH severity and its impact on outcome. This study addresses the contribution of IVH severity to outcome at time of hospital discharge after sICH.Methods: Two hundred and ten patients were included in the study. Baseline demographic and radiologic characteristics were abstracted. First available CT scans were reviewed for hematoma volume and location, IVH extension and presence of hydrocephalus (HCP). IVH severity was calculated using Graeb scale. Multivariate logistic regression models were developed to investigate the association of IVH severity with poor outcomes at hospital discharge, defined as modified Rankin scale score (mRS) >3.Results: Fifty-three percent of patients had IVH extension while 18% had surgical procedures done. Poor outcome (mRS >3) was seen for 56% of patients. Median IVH extension severity on the Graeb scale was two. Presence of IVH was associated with poor outcome in univariate and multivariate analysis (p < 0.005). Compared to patients with no IVH, IVH severity influenced outcome only when Graeb scores were ≥5 (OR = 1.3, 95% CI 0.49–3.23, p = 0.63, and OR = 2.9, 95% CI, 1.1–7.6, p = 0.03 for Graeb <5 and ≥5, respectively.Conclusions: Higher IVH severity (defined as Graeb score ≥5) is associated with worse outcome at time of hospital discharge, while lower IVH severity (Graeb scores 1–4) has similar outcomes to patients without IVH. IVH severity should be used in favor of IVH presence for prognostication purposes

Cerebral Hemodynamics in Sleep Apnea and Actigraphy-Determined Sleep Duration in a Sample of the Hispanic Community Health Study/ Study of Latinos.

STUDY OBJECTIVES: We sought to evaluate cerebral hemodynamics in obstructive sleep apnea (OSA) and actigraphy-defined short sleep duration using transcranial Doppler ultrasound (TCD) blood flow velocity in a subsample of Hispanics/Latinos without stroke and cardiovascular disease. METHODS: The sample consisted of consecutive participants at the Miami site of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) with overnight home sleep testing and 7 days of wrist actigraphy in the Sueño sleep ancillary study. Ninety-five participants had sleep data and TCD determined cerebral hemodynamics. We evaluated the association between OSA (apnea-hypopnea index [AHI] ≥ 5 events/h) and short sleep duration (< 6.8 hours; sample median) with cerebral blood flow velocities (CBFV) and pulsatility index (PI) for the middle cerebral (MCA) and basilar arteries (BA). RESULTS: Median age was 48 years (range 20-64) with 71% females. Twenty-eight percent of the sample had OSA (AHI ≥ 5 events/h) with median AHI of 10.0 (range 5.0-51.7) events/h. In unadjusted analyses, participants with OSA had lower median CBFV in the BA (30.5 cm/s [interquartile range:10.2] versus 39.4 cm/s [13.3] P < .05), but not the MCA, whereas short sleepers had higher median vascular resistance in the MCA (PI = 0.92 [0.18] versus 0.86 [0.14] P < .05) and BA (PI = 1.0 [0.17] versus 0.93 [0.24] P < .05). After full adjustment, OSA was associated with decreased CBFV (β [SE] = -5.1 [2.5] P < .05) in the BA. Short sleep was associated with increased PI (β [SE] = 0.05 [0.02] P < .05) in the MCA. CONCLUSIONS: In this sample of Hispanic/Latinos, OSA was associated with decreased daytime blood flow velocity in the BA, whereas actigraphy-defined short sleep duration was associated with increased cerebrovascular pulsatility in the MCA

Stroke Risk Factor Status and Use of Stroke Prevention Medications Among Hispanic/Latino Adults in HCHS/SOL

BACKGROUND AND PURPOSE: We investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack. METHODS: Sociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression. RESULTS: The analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia. CONCLUSIONS: Hispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060344

Stroke Risk Factor Status and Use of Stroke Prevention Medications Among Hispanic/Latino Adults in HCHS/SOL

Background and purposeWe investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack.MethodsSociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression.ResultsThe analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia.ConclusionsHispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060344

Association of Mediterranean Diet With Cognitive Decline Among Diverse Hispanic or Latino Adults From the Hispanic Community Health Study/Study of Latinos

