De nouvelles approches quantitatives ou fonctionnelles d'imagerie de la BPCO (bronchopneumopathie chronique obstructive) sont possibles en scanner à 64 coupes par rotation. Elles impliquent l'utilisation de logiciels dédiés, permettant la quantification de l'emphysème ou la détection de shunts via le foramen ovale, plus fréquents dans la BPCO, par analyse des courbes de rehaussement auriculaire gauche.<br />Une autre approche est d'utiliser la synchronisation cardiaque, pour évaluer les structures d'intérêt à différentes phases du cycle cardiaque, ce qui donne une information fonctionnelle utile pour la détection de l'hypertension artérielle pulmonaire (HTAP) de la BPCO.<br />Le but de ce travail, organisé en 3 parties, a été d'évaluer la faisabilité et les performances diagnostiques obtenues avec ces nouvelles applications.<br />1- Quantification des volumes pulmonaires et du pourcentage d'emphysème<br />Nous avons évalué un logiciel protoytpe (Mevis Pulmo) qui permet un calcul des volumes pulmonaires et une quantification de l'emphysème, après segmentation pulmonaire et seuillage des densités. Les résultats peuvent être obtenus de façon globale, individuellement pour chaque poumon et séparément pour chacun des 5 lobes. Les limites anatomiques lobaires sont reconnues de façon automatique (quantification automatique) mais elles peuvent être corrigées si nécessaire (quantification semi-automatique).<br />Nous avons comparé quantification automatique, semi-automatique et visuelle selon un score classique en 5 grades, chez 47 patients présentant une BPCO sévère. Ces patients étaient évalués avant éventuelle réduction endoscopique, par un scanner sans injection en inspiration et expiration.<br />Il n'y a pas de différence significative du pourcentage d'emphysème estimé par quantification automatique et semi automatique (p>0.05 dans les 5 lobes). Les coefficients de corrélation intraclasse sont supérieurs à 0.8 (concordance excellente) sauf pour le lobe supérieur droit (0.68, bonne concordance) et le lobe moyen (0.53, concordance moyenne). La concordance avec le score visuel est bonne (kappa: 0.76; IC 95% 0.58 à 0.94).<br />Le logiciel utilisé permet également d'évaluer les volumes pulmonaires en inspiration et expiration et de les comparer aux volumes de référence en pléthysmographie. Le volume tomodensitométrique (TDM) inspiratoire est corrélé à la capacité pulmonaire totale (CPT) en pléthysmographie (r= 0.8, p< 0.0001) ; la différence moyenne est de -7.7% (valeurs extrêmes: -48.8 à 28.2%). Le volume TDM expiratoire est corrélé au volume résiduel (VR) (r=0.79, p< 0.0001) ; la différence moyenne est de 9.7% (valeurs extrêmes: - 17.9 à 43.3%). Le volume TDM expiratoire est également corrélé au Volume expiratoire maximal en 1 seconde (VEMS) (r=-55, p<0.0001). Le pourcentage d'emphysème est corrélé aux volumes TDM inspiratoire et expiratoire (r= 0.56 et 0.53, p< 0.0001) et au VEMS (r= -0.69, p<0.0001).<br />Le logiciel testé permet donc une quantification lobaire automatique fiable de l'emphysème et une mesure des volumes pulmonaires en TDM pertinente pour évaluer fonctionnellement la sévérité de la BPCO.<br />2- Détection de la perméabilité du foramen ovale en scanner 64 coupes non synchronisé<br />Cette étude a été menée prospectivement chez 105 patients évalués en échographie transoesophagienne (ETO) pour rechercher un foramen ovale perméable et qui donnaient leur consentement pour une exploration tomodensitométrique réalisée le même jour. Après injection de contraste au cours d'une manoeuvre de Valsalva, une acquisition couvrant toute la largeur du détecteur (28.8 mm) était centrée sur la fosse ovale, en continu toutes les 0.5 secondes pendant 7 secondes. Les 128 images résultantes ont été analysées visuellement, à la recherche d'une opacification auriculaire gauche précédant le retour veineux pulmonaire. Les courbes de rehaussement auriculaire gauche (Logiciel DynEva) ont été analysées à la recherche d'un pic précoce de rehaussement.<br />La perméabilité du foramen ovale est détectée avec une sensibilité globale de 55% (IC 95%, 0.38 - 0.70) et une spécificité de 98% (IC 95%, 0.91 - 0.99). Les performances dépendent du grade du shunt en ETO, utilisé comme gold standard. La sensibilité varie entre 28% pour les shunts de grade 1 et 91% pour les shunts de grade 4. L'analyse des courbes de rehaussement n'augmente pas la sensibilité du scanner. La dose moyenne requise est de 2.3 mSv.