VEMPs and Dysautonomia Assessment in Definite Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome (CANVAS): a Case Series Study.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described slowly progressive ataxia with severe imbalance due to the compromise of three of the four sensory inputs for balance, leaving only vision unaffected. Bilateral vestibulopathy is present but saccular and utricular function, measured by vestibular evoked myogenic potentials (VEMPs), has not been widely studied in these patients. Dysautonomia has been reported but is not among the diagnostic criteria. We performed a database analysis to identify patients evaluated between 2003 and 2019 with probable diagnosis of CANVAS by using key words "bilateral vestibulopathy and/or cerebellar ataxia and/or sensory polyneuropathy." Five out of 842 met all conditions. Patients underwent neurological/neurootological exam, brain MRI, visually enhanced vestibulo-ocular reflex (VVOR) exam by high-speed video-oculography using video-Head Impulse Test (vHIT), VEMPs, neurophysiological studies, and genetic tests to exclude other causes of ataxia. Dysautonomia was addressed by the standardized survey of autonomic symptoms. All patients had clinically definite CANVAS as brain MRI showed vermal cerebellar atrophy, neurophysiological studies showed a sensory neuronopathy pattern (absent sensory action potentials), VVOR was abnormal bilaterally, and genetic tests ruled out other causes of ataxia including SCA 3 and Friedreich ataxia. Patients had at least 3 dysautonomic symptoms, including xerostomia/xerophthalmia (5/5). VEMP results varied among patients, ranging from normal to completely abnormal. We found inconsistent results with VEMPs. The utilization of VEMPs in more CANVAS cases will determine its utility in this syndrome. Dysautonomia may be included in the diagnostic criteria.

Interictal amylin levels in chronic migraine patients: A case-control study.

BACKGROUND: Recently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine. METHODS: We prospectively recruited patients with episodic migraine, chronic migraine and healthy controls. Interictal amylin and calcitonin gene-related peptide levels were assessed in blood samples using enzyme linked immunosorbent assay. RESULTS: We assessed plasma samples from 58 patients with episodic migraine (mean age 37.71 ± 10.47, 87.9% female), 191 with chronic migraine (mean age 46.03 ± 11.93, 95% female), and on 68 healthy controls (mean age 43.58 ± 11.08 years, 86% female). Body mass index was 25.94 ± 4.53 kg/m2 for migraine patients and 25.13 ± 4.92 kg/m2 for healthy controls (p = 0.0683). Interictal plasma amylin levels were higher in chronic migraine patients (47.1 pg/mL) than in the episodic migraine patients (28.84 pg/mL, p < 0.0001) and healthy controls (24.74 pg/mL, p < 0.0001). Plasma calcitonin gene-related peptide levels were increased (20.01 pg/mL) in chronic migraine patients when compared to healthy controls (11.37 pg/mL, p = 0.0016), but not to episodic migraine patients (18.89 pg/mL, p = 0.4369). Applying a cut-off concentration of 39.68 pg/mL plasma amylin, the sensitivity to differentiate chronic migraine from healthy controls was 57.6% and the specificity was 88.2%. Variables such as age, analgesic overuse, depression, allodynia, use of preventive medication or a history of aura did not influence the plasma concentrations of amylin or calcitonin gene-related peptide. CONCLUSION: Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a diagnostic biomarker for chronic migraine.

Amylin as a potential link between type 2 diabetes and alzheimer disease.

OBJECTIVE: Alzheimer disease (AD) is the leading cause of dementia, and although its etiology remains unclear, it seems that type 2 diabetes mellitus (T2DM) and other prediabetic states of insulin resistance could contribute to the appearance of sporadic AD. As such, we have assessed whether tau and ß-amyloid (Aß) deposits might be present in pancreatic tissue of subjects with AD, and whether amylin, an amyloidogenic protein deposited in the pancreas of T2DM patients, might accumulate in the brain of AD patients. METHODS: We studied pancreatic and brain tissue from 48 individuals with no neuropathological alterations and from 87 subjects diagnosed with AD. We examined Aß and tau accumulation in the pancreas as well as that of amylin in the brain. Moreover, we performed proximity ligation assays to ascertain whether tau and/or Aß interact with amylin in either the pancreas or brain of these subjects. RESULTS: Cytoplasmic tau and Aß protein deposits were detected in pancreatic ß cells of subjects with AD as well as in subjects with a normal neuropathological examination but with a history of T2DM and in a small cohort of control subjects without T2DM. Furthermore, we found amylin deposits in the brain of these subjects, providing histological evidence that amylin can interact with Aß and tau in both the pancreas and hippocampus. INTERPRETATION: The presence of both tau and Aß inclusions in pancreatic ß cells, and of amylin deposits in the brain, provides new evidence of a potential overlap in the mechanisms underlying the pathogenesis of T2DM and AD. ANN NEUROL 2019;86:539-551.

