Chronic Infarction Research Articles

Impact of cerebral small vessel disease on symptomatic in-stent restenosis in intracranial atherosclerosis.

Cerebral small vessel disease (CSVD) commonly coexists with intracranial atherosclerotic stenosis (ICAS). In-stent restenosis (ISR) affects the nonprocedural outcome of severe symptomatic ICAS after intracranial stenting. However, only 8%-27% of ISR patients are symptomatic, which highlights the importance of the investigation of risk factors associated with symptomatic ISR (SISR) to improve long-term functional outcome. Whether CSVD is associated with SISR remains unclear. The authors tested the hypothesis that CSVD is associated with SISR in ICAS patients after intracranial stenting. This retrospective study enrolled 97 patients who were symptomatic due to severe anterior circulation ICAS treated with intracranial stenting. SISR was evaluated with clinical and vascular imaging follow-up. CSVD subtypes, including white matter hyperintensities (WMHs), enlarged perivascular spaces, and chronic lacunar infarctions, were evaluated. Cox regression analysis was used to compare the incidence of SISR between patients with and without CSVD. Of the enrolled patients, 58.8% had CSVD. The 1- and 2-year ISR rates were 24.7% and 37.1%, respectively. Of the CSVD subtypes, SISR was associated with deep WMHs (DWMHs; HR 5.39, 95% CI 1.02-28.44). DWMH Fazekas scale grades 2 (HR 85.54, 95% CI 2.42-3018.93) and 3 (HR 66.24, 95% CI 1.87-2352.32) were associated with SISR, but DWMH Fazekas grades 0 and 1 were not. The proportions of SISR in patients with DWMH Fazekas grades 0, 1, 2, and 3 were 16.7%, 33.3%, 50%, and 100%, respectively. Patients with CSVD have a higher risk of SISR than those without CSVD. Of the CSVD subtypes, patients with DWMHs are associated with SISR. The DWMH Fazekas scale score is considered to be a predictor for SISR.

Trends in Postmortem Neurodegenerative and Cerebrovascular Neuropathologies Over 25 Years

With rapid aging of the US population, understanding trends over time in dementia occurrence is essential to public health planning and intervention; this understanding includes trends in neuropathologies underlying clinical dementia. To characterize trends in pathways underlying dementia by examining prevalence of postmortem neuropathologies in birth cohorts across 25 years. Two longitudinal cohorts, the Religious Orders Study and the Rush Memory and Aging Project, with autopsy data from 1997 to 2022 with up to 27 years follow-up were analyzed. Deceased individuals with complete postmortem neuropathology evaluations were included, and 177 individuals with most distant (<1905) or recent (>1930) years of birth were excluded. Four categories of year of birth: 1905-1914, 1915-1919, 1920-1924, and 1925-1930. Outcomes included pathologic diagnosis of Alzheimer disease (AD), global AD pathology, amyloid load, tau tangles, neocortical Lewy bodies, limbic-predominant age-related TDP-43 encephalopathy neuropathological change, atherosclerosis, arteriolosclerosis, gross chronic infarcts, and chronic microinfarcts. For comparison, pathologies in each birth epoch were age-standardized to age distribution of the cohorts. χ2 Tests were used for categorical outcomes, and analysis of variance was used to compare means across birth epochs. Overall, 1554 participants were examined (510 [33%] male; median [range] age at death, 90 [66-108] years). Participants were distributed fairly evenly across birth epochs (1905-1914: n = 374; 1915-1919: n = 360; 1920-1924: n = 466; 1925-1930: n = 354). Across year of birth groups, no differences were found in prevalence of pathologic AD diagnosis; age-standardized prevalence fluctuated between 62% and 68% in the birth cohorts (χ2 test: P = .76 across birth epochs). Similarly, no differences were found in mean levels of global AD pathology, although there was greater density specifically of tau tangles in later birth cohorts (eg, age-standardized mean [SD], 1.53 [1.20] years for the 1905-1914 cohort and 1.87 [1.47] years for the 1925-1930 cohort; analysis of variance test: P = .01 across birth cohorts). There were no differences over time in other neurodegenerative pathologies. In contrast, atherosclerosis and arteriosclerosis were dramatically lower over time; for example, age-standardized prevalence of moderate to severe atherosclerosis ranged from 54% among those born from 1905-1914 to 22% for 1925-1930 (χ2 test: P < .001 across birth epochs). In this study, few differences in neurodegenerative pathologies were found, but there may be worse levels of tau tangles across birth cohorts over 25 years. This indicates that any improvements over time in clinical dementia observed by cohorts are likely in part associated with improved resilience to pathology rather than reduced AD pathology. Finally, vessel pathologies were markedly lower over birth cohorts, indicating the assocation with brain health of populationwide improvements in several vascular risk factors.

