Outcomes after reperfusion therapies in patients with ACA stroke: A multicenter cohort study from the EVATRISP collaboration.

BACKGROUND: Patients with stroke secondary to occlusions of the anterior cerebral artery (ACA) often have poor outcomes. The optimal acute therapeutic intervention for these patients remains unknown. METHODS: Patients with isolated ACA-stroke were identified from 10 centers participating in the EndoVascular treatment And ThRombolysis in Ischemic Stroke Patients (EVATRISP) prospective registry. Patients treated with endovascular thrombectomy (EVT) were compared to those treated with intravenous thrombolysis (IVT). Odds ratios with 95% confidence intervals (OR; 95%CI) were calculated using multivariate regression analysis. RESULTS: Included were 92 patients with ACA-stroke. Of the 92 ACA patients, 55 (60%) were treated with IVT only and 37 (40%) with EVT (±bridging IVT). ACA patients treated with EVT had more often wake-up stroke (24% vs. 6%, p = 0.044) and proximal ACA occlusions (43% vs. 24%, p = 0.047) and tended to have higher stroke severity on admission [NIHSS: 10.0 vs 7.0, p = 0.054). However, odds for favorable outcome, mortality or symptomatic intracranial hemorrhage did not differ significantly between both groups. Exploration of the effect of clot location inside the ACA showed that in patients with A1 or A2/A3 ACA occlusions the chances of favorable outcome were not influenced by treatment allocation to IVT or EVT. DISCUSSION: Treatment with either IVT or EVT could be safe with similar effect in patients with ACA-strokes and these effects may be independent of clot location within the occluded ACA.

Functional and radiological outcomes after bridging therapy versus direct thrombectomy in stroke patients with unknown onset: Bridging therapy versus direct thrombectomy in unknown onset stroke patients with 10-point ASPECTS.

BACKGROUND AND PURPOSE: The aim was to assess functional and radiological outcomes after bridging therapy (intravenous thrombolysis plus mechanical thrombectomy) versus direct mechanical thrombectomy (MT) in unknown onset stroke patients. METHODS: A cohort study was conducted on prospectively collected data from unknown onset stroke patients who received endovascular procedures at ≤6 h from symptom recognition or awakening time. RESULTS: Of the 349 patients with a 10-point Alberta Stroke Program Early Computed Tomography Score (ASPECTS), 248 received bridging and 101 received direct MT. Of the 134 patients with 6-9-point ASPECTS, 123 received bridging and 111 received direct MT. Each patient treated with bridging was propensity score matched with a patient treated with direct MT for age, sex, study period, pre-stroke disability, stroke severity, type of stroke onset, symptom recognition to groin time (or awakening to groin time), ASPECTS and procedure time. In the two matched groups with 10-point ASPECTS (n = 73 vs. n = 73), bridging was associated with higher rates of excellent outcome (46.6% vs. 28.8%; odds ratio 2.302, 95% confidence interval 1.010-5.244) and successful recanalization (83.6% vs. 63%; odds ratio 3.028, 95% confidence interval 1.369-6.693) compared with direct MT; no significant association was found between bridging and direct MT with regard to rate of symptomatic intracerebral hemorrhage (0% vs. 1.4%). In the two matched groups with 6-9-point ASPECTS (n = 45 vs. n = 45), no significant associations were found between bridging and direct MT with regard to rates of excellent functional outcome (44.4% vs. 31.1%), successful recanalization (73.3% vs. 76.5%) and symptomatic intracerebral hemorrhage (0% vs. 0%). CONCLUSIONS: Bridging at ≤ 6 h of symptom recognition or awakening time was associated with better functional and radiological outcomes in unknown onset stroke patients with 10-point ASPECTS.

Cardiac sources of cerebral embolism in people with migraine.