<br />Ces résultats permettent d'envisager d'associer la recherche de shunts de haut grade via le foramen ovale à l'analyse tomodensitométrique du parenchyme pulmonaire, dans des contextes d'hypoxémie inexpliquée ou paradoxale,<br />3- Proposition de nouveaux critères prédictifs d'HTAP en scanner multi coupes synchronisé<br />La synchronisation à l'ECG permet d'étudier des paramètres tels que la distensibilité artérielle pulmonaire, l'épaisseur du myocarde infundibulaire et les variations en systole et diastole des mensurations infundibulaires.<br />Ces paramètres ont été analysés dans 2 groupes de patients (groupe 1, 21 patients avec HTAP; groupe 2, 24 patients sans HATP) évalués par cathétérisme cardiaque droit dans le cadre de leur prise en charge clinique. Les données brutes des examens tomodensitométriques (TDM) ont été reconstruites en coupes de 1mm d'épaisseur jointives, tous les 10% du cycle cardiaque.<br />La distensibilité de l'artère pulmonaire droite est calculée à partir de mesures de la surface de section de l'artère, effectuées tous les 10% de l'intervalle R-R. A partir des 10 valeurs obtenues, la valeur maximale de surface de section (SSmax) et la valeur minimale (SSmin) sont repérées. La distensibilité est calculée par l'équation suivante : (SSmax-SSmin)/SSmax.<br />La distensibilité est également calculée selon une méthode simplifiée à partir de deux mesures l'une à 20% du R-R, l'autre à 80%. Ces fenêtres temporelles ont été identifiées comme celles où les valeurs extrêmes de surface de section sont observées dans les deux groupes de patients. L'épaisseur myocardique, le diamètre antéropostérieur et la surface de section infundibulaires sont mesurés en systole et diastole à 30% et 90% du R-R, 1 cm au dessous de la valve pulmonaire. Les mesures de ces paramètres montrent une bonne concordance inter observateur, à l'exception de l'épaisseur systolique infundibulaire. Les valeurs médianes sont significativement différentes pour les deux groupes de patients, à l'exception des dimensions diastoliques infundibulaires. La distensibilité artérielle pulmonaire est le paramètre pour lequel l'aire sous la courbe ROC est la plus large (0.951 ; IC 95%, 0.894 - 1) et qui apparaît le mieux corrélé à la pression artérielle pulmonaire (r=-073, p<0.0001).<br />La distensibilité calculée selon la méthode simplifiée a les mêmes performances. Ce paramètre pourrait être évalué en routine pour détecter l'HTAP chez les patients présentant une BPCO, afin de restreindre les indications de cathétérisme cardiaque droit, méthode d'exploration invasive.

Abstract Patent foramen ovale (PFO) is a common finding in the general population and is present in approximately one quarter of adults. The potential role of PFO in the pathogenesis of ischaemic brain infarction of unknown aetiology in young adults has been investigated during the past 15 years, and associations with other diseases have been proposed. The most plausible mechanism of stroke associated with PFO is paradoxical embolism, but there is uncertainty about this because a venous source of emboli is seldom identified. If the theory of venous emboli is relevant, prothrombotic states should be associated with PFO and ischaemic stroke. Relatively little is known about the risk factors of cryptogenic brain infarction, although this subgroup of stroke is relatively common. As the present diagnostic methods for detecting PFO have certain limitations, new non-invasive, simple and reliable methods would be useful. Two new methods examined here, the dye dilution method and ear oximetry, were both found to be feasible and to be highly specific and sensitive in relation to the present gold standard, contrast transoesophageal echocardiography. A case-control study among adult patients with PFO and cryptogenic brain infarction showed the presence of a prothrombotic state, particularly factor V Leiden and prothrombin G2021OA gene mutation, to be associated with an increased risk of stroke, and migraine was also identified as a risk factor. Associations with the classical risk factors for venous thrombosis and Valsalva manoeuvre-like activities at the onset of stroke were also observed. The results lend support to the theory that paradoxical embolism is one of the pathogenic mechanisms behind cryptogenic brain infarction with associated PFO. In another case-control study among adult patients with cryptogenic brain infarction but without associated PFO, prothrombotic states were not identified as risk factors, except that an association was found between elevated factor VIII activity and stroke. The major independent risk factors for such cryptogenic strokes were current cigarette smoking, hypertension and a low level of high density lipoprotein cholesterol.