In vivo pulsed-field ablation in healthy vs. chronically infarcted ventricular myocardium: biophysical and histologic characterization.

Data on ventricular pulsed-field ablation (PFA) are sparse in the setting of chronic myocardial infarction (MI). The objective of this study was to compare the biophysical and histopathologic characteristics of PFA in healthy and MI swine ventricular myocardium. Myocardial infarction swine (n = 8) underwent coronary balloon occlusion and survived for 30 days. We then performed endocardial unipolar, biphasic PFA of the MI border zone and a dense scar with electroanatomic mapping and using an irrigated contact force (CF)-sensing catheter with the CENTAURI System (Galaxy Medical). Lesion and biophysical characteristics were compared with three controls: MI swine undergoing thermal ablation, MI swine undergoing no ablation, and healthy swine undergoing similar PFA applications that included linear lesion sets. Tissues were systematically assessed by gross pathology utilizing 2,3,5-triphenyl-2H-tetrazolium chloride staining and histologically with haematoxylin and eosin and trichrome. Pulsed-field ablation in healthy myocardium generated well-demarcated ellipsoid lesions (7.2 ± 2.1 mm depth) with contraction band necrosis and myocytolysis. Pulsed-field ablation in MI demonstrated slightly smaller lesions (depth 5.3 ± 1.9 mm, P = 0.0002), and lesions infiltrated into the irregular scar border, resulting in contraction band necrosis and myocytolysis of surviving myocytes and extending to the epicardial border of the scar. Coagulative necrosis was present in 75% of thermal ablation controls but only in 16% of PFA lesions. Linear PFA resulted in contiguous linear lesions with no gaps in gross pathology. Neither CF nor local R-wave amplitude reduction correlated with lesion size. Pulsed-field ablation of a heterogeneous chronic MI scar effectively ablates surviving myocytes within and beyond the scar, demonstrating promise for the clinical ablation of scar-mediated ventricular arrhythmias.

Computed Tomography Perfusion Imaging in Acute Ischemic Stroke: Accurate Interpretation Matters.

Computed Tomography Perfusion Imaging in Acute Ischemic Stroke: Accurate Interpretation Matters.

Abstract 33: Risk Scores And Brain Mri Markers In Distinguishing Ischemic Stroke And Intracerebral Hemorrhage Risk Among Atrial Fibrillation Patients: The Neuro-Afib Study

Background: Recent studies cast doubt on the accuracy of the most-commonly used risk scores (CHA 2 DS 2 -VASC and HAS-BLED) in differentiating the risk of acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) among patients with fibrillation (AF). Because of the importance of AIS/ICH risk determination for choice of proper preventive approaches, we aimed to compare the value of these risk scores and brain MRI markers to differentiate the occurrence of AIS and ICH in a large cohort of AF-related strokes. Methods: The Neuro-AFib study is a multicenter effort to elucidate the causes and consequences of AIS and ICH in AF patients. Demographics, CHA 2 DS 2 -VASC and HAS-BLED scores, and ischemic/hemorrhagic brain MRI markers were compared between AF patients admitted with AIS and ICH to 15 academic stroke centers in the US between 1/2018-12/2019. Results: Of 5694 stroke admissions with AF, 4826 (84.8%) had AIS and 868 (15.2%) ICH. Mean age was similar between groups (75.9±11.5 vs 76.6±11.9, p=0.1), more ICH patients were male (57% vs 50%). Pre-index event CHA 2 DS 2 -VASC (4.14±1.6 vs 4.22±1.6) and HAS-BLED (2.71±1.09 vs 2.68±1.13) were similar between groups [both p&gt;0.2]. Cerebral microbleeds (CMB, 56% vs 33.5%), cortical superficial siderosis (cSS, 15% vs 9.4%), and moderate-to-severe leukoaraiosis (41% vs 33.4%) were more commonly found among ICH patients compared to AIS (all p&lt;0.001). Chronic lacunar infarcts (43.5% vs 39.5%, p=0.03) and chronic non-lacunar infarcts (29% vs 18%, p&lt;0.001) were more commonly found in AIS. In a multivariable logistic regression model that included all variables above, male sex, presence of CMBs, cSS, moderate-to-severe leukoaraiosis were associated with ICH, chronic non-lacunar infarcts with AIS (all p&lt;0.005), while CHA 2 DS 2 -VASC (p=0.9) and HAS-BLED (p=0.9) were not related to the stroke type. Conclusions: Data from our multicenter study confirm the lack of specificity of CHA 2 DS 2 -VASC and HAS-BLED to categorize the risk of AIS vs ICH in AF patients. The chronic MRI findings (CMB, cSS, moderate-to-severe leukoaraiosis, chronic infarcts) should be incorporated into risk scores, and their predictive value for AIS and ICH should be investigated in prospective studies to select optimal stroke prevention methods in AF patients.