Elevated circulating metalloproteinase 7 predicts recurrent cardiovascular events in patients with carotid stenosis: a prospective cohort study.

BACKGROUND: Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS: This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (> 70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2 days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS: The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r = 0.42 P = .02) and with 18F-FDG uptake (r = 0.38 P = .05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077 days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR = 1.15 P = .006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS: Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.

Excess abdominal fat is associated with cutaneous allodynia in individuals with migraine: a prospective cohort study.

OBJECTIVE: To investigate the specific relationship between cutaneous allodynia (CA) and the percentages of body fat (BF) and abdominal fat in migraineurs. Additionally, we compared serum levels of inflammatory biomarkers in patients with and without CA. BACKGROUND: Excess abdominal fat might facilitate progressive changes in nociceptive thresholds causing central sensitization, clinically reflected as CA, which could drive migraine progression. METHODS: This prospective cohort study included 80 patients with migraine (mean age 39 years, 81.2% female) and 39 non-migraine controls. We analysed each participant's height, body weight, and body mass index (BMI). The amount and distribution of BF was also assessed by air displacement plethysmography (ADP) and ViScan, respectively. We analysed serum levels of markers of inflammation, during interictal periods. RESULTS: We studied 52 patients with episodic migraine (EM) and 28 with chronic migraine (CM). Of the 80 patients, 53 (53.8%) had CA. Migraineurs with CA had a higher proportion of abdominal fat values than patients without CA (p = 0.04). The independent risk factors for CA were the use of migraine prophylaxis (OR 3.26, 95% CI [1.14 to 9.32]; p = 0.03), proportion of abdominal fat (OR 1.13, 95% CI [1.01 to 1.27]; p = 0.04), and presence of sleep disorders (OR 1.13, 95% CI [00.01 to 1.27]; p = 0.04). The concordance correlation coefficient between the ADP and BMI measurements was 0.51 (0.3681 to 0.6247). CA was not correlated with the mean plasma levels of inflammatory biomarkers. CONCLUSIONS: There is a relation between excess abdominal fat and CA. Abdominal obesity might contribute to the development of central sensitization in migraineurs, leading to migraine chronification.

Citicoline for Acute Ischemic Stroke: A Systematic Review and Formal Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Trials.

BACKGROUND: Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo. METHODS: A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke. RESULTS: Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53). CONCLUSIONS: This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit.

The neuroprotection exerted by memantine, minocycline and lithium, against neurotoxicity of CSF from patients with amyotrophic lateral sclerosis, is antagonized by riluzole.

In a recent study we found that cerebrospinal fluids (CSFs) from amyotrophic lateral sclerosis (ALS) patients caused 20-30% loss of cell viability in primary cultures of rat embryo motor cortex neurons. We also found that the antioxidant resveratrol protected against such damaging effects and that, surprisingly, riluzole antagonized its protecting effects. Here we have extended this study to the interactions of riluzole with 3 other recognized neuroprotective agents, namely memantine, minocycline and lithium. We found: (1) by itself riluzole exerted neurotoxic effects at concentrations of 3-30 µM; this cell damage was similar to that elicited by 30 µM glutamate and a 10% dilution of ALS/CSF; (2) memantine (0.1-30 µM), minocycline (0.03-1 µM) and lithium (1-80 µg/ml) afforded 10-30% protection against ALS/CSF-elicited neurotoxicity, and (3) at 1-10 µM, riluzole antagonized the protection afforded by the 3 agents. These results strongly support the view that at the riluzole concentrations reached in the brain of patients, the neurotoxic effects of this drug could be masking the potential neuroprotective actions of new compounds being tested in clinical trials. Therefore, in the light of the present results, the inclusion of a group of patients free of riluzole treatment may be mandatory in future clinical trials performed in ALS patients with novel neuroprotective compounds.

Citicoline in the treatment of acute ischaemic stroke: an international, randomised, multicentre, placebo-controlled study (ICTUS trial).