Plasmodium is a genus well known for causing malaria, a life-threatening infection for many people where malaria is endemic. The blood-borne disease is transmitted by the female Anopheles mosquito. Till date, eight parasite species have been reported to cause malaria in humans that include P. falciparum, P. vivax, P. malariae, P. ovale curtisi, P. ovale wallikeri, P. cynomolgi, P. knowlesi and more recently P. simium. Amongst them, the most genetically understood species is P. falciparum, causing most of the deaths in children from malaria. Understanding genome variation at the population level of all malaria species is of utmost importance, including clinical cases with very low parasitemia. To achieve this purpose, we need sufficient amounts of parasite DNA material from the pool of host DNA, which always is overrepresented in clinical infections. We utilized a strategy of selective whole genome amplification (SWGA) technology on P. malariae and P. ovale curtisi (two neglected human infecting malaria parasites that often cause mild yet clinically relevant infections with low parasitemia) to efficiently enrich their genomic DNA for high-quality whole genome sequencing. Previous studies on SWGA applied on P. falciparum and P. vivax showed that SWGA could efficiently enrich the amount of starting DNA material from inadequate amounts of parasites directly from clinical samples without separating the host DNA using specifically designed primer sets. We have successfully designed multiple sets of primers and tested the efficiency of five best primer sets using polymerase chain reaction to enrich the genomes of P. malariae and P. ovale curtisi. The efficiency of primers in enriching the genome was tested on two clinical samples for each of P. malariae and P. ovale curtisi. We were able to enrich the genome of P. malariae with an average of 19-fold (19X) enrichment across both samples. For P. ovale curtisi, we could achieve an enrichment of 3 folds only. Nevertheless, we still obtained a sufficient amount of gDNA to prepare Illumina sequencing libraries and call for SNPs and Indels in a biologically reproducible manner at genome-scale.

Background: Malaria is a major public health issue. Artemisinin-based combination therapies are the WHO recommended treatment for uncomplicated malaria. Plasmodium malariae and Plasmodium ovale infections are considered underestimated and the effectiveness of artemisinin-based combination treatments against them is poorly documented. The aim of this study was to evaluate the efficacy of dihydroartemisinin-piperaquine against low parasite density Plasmodium malariae and ovale infections.  Methods: DNA was extracted from dried blood spots on filter papers with Chelex®-100 or a column-based extraction method. Species detection and determination was conducted by SYBR Green quantitative PCR targeting the cytochrome b gene (cytb-qPCR) followed by restriction fragment length polymorphism analyses. In total, 241 samples from 53 patients enrolled in a clinical trial were analysed. The obtained molecular data were compared with the microscopy data of the study. Results: Only 69 out of 143 microscopy-positive samples were confirmed as positive by cytb-qPCR. Ninety-three samples were identified as parasite negative by both microscopy and PCR. None of the 36 microscopy-defined coinfections were detected in the molecular analysis. The cytb-qPCR success rate was 72.9% (CI95% 61.4-82.6), 75.0% (CI95% 34.9-96.8) and 14.8% (CI95% 6.9-26.2) for parasite densities above 1000 parasites/ μL, between 600-1000 parasites/ μL and below 600 parasites/ μL, respectively. The observed poor qPCR success rate is most likely due to sample degradation under poor storage conditions. Conclusions: This study highlights the impact on the preservation and quality of Plasmodium genomic DNA on dried blood spots, when filter papers are stored for more than 3 years in tropical conditions.

