scholarly journals Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) – Still to be Considered in the Presence of Vascular Risk Factors

2020 ◽  
Vol 12 (Suppl. 1) ◽  
pp. 196-201
Author(s):  
Dinesh Naidu Ganesan ◽  
Thibault Coste ◽  
Narayanaswamy Venketasubramanian

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare hereditary vasculopathy that primarily affects the brain, caused mostly by missense mutations of the <i>NOTCH3</i> gene which is located on chromosome 19. Clinically, it manifests as transient ischemic attacks and strokes in individuals under the age of 60 years without vascular risk factors. We report a 46-year-old male with a 9 and 3-month history of progressive unilateral lower limb weakness and dysarthria, respectively. He had a history of diabetes mellitus but no hypertension, hyperlipidemia, or smoking history. Both parents had a stroke at the age of 65 years. Neurological examination was significant for moderate dysarthria and reduced right upper limb dexterity. Magnetic resonance imaging (MRI) of the brain revealed extensive white matter disease, lacunar infarcts, and a few microhemorrhages. Electron microscopy of his skin biopsy showed electron-dense deposits of extracellular osmiophilic granular material adjacent to smooth muscle cells. <i>NOTCH3</i> gene analysis revealed a heterozygous typical mutation in exon 6. He was commenced on aspirin and atorvastatin. Over time, he became more dysarthric and demented. MRI revealed the progression of the white matter disease and a new right subcortical infarct. His aspirin was switched to clopidogrel, and donepezil was added. CADASIL should be considered among younger stroke patients with vascular risk factors, especially in the presence of widespread white matter disease. Genetic counselling may be needed after the diagnosis is made.

2019 ◽  
Vol 82 (1-3) ◽  
pp. 23-31
Author(s):  
Miguel Viana-Baptista ◽  
Vera Cruz-e-Silva ◽  
André Caetano ◽  
João Pedro Marto ◽  
Elsa Azevedo ◽  
...  

Introduction: Although frequently assumed to be age-related changes, vascular white matter lesions (WML) are sometimes found in young adults. Etiology is usually attributed to sporadic small vessel disease; nevertheless, genetic disorders may also be implicated. We aimed to characterize the population of young adults with vascular WML in Neurology outpatient clinics. Methods: Neurologists from 12 Portuguese hospitals were invited to include patients aged 18–55 years evaluated in consultation, with vascular WML on MRI, scoring II or III in the Fazekas scale. Central imaging validation was performed by 2 independent, blinded, Neuroradiologists. Demographic and clinical data were collected as well as results of investigations performed. Results: During 2 years, 77 patients were included (mean age 47.7 years). Vascular risk factors were present in 88.3% patients (hypertension in 53.2%) and previous history of stroke in 36.4%. Patients without history of stroke were younger (46.6 ± 7.2 vs. 49.6 ± 3.9 years, p = 0.045) and had fewer vascular risk factors (p < 0.001). They were more frequently females (87.8 vs. 46.4%, p < 0.001), and headache (30.6 vs. 3.6%, p = 0.007), contrary to focal symptoms (16.3 vs. 53.6%, p = 0.001), was the most frequent reason of referral. Etiological investigations performed differed between Neurologists. A genetic disorder was identified in 6 out of 58 patients (CADASIL n = 5; COL4A1 n = 1). Conclusion: Young adults with vascular WML evaluated in Neurology outpatient clinics concentrate in the oldest age groups. Vascular risk factors should be screened carefully in this population. Among patients without history of stroke, females largely outweigh males. Diagnostic investigations performed do not follow a standardized protocol.


2018 ◽  
Vol 26 (2) ◽  
pp. 246-e18 ◽  
Author(s):  
L. M. Chahine ◽  
C. Dos Santos ◽  
M. Fullard ◽  
C. Scordia ◽  
D. Weintraub ◽  
...  

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Carlos Cantu-Brito ◽  
Erwin Chiquete ◽  
Jose L Ruiz-Sandoval ◽  
Fernando Flores-Silva

