Frequency Of Vascular Risk Factors Research Articles

Social determinants of health but not global genetic ancestry predict dementia prevalence in Latin America.

Leveraging the nonmonolithic structure of Latin America, which represents a large variability in social determinants of health (SDoH) and high levels of genetic admixture, we aim to evaluate the relative contributions of SDoH and genetic ancestry in predicting dementia prevalence in Latin American populations. Community-dwelling participants aged 65 and older (N=3808) from Cuba, Dominican Republic, Mexico, and Peru completed the 10/66 protocol assessments. Dementia was diagnosed using the cross-culturally validated 10/66 algorithm. Multivariate linear regression models adjusted for SDoH were used in the main analysis. This study used cross-sectional data from the 1066 population-based study. Individuals with higher proportions of Native American (>70%) and African American (>70%) ancestry were more likely to exhibit factors contributing to worse SDoH, such as lower educational levels (p<0.001), lower socioeconomic status (p<0.001), and higher frequency of vascular risk factors (p<0.001). After adjusting for measures of SDoH, there was no association between ancestry proportion and dementia probability, and ancestry proportions no longer significantly accounted for the variance in cognitive performance (African predominant p=0.31 [-0.19, 0.59] and Native predominant p=0.74 [-0.24, 0.33]). The findings suggest that social and environmental factors play a more crucial role than genetic ancestry in predicting dementia prevalence in Latin American populations. This underscores the need for public health strategies and policies that address these social determinants to effectively reduce dementia risk in these communities. Countries in Latin America express a large variability in social determinants of health and levels of admixture. After adjustment for downstream societal factors linked to SDoH, genetic ancestry shows no link to dementia. Population ancestry profiles alone do not influence cognitive performance. SDoH are key drivers of racial disparities in dementia and cognitive performance.

2.Cerebrovascular neuropathology in the brains of people with Down syndrome

AbstractBackgroundPeople with Down syndrome (DS) are at genetic risk of developing early‐onset Alzheimer’s disease (AD). By age 40 years, virtually all people with DS develop beta amyloid plaques and tau neurofibrillary tangles, typically followed by the development of AD dementia over a decade later. Despite having a low frequency of vascular risk factors (i.e., hypertension, atherosclerosis), people with DS show an age‐related progression of cerebral amyloid angiopathy (CAA), white matter hyperintensities, microbleeds, micro infarcts, and enlarged perivascular spaces by neuroimaging. Interestingly, the incidence of CAA at autopsy is significantly higher in people with DS than patients with late onset AD. Our main objective is to investigate the cerebrovascular pathology in DS autopsy cases.MethodFree floating 30 µm thick sections from the occipital cortex of DS cases with or without AD pathology (DSAD and DS, respectively, n = 5/group) were compared to age matched cognitively normal controls (n = 5). Sections were immunostained for collagen IV (basement membranes) and for fibrinogen (protein extravasation).ResultPreliminary results show that compared to controls, DSAD brains have impaired vascular integrity, observed as reduced collagen IV basement membrane labeling and evidence of protein extravasation which may reflect microbleeds observed using in vivo neuroimaging.ConclusionOur preliminary data suggest a disruption of blood vessel basement membranes observed as losses in collagen IV immunostaining in DSAD brains. Moreover, fibrinogen extravasation was consistently observed in DSAD brains. We are currently characterizing the age of onset of collagen IV disruption/losses and fibrinogen leakage into the brain parenchyma in the context of an AT(N) framework to understand when in AD progression, cerebrovascular pathology evolves in DS.

