Antithrombin deficiency caused by SERPINC1 gene mutation in white matter lesions: A case report.

RATIONALE: White matter lesions (WMLs) are structural changes in the brain that manifest as demyelination in the central nervous system pathologically. Vasogenic WMLs are the most prevalent type, primarily associated with advanced age and cerebrovascular risk factors. Conversely, immunogenic WMLs, typified by multiple sclerosis (MS), are more frequently observed in younger patients. It is crucial to distinguish between these 2 etiologies. Furthermore, in cases where multiple individuals exhibit WMLs within 1 family, genetic testing may offer a significant diagnostic perspective. PATIENT CONCERNS: A 25-year-old male presented to the Department of Neurology with recurrent headaches. He was healthy previously and the neurological examination was negative. Brain magnetic resonance imaging (MRI) showed widespread white matter hyperintensity lesions surrounding the ventricles and subcortical regions on T2-weighted and T2 fluid-attenuated inversion recovery images, mimicking immunogenic disease-MS. DIAGNOSES: The patient was diagnosed with a patent foramen ovale, which could explain his headache syndrome. Genetic testing unveiled a previously unidentified missense mutation in the SERPINC1 gene in the patient and his father. The specific abnormal laboratory finding was a reduction in antithrombin III activity, and the decrease may serve as the underlying cause for the presence of multiple intracranial WMLs observed in both the patient and his father. INTERVENTIONS: The patient received percutaneous patent foramen ovale closure surgery and took antiplatelet drug recommended by cardiologists and was followed up for 1 month and 6 months after operation. OUTCOMES: While the lesions on MRI remain unchanging during follow-up, the patient reported a significant relief in headaches compared to the initial presentation. LESSONS: This case introduces a novel perspective on the etiology of cerebral WMLs, suggesting that hereditary antithrombin deficiency (ATD) could contribute to altered blood composition and may serve as an underlying cause in certain individuals with asymptomatic WMLs.

Investigation of patent foramen ovale as a mechanism for brain metastasis in patients without prior lung involvement.

PURPOSE: The mechanisms of brain metastasis are incompletely understood. Circulating tumor cells travel to the right heart and through the pulmonary circulation, where they may become lung metastases, and can circulate further to the left heart and brain. In patients who develop brain metastases without lung involvement, we hypothesized that cancer cells may travel directly from the right atrium to left atrium via a patent foramen ovale (PFO), akin to paradoxical embolism. If the prevalence of PFO is greater in these individuals compared to the general population (20-30%), PFO may play a role in brain metastasis, and prophylactic closure may provide benefit. Accordingly, we investigated the prevalence of PFO in patients with brain metastases without prior lung involvement. METHODS: We prospectively identified patients with brain metastases from a non-lung primary cancer with no preceding or concurrent lung involvement. Nine eligible participants underwent a transcranial Doppler study with intravenous agitated saline to assess for PFO. RESULTS: Among nine participants, primary cancers were breast (n = 6), upper gastrointestinal (n = 2), and thyroid (n = 1). A positive bubble study was identified in 2/9 (22.2%) participants: one female with breast cancer and one male with duodenal adenocarcinoma. No participants developed lung metastases on subsequent chest imaging. CONCLUSION: In this prospective pilot study, we found a similar prevalence of PFO in patients who developed brain metastases without preceding lung involvement compared to estimates for the general population. Through a larger study is needed, the development of brain metastases in these individuals may primarily reflect tumor-specific biological factors diecting metastasis organotropism.

Avaliação Ecocardiográfica de Pacientes com Forame Oval Patente e Acidente Vascular Cerebral Criptogênico / Echocardiographic Evaluation of Patients with Patent Foramen Ovale and Cryptogenic Stroke

