Etiologic Subtypes Research Articles

Trimethylamine N-Oxide and Stroke Recurrence Depends on Ischemic Stroke Subtypes.

Trimethylamine N-oxide (TMAO) has been recognized as a risk factor for cardiovascular disease. However, the role of TMAO in ischemic stroke remains unclear. As we know, ischemic stroke is a heterogeneous disease with variable pathogenesis. Hence, we aimed to investigate the association between TMAO and stroke recurrence according to etiology subtypes. A total of 10 756 ischemic stroke/transient ischemic attack patients from the Third China National Stroke Registry were enrolled, and 1-year follow-up data for stroke recurrence were analyzed. TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria was used to classify the etiology subtypes. Plasma TMAO levels were quantified by liquid chromatography-mass spectrometry. The association between TMAO and stroke outcomes was analyzed using Cox regression models. We also conducted a meta-analysis on the association of TMAO levels and stroke risk. Elevated TMAO level was independently associated with the risk of stroke recurrence (Q4 versus Q1: adjusted hazard ratio, 1.37 [95% CI, 1.15-1.64]) in multivariate Cox regression model. After stratification by TOAST subtypes, there was a significant association between TMAO and stroke recurrence in small artery occlusion subtype (adjusted hazard ratio, 1.43 [95% CI, 1.03-2.00]) but not in the others subtype (large-artery atherosclerosis, 1.19 [0.95-1.48]; cardioembolism, 1.54 [0.95-2.48]; others, 1.19 [0.98-1.44]). The meta-analysis reported on stroke recurrence for the highest versus lowest TMAO levels with a pooled hazard ratio of 1.66 (95% CI, 0.91-3.01) and similarly found an increased risk of stroke recurrence. Elevated TMAO level is associated with increased risk of stroke recurrence in patients with small artery occlusion subtype, but this association seems to be attenuated in large-artery atherosclerosis, cardioembolism, and others subtypes.

Implications of the Presence of Hyperdense Middle Cerebral Artery Sign in Determining the Subtypes of Stroke Etiology

Background Identifying stroke subtypes is crucial in choosing appropriate treatment, predicting outcomes, and managing recurrent stroke prevention. Objectives To study the association of hyperdense middle cerebral artery sign (HMCAS) on noncontrast computed tomography (NCCT) brain and subtypes of stroke etiology. Methods This is a retrospective hypothesis testing study. Patients aged 18 or over who had middle cerebral artery occlusion symptoms with HMCAS with verification on brain NCCT and received intravenous thrombolysis between January 2016 and June 2019 were enrolled. The demographic data, clinical outcomes, stroke subtypes, and characteristics of HMCAS were collected from medical records. Results Ninety-nine out of 299 enrolled patients presented with HMCAS. The most common stroke subtype was cardioembolism (59%). Of the baseline characteristics, hypertension was more common in cases of large-artery atherosclerosis (LAA) (86.4%), and atrial fibrillation (AF) was the highest in cardioembolism (44.8%). HMCAS disappearance in cardioembolism was lowest compared to LAA and others (63% vs. 91% vs. 94.7%, respectively). The univariable analysis found that HMCAS disappearance is significantly associated with all stroke subtypes (Odds ratio, 95% confidence interval 10.58, 1.31-85.43; P = 0.027 for other and 5.88, 1.24-27.85; P = 0.026 for LAA). Multinomial logistic regression found that body weight and hypertension were associated with the LAA subtype. AF and intracranial hemorrhage (ICH) were associated with cardioembolism. Conclusion The most likely diagnosis from the presence of HMCAS is cardioembolism, but the definite stroke etiologic subtype can not be identified. Combining the patient risk factors, including body weight, hypertension, and AF, with HMCAS and its characteristics will predict stroke subtypes more accurately.

Treatment of Early-onset Scoliosis: Similar Outcomes Despite Different Etiologic Subtypes in Traditional Growing Rod Graduates.

