Scharf, Eugene

(1) Background: Cardiometabolic disease, including insulin resistance, hyperlipidemia, and hypertension, are major contributors to adverse health outcomes. Fasting has gained interest as a nonpharmacological therapeutic adjunct for these disorders. (2) Methods: We conducted a prospective, single-center study on the effects of prolonged water-only fasting followed by an exclusively whole-plant-food refeeding diet on accepted measures of cardiovascular risk and metabolic health. Participants were recruited from patients who had voluntarily elected to complete a water-only fast in order to improve their overall health according to an established protocol at an independent, residential medical center. Median fasting and refeed lengths were 17 and 8 days, respectively. The primary endpoint was to describe the mean glucose tolerance as indicated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores at baseline, end-of-fast (EOF), and end-of-refeed (EOR) visits. Secondary endpoints were to describe the mean weight, body mass index (BMI), abdominal circumference (AC), systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid panel, and high-sensitivity C-reactive protein (hsCRP) at the same time points. (3) Results: The study enrolled 48 overweight/obese non-diabetic participants, of which 26 completed the full study protocol. At the EOF visit, the median SBP, AC, low-density lipoprotein (LDL), and hsCRP were decreased and triglycerides (TG) and HOMA-IR scores were increased. Conclusion: Prolonged water-only fasting and whole-plant-food refeeding holds potential as a clinical therapy for cardiometabolic disease but increased TG and HOMA-IR values after refeeding necessitate further inquiry.

Introduction: A common risk factor of chronic, nontraumatic subdural hematoma (SDH) is anticoagulation therapy. Anticoagulation is generally held in patients who develop SDH, but this can lead to thromboembolic events. While prior studies have reported the clinical outcomes of patients with anticoagulation-related SDH, there remains little evidence regarding ongoing anticoagulation treatment. Case Report: We report the management of 2 patients who developed anticoagulation-related SDH and underwent middle meningeal artery (MMA) embolization and successful reinitiation of anticoagulation therapy. In both patients, we conservatively managed anticoagulation with heparin and/or enoxaparin as a bridge to warfarin after MMA embolization. Follow-up computed tomography head revealed interval decrease of SDH and stable neurological status. Conclusions: These cases provide anecdotal evidence of a challenging clinical scenario where there is a necessary indication for therapeutic anticoagulation (ie, venous sinus thrombosis or atrial appendage thrombus) and comorbid SDH. Endovascular MMA embolization may be an effective adjunct therapy for clinical scenarios in patients with SDH and an urgent indication for anticoagulation. Longer follow-up, prospective series, and future randomized clinical trials are needed to objectively assess outcomes in this clinically challenging patient population.

Background White matter hyperintensity (WMH), characterized by hyperintensities on T2‐weighted fluid‐attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS. Methods and Results We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson r =0.24, P =0.03; >50 years, Pearson r =0.62, P <0.0001; juxtacortical WMH: ≤50 years, Pearson r =0.09, P =0.40; >50 years, Pearson r =0.55, P <0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17, P =0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow‐up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92; P =0.03). Conclusions Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.

Purpose To assess whether an asymmetry exists in the prevalence of carotid artery intraplaque hemorrhage (IPH) between right- and left-sided arteries. Materials and methods The records of all patients with atherosclerotic carotid artery disease that underwent neck magnetic resonance angiography imaging with high-resolution plaque sequences between 2017 and 2020 at our institution were retrospectively reviewed. The prevalence of stenosis and IPH was determined for all patients and compared between the left and right carotid arteries of those with unilateral anterior circulation ischemic strokes. Multiple regression analysis was performed to determine potential independent associations of IPH laterality with ischemic strokes. Results A total of 368 patients were included overall and 241 were male (65.4%). There were a total of 125 asymptomatic patients and 211 patients with unilateral anterior circulation ischemic strokes. Of patients with ischemic strokes, 55.5% had left-sided strokes compared with 44.5% who had right-sided strokes ( p = 0.03). Patients with left-sided strokes had a higher prevalence of ipsilateral IPH than those with right-sided strokes (64.1% versus 36.2%, p < 0.0001), despite similar degrees of stenosis. Both age (odds ratio (OR): 1.0; 95% confidence interval (CI): 1.0–1.1; p = 0.007) and the presence of left-sided IPH (OR: 3.2; 95% CI: 1.5–6.8; p = 0.003) were independently associated with unilateral ischemic strokes. Conclusions Left-sided plaques more frequently have IPH and may be more likely to result in ipsilateral ischemic strokes compared with right-sided plaques. The underlying mechanism of asymmetric distribution of IPH between right and left carotids remains unclear.