Recentes estudos indicaram que o forame oval patente (FOP) pode ser responsável pelo acidente vascular cerebral criptogênico (AVC) em pacientes jovens que apresentam condições anatômicas favoráveis a essa anomalia e que a oclusão transcateter reduz a incidência do acidente vascular cerebral quando comparada ao tratamento clínico. A injeção de soro agitado durante o estudo ecocardiográfico, associada à manobra de Valsalva, pode evidenciar shunt direita-esquerda com alta sensibilidade (89%) e especificidade (92%) quando se utiliza o ecocardiograma transesofágico. Avaliando as características clínicas de pacientes com acidente vascular cerebral e forame oval patente, o trial Risk of Paradoxical Embolism, conhecido pela sigla RoPE, (Risk of Paradoxical Embolism) estabeleceu um escore de risco para acidente vascular cerebral criptogênico e, por meio de um modelo de regressão multivariada, identificou seis variáveis: idade, presença de isquemia cortical, diabetes, hipertensão, AVC e acidente isquêmico transitório prévio. Os escores mais elevados foram observados em jovens com AVC e sem fatores de risco vascular e os escores mais baixos em idosos com fatores de risco vascular, de modo que o forame oval patente sugere ser acidental. Condições anatômicas do FOP predispõem à embolia sistêmica (separação do FOP > 2 mm; túnel do FOP > 10 mm; ângulo entre a veia cava inferior e o flap do FOP <10°; intensidade do shunt com manobra de Valsalva; presença de aneurisma do septo interatrial e rede de Chiari ou válvula de Eustáquio proeminente). O fechamento do FOP pode prevenir a embolia paradoxal, reduzindo a incidência de acidente vascular cerebral em pacientes considerados com de risco elevado. A relação entre Acidente Vascular Cerebral (AVC) criptogênico e a presença de Forame Oval Patente (FOP) tem despertado particular interesse, baseada em estudos recentes que demonstraram que a oclusão transcateter do FOP reduziu a incidência de AVC criptogênico, quando comparado ao tratamento medicamentoso.1 Trombos atravessando o forame oval podem ser observados em exames ecocardiográficos e em autópsias, confirmando esse mecanismo como responsável pela embolia paradoxal, ou seja, um trombo venoso passando para a circulação arterial por um shunt direita-esquerda. Entretanto, essa visualização ecocardiográfica é rara e existem poucos estudos publicados2,3 (Figura 1). Alguns estudos clínicos demonstram a propensão do FOP ser o responsável pela embolia paradoxal. Pacientes portadores de diabetes, hipertensão arterial sistêmica e doença arterial coronária têm baixa prevalência para o FOP ser o responsável pela embolia paradoxal. Por outro lado, história de trombose venosa profunda, embolia pulmonar, hipertensão pulmonar, viagens prolongadas, manobra de Valsalva precedendo o início de sintomas de AVC, enxaqueca e apneia do sono tem sido descrita como fatores de risco independentes para a associação entre FOP e eventos cerebrovasculares.4 Mesmo sendo pouco frequente a visualização de trombos em forame oval, a observação epidemiológica nos leva a acreditar que o FOP é o responsável por um número considerável de acidentes vasculares cerebrais.5 A prevalência de FOP em um estudo com autópsia em 965 corações normais é de 27%, com similar distribuição entre homens e mulheres. Essa prevalência declina com a idade, sendo de 34% em menores de 30 anos, 25% entre 30 e 80 anos e 20% em maiores de 80 anos.6 Em pacientes com AVC criptogênico, entretanto, a prevalência é particularmente elevada, chegando a 40% em pacientes com idade inferior a 55 anos.7 É importante ressaltar que a presença de FOP em pacientes com AVC criptogênico não é a única etiologia para o embolismo paradoxal. Outros mecanismos podem ser responsáveis, como fibrilação atrial não detectada, tumores cardíacos (mixoma e fibroeslastomas), presença de contraste ecocardiográfico espontâneo em átrio esquerdo, valvopatia mitral reumática, calcificação do anel valvar mitral, próteses cardíacas biológicas e mecânicas, estados de hipercoagulabilidade e ateroma de aorta ascendente.8 O estudo ecocardiográfico é parte da rotina na avaliação do FOP, principalmente o Ecocardiograma Transesofágico (ETE) com utilização de solução salina agitada (macrobolhas). Considera-se um shunt pequeno quando passam de três a dez bolhas, médio de dez a 30 bolhas e grande se mais de 30 bolhas contadas nos primeiros batimentos após a injeção.9 Além da detecção do shunt, o ETE avalia as características anatômicas do FOP, assim como o diagnóstico diferencial com a comunicação interatrial e com o shunt pulmonar.10,11 Trabalhos comparando o ETE utilizando macrobolhas com os achados de autópsia mostram sensibilidade de 89% e especificidade de 92%, sendo que a autópsia é considerada padrão-ouro.12(AU)

Cannula migration through an undiagnosed patent foramen ovale and embolic cerebrovascular accident in a patient with femoral venoarterial extracorporeal membrane oxygenation.