BACKGROUND AND PURPOSE: Whether the reported association between migraine with aura (MA) and cardioembolic stroke may be explained by a higher rate of atrial fibrillation (AF) or by other potential cardiac sources of cerebral embolism remains to be determined. METHODS: In the setting of a single centre cohort study of consecutive patients with acute brain ischaemia stratified by migraine status, the association between AF as well as patent foramen ovale (PFO) and migraine was explored. RESULTS: In all, 1738 patients (1017 [58.5%] men, mean age 67.9 ± 14.9 years) qualified for the analysis. Aging was inversely associated with migraine, whilst women had a >3-fold increased disease risk (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.58-5.66). No association between AF and history of migraine or its pathogenic subtypes was detected. Conversely, migraine was associated with PFO, both in the entire cohort (OR 1.84, 95% CI 1.07-3.16) and in patients aged ≤55 years (OR 2.21, 95% CI 1.16-4.22). This association was significant for MA (OR 2.92, 95% CI 1.32-6.45 in the entire cohort; OR 2.92, 95% CI 1.15-7.41 in patients aged ≤55 years) and in women (OR 8.23, 95% CI 2.06-32.77), but not for migraine without aura. CONCLUSIONS: In patients with brain ischaemia migraine is not associated with AF. Conversely, there is a probable relation between migraine, especially MA, and PFO in patients who are younger and have a more favourable vascular risk factor profile, and in women.

Source-Based Morphometry Multivariate Approach to Analyze [123I]FP-CIT SPECT Imaging.

PURPOSE: [123I]FP-CIT (DaTSCAN®) single-photon emission computed tomography (SPECT) imaging is widely used to study neurodegenerative parkinsonism, by measuring presynaptic dopamine transporter (DAT) in striatal regions. Beyond DAT, [123I]FP-CIT may be considered for other monoaminergic systems, in particular the serotonin transporter (SERT). Independent component analysis (ICA) implemented in source-based morphometry (SBM) could represent an alternative method to explore monoaminergic pathways, studying the relationship among voxels and grouping them into "neurotransmission" networks. PROCEDURES: One hundred forty-three subjects [84 with Parkinson's disease (PD) and 59 control individuals (CG)] underwent DATSCAN® imaging. The [123I]FP-CIT binding was evaluated by multivariate SBM approach, as well as by a whole-brain voxel-wise univariate (statistical parametric mapping, SPM) approach. RESULTS: As compared to the univariate whole-brain approach (SPM) (only demonstrating striatal [123I]FP-CIT binding reduction in PD group), SBM identified six sources of non-artefactual origin, including basal ganglia and cortical regions as well as brainstem. Among them, three sources (basal ganglia and cortical regions) presented loading scores (as index of [123I]FP-CIT binding) significantly different between PD and CG. Notably, even if not significantly different between PD and CG, the remaining three non-artefactual sources were characterized by a predominant frontal, brainstem, and occipito-temporal involvement. CONCLUSION: The concept of source blind separation by the application of ICA (as implemented in SBM) represents a feasible approach to be considered in [123I]FP-CIT (DaTSCAN®) SPECT imaging. Taking advantage of this multivariate analysis, specific patterns of variance can be identified (involving either striatal than extrastriatal regions) that could be useful in differentiating neurodegenerative parkinsonisms.

Impulse control disorder in PD: A lateralized monoaminergic frontostriatal disconnection syndrome?

BACKGROUND: Impulse Control Disorder symptoms (ICD) in Parkinson's disease (PD) has been recently associated by magnetic Resonance imaging with impaired cortico-striatal connectivity, especially between left putamen and frontal associative areas. METHODS: 84 patients entered the study (21 PD-ICD+ and 64 PD-ICD-) and underwent DATSCAN imaging. The striatal tracer uptake was evaluated using BRASS software (Hermes, Sweden). The whole-brain analysis was performed with Statistical Parametric Mapping (SPM). RESULTS: PD-ICD+ showed a significant reduction of left putaminal and left inferior frontal gyrus tracer uptake compared to PD-ICD-. Functional covariance analysis using left putamen as the seed point showed that, in contrast to ICD-patients, ICD+ patients had no functional covariance with contralateral basal ganglia and ipsilateral cingulate cortex, as index of an impaired inter- and intra-hemispheric dopamine binding in PD-ICD+. DISCUSSION: the results support and expand the concept of a functional disconnection syndrome linked to ICD symptoms in PD patients through an asymmetric molecular frontostriatal network breakdown with left basal ganglia as central hub.