It is unclear whether traditional growing rod (TGR) treatment outcomes vary by early-onset scoliosis (EOS) subtype. The goal of this study was to compare radiographic outcomes and complications of TGR treatment by EOS subtype. We queried an international database of EOS patients from 20 centers to identify "graduates" who had (1) undergone primary TGR treatment from 1993 to 2014; (2) completed TGR treatment; and (3) had an uneventful clinical examination within 6 months after completion of TGR treatment with no anticipated further intervention. We included 202 patients in 4 etiologic subgroups: neuromuscular (n=65), syndromic (n=57), idiopathic (n=52), and congenital (n=28). Mean age at surgery was 7.1 years (range, 1.6 to 14.9 y); mean duration of follow-up was 8 years (range, 2 to 18.6 y). The groups did not differ by mean age, body mass index, sex, number of lengthenings, or duration of follow-up. The following preoperative differences were significant: (1) greater mean major curve in the neuromuscular versus idiopathic subgroup; (2) shorter spinal height (T1-S1) in the congenital versus idiopathic subgroup; and (3) smaller proportion of ambulatory patients in the neuromuscular subgroup versus all other subgroups. We found no significant differences among subgroups in mean major curve correction or changes in thoracic height (T1-T12), spinal height, or global kyphosis at any point. Rates of deep surgical site infection, implant-related complications, and neurological complications were not different among subgroups. The medical complication rate was significantly lower in the idiopathic group compared with the other groups. Major curve correction and spinal and thoracic height increases did not differ significantly at any point by EOS subtype. Rates of deep surgical site infection, implant-related complications, and neurological complications did not differ by subtype. Except for the lower rate of medical complications in the idiopathic group, our findings suggest that, after TGR treatment, patients can expect similar outcomes regardless of their EOS subtype. Level III, therapeutic.

Classifying etiology of infantile spasms syndrome in resource-limited settings: A study from the South Asian region.

ObjectiveEtiological classification of infantile spasms syndrome (ISS) is important, considering the influence on prognosis based on the presence or absence of a known etiology. This study was performed to describe the limitations and difficulties experienced within the South Asian region when classifying the etiology of ISS according to the current recommendation.MethodData on healthcare indices and facilities related to management of ISS for the nine countries in the South Asian region were gathered by the South Asian West Syndrome Research Group. A Google survey was performed among three hundred and thirty pediatric neurologists in the region. The capacity within each country for investigating etiology of ISS according to current described benchmarks was evaluated. The difficulties experienced in this regard and the potential solutions were investigated.ResultsOne hundred and sixty pediatric neurologists (response rate 48%) from Bangladesh (19/25), India (94/255), Myanmar (11/11), Nepal (6/8), Pakistan (19/25), and from Sri Lanka (7/8) responded. Three countries had no pediatric neurology services. Fifty‐six percent attempted to classify ISS etiology according to classification outlined by International League Against Epilepsy in 2017. The facilities to perform metabolic, genetic, and immunological investigations were very limited. Lack of funding for investigations and poor laboratory support were the two most frequent barriers encountered. Sixty percent indicated that a separate classification is suitable for low‐income setting; 78% suggested inclusion of separate category as “incompletely investigated” as an alternative solution to mitigate the barrier of achieving a better understanding of the etiological subtypes seen more frequently in this region.SignificanceThe resources in South Asian region are limited to meet the recommendations for investigating etiology of ISS. Including the etiological subcategory “incompletely investigated” is proposed as an alternative to understand the true proportions of children in this region, with a definite known etiology and those with an unknown etiology.

Thrombophilia and recurrence ischemic stroke in young adults

Ischemic stroke (IS) in young adults is a serious medical problem due to its potential socio-economic consequences. The risk of recurrence is highest 22% in the first year and 53% in the following five years. Moreover, recurrent stroke is the leading cause of disability and death. Data on long-term survival and recurrence after stroke are missing. We studied temporal trends in 5-year ischemic stroke case fatality and recurrence rates stratified by etiological subtype according to the ORG 10172 trial classification in acute stroke treatment (TOAST).

Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimer's disease

Amyloid beta (Aβ) deposition in the neocortex is a major hallmark of Alzheimer's disease (AD), but the extent of deposition does not readily explain phenotypic diversity and rate of disease progression. The prion strain–like model of disease heterogeneity suggests the existence of different conformers of Aβ. We explored this paradigm using conformation-dependent immunoassay (CDI) for Aβ and conformation-sensitive luminescent conjugated oligothiophenes (LCOs) in AD cases with variable progression rates. Mapping the Aβ conformations in the frontal, occipital, and temporal regions in 20 AD patients with CDI revealed extensive interindividual and anatomical diversity in the structural organization of Aβ with the most significant differences in the temporal cortex of rapidly progressive AD. The fluorescence emission spectra collected in situ from Aβ plaques in the same regions demonstrated considerable diversity of spectral characteristics of two LCOs—quatroformylthiophene acetic acid and heptaformylthiophene acetic acid. Heptaformylthiophene acetic acid detected a wider range of Aβ deposits, and both LCOs revealed distinct spectral attributes of diffuse and cored plaques in the temporal cortex of rapidly and slowly progressive AD and less frequent and discernible differences in the frontal and occipital cortex. These and CDI findings indicate a major conformational diversity of Aβ accumulating in the neocortex, with the most notable differences in temporal cortex of cases with shorter disease duration, and implicate distinct Aβ conformers (strains) in the rapid progression of AD.

658Familial aggregation of melanoma by anatomic site of occurrence

Abstract Background Evidence is emerging that melanoma has distinct etiologic pathways and subtypes, characterized by factors like anatomic site. For example, older men have more head and neck melanomas, and younger women more leg melanomas. Family history is a strong risk factor and familial risk genes have been identified. We therefore aimed to investigate familial aggregation of melanoma from an etiologic heterogeneity perspective, to determine whether melanoma subtypes aggregate within families. Methods Using population-level linked health data, we examined the extent to which melanomas in first-degree relatives (FDRs) of cases shared the same body site of occurrence. FDR-pairs diagnosed with melanoma were identified using the Western Australian Cancer Registry and genealogical Family Connections System. Site was categorized as head/neck, trunk/arms, or legs. We identified 1,006 pairs of tumours from 677 family pairs and used Chi-Squared tests to evaluate familial aggregation by site. Degrees of etiologic heterogeneity of individual site-pairs were characterized by site concordance odds ratios. Results Familial aggregation by site was statistically significant (P = 0.01). However, only the site pairings of head/neck versus trunk/arms showed strong evidence of familial concordance (OR = 1.7, 95% CI 1.1-1.7). Trends were broadly similar in same-sex pairs. Conclusions Results show modest evidence of familial aggregation of melanoma by site, with overall evidence of aggregation but inconsistent patterns between sites. Key messages Strong etiologic differences in incidence between anatomic sites for age and sex may be more strongly influenced by non-genetic factors, such as familial patterns of sun exposure.

Detection of Morphological Abnormalities in Schizophrenia: An Important Step to Identify Associated Genetic Disorders or Etiologic Subtypes.

Current research suggests that alterations in neurodevelopmental processes, involving gene X environment interactions during key stages of brain development (prenatal period and adolescence), are a major risk for schizophrenia. First, epidemiological studies supporting a genetic contribution to schizophrenia are presented in this article, including family, twin, and adoption studies. Then, an extensive literature review on genetic disorders associated with schizophrenia is reviewed. These epidemiological findings and clinical observations led researchers to conduct studies on genetic associations in schizophrenia, and more specifically on genomics (CNV: copy-number variant, and SNP: single nucleotide polymorphism). The main structural (CNV) and sequence (SNP) variants found in individuals with schizophrenia are reported here. Evidence of genetic contributions to schizophrenia and current knowledge on genetic syndromes associated with this psychiatric disorder highlight the importance of a clinical genetic examination to detect minor physical anomalies in individuals with ultra-high risk of schizophrenia. Several dysmorphic features have been described in schizophrenia, especially in early onset schizophrenia, and can be viewed as neurodevelopmental markers of vulnerability. Early detection of individuals with neurodevelopmental abnormalities is a fundamental issue to develop prevention and diagnostic strategies, therapeutic intervention and follow-up, and to ascertain better the underlying mechanisms involved in the pathophysiology of schizophrenia.