Blood‐brain barrier neuropathology in individuals with Down syndrome and Alzheimer’s disease

AbstractBackgroundIndividuals with Down syndrome (DS) are the largest population at genetic risk of developing early‐onset Alzheimer’s disease (AD). Throughout their lifespan, individuals with DS develop the spectrum of AD neuropathology. By 40 years of age, mature amyloid beta plaques and tau neurofibrillary tangles are present in DS brains, followed by the development of AD dementia. Despite having a low frequency of vascular risk factors (i.e., hypertension, atherosclerosis), individuals with DS display significant cerebrovascular pathology, including cerebral amyloid angiopathy, increased white matter hyperintensities, microbleeds, microinfarcts, and enlarged perivascular spaces. Such pathological changes suggest that the blood‐brain barrier (BBB) undergoes neuropathological alterations and may be associated with the development of AD pathology, in DS. Nevertheless, BBB integrity has not been studied in DS. Our main objective is to investigate BBB pathology in the brains of people with DS and AD (DSAD).MethodPost‐mortem brain tissue was obtained from the ABC‐DS study, NIH Neurobiobank, and BrightFocus Foundation. BBB components (basement membrane, endothelial cells, pericyte cell number) and BBB leakage were assessed by free‐floating immunohistochemistry in human brain tissue sections from the occipital cortex of individuals with DSAD (49‐55 years old), and their age‐matched neurotypical controls (48‐57 years old). Brain sections were digitized, and BBB components and vessel morphology were quantified using ImageJ.ResultOur preliminary data suggest that, compared to age‐matched controls, adults with DSAD have a lower number of pericytes and lower Collagen‐IV load. A proportion of DSAD cases also had lower endothelial cell coverage and shorter blood vessels. Moreover, fibrinogen leakage was observed in the brain parenchyma of DSAD brains. Interestingly, some individuals with DSAD displayed no BBB pathological changes.ConclusionIndividuals with DS have pathological alterations in the BBB. However, some people with DSAD may be resilient to such changes. Studies are ongoing to determine if BBB changes in DS are associated with the development and progression of AD neuropathology.

Vascular Schizophrenia-like Psychosis in Older Adults.

The aims of this study were to analyze prevalence and severity of vascular risk factors in older patients referred to our clinic due to onset of Very Late-Onset Schizophrenia-Like Psychosis (VLOSLP) and to create a specific phenotype based on pathophysiological insight rather than age of onset. In a longitudinal study, 103 (M = 39, F = 64; mean age of 80.32 ± 7.65 years) patients were evaluated with cognitive, neuropsychiatric, and functional assessment scales. Blood concentration of hemoglobin (Hb), mean corpuscular volume (MCV), platelets, total protein test (TPT), creatinine, azotemia, glycemia, total cholesterol (TC), triglycerides (TG), uric acid (UA), sodium (Na), potassium (K), chlorine (Cl), calcium (Ca), folate, vitamin B12 (Vit-B12), and homocysteine were measured. Presence/absence of tobacco use, alcohol consumption, psychoactive substance use, hypertension, hyperlipidemia, diabetes mellitus, and history of vascular disease were collected. Females were more apathetic than males (NPI-Apathy: p = 0.040). Males had a significantly higher level of Hb (p = 0.019) and UA (p = 0.001), and a lower level of platelets (p = 0.004) and Ca (p = 0.003), and used more tobacco (p = 0.046) and alcohol (p = 0.024) than females. Comparing patients < 80 and ≥80 years, we found differences in frequency of vascular risk factors among men (p = 0.027). In total, 102 patients were treated for psychosis (59.16% of them were using atypical antipsychotics). The results of this study could be useful for a progressive demonstration of the causal relationship between cardiac and cerebral vascular events and VLOSLP.

Elderly CADASIL patients with intact neurological status.

Background and Purpose Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is one of the most devastating cerebral small vessel diseases. However, despite its progression with aging, some patients remain neurologically intact (Nint) even when they get older. Their main characteristics are poorly known. We aimed to delineate their clinical, imaging, and molecular features. Methods Individuals aged over 65 years were selected from a cohort of 472 CADASIL patients. Subjects who had no focal deficit, cognitive impairment, or disability were considered Nint. Their demographic, genetic, clinical, and imaging features were compared to those with permanent neurological symptoms (Nps). Results Among 129 patients, 23 (17.8%) individuals were considered Nint. The frequency of vascular risk factors and NOTCH3 cysteine mutations in epidermal growth factor-like repeat (EGFr) domains 7-34 did not differ between Nint and Nps patients but Nint patients had less stroke events and were more likely to have migraine with aura. The number of lacunes and microbleeds and degree of brain atrophy were lower in the Nint group, but the volume of white matter hyperintensities did not differ between the two groups. Conclusions Nearly one in five CADASIL patients can remain Nint after the age of 65 years. Their clinical and imaging profile differed from that of other age-matched CADASIL patients. The location of NOTCH3 mutation inside or outside EGFr domains 1-6 cannot fully explain this discrepancy. The factors involved in their relative preservation of brain tissue from severe damage despite aging remain to be determined.