BACKGROUND: Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial. METHODS: We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890. RESULTS: 2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1·03, 95% CI 0·86-1·25; p=0·364). No significant differences were reported in the safety variables nor in the rate of adverse events. INTERPRETATION: Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderate-to-severe acute ischaemic stroke. FUNDING: Ferrer Grupo.

Cephalalgia alopecia or nummular headache with trophic changes? A new case with prolonged follow-up.

Cephalalgia alopecia is a rare and recently described headache syndrome in which recurrent, burning head and neck pain is associated with hair loss from areas of scalp affected by the pain. We here report the case of a 33-year-old woman with continuous unilateral occipital pain and colocalized alopecia, only responsive to onabotulinumtoxin A injections. We hypothesize whether this clinical phenotype may correspond to either cephalalgia alopecia or nummular headache with trophic changes, conditions that might represent 2 manifestations of the same spectrum of disorders.

Reversible cerebral vasoconstriction syndrome induced by adrenaline.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute severe thunderclap headaches and evidence of multifocal, segmental, reversible vasoconstrictions of the cerebral arteries. Several precipitating factors have been identified and reported, including the use of recreational substances or sympathomimetic drugs and the postpartum state. CASE DESCRIPTION: Here we present the case of a woman who developed RCVS after the administration of adrenaline (epinephrine) in the setting of an anaphylactic reaction during antibiotic allergy testing. DISCUSSION: To our knowledge, this is the first reported case of RCVS following the administration of exogenous adrenaline. This case contributes to the understanding of the physiopathological mechanisms underlying reversible cerebral vasoconstriction.

Chronic migraine: a therapeutic challenge for clinicians.

Chronic migraine is a common disabling condition. Severe migraine attacks should be treated with triptans, but these agents are contraindicated in patients with vascular problems and may not be effective or tolerated in around one third of the patients. New acute migraine therapies without vasoconstrictive activity and triptan-specific side effects are emerging. For the prophylaxis of chronic migraine, only topiramate and OnabotulinumtoxinA have been shown to be effective in placebo-controlled randomized trials, so novel therapeutic strategies are needed. The growing understanding of the pathophysiology of chronic migraine will contribute to the identification of new treatment targets.

The influence of obesity on the assessment of carotid intima-media thickness.

BACKGROUND: The assessment of carotid intima-media thickness (CIMT) may improve cardiovascular risk prediction. The optimal protocol for CIMT measurement is unclear. CIMT may be measured in the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA), but measurements from CB and ICA are more difficult to obtain. We studied the influence of body mass index (BMI) and atheroma plaques on the capacity to obtain CIMT measurements at different carotid sites. METHODS: Using an automatic system, CIMT was measured in 700 subjects aged 45-75, in the near and far walls of CCA, CB, and ICA bilaterally. The presence of atheroma plaques, BMI and vascular risk factors were recorded. RESULTS: CIMT measurements in CCA were possible in all except one subject. It was not possible to obtain CIMT measurements at CB or ICA in 24.1% of normal weight and 58.8% of obese subjects. The likelihood of obtaining CIMT measurement at all carotid sites decreased as the BMI increased. Atheroma plaques in a carotid segment did not preclude CIMT measurement at this site. CONCLUSIONS: CIMT measurements in distal carotid segments are more challenging in obese subjects. Measuring CIMT at CCA remains feasible in obese subjects and should be the primary endpoint in these subjects. Nevertheless, CB and ICA measurements, when feasible, would improve risk classification.

Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma.

Central nervous system (CNS) prophylaxis is required during initial treatment of non-Hodgkin lymphoma (NHL) subtypes that carry a high risk of CNS involvement. Intrathecal (IT) liposomal cytarabine, a formulation with prolonged half-life, has been shown to be safe and effective in the treatment of meningeal disease in patients with high-grade lymphoma. We retrospectively reviewed all adult patients with high-grade NHL that received prophylactic therapy with IT liposomal cytarabine and developed neurologic complications in our institution between April 2007 and May 2009. We recorded information on hospital admission, chemotherapy regimens, clinical features, neuroimaging, cerebrospinal fluid, neurophysiology data, and outcome. Neurotoxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC). Four of fourteen patients (28%) developed moderate or severe neurotoxicity (grades 2 and 3 of the NCI-CTC), manifested as conus medullaris/cauda equine syndrome or pseudotumour cerebri-like syndrome, after a median of 3.5 IT courses of liposomal cytarabine. All patients had received corticosteroids to prevent arachnoiditis. Liposomal cytarabine given via the IT route, even with concomitant corticosteroid administration, can result in significant neurotoxicity in some patients. We discuss the potential pathogenesis of these effects and suggest hypothetical therapeutic measures to prevent these complications. Specialists should be aware of these possible complications when administering prophylactic IT liposomal cytarabine in high-grade NHL patients, and additional prospective studies should be conducted to more clearly delineate the frequency and characteristics of these complications.