Etiology and risk factors of intracranial hemorrhage and ischemic stroke in young adults.

Young stroke incidence has increased worldwide with lifestyle changes. Etiology and risk factors for both ischemic and hemorrhagic stroke in young Asians remain underexplored. We retrospectively reviewed consecutive acute stroke patients aged 16-45 years admitted to the Taipei Veterans General Hospital between 2009 and 2019 to analyze etiologic subtypes, risk factors, and serial modified Rankin Scale scores for 1 year and compare the age groups of 16-30 and 31-45 years. Among 670 young Taiwanese patients (mean age at onset 37.5 ± 7.0 years; male 65.1%), there were 366 nontraumatic spontaneous hemorrhagic stroke (including 259 intracerebral hemorrhage [ICH] and 107 subarachnoid hemorrhage, SAH), 292 ischemic stroke and 12 cerebral venous thromboses. Notably, ICH was more prevalent in patients aged 16-30 than in those aged 31-45 (54.8% vs 36.8%). Specifically, structural vasculopathy (e.g., arteriovenous malformation, cavernoma) was the most common etiologic subtype in patients aged 16-30 (p < 0.001), whereas hypertensive ICH was the most common subtype in patients aged 31-45 (p < 0.001). On the other hand, the top ischemic subtype for both age groups was other determined diseases (e.g., arterial dissection, autoimmune diseases, moyamoya disease, etc.) rather than large artery atherosclerosis. Hyperlipidemia, diabetes, and cigarette smoking were more common risk factors for infarction than ICH. Familial stroke patients whose first- or second-degree relatives had a stroke by age 80 (n = 104, 15.5%) had more infarctions than those without a familial stroke history. In multivariate analyses, initial stroke severity, and infarction type were important predictors of favorable outcomes after 3 months. At the 1-year follow-up, patients with ICH and SAH had worse functional outcomes and survival rates than those with infarction. An aggressive approach to elucidate the etiology of stroke is indicated because structural vasculopathy-induced ICH and other determined infarction are distinctively prevalent in young adults, particularly those aged 16-30.

Abstract 876: TP53 pathway function, estrogen receptor status, and breast cancer risk factors in the Carolina Breast Cancer Study