[The role of the ASL of Brescia in the health and safety of immigrant workers]. / Il ruolo dell'ASL di Brescia nella tutela della salute e della sicurezza dei lavoratori immigrati.

According to available studies, migrant workers represent a vulnerable workers' category. For this reason, the Italian law on safety and health at work (art. 11, D.Lgs 81/08) points out the need for Public Administration initiatives devoted to migrant workers' health and safety at work. Local Public Health Department of Brescia for years now had a significant commitment in migrants' health. Thanks to the collaboration of occupational physicians and expert physicians on migration health, it was developed a multidimensional method to assess working risks taking into account also the fragile conditions of migrant workers, considering both personal and social characteristics and professional experience, in order to support companies in the planning of necessary actions to improve health and safety at work. The method was shared by both local industrial association and trade unions and then tested in some manufactures.

The evolving burden of HIV infection compared with other chronic diseases in northern Italy.

OBJECTIVES: The aim of the study was to estimate the burden and direct costs of diseases in HIV-infected patients (either opportunistic illnesses or other chronic diseases) with respect to the HIV-uninfected population. These estimates will be useful for the projection of future direct costs of HIV care. PATIENTS AND METHODS: A population-based study was conducted in the Brescia Local Health Agency in northern Italy. An administrative database recorded diagnoses, deaths, drug prescriptions and health resource utilization for all medical and surgical patients in the region from 2003 to 2007. The study estimated the prevalence of HIV infection as well as HIV-related mortality and annual cost per patient, and compared mortality and costs related to HIV infection with those for a set of 15 other chronic diseases. The standardized hazard ratio (SHR) and standardized mortality ratio (SMR) were obtained using an indirect standardization method. RESULTS: The prevalence of HIV infection increased from 218 per 100,000 inhabitants in 2003 to 263 per 100,000 in 2007. Although mortality rates decreased markedly (from 24 per 1000 HIV-infected patients in 2003 to 16 per 1000 in 2007), the data show that mortality was still higher in HIV-infected patients compared with the general population in the most recent years (SMR 8.8 in 2007). In each year included in the study, HIV-infected patients had higher rates of care-seeking for chronic diseases, including liver diseases (SHR>8), neuropathy, oesophagus-gastro-duodenum diseases, serious psychiatric disorders and renal failure (SHR approximately 3 for each). Also, the rate of medical attendance for neoplasias, chronic pulmonary disease, diabetes, and cardiovascular disease increased over time in HIV-infected patients compared with the general population. Ranking diseases in order of their total cost to the health system, HIV infection ranked 12th, with total costs of €28.6 million in 2007. Ranking in order of cost per patient, HIV infection ranked third, with a cost per patient of €9894 in 2007. HIV-infected patients with concomitant chronic diseases had higher average costs. The cost per patient in 2007 was €8104 for HIV-infected patients without other chronic diseases, €9908 for HIV infection plus cardiovascular disease, €11,370 for HIV infection plus chronic liver disease and €12,013 for HIV infection plus neoplasias. CONCLUSIONS: The prevalence and population cost of people living with HIV are likely to increase as a result of prolonged survival, aging of HIV-infected patients and increased risk of other chronic diseases. In the near future, HIV infection will rank as one of the most costly chronic diseases. Prevention strategies need to be more widely adopted to control the growing burden of the HIV epidemic and other chronic diseases affecting HIV-infected patients.