We present a case report of a patient with a pulmonary embolus placed on venoarterial extracorporeal membrane oxygenation who developed venous cannula migration through an undiagnosed patent foramen ovale causing an ischemic stroke due to a thrombus and requiring thrombectomy and device closure of the atrial defect.

Systemic Dissemination of Injected Foreign Material.

A 32-year-old woman collapsed following an intravenous injection of material that included crushed pharmaceutical tablets. Resuscitation was attempted but was unsuccessful. She had an extensive past medical history of complications resulting from intravenous drug use. Death was due to mixed drug toxicity. The major findings at autopsy included a 10 mm deep skin sinus over the right femoral vein that was used as an injection site. Polarizable foreign material was present at the injection site and also within the lungs with a granulomatous reaction. Of note, a probe-patent foramen ovale had permitted paradoxical embolization of this material into the systemic circulation with lodgement within the liver, portal lymph nodes, myocardium, spleen, kidneys, and pancreas. This case highlights the importance of checking for any intracardiac shunts, which may be quite small, and systemic dissemination of foreign material to multiple organs in intravenous drug users who present for medicolegal assessment.

Carcinoid heart disease revealed by cyanosis with both right and left valvular involvement: a case report.

BACKGROUND: Carcinoid heart disease is a frequent complication of carcinoid syndrome. It is related to the release by the carcinoid tumor and/or its metastases of bioactive substances such as serotonin. It is characterized by right-sided valvular involvement and can lead to right-sided heart failure. It is a prognostic factor of carcinoid syndrome. CASE PRESENTATION: We report the case of a 53-year-old African woman with an endocrine tumor of her small intestine complicated by carcinoid heart disease, revealed by right-sided heart failure. The diagnosis was confirmed by transthoracic echocardiography, which showed a severe tricuspid regurgitation with a patent foramen ovale, and by increased serum chromogranin A and urinary 5-hydroxyindoleacetic acid. Initially she was treated with medical therapy (furosemide and injection of somatostatin). Afterwards she was proposed for surgery. The evolution of her treatment was good. CONCLUSIONS: Carcinoid syndrome is complicated in 60% of the cases of a heart disease, and is responsible for an important morbidity and mortality. The prognosis of patients with carcinoid heart disease has improved in recent years through somatostatin analogues and the cardiac surgery.

Hypoxia due to positive pressure ventilation in Edwards' syndrome: A case report.

Edwards' syndrome also known as trisomy 18 is a congenital disorder associated with cardiovascular issues including ventricular septal defect (VSD), atrial septal defect (ASD) and patent duct arteriosus (PDA). An emergency colostomy was performed on a neonate born with an imperforate anus. Pre-operative transthoracic echocardiography showed presence of VSD, a patent foramen ovale (PFO) or ASD. Even though the baby had a good general condition and optimal peripheral oxygen saturation (SpO2), during positive pressure ventilation, she suffered severe hypoxia (50% SpO2). The cause of the hypoxia was thought to be the right-left shunt and so during a second attempt at anaesthesia a vasopressor (noradrenaline 0.03 µg/kg/min) was infused to increase systemic vascular resistance. Thereafter, SpO2 increased to 80-90% and the surgery was completed. The baby recovered without any neurological complications. Genetic testing post-partum showed she had Edwards' syndrome.

A very rare association between giant right atrial myxoma and patent foramen ovale. Extracellular matrix and morphological aspects: a case report.

We report a case of sporadic giant cardiac myxoma with a rare localization in the right atrium, operated in our Service, in a 73-year-old female patient who also presented a patent foramen ovale and a history of ischemic stroke in the year prior to current admission. Intra-operatively, the tumor had a very friable, gelatinous aspect, with a high potential for embolization due to its reduced consistency. The present paper refers to clinical, histochemical and immunohistochemical particularities, as well as to macroscopic and microscopic characteristics of the cardiac myxoma, emphasizing the extracellular matrix aspects, and without leaving out the cellular components of this rare tumor, with possible inference in the management of this disease. The authors present their own observations related to the data from the literature. Also, there are some particularities of the case which justify the current presentation.