The vascular risk factors and vascular neuropathology in subjects with autopsy-confirmed dementia with Lewy bodies.

The frequency of vascular risk factors (VRFs) and the relationship between vascular pathology and cognitive function in neurodegenerative disease remains incompletely understood. The purpose of this study was to describe the frequency of VRFs and vascular pathology and explore the relationship between vascular pathology and cognitive function in dementia with Lewy bodies (DLB). This study included 363 autopsy-confirmed DLB and 753 Alzheimer's disease (AD) patients from the National Alzheimer's Coordinating Center (NACC) database. We used chi-squared test and analysis of variance to compare the VRFs and related factors in DLB and AD. Multinomial logistic regression and Spearman's correlation test were used to examine the relationship between vascular pathology and cognitive function. No significant differences of VRFs were identified between DLB and AD. Alzheimer's disease patients had higher rates of microinfarcts (23.5% vs. 16.3%, p=0.005) and moderate to severe amyloid angiopathy (45.9% vs. 36.1%, p=0.002). In DLB patients, only cerebral amyloid angiopathy (CAA) pathology was negatively correlated with memory domain (r=-0.263, p < 0.001) and language (r=-0.112,p=0.034). The rates of APOE ε4 allele carriers (60.0% vs. 44.9%, p=0.004) and CAA pathology (45.9% vs.23.4%, p < 0.001) were much higher in the group with an intermediate likelihood of DLB than in the group with a high likelihood. There was a negative correlation between CAA pathology and memory (logical memory) in the group with an intermediate likelihood of DLB. No difference of VRFs was identified between autopsy-confirmed DLB and AD. Cerebral amyloid angiopathy was shown to be an important pathology in DLB, which specifically correlated with memory and language. The groups with high and intermediate likelihood of DLB differed in terms of CAA pathology, and CAA pathology may play an important role in the development of DLB.

Socioeconomic factors and stroke

Low socioeconomic status increases the risk of development of stroke by 67%, it also has negative influence on its severity and outcomes. The mortality among stroke survivors with low socioeconomic status is higher by 39% in comparison to those with high socioeconomic status. The link between socioeconomic status and increased risk of stroke and its poor outcomes could be explained by higher frequency of vascular risk factors, lower compliance, late presentation to hospital after a stroke onset and lower access to high-quality specialized medical care in some countries. Socioeconomic factors should be taken into account while planning stroke prevention measures.

Adherence to dietary guidelines and risk of dementia: a prospective cohort study of 94 184 individuals.

Recent estimates suggest that 40% of dementia cases could be avoided by treating recognised cardiovascular risk factors such as hypertension, diabetes, smoking and physical inactivity. Whether diet is associated with dementia remains largely unknown. We tested if low adherence to established dietary guidelines is associated with elevated lipids and lipoproteins and with increased risk of Alzheimer's disease and non-Alzheimer's dementia – a dementia subtype with a high frequency of cardiovascular risk factors. We used the prospective Copenhagen General Population Study including 94 184 individuals with dietary information and free of dementia at baseline. Mean age at study entry was 58 years, and 55% (N = 51 720) were women and 45% (N = 42 464) were men. Adherence to dietary guidelines was grouped into low, intermediate and high adherence based on food frequency questionnaires. Main outcomes were non-Alzheimer's dementia and Alzheimer's disease. Low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and plasma triglyceride levels were higher in individuals with intermediate and low adherence to dietary guidelines compared with individuals with high adherence (all p for trends <0.001). Age and sex-adjusted hazard ratios (HRs) for non-Alzheimer's dementia v. individuals with high adherence were 1.19 (95% confidence interval 0.97–1.46) for intermediate adherence, and 1.54 (1.18–2.00) for low adherence. Corresponding HRs in multivariable-adjusted models including APOE genotype were 1.14 (0.92–1.40) and 1.35 (1.03–1.79). These relationships were not observed in individuals on lipid-lowering therapy. Low adherence to national dietary guidelines is associated with an atherogenic lipid profile and with increased risk of non-Alzheimer's dementia – the subtype of dementia with a high frequency of vascular risk factors. This study suggests that implementation of dietary guidelines associated with an anti-atherogenic lipid profile could be important for prevention of non-Alzheimer's dementia.