Abstract WP188: Relationships Of Hematocrit With Asymptomatic And Symptomatic Lacunar Ischemic Lesions

Introduction: Hematocrit at both low and high extremes can result in both hypoxia and thrombosis respectively. While both scenarios may predispose to ischemia, it is unclear whether hematocrit associates with small vessel cerebrovascular lacunar infarcts. Hypothesis: Hematocrit levels will associate with both asymptomatic and symptomatic cerebrovascular lacunar infarcts in stroke-free participants and ischemic stroke patients, respectively. Methods: A cross sectional observational analysis of a prospective, population-based cohort study of stroke-free, older adult (&gt;50) participants from the Northern Manhattan study (NOMAS) receiving baseline hematocrit testing and MRI between 2003-2008 were analyzed. A second, single center prospective cohort of admitted adult ischemic stroke patients receiving baseline hematocrit testing and MRI between 2005-2018 was evaluated. Associations of hematocrit with covert, asymptomatic chronic lacunar infarcts from stroke-free participants in NOMAS were assessed using general additive models after adjusting for relevant covariates. Separate analyses were performed to assess associations of hematocrit with symptomatic acute lacunar infarct stroke etiology using similar adjusted models for patients admitted and enrolled into the ischemic stroke registry. Results: Of 1218 NOMAS participants analyzed, 6% had covert chronic lacunar infarcts. The association between hematocrit and covert chronic lacunar infarcts was U-shaped (X2: 9.21; p-value: 0.03). In the 1489 patients from the ischemic stroke registry, 23% were identified to have symptomatic acute lacunar infarcts. Linear relationships were identified with higher hematocrit and symptomatic acute lacunar infarct etiology (adjusted coefficient beta: 0.020; standard error: 0.009; p=0.03). Conclusions: We identified relationships of hematocrit with both asymptomatic and symptomatic lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. There may be a relevant role of red blood cell volumes with ischemic cerebral small vessel disease pathophysiology. However, further studies are required to clarify the mechanisms behind these relationships.

Abstract WMP57: Brain Frailty Mediates The Relationship Between Age And 90-day Functional Outcome After Endovascular Therapy: Analysis Of The Escape-na1 Trial

Introduction: Age is a predictor of functional outcome after acute ischemic stroke (AIS). Frailty increases with age and comorbidities, and imaging markers of brain-frailty (e.g. atrophy, small-vessel-disease) are associated with outcomes. However, the extent to which the association of age and 90-day outcome is mediated by brain-frailty is unknown. We explored this mediation in AIS patients receiving endovascular therapy (EVT), with a particular interest in neuroimaging. Methods: In this post-hoc analysis of the ESCAPE-NA1 trial, in which all patients underwent EVT, we assessed brain atrophy (subcortical/cortical), white-matter disease (periventricular/deep) and the number of lacunes and chronic infarctions. Structural equation modelling (SEM) was used to create 3 latent variables: “imaging-frailty” (above-mentioned markers), “clinical-frailty” (e.g. pre-stroke mRS, cardiovascular risk factors, cancer) and “total-frailty” (imaging + clinical markers). We created 3 models ( figure1) including each latent variable as a potential mediator of the association of age and 90-day outcome, adjusting for baseline ASPECTS, NIHSS, onset-to-puncture-time, nerinetide and alteplase. Results: Among 1,092 patients, the indirect effect of age on 90-day outcome, mediated by imaging-frailty, contributed 96% of the total effect(β=0.047;p=0.02), while the indirect effect through clinical-frailty accounted for only 21%(β=0.01;p=0.001) of the total effect. When including both frailty constructs, the indirect pathway accounted for 86% of the total effect(β=0.06;p&lt;0.01). These proportions were similar when imaging features were assessed on MRI. Conclusions: Brian frailty mediates the association of age and 90-day outcome after EVT, with most of the effect mediated by imaging as opposed to clinical markers of frailty. This work underscores the importance of considering brain-frailty, as opposed to chronological age alone, in predicting post-stroke outcomes.