Refractory migraine in a headache clinic population.

BACKGROUND: Many migraineurs who seek care in headache clinics are refractory to treatment, despite advances in headache therapies. Epidemiology is poorly characterized, because diagnostic criteria for refractory migraine were not available until recently. We aimed to determine the frequency of refractory migraine in patients attended in the Headache Unit in a tertiary care center, according to recently proposed criteria. METHODS: The study population consisted of a consecutive sample of 370 patients (60.8% females) with a mean age of 43 years (range 14-86) evaluated for the first time in our headache unit over a one-year period (between October 2008 and October 2009). We recorded information on clinical features, previous treatments, Migraine Disability Assessment Score (MIDAS), and final diagnosis. RESULTS: Overall migraine and tension-type headache were found in 46.4% and 20.5% of patients, respectively. Refractory migraine was found in 5.1% of patients. In refractory migraineurs, the mean MIDAS score was 96, and 36.8% were medication-overusers. CONCLUSIONS: Refractory migraine is a relatively common and very disabling condition between the patients attended in a headache unit. The proposed operational criteria may be useful in identifying those patients who require care in headache units, the selection of candidates for combinations of prophylactic drugs or invasive treatments such as neurostimulation, but also to facilitate clinical studies in this patient group.

RNU6-1 in circulating exosomes differentiates GBM from non-neoplastic brain lesions and PCNSL but not from brain metastases.

BACKGROUND: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Circulating biomarkers may assist in the processes of differential diagnosis and response assessment. GBM cells release extracellular vesicles containing a subset of proteins and nucleic acids. We previously demonstrated that exosomes isolated from the serum of GBM patients had an increased expression of RNU6-1 compared to healthy subjects. In this exploratory study, we investigated the role of this small noncoding RNA as a diagnostic biomarker for GBM versus other brain lesions with some potential radiological similarities. METHODS: We analyzed the expression of RNU6-1 in circulating exosomes of GBM patients (n = 18), healthy controls (n = 30), and patients with subacute stroke (n = 30), acute/subacute hemorrhage (n = 30), acute demyelinating lesions (n = 18), brain metastases (n = 21), and primary central nervous system lymphoma (PCNSL; n = 12) using digital droplet PCR. RESULTS: Expression of RNU6-1 was significantly higher in GBM patients than in healthy controls (P = .002). RNU6-1 levels were also significantly higher in exosomes from GBM patients than from patients with non-neoplastic lesions (stroke [P = .05], hemorrhage [P = .01], demyelinating lesions [P = .019]) and PCNSL (P = .004). In contrast, no significant differences were found between patients with GBM and brain metastases (P = .573). Receiver operator characteristic curve analyses supported the role of this biomarker in differentiating GBM from subacute stroke, acute/subacute hemorrhage, acute demyelinating lesions, and PCNSL (P < .05), but again not from brain metastases (P = .575). CONCLUSIONS: Our data suggest that the expression of RNU6-1 in circulating exosomes could be useful for the differentiation of GBM from non-neoplastic brain lesions and PCNSL, but not from brain metastases.

Emergent cerebrovascular disease risk factor weighting: is transient ischemic attack an imminent threat?

Transient ischemic attack (TIA) is a neglected condition and a marker of atherothrombotic disease. Several cohort studies have demonstrated that the risk of early cerebral infarct after TIA is much higher than previously thought. Many studies have shown that the risk of stroke is high after TIA, and is on average 4-6% in the first 2 days. Up to 23% of strokes are preceded by transient ischemic attack (TIA), and there is substantial research interest in improving prevention during the short window between TIA and stroke. Nonetheless, patients with TIA are often managed without urgency. The currently available evidence suggests that the application of clinical scales is useful for the detection of patients with high risk of recurrence, and this is increased significantly when the information from neuroimaging and Doppler assessments is added. However, the limited prognostic value of these clinical variables together with the elevated risk of suffering an adverse vascular event are driving the search for new predictive factors (biological markers, neuroimaging data, ultrasound) that will help towards a better discrimination of high-risk patients. Recent studies have demonstrated that prompt evaluation and treatment of patients with TIA in a dedicated outpatient unit is associated with a lower than expected risk of subsequent stroke.