The Association between Substance Use Disorders and Long-Term Outcome of Stroke: Results from a Population-Based Study of Stroke among 450,229 Urban Citizens

Introduction: Little is known regarding long-term stroke outcomes in patients with substance use disorder (SUD). Based on anecdotal data, some individuals use illicit drugs, particularly opioids, in an attempt to reduce stroke mortality, disability, or recurrence. This study is aimed to assess the effect of SUD on stroke outcomes. Methods: Patients were recruited from the Mashhad Stroke Incidence Study, a population-based study of stroke in Iran. For a period of 1 year, all patients with first-ever stroke (FES) were recruited and then followed up for the next 5 years. Disability and functional dependency were defined using modified Rankin Scale (>2) and Barthel Index (<60), respectively. We compared the cumulative rates of mortality in follow-up points using the log-rank test. We used multivariable logistic, Cox regression and competing risk models to assess adjusted hazard ratio (aHR) with 95% confidence interval (CI) of stroke disability, functional dependency, mortality, and recurrence among those with a history of SUD. Results: 595 FES patients (mean age of 64.6 ± 14.8 years) were recruited in this study. Eighty-one (13.6%) were current substance users, including opium (n = 68), naswar (n = 5, 6.1%), hashish (n = 1), heroin (n = 1), and (n = 7) others. The frequency of vascular risk factors was similar between the SUD and non-SUD groups, except for a higher rate of cigarette smoking in the SUD group (p < 0.001). After adjusting for various sociodemographic variables, vascular risk factors, and the severity of stroke at admission, SUD increased the 3-month (aHR: 1.60, CI: 1.01–2.49), 1-year (aHR: 1.73, CI: 1.20–2.65), and 5-year (aHR: 1.72, CI: 1.23–2.35) poststroke mortality risk. We did not observe a significant change in the risk of stroke recurrence, disability, and functional dependency in those with a history of SUD. Conclusion: SUD increased the hazard ratio of stroke mortality with no effect on the disability rate. The public should be advised about the potential harm of substance abuse.

Association of early and later depressive symptoms with functional outcome after ischemic stroke

BackgroundPost-stroke depressive symptoms (DS) can be chronic or transient, occurring shortly or long after stroke and lasting only few months. It remains unclear if the prognosis differs between patients with DS in the acute phase of stroke and those who develop DS several months later. We aimed to determine whether outcomes vary among patients with different trajectories of post-stroke depressive symptoms.MethodsOf 698 enrolled patients with ischemic stroke, we included 335 participants (median age: 68, 48% female) who were assessed for DS both 8 days and 3 months post-stroke. We divided patients into 4 groups: without greater DS (Group 1), only earlier DS (Group 2), only later DS (Group 3), and persistent DS (Group 4). Logistic regression was used to determine the association between DS and 3- and 12-month functional outcome.ResultsGroup 2 was predominantly female and had the highest rate of previous stroke or transient ischemic attack. Group 3 was more likely to suffer from delirium and more severe stroke. Group 4 had the highest frequency of vascular risk factors, pre-morbid psychiatric symptoms, and cognitive decline. In multivariate analysis, Group 3, but not Groups 2 and 4, had an increased risk of poor 3- and 12-month functional outcome (adjusted OR 2.59, 95% CI 1.64–4.07, P < 0.01 and OR 3.97, 95% CI 2.32–6.76, P < 0.01, respectively) compared with Group 1.ConclusionsDifferent trajectories of post-stroke DS are related to different outcomes. Patients who only have later DS also have the worst prognosis.