Deoxy-ATP producing hiPSC-derived cardiomyocytes improve cardiac function in chronically infarcted hearts.

We have demonstrated that 2-deoxy-ATP (dATP) improves contractility by activating myosin and increasing crossbridge cycling without impairing relaxations, making it a promising sarcomere targeted molecule to mitigate cardiac dysfunction. Over-expression of Ribonucleotide Reductase (RNR) elevates dATP in cardiomyocytes sufficient to increase contractile function. We have shown that dATP from RNR over-expressing cells spreads to neighboring cells via gap junctions and increases their contractile function. This suggests transplantation of RNR over-expressing human-induced pluripotent stem cell-derived cardiomyocytes (RNR-hiPSC-CMs) could significantly increase the effectiveness of cardiac cell therapy in chronic myocardial infarcted (MI) hearts. In initial studies, overexpressing a proteolytic degradation resistant form of RNR in hiPSC-CMs, using a CAG promoter (CAG-RNR-CMs), resulted in elevated levels of dATP % (4.7-fold ± 0.38), and improved cell shortening (2-fold ± 0.15) compared to WT-CMs (N=3). Upon transplantation into normal rat hearts, left ventricular (LV) % fractional shortening (FS) was significantly increased with CAG-RNR-CMs (N=4-6, p ≤ 0.05) and increased dATP levels of native myocardium. When transplanted into chronically infarcted hearts, CAG-RNR-CMs had a protective effect on LV dilation and stabilized %FS from deteriorating post-MI compared to WT-CM transplants. To maximize these benefits, we engineered a new cell line using a muscle specific CK8m promoter to drive dATP levels higher. Compared to CAG-RNR-CMs, CK8m-RNR-CMs had significantly higher RNR and dATP % (∼5-fold). At 3 months post-transplant, these CK8m-RNR-CMs demonstrated greatly increased efficacy of dATP delivery to host myocardium. This greater level of dATP translated to significantly improved LV function at 3 months post-transplantation compared to WT-CMs, with more organized grafts of similar size, and improved voluntary exercise. R01HL128368

Abstract TP183: Impaired Kidney Function Small Vessel Disease Markers And Its Association With Periventricular White Matter Hyperintensities

Introduction: Small vessel disease (SVD) is a condition associated with aging and vascular risk factors to which the brain and kidney are susceptible. However, whether kidney dysfunction may directly contribute to brain SVD as opposed to both organs being affected as an epiphenomenon of aging is less clear. We hypothesize that impaired kidney function is differentially associated with brain markers of SVD, and the association is greater with SVD markers restricted to deep, penetrating arteries. Methods: We leveraged existing data from the Columbia University Irving Medical Center/ New York Presbyterian Hospital Stroke Registry. Odds ratio (OR), estimate, confidence intervals (CI), and p values were calculated. We rated visually the presence an anatomical location of cerebral microbleeds and chronic lacunar infarcts and used the Fazekas scale to semi-quantitate white matter hyperintensities. We created linear regression models adjusted for age, sex, race/ethnicity and vascular risk factors to evaluate the relationship between kidney function (defined as self-reported chronic kidney disease or creatinine on admission). Results: We included 973 patients (mean age 65±16 years, 51 % female). The prevalence of self-reported CKD/ESRD was 14% and the mean creatinine on admission was 1.61±2.04 mg/dl. The prevalence of chronic brain infarct was 40%, cerebral microbleeds 24%, and all had some degree of white matter hyperintensity. Conclusion: There is association between previous history of CKD-ESRD and creatinine levels on admission with periventricular WMH. These data also hint a possible association between CMB of deep location with history of CKD-ESRD, but a bigger sample is required for significance.