Background and Purpose: The objective of this study were to describe the proportion of patients eligible for the COMPASS trial among stable outpatients with either established atherothrombotic disease or major vascular risk factors, and to analyze 6-month incident stroke risk according vascular risk factors at baseline. Methods: We prospectively recruited 5,101 stable outpatients in 172 sites, within the Mexican INDAGA cohort study. Inclusion criteria were age >18 years and established atherothrombotic disease [history of either acute coronary syndromes (ACS), acute ischemic stroke (AIS)/transient ischemic attack (TIA) or peripheral artery disease (PAD)] or major vascular risk factors (age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors). Among these patients, we applied the selection criteria of the COMPASS trial for analysis, dividing the population in no COMPASS criteria met and COMPASS criteria met, and this last group subdivided among patients with previous AIS/TIA and without this antecedent, in order to stratify the risk for stroke during 6-month follow-up (incident AIS/TIA). Results: Among 5,101 stable outpatients with either established atherothrombotic disease (n=2,827) or major vascular risk factors (n=2,274), a total of 1,927 (37.8%) met COMPASS trial criteria: 1,054 (54.7%) with established cerebrovascular disease (past history of AIS/TIA) and 873 (45.3%) without. During 6-month follow-up, there were 89 incident AIS/TIA (39 AIS and 54 TIA): 1.7% among the whole population and 2.2% among the COMPASS subgroup. AIS/TIA occurred in a similar frequency among the COMPASS subgroup with established cerebrovascular disease (1.6%) and COMPASS without cerebrovascular disease (0.9%) (P=0.18). After a Cox-proportional hazards model, independent predictors of incident AIS/TIA were age ≥65 years (HR: 1.99, 95% CI: 1.29-3.07) and established cerebrovascular disease at baseline (HR: 1.61, 95% CI: 1.02-2.53). Conclusions: The majority of stable outpatients at vascular risk met COMPASS selection criteria and could be good candidates for low-dose rivaroxaban in addition to aspirin. Short-term predictors of AIS/TIA were old age and history of cerebrovascular disease


Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Rakhee Lalla ◽  
Ryan Dunlow ◽  
Karen L Yarbrough ◽  
Prachi Mehndiratta ◽  
Michael S Phipps ◽  
...  

Introduction: The AHA notes that more than 76% of strokes are the first occurrence. There are class 1 recommendations for the management of common risk factors such as atrial fibrillation (AF), hyperlipidemia (HLD), hypertension (HTN), diabetes (DM), and vascular disease. The purpose of this study is to investigate the percentage of large vessel strokes that are potentially preventable with adequate management of vascular risk factors. Methods: A retrospective chart review was conducted on all patients undergoing endovascular therapy (EVT) from 2012-2019. Data was collected on vascular risk factors present prior to admission including HTN, DM, HLD, AF, and smoking. Preventable stroke was defined as having at least one of the following: untreated AF, untreated HLD, poorly controlled HTN (presence of left ventricular hypertrophy on transthoracic echo), history of vascular disease not on an antiplatelet agent, poorly controlled DM (A1c>10), current smoking. Groups were compared based on age, sex and 90 day functional outcomes, with favorable outcome defined as mRS ≤ 2. Results: Our sample included 396 patients who underwent EVT (mean age 65, 50% female). 42% of patients with Afib were not on anticoagulation, 31% of patients with HLD were untreated, 39% of patients with HTN were poorly controlled, 27% of patients with a history of vascular disease were not on an antiplatelet, 14% of patients with DM were poorly controlled, and 46% of all patients were smokers. In total, 78% of patients had at least 1 poorly controlled risk factor and 37% had at least 2. There was no difference in rates of preventable stroke between males and females (48% vs 52%, p=0.30) and between age groups above and below 70 (40% vs 60%, p=0.68). 64% of patients with well controlled risk factors had a favorable outcome compared to 51% with at least one poorly controlled risk factor (p=0.03). Conclusions: Our data suggests that despite guidelines on management of vascular risk factors, a large number of these are poorly controlled prior to admission for large vessel stroke, leading to a potentially preventable procedure. Not only could improved primary prevention save the wide array of resources utilized in EVT, but it could also influence long term outcomes in this cohort of patients.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Daphne Antillon ◽  
Natalie Valle ◽  
Kaiwen Lin ◽  
Waimei Tai ◽  
Mary Ann Gallup ◽  
...  