Triptanophobia in migraine: A case-control study on the causes and consequences of the nonuse of triptans in chronic migraine patients

ABSTRACT Background: Triptanophobia is the excessive and inadequately justified concern about potential risks of triptans. We evaluated causes and consequences of nonuse of triptans in chronic migraine (CM) Methods: Case-control study. We included CM patients firstly referred to aheadache unit. Patients were cases or controls depending on whether they were triptan naïve, or not. We analyzed if nonuse of triptans was justified by formal contraindications or adverse events. We assessed if triptan naïve patients had higher frequency of vascular risk factors (VRF), contraceptive drugs or older age. Results: We included 941 patients, 247 (26.2%) triptan users. Triptans had been discontinued due to tolerability in 116 patients (12.3%), being 578 patients (61.4%) triptan naïve. Formal contraindications were found in 23 patients (2.4%). Frequency of VRF, contraceptive drugs or age did not differ between the groups (p > 0.1). Triptan users consumed symptomatic medications fewer days/month (13.9 vs 17.1, p < 0.001), were under prophylactic treatment more frequently (79.4% vs 34.8%, p < 0.001) and had medication overuse headache less frequently (55.1% vs. 63.0%, p = 0.03). Conclusion: Triptans were not used by three-quartersof CM patients. Nonuse of triptans was not justified by tolerability, frequency of contraindications, or frequency of VRF. Expert opinion: In the present study, we evaluated causes and consequences of the nonuse of triptans in CM sufferers. We analyzed frequency of triptan use in CM patients. We compared, between triptan users and triptan naïve patients, the presence of contraindications, frequency of vascular risk factors, and differences in management prior to the referral to a headache unit.

Comparing frequency of vascular risk factors in dementia with Lewy bodies and Alzheimer’s disease: A meta-analysis of observational cohort studies (2355)

Comparing frequency of vascular risk factors in dementia with Lewy bodies and Alzheimer’s disease: A meta-analysis of observational cohort studies (2355)

Patterns and outcomes of stroke thrombolysis in a large tertiary care hospital in Riyadh, Saudi Arabia - Single center experience

Thrombolysis in acute ischemic stroke although being standard of care is still significantly underutilized. There is no published data from Saudi Arabia about the use and outcomes of thrombolysis in stroke. To present single center experience of stroke thrombolysis from a tertiary care center in Riyadh, KSA. An IRB approved cross-sectional, observational study of patients receiving thrombolysis between January 2012 and December 2018. A total of 148 patients received thrombolysis, 94 (63%) were men; mean age 58.2 + 14.5years. Mean time from stroke onset to hospital arrival was 89 + 48 minutes; 25% arrived within one hour. Mean NIHSS score on admission was 13.4. Hypertension (68.9%), diabetes (56.1%), and dyslipidemia (40.5%) were commonest risk factors. Cardioembolism was the commonest mechanism of stroke (43.2%) and was associated with more severe presentation (p=0.031). Intravenous thrombolysis alone was given to 98 (66.2%); the rest had IV tPA and endovascular therapy or endovascular therapy alone. Mean door-to-needle time was 79.7 minutes, showing significant improvement between 2012 (111.6 minutes) and 2018 (69.9 minutes); p-value <0.001. Good outcome (mRS of 0-2) was seen in 35.8%, whereas 14 (9.5%) patients died. Symptomatic ICH was seen in 11.5%. All vascular risk factors were more common in age > 60 years except smoking which was more common in younger (p = 0.007). In our cohort, high frequency of vascular risk factors was seen. One-third of patients received endovascular treatment. The mean door-to-needle time improved significantly over years. Cardioembolic strokes were the most frequent and more severe.

A role of vascular risk factors in the development of peripheral vestibulopathy

The development of peripheral vestibular disorders are often thought to be associated with vascular mechanisms, taking into account terminal type of inner ear blood supply and other predisposing factors. A number of studies indicates a high frequency of vascular risk factors in the patients with vestibular neuronitis and benign paroxysmal positional vertigo (BPPV). According to other results, migraine is widely spread among patients with Meniere's disease and BPPV. However currently there is no evidence for casual relationship between vascular factors and development of peripheral vestibulopathy. The only exclusion is labyrinthine infarction, which develops as a result of posterior circulation disorder. More research is needed in this area.