Abstract 147: First-in-human Phase 1/2a Study Of Intracerebral Transplantation Using Embryonic-derived Neural Stem Cells (NR1) For Chronic Ischemic Stroke

Introduction: Currently, no treatment exists to restore function in chronic stroke patients. Several prior intracerebral stem cell trials showed safety, but are not being further developed. Objective: NR1 is a human embryonic derived neural stem cell that improved motor-sensory function in rodent stroke models, and was expanded to produce GMP cryopreserved Cell Lots (P18). The aim is to assess the safety, tolerability and efficacy using intracerebral transplantation of NR1 cells in chronic stroke patients (NCT04631406). Methods: Inclusion Criteria: 18-75 yo; 6-60 months post-ischemic subcortical MCA stroke; mRS 3-4. Subjects are transplanted with NR1 (2.5M, 5M, 10M or 20M). Primary Outcomes: Adverse events 0-6 mos; Change in Fugl-Meyer (FM) motor score (maximum FM 100) compared to baseline at 6 months (≥10 points improvement considered “clinically meaningful”). Other outcomes: Barthel Index, NIHSS, Gait Speed test, mRS, MRI DTI, FLAIR, Resting State fMRI and [18F] FDG PET. Results: Six patients have been transplanted. Adverse events included headache and worsened speech, all resolving spontaneously. At 6 mos post-transplant: FM improved 15, 13 and 9 points in patients 1, 2 and 3 (all with faster gait); Barthel Index improved 5, 10 and 15 points. At 3 months FM improved 15 points (with faster gait) in patient 4. NIHSS improved 2 points in 2 patients and worsened 1 point in 1 patient. There was no change in mRS. All 6 patients demonstrated a new transient FLAIR signal in premotor cortex at d7, that resolved by 2 mos, which in prior studies was highly correlated with sustained neurologic recovery. An increase in regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs) was observed in the sensorimotor network ipsilateral to the chronic infarction in patients with clinical improvement. Six additional patients are scheduled in the next 6 months. Conclusions: Intraparenchymal transplantation with NR1 cells in chronic stroke patients appears safe and well tolerated. Early results suggest improved motor function at 1-6 months post-implant.

ROLE OF DIFFUSION-WEIGHTED IMAGING AND APPARENT DIFFUSION COEFFICIENT IN MAGNETIC RESONANCE IMAGING FOR THE EVALUATION OF BRAIN INFARCTION

Cerebral infarction is the leading cause of mortality and morbidity worldwide. The time of diagnosis of cerebral infarction plays a crucial role in the treatment and prognosis of the patient. The intravenous tissue plasminogen activator (tPA) given within three hours after the onset of stroke or early revascularization by percutaneous interventions are the early treatment of choices and has good prognostic value. MRI plays a vital role in the diagnosis of cerebral infarction. A less time-consuming MRI sequence like diffusion with ADC correlation is a highly sensitive imaging technique for early detection. During the early stages of brain infarction which is less than 6 hours after the onset of symptoms, MRI sequences such as T1 and T2 showed no changes. Therefore, DWI and ADC correlation with magnetic resonance imaging plays a vital role improved in the early diagnosis and assessing the prognosis of the patient. The present study is a hospitalbased prospective, cross-sectional study done in 75 patients, who underwent MRI brain evaluation in the department of radiodiagnosis, at Kona Seema institute of medical sciences, for a period of 12 months. Patients who fullled the inclusion and exclusion criteria were selected. ADC and r ADC values are calculated in all patients. The aim of the study is to show that the Apparent Diffusion Coefcient (ADC), diffusion-weighted imaging (DWI) varies with time and space in cerebral infarction and to determine the stage of the infarction using r ADC values, ADC and DWI. In our present study, we proved that the average ADC values and the rADC values change with time and space which helps us to accurately stage the brain infarction in terms of acute, subacute, and chronic cerebral infarction. Combined analysis of DWI with ADC correlation and routine MRI sequences are used for the accurate evaluation of the brain infarction and to assess the progress and treatment plans after brain infarction

Prevalence of Gallbladder Cancer in Cases Presented to Tertiary Care Hospital, Retrospective Five-Year Study on Cholecystectomy Specimen