Fluoroscopy-Free Pulmonary Vein Isolation in Patients with Atrial Fibrillation and a Patent Foramen Ovale Using Solely an Electroanatomic Mapping System.

INTRODUCTION: The advent of electroanatomical mapping (EAM) systems for pulmonary vein isolation (PVI) has dramatically decreased radiation exposure. However, the need for some fluoroscopy remains for obtaining left atrial (LA) access. The aim was to test the feasibility of fluoroscopy-free PVI in patients with atrial fibrillation (AF) and a patent foramen ovale (PFO) guided solely by an EAM system. METHODS: Consecutive patients with AF undergoing PVI and documented PFO were studied. An EAM-guided approach without fluoroscopy and ultrasound was used. After completing the map of the right atrium, the superior vena cava and the coronary sinus, a catheter pull-down to the PFO was performed allowing LA access. The map of the LA and subsequent PVI was also performed without fluoroscopy. RESULTS: 30 patients [age 61±12 years, 73% male, ejection fraction 0.64 (0.53-0.65), LA size in parasternal long axis 38±7 mm] undergoing PVI were included. The time required for right atrial mapping including transseptal crossing was 9±4 minutes. Total procedure time was 127±37 minutes. Fluoroscopy-free PVI was feasible in 26/30 (87%) patients. In four patients, fluoroscopy was needed to access (n = 3) or to re-access (n = 1) the LA. In these four patients, total fluoroscopy time was 5±3 min and the DAP was 14.9±13.4 Gy*cm2. Single-procedure success rate was 80% (24/30) after a median follow-up of 12 months. CONCLUSION: In patients with a documented PFO, completely fluoroscopy-free PVI is feasible in the vast majority of cases.

An audit of persistent foramen ovale closure in 105 divers.

INTRODUCTION: Right-to-left shunt across a persistent foramen ovale (PFO) has been associated with cutaneous, neurological and vestibular decompression illness (DCI). Percutaneous closure of a PFO has been used to reduce the risk of DCI. There are no randomised controlled trial data to support PFO closure for the prevention of decompression illness (DCI), so the need for audit data on the safety and efficacy of this technique has been recognised by the National Institute of Health and Clinical Excellence in the UK. METHOD: Retrospective audit of all transcatheter PFO closures to reduce the risk of DCI performed by a single cardiologist with an interest in diving medicine. RESULTS: A total of 105 eligible divers undergoing 107 procedures was identified. There was a low rate of procedural complications; a rate lower than a recent randomised trial of PFO closure for stroke. Atrial fibrillation required treatment in two patients. One patient with a previously repaired mitral valve had a stroke that was thought to be unrelated to the PFO closure. Sixteen divers had minor post-procedure symptoms not requiring any treatment. Two divers required a second procedure because of residual shunt; both subsequently returned to unrestricted diving. Eighty-one of 95 divers in whom follow-up bubble contrast echocardiography was available returned to unrestricted diving. CONCLUSIONS: The PFO closure procedure appeared to be safe and was associated with the majority of divers being able to successfully return to unrestricted diving.

Paradoxical embolism interrupted.

A 41 year-old African-American male presented with syncope preceded by shortness of breath at outside facility and transferred to us for management of extensive pulmonary embolism with unstable vital signs. Electrocardiogram showed sinus tachycardia with S1Q3T3 pattern. A transthoracic echocardiogram revealed a freely mobile strand like mass in the left atrium. A transoesophageal echocardiogram showed a very large freely mobile thrombus extending from a patent foramen ovale in to the left atrium. He underwent emergent surgery for the extraction of clot followed by thromboembolectomy from both pulmonary arteries. He made a remarkable recovery and was discharged after seven days of hospital stay.

Role of cross-sectional imaging for structural heart disease interventions.