Abstract T P315: Wake-up Intracerebral Hemorrhage Is Not Different From Intracerebral Hemorrhage With Known Onset Time

Background: The frequency of wake-up Intracerebral Hemorrhage (WU-ICH) is uncertain. It is also unknown whether there are clinical, radiological and prognostic differences between WU-ICH and non-WU-ICH. We assessed the hypothesis that both types of ICH do not differ. Methods: This is a multicentre (n=6 tertiary hospitals) registry of consecutive patients with ICH. We collected the following variables: Time of onset. WU onset was defined as stroke detected on awakening, independently of the time of the day; Demographics (age, sex); Traditional vascular risk factors; Severity of the neurological deficit at admission (NIHSS score and/or Glasgow coma scale score -GCS-); Neurological deterioration (decrease in &gt;1 point in GCS and/or increase in &gt;3 points in NIHSS score); Etiology; Neuroimaging at admission (location, secondary intraventricular hemorrhage, hematoma volume); Blood pressure, blood glucose, platelet count and INR at admission; and Outcome (modified Rankin scale score -mRS- at discharge and at 3 months; favourable outcome when mRS ≤ 2). Patients were treated according to national guidelines of ICH. Comparison between groups was achieved with Student’s t-test, Chi-square test and Mann-Whitney’s U test. Results: We included a total of 270 patients, whose mean age was 70.2 ± 14.4 years, and 60% of them were men. WU-ICH was diagnosed in 49 (18%) patients. We found no significant differences between groups in demographics, frequency of vascular risk factors, severity of the neurological deficit, etiology, blood pressure, blood analysis and neuroradiological findings. Patients with WU-ICH had a lower frequency of neurological deterioration when assessed by the NIHSS scale (p= 0.04) but not by the GCS scale. The outcome at discharge and at 3-months was equivalent between groups. Conclusions: In conclusion, 18% of ICHs are detected on awakening. Patients with wake-up ICH do not differ from patients with known onset time either in most clinical and radiological variables or in the long-term prognosis. WU-ICH patients may have a lower likelihood of neurological worsening within the acute stage.

Letter by Sposato and Saposnik Regarding Article, “Socioeconomic Status and Stroke: An Updated Review”

To the Editor: We read with great interest the article “Socioeconomic Status and Stroke: An Updated Review” by Addo et al.1 The authors analyzed articles reporting the association between measures of socioeconomic status and stroke between January 2006 and July 2011. They found a >3-fold greater stroke impact (eg, disability-adjusted life-years lost and mortality rates), a higher stroke incidence, and a greater frequency of vascular risk factors in low-income compared with high- and middle-income countries. Similarly, in a systematic review of population-based studies published between 2000 and 2010, reporting incident stroke risk and/or 30-day case-fatality, we found that lower per-capita gross domestic product adjusted for purchasing power parity and total health expenditure per capita at purchasing power parity were associated …

Epidemiología de los subtipos de ictus en pacientes hospitalizados atendidos por neurólogos: resultados del registro EPICES (I)

Hospital-based population studies are a good way to determinate the number and features of strokes that occur in a given society. The major stroke subtypes have different patterns of incidence and outcome, for that reason information on the natural history of stroke subtypes is essential. To determine the incidence of the stroke subtypes and the prevalence of the major risk factors in the Spanish population. EPICES is an observational, multicenter and prospective study. Methodology includes systematic review of consecutive medical records of hospitalized stroke patients in neurological care. 6,197 patients were included during the period April 2008 and January 2009. 3,544 (57.2%) were men. Mean age was 71.4 ± 12.8 years. Intracerebral haemorrhage was diagnosed in 771 patients (12.4%) and ischemic stroke in 5,426 (87.6%). 1,543 (28.4%) were classified as large-artery atherosclerosis, cardioembolic 1,424 (26.2%), small-vessel occlusion 1,202 (22.5%), undetermined etiology 1,125 (20.7%). Stroke of other uncommon origin was founded in 132 (2.4%). Hypertension is the most common risk factor in both ischemic stroke (67%) and intracerebral haemorrhage (69.1%). The different types of ischemic and hemorrhagic stroke showed differences in risk factors prevalence. The overall distribution of stroke subtypes are not significantly different from those of most Western countries. The frequency of vascular risk factors differs between stroke subtypes. Hypertension remains the most important modifiable risk factor.