Background: The gallbladder is surgically removed in a cholecystectomy. The prevalence of gallbladder carcinoma is determined by examining cholecystectomy specimens. Gallbladder carcinoma is an extremely unusual condition that affects more women than men. The goal of this study is to find out how common gallbladder cancer is in medical centers over five years. Objective: To determine the frequency and prevalence of Gallbladder cancer (GBC) in tertiary care hospitals over five years Methods: We analyzed the record of 1835 patients who underwent cholecystectomy at our tertiary care center, Mayo Hospital Lahore. Results: Adenocarcinoma was found in only 7 cases (0.4%) out of 1835 cholecystectomy specimens. Gallbladder cancer is more common in females (6, 85.71%) than in males (1 case, 14.78%). Chronic cholecystitis accounted for the majority of the cases (1703, or 92.8%), followed by acute cholecystitis (66, or 3.6%), Xanthogranulomatous, cholecystitis (30, or 1.6%), gangrenous cholecystitis (6, or 0.34%), follicular cholecystitis (3, or 0.016%) and one case (0.05%) each of cholesterolosis, foci of chronic inflammation, hemorrhagic infarction and empyema gallbladder. 13 cases (0.79%) was partially or fully autolyzed. Conclusion: Chronic cholecystitis is the most common disease in cholecystectomy specimens followed by acute cholecystitis, Xanthogranulomatous cholecystitis, gangrenous cholecystitis, follicular cholecystitis, and empyema gallbladder. Gallbladder carcinoma is very rare and more common in females than males.

Association of Chronic Covert Cerebral Infarctions and White Matter Hyperintensities With Atrial Fibrillation Detection on Post-Stroke Cardiac Rhythm Monitoring: A Cohort Study.

Background This study was conducted to explore the association of different phenotypes, count, and location of chronic covert brain infarctions (CBIs) with detection of atrial fibrillation (AF) on prolonged post-stroke cardiac rhythm monitoring (PCM). Methods and Results We conducted a cohort single-center study of consecutive first-ever ischemic stroke or transient ischemic attack patients undergoing PCM between January 2015 and December 2017. We blindly rated CBI phenotypes according to established definitions and white matter hyperintensities (WMHs) according to the age-related white matter changes rating scale. We used (multiple) regression models to assess the association of the imaging biomarkers and incident AF on PCM. A total of 795 patients (median [interquartile range]) aged 69 (57-78) years, 41% women, median National Institutes of Health Stroke Scale score 2 (0-5), median PCM duration 14 (7-14) days, and AF detection in 61 patients (7.7%) were included. On univariate analysis, WMHs (per point odds ratio, 1.35 [95% CI, 1.03-1.78]) but not CBIs (odds ratio, 0.90 [95% CI, 0.52-1.56]) were associated with AF detection. Neither CBI phenotype, count, nor location were associated with AF detection. After adjustment for age, hypertension, and stroke severity, neither increasing WMHs (per point adjusted odds ratio, 0.85 [95% CI, 0.60-1.20]) nor CBIs (adjusted odds ratio, 0.60 [95% CI, 0.33-1.09]) were independently associated with AF detection. Conclusions Although WMHs and CBIs represent surrogate biomarkers of vascular risk factors, neither WMHs nor CBIs, including their phenotypes, count, and location, were independently associated with AF detection on PCM. In patients with manifest ischemic stroke or transient ischemic attack, the presence of imaging biomarkers of chronic ischemic injury does not seem promising to further refine prediction tools for AF detection on PCM.

Loneliness predicts stronger negative associations between cerebrovascular, but not Alzheimer’s, pathology and cognition

AbstractBackgroundAlzheimer’s disease (AD) and cerebrovascular disease are the two most common pathologies underlying dementia. Loneliness is associated with faster cognitive decline and greater AD risk independent of pathology. Risk reduction efforts would benefit from knowing whether loneliness exacerbates the cognitive impact of pathology. Our objective was to characterize the interaction between loneliness and AD or cerebrovascular pathology on cognitive performance.MethodsParticipants with neuropathological data were drawn from the Religious Orders Study, the Memory and Aging Project, and the Minority Aging Research Study (Table 1). Loneliness was assessed with a modified version of the de Jong‐Gierveld Loneliness Scale. Amyloid and tau pathology were assessed jointly with the NIA‐Reagan scale as high/intermediate likelihood or low likelihood/no AD. Chronic infarcts and chronic microinfarcts were each assessed as present or not present. Composite domain scores for episodic memory, working memory, semantic memory, perceptual speed, and perceptual orientation were obtained from the study visit proximal to death. Separate general linear models were run for each domain and each pathology, including an interaction between loneliness and pathology and adjusting for covariates.ResultsGreater loneliness was associated with older age and lower education, and loneliness was greater in men compared to women, but not different by race or APOE‐ε4 (2). Loneliness was not associated with AD or cerebrovascular pathology (Table 3). Greater loneliness was independently associated with lower cognitive scores in all domains. Greater pathology was independently associated with lower episodic memory and semantic memory scores, while cerebrovascular disease was not independently associated with cognitive scores. We additionally found that negative associations between microinfarcts and cognitive scores in working memory, semantic memory, and perceptual orientation were stronger among individuals with greater (Table 4).ConclusionsNegative associations between loneliness and cognition are apparent across domains and independent of pathology. While loneliness does not appear to be related to AD or cerebrovascular pathology directly, it may increase susceptibility to cognitive impairment due to microinfarcts. Social support‐based interventions may benefit optimal brain aging, particularly in older adults exposed to greater loneliness.