Background: Recent nationally representative studies of stroke patients have revealed that vascular risk factors are not as aggressively controlled in women compared to men. Medically underserved minority populations are at particularly high risk for poor control of vascular risk factors; however, little is known about sex differences in this population. Methods: Sex-specific vascular risk factors and admission medications were assessed for 440 consecutive ischemic stroke patients (39% female) admitted to a safety-net public hospital in Los Angeles County. Multivariate logistic regression was used to determine sex differences in vascular risk factors, adjusting for age and race. Results: The mean age was 58.9 (SE 10.6) years, 58% were Hispanic, 7% were white, 13% were black, 20% were Asian, and 1% were Native American. Stroke classification (using modified TOAST) revealed the following distribution: 35% small vessel, 20% large vessel, 7% cardioembolic, 23% cryptogenic, 13% >1 possible etiology, and 3% other mechanisms (e.g. drug use). Women had higher mean glycosylated hemoglobin levels than men (8.0% vs 7.4%, p<0.01) and were more likely than men to have a history of type 2 diabetes (49% vs. 40% male, p=0.04), systolic blood pressure > 140 mm Hg (72% vs. 62%, p=0.03), total cholesterol > 200 mg/dL (46% vs. 36%, p=0.04), and low HDL levels (<40 mg/dL for men and <50 mg/dL for women)(83% vs. 79%, p <0.01). Men were more likely than women to have a previous history of stroke (19% vs. 13%, p = 0.05), smoking (49% vs 19%, p<0.01), and alcohol abuse (28% vs. 7%, p<0.01). After adjustment for race and age, women were more likely than men to have total cholesterol > 200 mg/dL (OR 1.56, 95% CI 1.05-2.31), BMI ≥ 30 kg/m 2 (OR 1.55, 95% CI 1.03-2.34), systolic blood pressure >140 mm Hg (OR 1.46, 95% CI 0.96-2.22), low HDL (1.26, 95% CI 0.76-2.08), and triglyceride level > 150 mg/dL (OR 1.09, 95% CI 0.74-1.63); however, the latter 3 were not significant. After adjustment for race and age, men were more likely than women to have a history of smoking (OR 4.54, 95% CI 2.78-7.14) and alcohol abuse (OR 5.56, 95% CI 2.86-11.11). Conclusions: In this multi-ethnic population with inadequate access to care, women are more likely than men to have obesity, hypertension, and dyslipidemia while men are more likely than women to smoke or abuse alcohol. Larger studies are necessary to validate these findings. In the meantime, interventions aimed at reducing the incidence of metabolic syndrome components among women and smoking and alcohol abuse among men in underserved communities are likely warranted.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Anne-Katrin Giese ◽  
Markus D Schirmer ◽  
Adrian V Dalca ◽  
Ramesh Sridharan ◽  
Lisa Cloonan ◽  
...  

Introduction: White matter hyperintensity (WMH) is a highly heritable trait and a significant contributor to stroke risk and severity. Vascular risk factors contribute to WMH severity; however, knowledge of the determinants of WMH in acute ischemic stroke (AIS) is still limited. Hypothesis: WMH volume (WMHv) varies across AIS subtypes and is modified by vascular risk factors. Methods: We extracted WMHv from the clinical MRI scans of 2683 AIS subjects from the MRI-Genetics Interface Exploration (MRI-GENIE) study using a novel fully-automated, volumetric analysis pipeline. Demographic data, stroke risk factors and stroke subtyping for the Causative Classification of Stroke (CCS) were performed at each of the 12 international study sites. WMHv was natural log-transformed for linear regression analyses. Results: Median WMHv was 5.7cm 3 (interquartile range (IQR): 2.2-12.8cm 3 ). In univariable analysis, age (63.1 ± 14.7 years, β=0.04, SE=0.002), prior stroke (10.2%, β=0.66, SE=0.08), hypertension (65.4%, β=0.75, SE=0.05), diabetes mellitus (23.1%, β=0.35, SE=0.06), coronary artery disease (17.6%, β=0.04, SE=0.002), and atrial fibrillation (14.6%, β=0.48, SE=0.07) were significant predictors of WMHv (all p<0.0001), as well as smoking status (52.2%, β=0.15, SE=0.05, p=0.005), race (16.5% Non-Caucasian, β=0.25, SE=0.07) and ethnicity (8.2% Hispanic, β=0.30, SE=0.11) (all p<0.01). In multivariable analysis, age (β=0.04, SE=0.002), prior stroke (β=0.56, SE=0.08), hypertension (β=0.33, SE=0.05), smoking status (β=0.16, SE=0.05), race (β=0.42, SE=0.06), and ethnicity (β=0.34, SE=0.09) were independent predictors of WMHv (all p<0.0001), as well as diabetes mellitus (β=0.13, SE=0.06, p=0.02). WMHv differed significantly (p<0.0001, unadjusted) across CCS stroke subtypes: cardioembolic stroke (8.0cm 3 , IQR: 4.2-15.4cm 3 ), large-artery stroke (6.9cm 3 , IQR: 3.1-14.7cm 3 ), small-vessel stroke (5.8cm 3 , IQR: 2.5-13.5cm 3 ), stroke of undetermined (4.7cm 3 , IQR: 1.6-11.0cm 3 ) or other (2.55cm 3 , IQR: 0.9-8.8cm 3 ) causes. Conclusion: In this largest-to-date, multicenter hospital-based cohort of AIS patients with automated WMHv analysis, common vascular risk factors contribute significantly to WMH burden and WMHv varies by CCS subtype.


2013 ◽  
Vol 333 ◽  
pp. e254-e255
Author(s):  
A. Amintaeva ◽  
M. Kravchenko ◽  
O. Andreeva ◽  
Y. Varakin ◽  
G. Gornostaeva ◽  
...  

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