Abstract Purpose: TP53 and estrogen receptor (ER) both play essential roles in breast cancer development and progression, with recent research revealing crosstalk between TP53 and ER signaling pathways. While many studies have demonstrated heterogeneity of risk factor associations across ER subtypes, TP53 status has been inconsistently linked to breast cancer risk factors. This may be due to few studies evaluating TP53 effects in the context of ER. Additionally, studies have generally classified TP53 status using immunohistochemistry (IHC) staining or DNA sequencing, which are prone to misclassification of TP53 pathway function. RNA-based methods of measuring TP53 pathway activity may reduce misclassification and clarify etiologic associations. Methods: This case-only analysis included 4,466 incident breast cancer cases from the Carolina Breast Cancer Study (1993-2013). Using RNA expression previously quantified using NanoString assays on FFPE tumor samples, tumors were classified for TP53 functional status (mutant-like or wildtype-like) using a validated 52-gene RNA signature. We used a two-stage polytomous logistic regression model to evaluate sources of risk factor heterogeneity due to RNA-based TP53 or ER, adjusting for each other and for PR, HER2, and grade, while accounting for missing tumor marker data. Risk factor heterogeneity was also evaluated for IHC-based TP53 and ER. For each risk factor, joint effects of TP53 and ER were evaluated by allowing for an interaction between the two markers. Results: When classifying TP53 status using the RNA signature, the effects of several hormone-related factors (oral contraceptive use, menopausal status, age at menopause, and pre- and post-menopausal BMI) were heterogeneous across TP53 subtypes, while heterogeneity of reproductive factors (age at first birth and parity) and smoking status was observed across ER subtypes. The effect of number of births was heterogenous across both TP53 and ER-based subtype definitions. Additionally, we observed an interaction between RNA-based TP53 and ER status with family history of breast cancer in a first-degree relative (p=0.05). When classifying TP53 status using IHC, the TP53 effects were not recapitulated but there was minimal change in the ER effects. We observed an interaction between IHC-based TP53 and ER status with age at menarche (p=0.02), smoking status (p=0.05), and alcohol use (p=0.06). Conclusions: This study demonstrates that TP53 and ER are valuable for defining etiologic subtypes of breast cancer, although IHC measures may not have as much value as RNA. Analyses of the joint effects of TP53 and ER with breast cancer risk factors revealed intriguing findings that could lead to new hypotheses. However, larger studies incorporating multiple correlated tumor characteristics will be required to confirm our findings to conclusively define etiologically relevant subtypes of breast cancer. Citation Format: Amber N. Hurson, Mustapha Abubakar, Kathleen Conway-Dorsey, Katherine Hoadley, Michael I. Love, Andrew F. Olshan, Montserrat Garcia-Closas, Melissa A. Troester. TP53 pathway function, estrogen receptor status, and breast cancer risk factors in the Carolina Breast Cancer Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 876.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2-Evidence Base and Standardized Methods of Imaging.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 1 of 2-Evidence Base and Standardized Methods of Imaging.

Etiologic Subtypes, Risk Factors and Early Outcome of Acute Ischemic Stroke in Females

Etiologic Subtypes, Risk Factors and Early Outcome of Acute Ischemic Stroke in Females

Modifiable and Non-Modifiable Risk Factors for Atherothrombotic Ischemic Stroke among Subjects in the Malmö Diet and Cancer Study.

Risk factors for ischemic stroke is suggested to differ by etiologic subtypes. The purpose of this study was to examine the associations between modifiable and non-modifiable risk factors and atherothrombotic stroke (i.e., excluding cardioembolic stroke), and to examine if the potential benefit of modifiable lifestyle factors differs among subjects with and without predisposing comorbidities. After a median follow-up of 21.2 years, 2339 individuals were diagnosed with atherothrombotic stroke out of 26,547 study participants from the Malmö Diet and Cancer study. Using multivariable Cox regression, we examined non-modifiable (demographics and family history of stroke), semi-modifiable comorbidities (hypertension, dyslipidemia, diabetes mellitus and atherosclerotic disease), and modifiable (smoking, body mass index, diet quality, physical activity, and alcohol intake) risk factors in relation to atherothrombotic stroke. Higher age, male gender, family history of stroke, and low educational level increased the risk of atherothrombotic stroke as did predisposing comorbidities. Non-smoking (hazard ratio (HR) = 0.62, 95% confidence interval (CI) 0.56–0.68), high diet quality (HR = 0.83, 95% CI 0.72–0.97) and high leisure-time physical activity (HR = 0.89, 95% CI 0.80–0.98) decreased the risk of atherothrombotic ischemic stroke independent of established risk factors, with non-significant associations with body mass index and alcohol intake. The effect of the lifestyle factors was independent of predisposing comorbidities at baseline. The adverse effects of several cardiovascular risk factors were confirmed in this study of atherothrombotic stroke. Smoking cessation, improving diet quality and increasing physical activity level is likely to lower risk of atherothrombotic stroke in the general population as well as in patient groups at high risk.