Common genetic markers and prediction of recurrent events after ischemic stroke in young adults.

BACKGROUND: Scarce information is available on the usefulness of new prediction markers for identifying young ischemic stroke patients at highest risk of recurrence. METHODS: The predictive effect of traditional risk factors as well as of the 20210A variant of prothrombin gene, the 1691A variant of factor V gene, and the TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR) gene on the risk of recurrence was investigated in a hospital-based cohort study of 511 ischemic stroke patients younger than 45 years followed up for a mean of 43.4 months. Outcome measures were fatal/nonfatal myocardial infarction, ischemic stroke, or TIA. Risk prediction was assessed with the use of the concordance c (c index), and the Net Reclassification Improvement (NRI). RESULTS: The risk of recurrence increased with increasing number of traditional factors (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.57-3.35 for subjects with 1 factor: HR 5.25, 95% CI 2.45-11.2 for subjects with 2), as well as with that of predisposing genotypes (HR 1.96, 95% CI 1.33-2.89 for subjects carrying 1 at-risk genotype; HR 3.83, 95% CI 1.76-8.34 for those carrying 2). The c statistics increased significantly when the genotypes were included into a model with traditional risk factors (0.696 vs 0.635, test z = 2.41). The NRI was also significant (NRI = 0.172, test z = 2.17). CONCLUSIONS: Addition of common genetic variants to traditional risk factors may be an effective method for discriminating young stroke patients at different risk of future ischemic events.

Effectiveness of hepatitis-B vaccination in Ivory Coast: the case of the Grand Bassam health district.

Ivory Coast has a high prevalence of infection with hepatitis B virus (HBV). The effects of a control programme based on the anti-HBV vaccine, which has formed part of the national Expanded Programme on Immunization (EPI) since 2000, have recently been evaluated in the country, for the first time. In this, cross-sectional investigation, two-stage cluster sampling stratified by age was used to assess the impact of the programme of universal childhood HBV vaccination in the Grand Bassam health district. The seroprevalences of carriage of the HBV surface antigen (HBsAg) and of antibodies to this antigen (HBsAb) and to the core antigen of HBV (HBcAb) were estimated among children aged 12-59 months and their mothers. Serology was successful for 1038 children (of 1172 in the original sample) and 836 mothers. Of the children enrolled, 46.8% had had a standard vaccination (completed before the age of 6 months, with the correct schedule), 4.6% had had no vaccination against HBV, and the rest had received incomplete or incorrectly timed vaccination. The prevalence of HBsAg carriage was 0.7% among the tested children and 9.9% among the tested mothers. The prevalence of seroprotection (i.e. an HBsAb titre of >10 mIU/ml), which was 74.2% overall, was strongly correlated with the number of vaccination doses, ranging from 16.7% in the unvaccinated infants to 85.5% in the children who had each received four doses. Circulation of the virus (indicated by seropositivity for HBcAb) was much higher among the unvaccinated children (10.4%) than the fully vaccinated ones (2.9%). The prevalences of both HBsAg and HBcAb were higher in rural areas, where vaccine coverage was relatively low, than in the urban areas. It appears that HBV vaccine is highly effective within the framework of the EPI in Ivory Coast, where it has already had a positive impact in reducing HBsAg carriage among children under 5 years of age. Improving vaccination coverage in the rural areas of the country is now a public-health priority.

Perfusion CT in patients with acute ischemic stroke treated with intra-arterial thrombolysis: predictive value of infarct core size on clinical outcome.