Troubles cognitifs et insuffisance rénale: quels liens ?

Ageing of the population leads to an increase of cognitive disorders and chronic renal failure incidence. Compared to the general population, prevalence of cognitive impairment is more important in renal failure patients, especially in dialyzed patients. No direct link has been established between renal failure and cognitive impairment. The care of older and older patients and the high frequency of vascular risk factors, in particular hypertension and diabetes, partially explain the prevalence of vascular dementia and Alzheimer disease in this population. Other factors as the anemia, phosphocalcic metabolism disorders facilitate the cognitive impairment. The present work reviews the links existing between chronic renal failure and cognitive impairment.

Comparison of clinical, familial, and MRI features of CADASIL and NOTCH3 -negative patients

To report the characteristics of patients suspected to have cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) but in whom no NOTCH3 gene pathogenic mutation was found. Between 2002 and 2008, we performed NOTCH3 gene analysis (exons 2-23) in 81 probands because CADASIL was clinically suspected. A retrospective analysis and comparison of clinical, familial, and neuroimaging features of patients with and without pathogenic mutations was performed. CADASIL was diagnosed in 16/81 (20%) probands by finding a mutation leading to a cysteine substitution within the epidermal growth factor (EGF)-like repeats of the NOTCH3 receptor. In the remaining 65 patients, no pathogenic mutation was found. Some features were significantly (Fisher exact test p < 0.05) more frequent in CADASIL than in NOTCH3-negative patients: history of migraine (73 vs 39%), stroke before the age of 60 among relatives (71 vs 32%), severe leukoencephalopathy (94 vs 62%), white matter changes extended to the anterior temporal lobes (93 vs 45%), external capsule involvement (100 vs 50%), and presence of lacunar infarcts (100 vs 65%). The frequency of vascular risk factors was balanced between the 2 groups. No feature was peculiar to either group. Although certain clinical and neuroimaging features are more frequent in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) than in NOTCH3-negative patients, none is pathognomonic. Clinicians should be aware that when diagnosing CADASIL, a number of patients with a cerebral disease phenotypically similar to CADASIL emerge. The genetic profile of these diseases and the full phenotypic difference with CADASIL remain to be further defined.

Migraña y alteraciones del septo auricular en pacientes menores de 55 años con infarto cerebral criptogenético

Patent foramen ovale (PFO) is more frequent in migraine patients and is a cause of brain infarct among patients under 55 years old. Our goal was to study the association between PFO and migraine in ischemic stroke patients under 55 years old. Observational study with inclusion of consecutive stroke patients admitted to a stroke unit (1995--2005). We selected patients under 55 years of age with first-ever acute cerebral infarction of cryptogenic origin. Demographic data, vascular risk factors, stroke vascular territory, stroke severity, the presence of PFO and/or atrial septal aneurysm (ASA) in echocardiography and functional status at discharge by the modified Rankin Scale score were analysed according to previous migraine. From a total of 130 patients, 76 were males. The 13.8% had previous migraine, 3.9% among male and 27.8% among female (p < 0.001). Migraine patients were younger than non migraine ones (p = 0.041) and had a higher frequency of vascular risk factors (not significant [NS]). Stroke severity and functional status at discharge were similar in both groups. Previous history of migraine was associated with FOP (38.9% vs. 26.8%; NS) and FOP plus ASA (odds ratio = 5; 95% confidence interval, 1.422-17.580). The latter association was higher in female (33.3% vs. 0%; NS). Previous migraine is more frequently associated with double interatrial septal abnormality (PFO plus ASA) in cerebral infarct patients under 55 years of age. This association could be higher in women.