Delirium due to brain microembolism: diagnostic value of diffusion-weighted MRI.

Delirum is a common complication in hospitalized patients and it is characterized by acute disturbances of consciousness, attention, cognition, and perception. Despite the frequency with which it is observed, ischemic stroke is generally considered as an unusual cause of delirium. A subtype of brain embolism is characterized by multiple small emboli in different vascular territories, a condition known as "brain microembolism." Given the high contrast of acute ischemic lesions in diffusion weighted imaging (DWI) this technique is particularly helpful to detect these small infarctions. We present here a patient with pulmonary metastases who was treated with bronchial artery embolization and who subsequently developed delirium due to brain microembolism. The embolic material crossed through pulmonary arteriovenous fistulas, producing multiple areas of cerebral ischemia. The ischemic lesions could be visualized only on DWI, and they affected the periventricular region, caudate nucleus, thalamus, and cerebellum.

Epicardial Adipose Tissue in the General Middle-aged Population and Its Association With Metabolic Syndrome.

INTRODUCTION AND OBJECTIVES: There is currently increasing interest in epicardial adipose tissue (EAT) as a marker of cardiovascular disease. Our purpose was to describe EAT, measured by transthoracic echocardiography, and to assess its association with metabolic syndrome (MS) in the RIVANA population-based study. METHODS: Physical examination was performed in 880 participants aged 45 to 74 years (492 of them with MS according to the harmonized definition). Fasting glucose, high-density lipoprotein cholesterol, triglyceride, and C-reactive protein concentrations were determined in a blood sample. In all participants, EAT thickness was measured with transthoracic echocardiography at end-systole. RESULTS: Among participants without MS, the prevalence of EAT ≥ 5mm significantly increased with age (OR > 65 years vs 45-54 years=8.22; 95%CI, 3.90-17.35; P for trend<.001). Increasing EAT quintiles were significantly associated with MS (OR fifth quintile vs first quintile=3.26; 95%CI, 1.59-6.71; P for trend=.001). Considering the different MS criteria, increasing quintiles of EAT were independently associated with low high-density lipoprotein cholesterol (OR fifth quintile vs first quintile=2.65; 95%CI, 1.16-6.05; P for trend=.028), high triglycerides (OR fifth quintile vs first quintile=2.22; 95%CI, 1.26-3.90; P for trend=.003), and elevated waist circumference (OR fifth quintile vs first quintile=6.85; 95%CI, 2.91-16.11; P for trend<.001). CONCLUSIONS: In a subsample of the general population, EAT measured by echocardiography increased significantly and independently with age. Increased EAT thickness was independently associated with MS and with low high-density lipoprotein cholesterol, high triglycerides, and elevated waist circumference as individual criteria.

Severe sleep apnea and risk of ischemic stroke in the elderly.

BACKGROUND AND PURPOSE: Convincing evidence of a causal relationship between sleep apnea and stroke has been shown recently in several prospective, well-designed studies. However, these studies have focused on middle-aged people, excluding the elderly population from analysis. To investigate whether sleep apnea represents an independent risk factor in this population, we performed a prospective longitudinal study in a population-based cohort of subjects from 70 to 100 years old. METHODS: Within the context of the Vitoria Sleep Project, a population-based study designed to investigate the prevalence of sleep apnea in the population of Vitoria, Spain, we performed a 6-year longitudinal study in a subsample cohort of 394 noninstitutionalized, initially event-free subjects (70 to 100 years old, median 77.28 years, 57.1% males). Demographic and polysomnographic data and known confounding factors (age, sex, smoking and alcohol consumption status, body mass index, systolic and diastolic blood pressure, total serum cholesterol levels, and the presence or absence of diabetes mellitus, atrial fibrillation, and hypertension) were assessed at baseline. Hazard ratio for developing an ischemic stroke in relation to the apnea-hypopnea index at baseline was calculated. RESULTS: Over the 6-year follow-up period, 20 ischemic strokes were registered. After adjustment for confounding factors, subjects with severe obstructive sleep apnea hypopnea (defined as apnea-hypopnea index >or=30) at baseline had an increased risk of developing a stroke (hazard ratio=2.52, 95% CI=1.04 to 6.01, P=0.04). CONCLUSIONS: This study shows that severe obstructive sleep apnea hypopnea (defined as apnea-hypopnea index >or=30) increases the risk of ischemic stroke in the elderly population, independent of known confounding factors.