BACKGROUND AND PURPOSE: A potential role of perfusion CT (PCT) in selecting patients with stroke for reperfusion therapies has been recently advocated. The purpose of the study was to assess the reliability of PCT in predicting clinical outcome of patients with acute ischemic stroke treated with intra-arterial thrombolysis (IAT). MATERIALS AND METHODS: Twenty-seven patients with acute hemispheric ischemic stroke were investigated with PCT and treated with IAT between 3 and 6 hours of stroke onset. The infarct core was outlined on cerebral blood volume (CBV) maps by using accepted viability thresholds. The penumbra was defined as time-to-peak (TTP)-CBV mismatch. Clinical outcome was assessed by modified Rankin Scale (mRS) scores at 3 months and dichotomized into favorable (mRS score, 0-2) and unfavorable (mRS score, 3-6). Data were retrospectively analyzed by multiple regression to identify predictors of clinical outcome among the following variables: age, sex, National Institutes of Health Stroke Scale score, serum glucose level, thrombolytic agent, infarct core and mismatch size, collateral circulation, time to recanalization, and recanalization rate after IAT. RESULTS: Patients with favorable outcome had smaller cores (P = .03), increased mismatch ratios (P = .03), smaller final infarct sizes (P < .01), higher recanalization rates (P = .03), and reduced infarct growth rates (P < .01), compared with patients with unfavorable outcome. The core size was the strongest predictor of clinical outcome in an "all subset" model search (P = .01; 0.96 point increase in mRS score per any increment of 1 SD; 95% confidence interval, +0.17 to +1.75). CONCLUSIONS: PCT is a reliable tool for the identification of irreversibly damaged brain tissue and for the prediction of clinical outcome of patients with acute stroke treated with IAT.

Implementation of a programme for the prevention of mother-to-child transmission of HIV in a Ugandan hospital over five years: challenges, improvements and lessons learned.

To identify factors that may limit acceptance of HIV testing and enrolment in the programmes for the prevention of mother-to-child-transmission of HIV, we retrospectively assessed the performance of the service at St Francis Hospital, Nsambya in Kampala. Over five years, a total of 26,556 pregnant women were offered voluntary counselling and confidential HIV testing and, if HIV positive, enrolment in the programme. Acceptance of the HIV test increased in the last two years (from 72.7% in 2001-2002 to 79.9% in 2003-2004). Enrolment in the programme increased over time and was greater among older (64% in women older than 30 years and 44.8% in those aged less than 20 years) and highly educated women. HIV prevalence was associated with age and inversely associated with the level of education. The need for specific personnel for counselling, male partners' involvement and availability of antiretroviral drugs for those who needed treatment were identified as factors possibly affecting implementation.

Human T-cell lymphotropic virus type I (HTLV-I) confirmed by PCR-Southern blot and sequencing analysis in a woman with tropical spastic paraparesis.

Human T-cell lymphotropic virus type I (HTLV-I) is a human retrovirus and the aetiological agent of a progressive neurological disease called tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), as confirmed by evidence accumulated in HTLV-I seroprevalence studies. TSP/HAM is rarely diagnosed in Italy, given the low prevalence of HTLV-I in the population. TSP/HAM begins insidiously in the fourth decade, mainly with spastic paraparesis of the lower extremities and positive Babinski reflex, as well as interfering with bowel and bladder functions. In this study we report the clinical, virological and haemato chemical data of a 54-year-old woman, born in the Ivory Cost, with symptoms suggestive of TSP. The presence of HTLV-I infection was demonstrated by the detection of antibodies in serum and in cerebrospinal fluid by immunoenzymatic assay and Western blot analysis. In addition, viral isolation was carried out in peripheral blood cells, and the presence of HTLV-I proviral DNA was confirmed by polymerase chain reaction/Southern blot and sequencing analysis. According to our results, HTLV-I testing might be useful when TSP/HAM is suspected.

Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease: evidence from an ultrasonographic study.