Background: The ideal treatment strategy for patients with cryptogenic stroke and patent foramen ovale (PFO) is not yet clear. Previous randomized controlled trials (RCTs) comparing transcatheter PFO closure with medical therapy in patients with cryptogenic stroke to prevent recurrent ischemic stroke showed mixed results. This meta-analysis aims to compare rates of recurrent stroke, transient ischemic attack (TIA) and all-cause mortality with PFO closure and medical therapy vs. medical therapy alone. Methods: PubMed and the Cochrane Center Register of Controlled Trials were searched for studies published through June 2018, comparing PFO closure plus medical therapy versus medical therapy alone. Six RCTs (n = 3750) comparing PFO closure with medical therapy were included in the analysis. End points were recurrent stroke, TIA and all-cause mortality. The odds ratios (OR) with 95% confidence interval (CI) were computed and p < 0.05 was considered as a level of significance. Results: A total of 1889 patients were assigned to PFO closure plus medical therapy and 1861 patients were assigned to medical therapy only. Risk of recurrent stroke was significantly lower in the PFO closure plus medical therapy group compared to medical therapy alone. (OR 0.47, 95% CI 0.33–0.67, p < 0.0001). Rate of TIA was similar between the two groups (OR 0.76, 95% CI 0.52–1.14), p = 0.18). There was no difference in all-cause mortality between two groups (OR 0.73, CI 0.33–1.58, p = 0.42). Patients undergoing PFO closure were more likely to develop transient atrial fibrillation than medical therapy alone (OR: 5.85; CI: 3.06–11.18, p ≤0.0001) whereas the risk of bleeding was similar between the groups (OR: 0.93; CI: 0.55–1.57, p = 0.78). Conclusions: The results of this meta-analysis suggest that transcatheter closure of PFO plus medical therapy is superior to medical therapy alone for the prevention of recurrent cryptogenic stroke. However, PFO closure in these patients has not been shown to reduce the risk of recurrent TIA or all-cause mortality. There is a higher rate of transient atrial fibrillation post PFO closure device placement, the long-term effects of which have yet to be studied.

Introdução:O Forame Oval Patente (FOP) é a comunicação direita-esquerda (CDE) ou shunt direita-esquerda (SDE) mais comum e frequentemente encontrada em adultos jovens com Acidente Vascular Cerebral (AVC) relacionado ao mecanismo de embolia paradoxal. A Ecocardiografia Transesofágia (ETE) é considerada o padrão para visualização direta do FOP. O Doppler Transcraniano com o teste de microbolhas é frequentemente usado para detectar CDE com boa correlação com o ETE para o diagnóstico de FOP. Mais recentemente, a Ultrassonografia Transcraniana Colorida (TCCS) com inclusão do modo-B e fluxo de cor tem superado o DTC (que é realizado \"as cegas\") em muitas aplicações clínicas mas a acurácia do TCCS para a detecção de CDE e FOP não tem sido sistematicamente avaliada. Objetivo: Determinar se o TCCS é uma ferramenta acurada para identificar tanto FOP quanto CDE. Métodos: Foram recrutados 106 pacientes prospectivamente com Acidente Vascular Cerebral Isquêmico menores de 55 anos admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP). Os pacientes foram submetidos aos exames de ETE, DTC e TCCS e todos os exames incluíram a técnica do teste de microbolhas. Os examinadores foram cegos para os resultados desses exames e foi calculado a concordância Kappa de Cohen inter-examinadores para o TCCS e DTC. A acurácia para o TCCS foi calculada em comparação ao ETE. Resultados: Foram detectados CDE em 54 (50.9%) dos pacientes (idade média 43.9 ± 8.2 anos) com Kappa de Cohen de 0.92 (IC 95% 0.78-1.0) quando realizados TCCS e TCD. TEE e TCSS foram positivos em 23/98 (23.4%) e ETE negative em 20/98 (20.4%). Em 30 (28.3%) o ETE revelou FOP. O TCSS teve uma sensibilidade de 88.4%(IC 95% 0.68-0.97) e especificidade de 72.2%(IC 95% 0.60-0.81) e uma razão de verossimilhança positive de 3.18 (IC 95% 2.14-4.73) para o diagnóstico de FOP. Conclusão: TCCS e DTC tiveram excelente concordância. TCCS tem uma boa acurácia para a detecção de FOP e CDE em pacientes jovens com Acidente Vascular Isquêmico / Introduction: Patent Foramen Ovale (PFO) is the most common right-to-left shunt (RLS) and is often found in young