Cushing Reflex Variant: A case report

In our case, we report a 67-year-old male admitted with lower limb ischemia for angiography under vascular surgery. During the procedure, he exhibited a sudden change in consciousness level, an abnormal breathing pattern, and bradycardia associated with normal blood pressure. This case represents a rare and detrimental manifestation of the Cushing reflex present with isolated bradycardia. This case report concluded a possible early haemorrhagic insult on top of chronic infarction. To direct the patient to the appropriate course of action, they must be monitored in an intensive care unit and have their intracranial pressure continuously checked.

Hearing Loss from S. Suis Meningitis In A Middle-Aged Couple

Hearing Loss from S. Suis Meningitis In A Middle-Aged Couple

Abstract 12655: Lipomatous Metaplasia in Chronic Infarcts is Associated With Prolonged Activation Recovery Interval Within Ventricular Tachycardia Corridors

Introduction: We studied the association of infarct scar versus lipomatous metaplasia (LM) with the activation recovery interval (ARI) in putative ventricular tachycardia (VT) corridors traversing the infarct zone. Methods: The cohort included 32 patients from the prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Ischemic Cardiomyopathy (INFINITY) study. We defined myocardial scar, border zone (BZ) and potential viable corridors through infarct by late gadolinium enhancement (LGE)-cardiac magnetic resonance (CMR), and LM by computed tomography (CT). The images were registered with electroanatomic maps wherein the ARI of each point (1,530 within LM, 4,946 within scar) was calculated using a custom Python code as the time interval from the minimum derivative within the QRS to the maximum derivative within the T wave. ARI dispersion was defined as the standard deviation (SD) of ARI per AHA segment. Multilevel random effects linear regression models, clustered by patient, were used to evaluate the association between ARI (or ARI dispersion) with tissue types. Results: LM exhibited higher myocardial ARI than normal myocardium, BZ, scar [regression coefficient: 35.5 vs. 0, 11.4, and 25.4, P &lt;0.001]. Of 100 corridors computed from LGE-CMR and electrophysiologically confirmed to participate in VT reentry, 97 traversed through or near LM, and displayed prolonged ARI compared to 123 non-critical corridors distant from LM [356 (319, 396) vs. 283 (266, 316) ms, P &lt;0.001, Figure 1]. The association of LM with Log(ARI SD ) was more robust than that of scar (likelihood ratio χ 2 47.5 vs. 23.4, and 5.9% vs. 1.6% increase in Log(ARI SD ) /1 cm 2 increase per AHA segment, respectively). Additionally, LM and scar exhibited interaction (p&lt;0.001) in their association with Log(ARI SD ). Conclusion: LM is closely associated with prolonged local action potential duration of corridors and ARI dispersion, which may facilitate the propensity of VT circuit reentry.

Abstract 12352: Left Ventricular Chordal Aberrancy: The Case of a Friend Turned Foe

Introduction: Aberrant cardiac structures reported on echocardiography include aberrant papillary muscles, accessory chordae tendineae, ventricular bands, and accessory mitral valve tissue. These usually present with conduction abnormality, obstruction, and heart failure. We report a diagnostic dilemma with a structurally anomalous chord noted on the echocardiogram presenting as recurrent stroke. Case: A 70 year old man presented with complaints of left facial droop, confusion and slurred speech, currently on aspirin and clopidogrel. CT head and MRI brain revealed right middle cerebral artery occlusion and acute on chronic infarcts in multiple vascular territories. Past medical history of recurrent strokes involving the right frontal, occipital lobes, and thalamus suggested embolic aetiology. Transthoracic and Transesophageal Echocardiographic (TEE) examination revealed an anomalous redundant chordal tissue attached to the papillary muscle with no distal attachment, normal mitral valve function without left ventricular outflow tract obstruction. This anomalous chord was present on TEE done 1 year prior but not well visualised at that time. Differentials included ruptured aberrant ventricular band, ruptured chordae tendineae, ruptured papillary muscle with a thrombus or vegetation formation. Due to the chronicity of the condition and negative blood cultures, vegetation was less likely. Recurrent mural thrombus associated with the aberrant chord was identified as the culprit and patient was started on anticoagulation to prevent stroke. Results: All of the aberrant structures reported in current literature have been characterized based on their distal attachment. We excluded accessory papillary muscle and chordae tendineae from the list of differentials as its rupture presents as mitral regurgitation and acute heart failure. The most plausible explanation includes a ruptured false tendon serving as a nidus for thrombus formation with no prior echocardiographic evidence of distal attachment of the fibrous chord. Conclusions: Our case illustrates a very rare entity of an idiopathic primary rupture of a left ventricle false tendon serving as a nidus for clot formation leading to recurrent stroke warranting anticoagulation.