The association of decreased cerebral blood flow with the development of Alzheimer's disease (AD) has been a recent target of interest. By using neuroimaging techniques, growing attention has been devoted to the identification of preclinical AD. In this study, color duplex sonography of cervical arteries was used to measure mean cerebral blood flow (CBF) on 55 amnestic Mild Cognitive Impairment (MCI) patients. Two years after enrollment, excluding patients who progressed to dementia other than AD, two subgroups were identified, patients who developed AD (MCI converters) and patients with preserved cognitive and functional level (MCI non-converters). Examining the mean difference of CBF measured at baseline in the two subgroups obtained, a significant difference was noticed (MCI converters 539.3 +/- 114.3 vs MCI non converters 636.0 +/- 143.9, p < 0.05). MCI patients with CBF higher than median value (558 ml/min) had lower risk of developing AD (specificity 72.2%, sensitivity 68.4%) within a two year follow-up. Ultrasonography of the cervical arteries is a simple, non invasive and widespread technique useful in detecting CBF decline during the MCI stage, thus identifying patients who later will convert to AD.

Volume reduction in cerebral blood flow in patients with Alzheimer's disease: a sonographic study.

Neuroimaging techniques such as PET and SPECT demonstrated a consistent reduction of cerebral blood flow (CBF) in Alzheimer's disease (AD). The aim of the study was to assess the potential role of ultrasonography for CBF measurement in AD patients and whether the CBF volume correlates positively with disease severity. Fifty patients who met the diagnostic criteria of probable AD (NINDS-ADRDA) were compared to 50 age-matched healthy elderly volunteers. The extracranial internal carotid arteries (ICAs) and the vertebral arteries (VAs) of the patients and controls were examined. Angle-corrected time-averaged flow velocity (TAV) and the diameter of the vessel were measured. Intravascular flow volumes were calculated as the product of TAV and the cross-sectional area of the circular vessel. CBF volume was calculated as the sum of flow volumes in the ICAs and VAs of both sides. All subjects underwent the MMSE. The mean global CBF (474.87 +/- 94.085 vs. 744.26 +/- 94.082 ml/min; p < 0.0001) was lower in AD patients than in healthy volunteers. A significant decline in global flow volumes (r = 0.48; p < 0.0007) with the degree of cognitive impairment was also present. The ability of ultrasonography to characterize flow decreases makes such a technique an attractive tool for the study of AD, for the evaluation of pharmacological therapies and, possibly, for early diagnosis.

Transient global amnesia: a clinical and sonographic study.

BACKGROUND: The aetiology of transient global amnesia (TGA) is still unknown. The aim of this study was to identify potential risk factors for TGA, vascular risk factors, the role of patent foramen ovale (PFO) and of retrograde jugular venous flow. METHODS: 138 subjects entered the study, including 48 patients with TGA, 42 age-matched patients with transient ischaemic attack (TIA) and 48 controls. PFO was studied by contrast transcranial duplex sonography. Retrograde jugular venous flow was tested with air contrast ultrasound venography (ACUV). RESULTS: TGA patients and controls showed a lower prevalence for vascular risk factors than TIA patients. No statistical difference was found between the 3 groups with regard to PFO. ACUV detected jugular valve incompetence in 72.9% TGA, 35.7% TIA and 39.5% controls (TGA vs. TIA and TGA vs. controls p < 0.01). CONCLUSIONS: TGA patients have fewer vascular risk factors than TIA patients. Paradoxical embolism due to PFO as a cause of TGA is not confirmed in our study. Cerebral venous hypertension due to incompetence of the internal jugular valve may play a role in the pathogenesis of TGA.

The environment in the provincial plan of Cremona, Italy.

Recent Italian laws mandate the consideration of environmental factors in local plans, especially at the provincial level of government. The plan for the province of Cremona in northern Italy illustrates the integration of the environment in provincial-level planning. The Cremona plan was developed through an ecological planning approach that occurred from 1994 to 1998. As part of this process, the planning team designed an environmental sustainability index. This index was integrated with an environmental capability analysis. To improve the quality of the Cremona landscape, the planning team developed an ecological network. This network seeks to weave together the natural areas of the province, especially by connecting provincial parks to regional river parks throughout Lombardy. The experience of the Cremona provincial plan has implications for environmental management elsewhere in Italy, Europe, and abroad.