patients with stroke related to paradoxical embolism. ContrastEnhanced Transesophageal Echocardiography (TEE) is considered a gold standard to visualize PFO. Transcranial Doppler (TCD) with bubble test is often used to detect RLS with good correlation to TEE for the diagnostic of PFO. More recently, Transcranial Color Coded Sonography (TCCS) which included B-mode and color coded imaging has overcome blind TCD in many clinical applications but the accuracy of TCCS for detection of RLS and PFO has not been systematically evaluated. Hypothesis: To determine if the TCCS is an accurate tool to identify both PFO and RLS. Methods: We investigate 106 patients with ischemic stroke under 55 years-old admitted from 2012 to 2014 in a tertiary academic hospital. Patients were evaluated with TEE, TCD and TCCS, and all exams included a saline bubble test. The examiners were blinded for the other tests results. Kappa agreement was calculated inter-examiners for TCCS and TCD. Accuracy of TCCS was calculated in comparison to TEE. Results: We detected a RLS in 54 (50.9%) patients (age mean 43.9 ± 8.2) with kappa agreement 0.92 (95%CI 0.78-1.0) when performed TCCS and TCD. TEE and TCSS were positive in 23/98 (23.4%) and TEE did not reveal contrast in 20/98 (20.4%). In 30 (28.3%) patients only TEE revealed a PFO. TCSS had a sensitivity of 88.4% (95%CI 0.68-0.97), specificity of 72.2% (95%CI 0.60-0.81) and positive likelihood ratio of 3.18 (2.14-4.73) of the diagnosis of PFO. Conclusion: TCCS and TCD had an excellent agreement. TCCS has a good accuracy for the detection of PFO and RLS in young patients with stroke

Introdução:O Forame Oval Patente (FOP) é a comunicação direita-esquerda (CDE) ou shunt direita-esquerda (SDE) mais comum e frequentemente encontrada em adultos jovens com Acidente Vascular Cerebral (AVC) relacionado ao mecanismo de embolia paradoxal. A Ecocardiografia Transesofágia (ETE) é considerada o padrão para visualização direta do FOP. O Doppler Transcraniano com o teste de microbolhas é frequentemente usado para detectar CDE com boa correlação com o ETE para o diagnóstico de FOP. Mais recentemente, a Ultrassonografia Transcraniana Colorida (TCCS) com inclusão do modo-B e fluxo de cor tem superado o DTC (que é realizado \"as cegas\") em muitas aplicações clínicas mas a acurácia do TCCS para a detecção de CDE e FOP não tem sido sistematicamente avaliada. Objetivo: Determinar se o TCCS é uma ferramenta acurada para identificar tanto FOP quanto CDE. Métodos: Foram recrutados 106 pacientes prospectivamente com Acidente Vascular Cerebral Isquêmico menores de 55 anos admitidos na Unidade de Emergência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HCFMRP). Os pacientes foram submetidos aos exames de ETE, DTC e TCCS e todos os exames incluíram a técnica do teste de microbolhas. Os examinadores foram cegos para os resultados desses exames e foi calculado a concordância Kappa de Cohen inter-examinadores para o TCCS e DTC. A acurácia para o TCCS foi calculada em comparação ao ETE. Resultados: Foram detectados CDE em 54 (50.9%) dos pacientes (idade média 43.9 ± 8.2 anos) com Kappa de Cohen de 0.92 (IC 95% 0.78-1.0) quando realizados TCCS e TCD. TEE e TCSS foram positivos em 23/98 (23.4%) e ETE negative em 20/98 (20.4%). Em 30 (28.3%) o ETE revelou FOP. O TCSS teve uma sensibilidade de 88.4%(IC 95% 0.68-0.97) e especificidade de 72.2%(IC 95% 0.60-0.81) e uma razão de verossimilhança positive de 3.18 (IC 95% 2.14-4.73) para o diagnóstico de FOP. Conclusão: TCCS e DTC tiveram excelente concordância. TCCS tem uma boa acurácia para a detecção de FOP e CDE em pacientes jovens com Acidente Vascular Isquêmico / Introduction: Patent Foramen Ovale (PFO) is the most common right-to-left shunt (RLS) and is often found in young patients with stroke related to paradoxical embolism. ContrastEnhanced Transesophageal Echocardiography (TEE) is considered a gold standard to visualize PFO. Transcranial Doppler (TCD) with bubble test is often used to detect RLS with good correlation to TEE for the diagnostic of PFO. More recently, Transcranial Color Coded Sonography (TCCS) which included B-mode and color coded imaging has overcome blind TCD in many clinical applications but the accuracy of TCCS for detection of RLS and PFO has not been systematically evaluated. Hypothesis: To