Importance: The Mediterranean diet may reduce the burden of Alzheimer disease and other associated dementias in Hispanic or Latino people. Objective: To investigate the association of a Mediterranean diet with cognitive performance among community-dwelling Hispanic or Latino adults. Design, Setting, and Participants: This cohort study analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), an HCHS/SOL ancillary study. Cognition tests were administered in the HCHS/SOL from March 2008 to June 2011 (visit 1) and in the SOL-INCA from October 2015 to March 2018 (visit 2). Participants included in the present study had completed a diet assessment at visit 1 and neurocognitive evaluations at visits 1 and 2. Data were analyzed from September 2021 to May 2022. Exposures: Mediterranean diet adherence was ascertained using the Mediterranean diet score (MDS) and was categorized as low (MDS: 0-4 points), moderate (MDS: 5-6 points), or high (MDS: 7-9 points). The mean of two 24-hour dietary recalls was used to calculate the MDS. Main Outcomes and Measures: Cognitive change between visits 1 and 2 was calculated by subtracting the cognitive score at visit 2 from the cognitive score at visit 1 and adjusting by the time elapsed between visits and cognitive score at visit 1. Neurocognitive tests administered were Brief Spanish-English Verbal Learning Test (B-SEVLT) Sum, B-SEVLT Recall, word fluency, and Digit Symbol Substitution Test (DSST). Results of each test were z score-transformed and the means were averaged to create a global cognition score. Complex sample linear regression analysis was used to ascertain the association between MDS and neurocognitive performance at each visit and neurocognitive change. Results: A total of 6321 participants (mean [SE] age, 56.1 [0.18] years at visit 1; n = 4077 women [57.8%]) were included. Mediterranean diet adherence weighted frequencies were 35.8% (n = 2112 of 6321) for the low adherence group, 45.4% (n = 2795) for the moderate adherence group, and 18.8% (n = 1414) for the high adherence group. In the fully adjusted model, z score-transformed cognitive scores at visit 1 in the high vs low adherence groups were higher for B-SEVLT Sum (β = 0.11; 95% CI, 0.02-0.20), B-SEVLT Recall (β = 0.16; 95% CI, 0.07-0.25), and global cognition (β = 0.10; 95% CI, 0.04-0.16) tests. In the mean follow-up time of 7 years, cognitive change in the high vs low adherence groups was less pronounced for B-SEVLT Sum (β = 0.12; 95% CI, 0.05-0.20) and B-SEVLT Recall (β = 0.14; 95% CI, 0.05-0.23), but not for word fluency, DSST score, or global cognition score. Conclusions and Relevance: Results of this cohort study suggested that high adherence to a Mediterranean diet was associated with better cognitive performance and decreased 7-year learning and memory decline among middle-aged and older Hispanic or Latino adults. Culturally tailored Mediterranean diet may reduce the risk of cognitive decline and Alzheimer disease in this population

Hearing Loss and Associated 7-Year Cognitive Outcomes Among Hispanic and Latino Adults

Importance: Hearing loss appears to have adverse effects on cognition and increases risk for cognitive impairment. These associations have not been thoroughly investigated in the Hispanic and Latino population, which faces hearing health disparities. Objective: To examine associations between hearing loss with 7-year cognitive change and mild cognitive impairment (MCI) prevalence among a diverse cohort of Hispanic/Latino adults. Design, Setting, and Participants: This cohort study used data from a large community health survey of Hispanic Latino adults in 4 major US cities. Eligible participants were aged 50 years or older at their second visit to study field centers. Cognitive data were collected at visit 1 and visit 2, an average of 7 years later. Data were last analyzed between September 2023 and January 2024. Exposure: Hearing loss at visit 1 was defined as a pure-tone average (500, 1000, 2000, and 4000 Hz) greater than 25 dB hearing loss in the better ear. Main outcomes and measures: Cognitive data were collected at visit 1 and visit 2, an average of 7 years later and included measures of episodic learning and memory (the Brief-Spanish English Verbal Learning Test Sum of Trials and Delayed Recall), verbal fluency (word fluency-phonemic fluency), executive functioning (Trails Making Test-Trail B), and processing speed (Digit-Symbol Substitution, Trails Making Test-Trail A). MCI at visit 2 was defined using the National Institute on Aging-Alzheimer Association criteria. Results: A total of 6113 Hispanic Latino adults were included (mean [SD] age, 56.4 [8.1] years; 3919 women [64.1%]). Hearing loss at visit 1 was associated with worse cognitive performance at 7-year follow-up (global cognition: β = -0.11 [95% CI, -0.18 to -0.05]), equivalent to 4.6 years of aging and greater adverse change (slowing) in processing speed (β = -0.12 [95% CI, -0.23 to -0.003]) equivalent to 5.4 years of cognitive change due to aging. There were no associations with MCI. Conclusions and relevance: The findings of this cohort study suggest that hearing loss decreases cognitive performance and increases rate of adverse change in processing speed. These findings underscore the need to prevent, assess, and treat hearing loss in the Hispanic and Latino community

Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development