Stroke Mechanism in COVID-19 Infection: A Prospective Case-Control Study

BackgroundThe characteristics and pathophysiological mechanisms involved in acute ischemic stroke in patients with COVID-19 infection have not been fully clarified. We prospectively studied the phenotypic and etiological features of acute stroke occurring in COVID-19 infection. Patients & methodsWithin nine months starting from April-2020, the presence of COVID-19 infection was determined by thoracic CT and SARS-CoV-2 PCR in all acute stroke cases managed in a single tertiary center. Consecutive and prospective data on vascular risk factors/comorbidities, in-hospital quality metrics, discharge outcomes, etiological subclassification and blood markers of thrombosis / inflammation were compared in 44 COVID-19 positive cases (37 acute ischemic stroke, 5 TIA, 2 intracerebral hematoma) and 509 COVID-19 negative patients (355 ischemic, 105 TIA, 44 hematoma and 5 stroke mimic). ResultsCOVID-19 positive patients had more severe strokes, delayed hospital admission, longer hospital stay, higher mortality rates, but had similar vascular risk factors/comorbidities frequency, thrombolysis/thrombectomy utilization rates, metrics, and stroke etiological subtype. They had significantly higher CRP, fibrinogen, ferritin, leukocyte count and lower lymphocyte count. No difference was detected in aPTT, INR, D-dimer, platelet, hemoglobin, homocysteine levels and ANA, anti-dsDNA antibody and ENA panel positivity rates. Anti-phospholipid antibodies have been studied in 70% of COVID-19 positive and all cryptogenic patients, but were never found positive. Tests for coagulation factor levels and hereditary thrombophilia did not show major thrombophilia in any of the stroke patients with COVID-19. ConclusionWe documented that there is no significant difference in etiological spectrum in acute stroke patients with COVID-19 infection. In addition, cryptogenic stroke and antiphospholipid antibody positivity rates did not increase.

Fibroblast Growth Factor 19 is an Independent Prognostic Parameter for Hepatocellular Carcinoma Recurrence

Background: Hepatocellular carcinoma (HCC) remains a common cancer associated with a high mortality rate. Genes that drive HCC development accumulate randomly that could be a target for therapeutic management. In large-scale studies, the dysregulation of fibroblast growth factors (FGFRs) was detected in over 7% of cancers and served as an oncogenic signalling pathway. Amplification of FGF19 was found to be associated with the development of HBV and NAFLD related HCC with an ongoing clinical trial for targeting this pathway. Therefore, we aimed to study FGF19 in HCV related HCC and to compare its expression within the two main morphological patterns. Material and methods: This was a retrospective, case-control study that included 76 HCC cases and 53 adjacent non-tumour liver, 20 cirrhosis and 20 normal liver tissue as normal control. The Immunohistochemical expression turned into assessed in the studied groups. Results: FGF19 was expressed in 26.3% of HCC cases with no significant difference in its expression between two HCC subgroups (P=0.073). The expression of FGF19 was not differed in the HCC group according to the aetiology (P=0.605), prior HCV treatment (P=0.912) or background liver cirrhosis (P=0.931). The only factor increased FGF19 expression with the marked inflammatory activity of the background liver (P=0.026). COX regression analysis revealed that FGF19 was the single independent factor affecting tumour recurrence (P=0.04). Conclusions: FGF19 is commonly expressed in HCC cases independent from the etiological, background liver or morphological subtypes. FGF19 could be used as an indicator to predict tumour recurrence.