determine if the TCCS is an accurate tool to identify both PFO and RLS. Methods: We investigate 106 patients with ischemic stroke under 55 years-old admitted from 2012 to 2014 in a tertiary academic hospital. Patients were evaluated with TEE, TCD and TCCS, and all exams included a saline bubble test. The examiners were blinded for the other tests results. Kappa agreement was calculated inter-examiners for TCCS and TCD. Accuracy of TCCS was calculated in comparison to TEE. Results: We detected a RLS in 54 (50.9%) patients (age mean 43.9 ± 8.2) with kappa agreement 0.92 (95%CI 0.78-1.0) when performed TCCS and TCD. TEE and TCSS were positive in 23/98 (23.4%) and TEE did not reveal contrast in 20/98 (20.4%). In 30 (28.3%) patients only TEE revealed a PFO. TCSS had a sensitivity of 88.4% (95%CI 0.68-0.97), specificity of 72.2% (95%CI 0.60-0.81) and positive likelihood ratio of 3.18 (2.14-4.73) of the diagnosis of PFO. Conclusion: TCCS and TCD had an excellent agreement. TCCS has a good accuracy for the detection of PFO and RLS in young patients with stroke

Background: Patent Foramen Ovale (PFO), a remnant of the foetal circulation, is emerging as a new cause of disease. It has been found to be associated with cryptogenic stroke in young adults, peripheral arterial embolism and neurological decompression sickness in divers. The detection of PFO remains a diagnostic challenge; transoesophageal echocardiogram being currently considered the ‘gold standard’. The development of a non-invasive technique is crucial for the identification of a venous-to-arterial shunt (v-aCS) which may permit paradoxical embolism. Little is known about the genetic basis of PFO and our limited knowledge is based on animal studies and gene mutations detected in patients with other cardiac septal defects. Methods: Study 1: PFO Detection and Evaluation: This study was designed to evaluate transcranial Doppler (TCD), transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) with administration of contrast via arm and femoral veins. We then developed a standardized protocol for PFO detection and quantification using TCD. Study 2: PFO and Migraine: The PFO detection protocol developed from the first study formed the diagnostic technique to detect v-aCS in an adequately powered matched case control study to explore the association between PFO and migraine. Study 3: The Genetic basis of PFO: This study was designed to explore the genetic basis of a PFO using a candidate gene approach. Results: Study 1 - PFO Detection Study: When compared with TOE with femoral vein contrast injection as the ‘gold standard’, TCD with arm vein contrast was 100% sensitive and 97.4% specific for detecting a PFO. We defined a PFO positive (+ve) study on TCD as > 15 microbubbles entering the cerebral circulation, on TCD following arm vein injection and >16 microbubbles with a femoral contrast injection. A ‘major’ PFO+ve v-aCS was defined as >35 microbubbles with arm vein injection or >90 microbubbles with femoral vein injection. We then developed a new diagnostic pathway for PFO detection in clinical practice. Study 2 - PFO Migraine study: A significant difference in prevalence of v-aCS between migraine with aura M+A) and their matched controls was demonstrated with adjusted OR=3.72 (1.48-9.38) p=0.005 for a PFO+ve v-aCS, and a highly significant difference between M+A and controls for a ‘major’ PFO+ve v-aCS with adjusted OR = 6.38 (1.89 – 21.48) p = 0.003. There was significant association with APC resistance and migraine on thrombophilia screen. Study 3 - The PFO Genetics Study: This study detected mutations of GATA4 and NKX2-5 in both PFO+ve cases and PFO-ve controls. Two novel non synonymous mutations of GATA4, c.461T>A and c.994G>A were found only in PFO positive individuals and may be associated with a PFO. All the PFO+ve cases with a GATA4 gene mutation had a major PFO+ve v-aCSConclusion:TCD detects PFO with a sensitivity of 100% and specificity of 92.3% and is the most reliable non-invasive technique for PFO detection. When arm vein injections are used both cough and valsalva provocation is essential. There was a highly significant association between PFO+ve v- aCS and M+A, especially with a ‘major’ PFO+ve v-aCS. GATA 4 mutations though infrequent were found PFO+ve cases and all had major v-aCS.