Abstract 11288: Conduction Velocity is Slower in Corridors Traversing Lipomatous Metaplasia Than in Corridors Traversing Scar in Chronic Infarcts

Introduction: We sought to examine the association of infarct scar versus lipomatous metaplasia (LM) with impulse conduction velocity (CV) in putative ventricular tachycardia (VT) corridors that traverse the infarct zone in patients with prior myocardial infarction (MI). Methods: The cohort included 31 patients from the prospective In tra-Myocardial F at Deposition and Ventricular Tachycardia in Ischemic Card i omyopa t h y (INFINITY) study. CV was calculated as the mean CV between that point and five adjacent points along the activation wavefront using an automated Python script in myocardial scar, border zone (BZ), and potential viable corridors defined by late gadolinium enhancement (LGE)-cardiac magnetic resonance (CMR), and LM identified by computed tomography (CT). Both image sets were registered with electroanatomic maps (EAM). Results: Regions with LM exhibited lower myocardial CV than scar (median 12.0 vs. 13.5 cm/s, P &lt;0.001). Of 96 corridors computed from LGE-CMR and electrophysiologically confirmed to participate in VT reentry, 95 traversed through or near LM identified on CT. These critical corridors displayed slower CV {median 8.8 [interquartile range (IQR) 6.0, 15.4] vs. 39.0 (IQR 27.8, 56.5) cm/s, P &lt;0.001, Figure 1}, and demonstrated low-peripheral-high-center (mountain-shaped, 25%), or mean low level (45.7%) CV patterns, when compared to 122 non-critical corridors distant from LM that displayed high-peripheral-low-center (valley-shaped, 20.5%) or mean high level (59%) CV patterns. Conclusion: Myocardial LM is a crucial contributor to VT propensity. Corridors traversing through or near LM exhibit significantly slower CV, which likely facilitate the presence and stability of the VT circuit reentry.

Abstract 15654: Mitral Valve Strands in a Patient With Cerebellar Infarcts

Case Description: A 56-year-old man with a history of hypertension, diabetes, hyperlipidemia, and ischemic stroke 2 years ago presented with left-sided weakness, unsteady gait, and vomiting for 12 hours. The patient was vitally stable, and examination revealed dysarthria, left ataxic hemiparesis, and chronic right facial droop. Magnetic Resonance Imaging (MRI) brain showed an evolving acute infarct in the left superior cerebellum with trace petechial hemorrhage, chronic small right posterior inferior cerebellar infarct, and chronic bilateral cerebellar lacunar infarcts. The patient had an implantable loop recorder placed after his previous stroke, which did not show any arrhythmias on interrogation. MRI Angiography of the head/neck did not show large vessel occlusions. Transesophageal echocardiography (TEE) ruled out a patent foramen ovale but did reveal multiple filamentous structures (&lt;5mm in size) on the atrial side of the posterior mitral valve leaflet (figure 1); these were consistent with fibrin valve strands, or Lambl’s excrescences (LE). Anticoagulation therapy was started, and surgical excision was recommended. Discussion: LE are rare fibrous/filamentous valvular strands caused by wear and tear at the closure lines of left-sided heart valves. LE can be associated with thromboembolic strokes and acute coronary syndromes; however, it can also be found incidentally. TEE is the gold standard in diagnosis. This is a middle-aged man without a clear cause of ischemic strokes, subsequently found to have LE on the mitral valve. There is a paucity of evidence on the management of LE due to its rarity. Prior case reports suggest the use of antiplatelets/anticoagulants in symptomatic patients and surgery in cases of recurrent thromboembolic episodes refractory to conservative treatment. Given multiple strokes, this patient was started on anticoagulation and will be evaluated for surgery. Further high-powered studies are needed to guide management.