Lemierre's syndrome complicated by carotid thrombosis.

Lemierre's syndrome, also known as postanginal sepsis, is a rare condition that presents as an increasing sore throat due to acute pharyngitis or tonsillitis and progresses to sepsis, due to suppurative thrombophlebitis of the internal jugular vein. We present an atypical case of Lemierre's syndrome complicated by carotid thrombosis. The etiological factors and the diagnostic and therapeutic measures are discussed.

[Alpha 1-antitrypsin deficiency: the Brescia clinical study]. / Il deficit di alpha 1-antitripsina: lo studio clinico di Brescia.

In a longitudinal clinical study, two hundred subjects have been evaluated in order to identify alpha 1-antitrypsin deficiency patients. According to their serum alpha 1-antitrypsin levels, they have been divided into three groups: 25 patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and rare deficiency allele--and, if clinically suggested, to be treated with augmentation therapy), 92 patients with intermediate deficiency (with one pathological allele, to be followed up in order to evaluate the risk to develop deficiency related disease) and 63 healthy subjects (normal alleles MM). They performed lung function test (including cardiopulmonary exercise test and methacholine bronchial challenge) chest X-ray and high resolution computed tomography, blood tests. Severe deficiency patients also performed perfusional lung scan to detect early disorders of blood flow, evaluation of arterial blood gases and liver echotomography. Expiratory flow limitation, the prevalence of vascular disease, the amount of urine elastin products and correlations between the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been also investigated. The study showed that in Brescia county the deficiency is more common than expected and that evaluation of liver and vessels might be as useful as lung function tests. In addition, beneficial effect on local system has been observed. The longitudinal study might permit to detect early organ damage and to eliminate additive risk factors.

Potential source of cerebral embolism in migraine with aura: a transcranial Doppler study.

BACKGROUND: The recently found association between patent foramen ovale (PFO) and transient global amnesia (TGA) has suggested that paradoxical microembolization in the terminal vertebrobasilar territory might underlie at least some TGA cases. Migraine with visual aura is another paroxysmal disturbance in which a sudden dysfunction of cortical areas fed by the terminal branches of the basilar artery is believed to trigger the attack. Therefore we investigated the prevalence of PFO in a consecutive unselected cohort of migraine patients. OBJECTIVE: To investigate the prevalence of PFO in a consecutive unselected cohort of migraine patients to search for a possible mechanism for the reported association of migraine with stroke. METHODS AND RESULTS: A total of 113 patients, consecutively referred by the Headache Outpatient Clinic for migraine with aura (MA+, mean age 34+/-12 years) were compared with 53 patients with migraine without aura (MA-, mean age 36+/-13 years) and with 25 age-matched nonmigraine subjects (mean age 31+/-10 years) selected from the hospital staff. PFO was assessed with transcranial Doppler sonography with IV injection of agitated saline, a technique that is 90% sensitive and 100% specific. The prevalence of PFO was 48% (54/113) in MA+ patients, 23% (12/53) in MA- patients, and 20% (5/25) in control subjects. The difference between MA+ and MA- patients was significant (odds ratio [OR] = 3.13, 95% confidence interval [CI] = 1.41 to 7.04, chi2 = 9.52,p = 0.002) as was the difference between MA+ patients and controls (OR = 3.66, 95% CI = 1.21 to 13.25, chi2 = 6.46, p = 0.01), whereas MA- patients did not differ from controls (OR = 1.17, 95% CI = 0.32 to 4.45, chi2 = 0.07). MRI was negative in 22 MA+ and 8 MA- patients. CONCLUSIONS: Patency of the foramen ovale is associated with migraine with aura but not with migraine without aura. The increased risk of stroke found in epidemiologic studies in patients with migraine with aura may be explained by an increased propensity to paradoxical cerebral embolism.