Hyperbilirubinemia and Asphyxia in Children With Dyskinetic Cerebral Palsy

BackgroundWe aimed to study the clinical, etiologic, and radiological characteristics in children with dyskinetic cerebral palsy (DCP) and to compare the etiologic subtypes of hyperbilirubinemia and perinatal asphyxia. MethodsThis is a cross-sectional, observational study that enrolled consecutive children with DCP, aged one to 14 years. ResultsSixty-five children with DCP were evaluated. Most children were boys (77%, n = 50), and term gestation (80%, n = 52). Presenting concerns were global developmental delay (97%, n = 63) and involuntary movements (60%, n = 39). Hyperbilirubinemia (66%, n = 43) and perinatal asphyxia (29%, n = 19) were the most important causes. The majority (83%, n = 54) of children were severely disabled (level V and IV). The hyperbilirubinemia group had significant motor delay (63% vs 37%, P = 0.03) and upward gaze palsy (69.7% vs 31.5%, P = 0.005) when compared with the perinatal asphyxia group. Hyperbilirubinemia significantly involved pallidi (86% vs 10% P = 0.0001) and subthalamic nucleus (26% vs none, P = 0.01), whereas asphyxia significantly involved the putamen (58% vs none, P = 0.0001), thalamus (63% vs none, P = 0.0001), and periventricular white matter (79% vs 19%, P = 0.0001). ConclusionsDCP is the dominant type of cerebral palsy seen in term-born babies with severe dystonia, developmental delay, and motor impairment. Hyperbilirubinemia is the major cause of DCP in the study. Hyperbilirubinemia is associated with motor delay, upward gaze palsy, prominent dystonia, and involvement of globus pallidi and subthalamic nuclei.

Abstract P720: Primary Stroke Prevention by Primary Care Providers: An Unmet Need

Introduction: The majority of patients who present with acute ischemic stroke (AIS) have known stroke risk factors which are not optimally managed. It has been suggested that a CHADS-VASC score can assist with primary prevention by calculating future stroke risk. This however, has not been widely adapted in the primary care setting. Methods: From 2018-2019, 686 AIS patients were included in retrospective analysis. Data elements included: historical stroke risk factors, historical CHADS-VASC score, antiplatelet/anticoagulant use at time of presentation, discharge location, and mRS. Results: Of the 686 AIS patients, 77% were age &gt; 60, and 52% were male. Etiology subtypes were small vessel/lacunar 20%, large vessel 22%, cardioembolic 20%, undetermined 31% (cryptogenic 15%), and other determined 5%. On presentation, the majority of patients had 2 or more stroke risk factors and a calculated historical CHADS-VASC score &gt; 2 (Table 1). Over half of the patients with large vessel or small vessel/lacunar etiology were not on any antiplatelets and 53% of patients with known history of atrial fibrillation weren’t on anticoagulants. Forty-nine percent of patients had a mRS &gt; 3 at discharge. Conclusion: Patients with several stroke risk factors are sub optimally managed by primary care providers. Primary prevention education for PCPs in management of higher stroke risk individuals and additional analysis of the CHADS-VASC tool for this setting is needed. If widely adapted, this tool may prevent strokes by providing adequate risk reduction in the primary care setting.

Abstract P653: Intracranial Artery Calcification Variations by Stroke Subtypes

Introduction: Intracranial artery calcification (IAC) is a common radiological finding on Computed Tomography (CT) scan. Although IAC occurs with aging, it is uncertain whether IAC varies by stroke subtypes. Method: We included patients admitted to our hospital with acute stroke. We quantified calcification volume of both clinoid and siphon carotid arteries, vertebral arteries at the V4 segment, and the basilar artery using an in-house quantification tool for non-contrast brain CT. Stroke etiological subtypes were determined according to the Trial of Organon in Acute Stroke Trial (TOAST) classification system independent of the calcification quantification. Demographic and clinical information was extracted from the medical records. We determined the prevalence of IAC in 51% of patients. (31% anterior, 7% posterior, and 14 % in both circulations) Result: We included 694 patients with stroke history (mean age 68 ± 16, range 21-101, 55% women, 71% nonwhite or mixed). IAC was associated with male sex (OR 1.47 [95%-CI 1.41-2.08), older age (OR 1.05 [95%-CI, 1.04-1.06]), hypertension (OR 1.55 [95%-CI, 1.01-2.36], dyslipidemia (OR 1.54 [95%-CI, 1.06-2.25]), and smoking (OR 1.79 [95%-CI, 1.18-2.71]). Anterior IAC was associated with dyslipidemia (OR 1.57 [95%-CI, 1.08-2.28], smoking (1.9 [95%-CI, 1.25-2.88]), and older age (OR 1.05 [95%-CI, 1.36-1.66). Posterior IAC was associated with myocardial infarction (OR 1.58 [95%-CI, 1.01-2.47] and older age (OR 1.02 [95%-CI, 1.01-1.03]. In multivariate analyses, any IAC was associated with small artery disease stroke (OR 1.01[95%-CI, 1.41-3.98]). Stratifying by circulations, however, demonstrated that the association was only with posterior (OR 1.22[95%-CI, 1.02-2.28]) and not anterior IAC (OR 1.20[95%-CI, 0.86-1.1.69]). There was no association between IAC and intracranial large artery stenoses OR (1.22[95%-CI, 0.78-1.1.92]). Conclusion: IAC is a marker of arterial disease, and its prevalence relates to vascular risk factors and small artery disease strokes. Understanding the mechanism by which IAC may relate to small artery disease may help us understand small artery stroke physiopathology and discover novel therapies for its treatment.