Background and Purpose— White matter hyperintensity (WMH) burden is associated with stroke and cognitive decline. Risk factors associated with the longitudinal progression of WMH in the general population have not been systematically investigated. To investigate the primary midlife and current cardiometabolic risk factors associated with changes in WMH over time in a population cohort. Methods— This cohort study included participants enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study in Olmsted County, Minnesota with at least 2 consecutive WMH assessments on fluid-attenuated inversion recovery-magnetic resonance images (n=554, ≥60 years with midlife assessments) with relevant baseline laboratory measures of interest. Linear mixed model regression was used to determine the important components of cardiometabolic risk profile at baseline that were associated with future progression of WMH. These analyses were controlled for age and sex. Sensitivity analyses were conducted using stratification by sex. The main outcome measure was percent change in WMH normalized to total intracranial volume. Three sets of models were constructed to evaluate individual (1) midlife risk factors, (2) current risk factors including the presence of metabolic syndrome and its constituents, and (3) baseline measurements of continuous laboratory measures of cardiometabolic risk. Results— Age was the strongest predictor of progression in WMH ( P <0.001). Baseline hypertension ( P <0.001), midlife hypertension ( P =0.003), and baseline fasting glucose in males ( P =0.01) were predictive of WMH change. The presence of metabolic syndrome was not associated with progressive WMH. In sensitivity analyses, associations between hypertension and WMH progression were stronger in females. Baseline serum glucose was associated with increase in WMH but was not significant in females in the stratified analysis. Other continuous laboratory measures of vascular risk were not associated with progressive WMH. Conclusions— Midlife and current hypertension in all participants and fasting glucose in males were associated with quantitative changes in white matter. Prospective clinical studies should determine optimal blood pressure to reduce stroke and cognitive impairment during aging.

The societal burden of ischemic stroke suggests a need for additional therapeutic categories in stroke prevention. Modulation of the endocannabinoid system (ECS) is a rational target for stroke prevention because of its effects on inflammation, vascular tone, and metabolic balance, all well-described stroke risk factors. In this article, we summarize the existing ECS clinical studies in human subjects' research as they relate to conventional vascular risk factors associated with ischemic stroke. To date, 2-arachidonoylglycerol (2-AG) derivative endocannabinoids are consistently reported to be elevated in insulin resistance, whereas the N-arachidonoylethanolamine (AEA) endocannabinoid derivatives are elevated in obesity. The ECS role in metabolic health should examine the effects of 2-AG reduction and AEA augmentation as a means of stroke risk reduction. Cannabinoid receptors are reported on macrophages within atherosclerotic plaques and suggest a role for immunomodulation as a therapeutic for atherosclerosis through both peripheral immune cell CB1 antagonism and/or CB2 agonist. The effects of ECS on hypertension, smoking, physical activity, obstructive sleep apnea, heart failure, and atrial fibrillation are incompletely described and deserve further study. A limitation to ECS research is significant overlap with noncannabinoid molecular targets. Further exploration of the ECS needs to include the larger metabolomics context for a greater understanding of its therapeutic potential. Clinical translational studies in stroke prevention should be directed at ECS in metabolic balance and atherosclerosis.

We report a unique case and presentation of a 77-year-old man with atrial fibrillation who presented with complex imaging features, including bifrontal cerebral hematomas that progressed to multifocal macro- and microhemorrhages, vasogenic edema, and cortical/meningeal enhancement. Cerebrospinal fluid analysis was only remarkable for a protein elevation of 65 mg/dL. Leptomeningeal vessel biopsy failed to demonstrate evidence of amyloid angiopathy but did show concentric obstructive intimal fibroplasia, suggestive of chronic venous congestion. Conventional cerebral angiography showed a Cognard type IV dural arteriovenous fistulae fed by bilateral ethmoidal arteries draining directly into ectatic cortical veins. A chronic occlusion of the anterior third of the superior sagittal sinus was also noted. The fistula was successfully surgically obliterated via an uncomplicated left frontal craniotomy approach. After rehabilitation therapy, he was discharged home with a modified Rankin Scale score of 3. Because effective treatment exists, this case underscores the importance of identifying this rare etiology of intracerebral hemorrhage and pursuing adequate workup.