The role of patent foramen ovale (PFO) in stroke was debated for decades. Randomized clinical trials (RCTs) have shown fewer recurrent events after PFO closure in patients with cryptogenic stroke (CS). However, in clinical practice, treating stroke patients with coexisting PFO raises some questions. This brief review summarizes current knowledge and challenges in handling stroke patients with PFO and identifies issues for future research. The rationale for PFO closure was initially based on the concept of paradoxical embolism from deep vein thrombosis (DVT). However, RCTs did not consider such details, limiting their impact from a pathophysiological perspective. Only a few studies explored the coexistence of PFO and DVT in CS with varying results. Consequently, the PFO itself might play a role as a prothrombotic structure. Transesophageal echocardiography thus appears most appropriate for PFO detection, while a large shunt size or an associated atrial septum aneurysm qualify for a high-risk PFO. For drug-based treatment alone, studies did not find a definite superiority of oral anticoagulation over antiplatelet therapy. Remarkably, drug-based treatment in addition to PFO closure was not standardized in RCTs. The available literature rarely considers patients with transient ischemic attack (TIA), over 60 years of age, and competing etiologies like atrial fibrillation. In summary, RCTs suggest efficacy for closure of high-risk PFO only in a small subgroup of stroke patients. However, research is also needed to reevaluate the pathophysiological concept of PFO-related stroke and establish strategies for older and TIA patients and those with competing risk factors or low-risk PFO.

Background: Stroke is a leading cause of significant physical, cognitive, and psychiatric morbidity. One risk factor for stroke is paradoxical embolization through a patent foramen ovale (PFO). In cardiac clinical practice, power M-mode Transcranial Doppler (TCD) evaluation is the gold standard for diagnosis of PFO, or right-to-left cardiac shunt (RLS). Brain micro-embolization due to diagnostic bubble contrast echocardiography may cause neurological symptoms in patients with PFO. However, the neurocognitive effects of TCD have not been studied. Objective: The purpose of this study was to evaluate cognitive outcomes in patients who undergo routine diagnostic bubble contrast TCD. The aims of the study were (1) to determine if cognitive function declines pre- to post-TCD evaluation and, (2) to assess the relationship between cognitive function and severity of the RLS measured using the Spencer Grading System. Methods: One hundred and four participants referred to Sorensen Cardiovascular Group for diagnosis of RLS were evaluated for changes in cognitive functioning at three time points. A dual baseline (pre-test and baseline test) was administered to mitigate practice effects between the first and second administrations. All pre and post-TCD comparisons were analyzed using the baseline test and post-TCD test, controlling for the effects of practice, if present. Results: Practice effects were observed for the working memory task, with significant improvement in working memory scores occurring between the first (pre-test) and second (baseline) administrations. The main effect for shunt group (no shunt vs. moderate-to-severe shunt) and the shunt group by time interactions were not significant for processing speed, attention, or working memory, adjusting for practice effects, age, and education. Migraine did not predict group status for mood or shunt variables. Conclusion: Cardiac patients with both small and large RLS did not experience a decline in processing speed, attention, or working memory ability following TCD, suggesting that TCD-induced microemboli do not result in immediate cognitive deficits in these domains. These findings support the use of TCD for routine evaluation of PFO, even in patients with severe RLS, although findings are limited to young (30s), medically healthy, predominately Caucasian individuals assessed immediately following TCD. Results do not exclude the possibility of cognitive impairment at follow-up, on other cognitive tests, or in other cognitive domains.