Phospholipase A2 and Ischemic Stroke Etiology.

Lipoprotein-associated phospholipase A2 (Lp-PLA2), which is involved in the inflammatory atherosclerotic process, has emerged as an independent risk factor for atheromatous vascular events. Its impact on coronary disease has already been demonstrated, however, its influence in cerebrovascular etiology is still unknown. We aimed to observe and describe the potential association between Lp-PLA2 levels and the etiologic subtype of ischemic stroke. Unicentric, observational, and prospective cohort study of consecutive patients with acute ischemic stroke, admitted in a comprehensive stroke center. Patients with incomplete investigation or coexisting causes were excluded. Lp-PLA2 was dosed in peripheral blood between day 3 and 14 postevent with "Lp-PLA2-SNIBE" kit. Statistical significance was set for P<0.05. A total of 96 patients were enrolled, with mean age of 75.31±11.88 years, 41 males (42.7%); 12.5% with lacunar stroke, 16.7% atherothrombotic, 46.9% cardioembolic, and 24% embolic stroke of undetermined source (ESUS). The level of Lp-PLA2 was different between etiologies (F=2.982, P=0.035), being lower in ESUS (143.3±42.8 ng/mL). There were no significant associations with previous vascular risk factors, history of ischemic stroke and modified-Rankin scale (mRS) score 3 months postevent. In ESUS patients, Lp-PLA2 was not associated with cervical ultrasound findings or frequent supraventricular extrasystoles. Lp-PLA2 levels are different between etiologic subtypes of ischemic stroke, being lower in ESUS patients. The results of this study reinforce the existence of distinct pathophysiological mechanisms in patients with ESUS. Multicenter clinical trials with larger sample sizes are needed to clarify the role Lp-PLA2 on the etiology of stroke.

Advancing Personalized Medicine in Common Forms of Parkinson's Disease through Genetics: Current Therapeutics and the Future of Individualized Management.

Parkinson’s disease (PD) is a condition with heterogeneous clinical manifestations that vary in age at onset, rate of progression, disease course, severity, motor and non-motor symptoms, and a variable response to antiparkinsonian drugs. It is considered that there are multiple PD etiological subtypes, some of which could be predicted by genetics. The characterization and prediction of these distinct molecular entities provides a growing opportunity to use individualized management and personalized therapies. Dissecting the genetic architecture of PD is a critical step in identifying therapeutic targets, and genetics represents a step forward to sub-categorize and predict PD risk and progression. A better understanding and separation of genetic subtypes has immediate implications in clinical trial design by unraveling the different flavors of clinical presentation and development. Personalized medicine is a nascent area of research and represents a paramount challenge in the treatment and cure of PD. This manuscript summarizes the current state of precision medicine in the PD field and discusses how genetics has become the engine to gain insights into disease during our constant effort to develop potential etiological based interventions.