With the aging population, significant valvular heart disease is increasingly identified in patients too frail to undergo surgery. Transcatheter therapies for structural heart disease represent an alternative therapeutic approach for these patients. During these procedures, direct visualization of the surgical field is replaced by image guidance for intraprocedural decision making. Advances in percutaneous devices and delivery systems, coupled with enhancements in 3-dimensional imaging with multiplanar reformatting, have allowed these procedures to be performed safely and with excellent results. This article describes the role of cross-sectional imaging for detailed assessment and preprocedural planning of aortic, mitral, and pulmonic valve interventions.

Systemic thromboembolism after deep vein thrombosis caused by uterine myomas.

A systemic thrombus embolization after deep vein thrombosis (DVT) caused by uterine myomas is very rare. The authors recently had experienced this association in a single 46-year-old Thai woman with previous healthy history and no other known risk factors for development of DVT. On arrival at a nearby small hospital, the deceased had presented with an abrupt onset of right hemiparesis, and 34 hours after admission to the hospital, she suddenly developed a cardiopulmonary collapse and was pronounced dead. Autopsy examination revealed that her death was attributed to massive pulmonary thromboembolism with systemic embolization through coexistent patent foramen ovale after DVT of her bilateral lower extremities caused by uterine myomas.

[Threshold rat neonatal cardiomyocyte response to gradual cryptosporidial infection severity increase].

Infectious gastroenteritis is one of the common causes of tachyarrythmia, malabsorbtion and growth retardation in children. Our recent studies have indicated that neonatal.cryptosporidial gastroenteritis is associated with long-term cardiomyocyte abnormalities. The aim of the present study was to find out how neonatal cryptosporidiosis of various severities affects cardiac anatomy and cardiomyocyte polyploidization, remodeling and HIF-1α expression. Using real-time PCR, cytometry, immunohistochemistry, image analysis and interatrial septum visual examination, we revealed that gradual increase in cryptosporidial invasion was associated with threshold changes. At weak parasitic infection, interatrial septum was entire and there was no statistically significant change in cardiomyocytes. At moderate and severe infection, all changes in cardiac anatomy and cardiomyocytes were statistically significant and demonstrated approximately similar degree. Compared to control, heart were atrophied and elongated, interatrial septum contained a small window (patentforamrn ovale), and cardiomyocytes lost protein, became elongated, thin and accumulated additional genomes. Also we found HIF-1α mRNA hyperexpression. Notable, the threshold response to gradual stimulus is an important criterion of development programming since such a response is commonly a consequence of abnormal anatomic structure formation and cell differentiation failure. Our results can be interesting for physicians because they indicate that even moderate cryptosporidiosis can be dangerous for neonatal heart and can trigger neonatal programming of cardiovascular pathology. Also, our results for the first time demonstrate the association between gastroenteritis, patent foramen ovale and cardiomyocyte malfunction.

Young patient with acute ischemic stroke due to papillary carcinoma of the thyroid.

Hypercoagulability is a condition predisposing to arterial or venous thrombosis and is associated frequently with malignancy. We present a rare acute ischemic stroke in a young patient that was the presenting feature for a newly diagnosed papillary carcinoma of the thyroid. Extensive vascular and hematological work-up was normal except for a large patent foramen ovale (PFO). This finding, along with the association of most vascular events with hypercoagulability being of venous origin, makes the mechanism of paradoxical embolism through the large PFO the probable cause of stroke in our patient.

Fatal paradoxical air embolism diagnosed by postmortem imaging and autopsy.

The recognition and visualization of an arterial gas embolism are difficult. We report a case of sudden death caused by paradoxical air embolism of coronary and cerebral arteries, diagnosed by the pre autopsy computed tomography (CT) scanning. A 54-year-old woman suddenly died after the self-removal of the jugular vein catheter. Postmortem imaging examination using CT scanning showed multiple gas embolisms in the cerebral arteries, pulmonary artery, right atrium and ventricle, left ventricle, aorta, and coronary arteries. These findings suggested that the occurrence of acute ischemia of the brain and heart caused by massive air inflow to the artery. Conventional autopsy revealed a patent foramen ovale of the heart. These results indicated that the patient died of paradoxical air embolization of the coronary and cerebral arteries through a patent foramen ovale because of right-to-left shunting. The use of postmortem imaging as an aid for conventional autopsy has proved to be of advantage in the case of gas embolism.

Intramedullary abscess of the spinal cord in the setting of patent foramen ovale.

BACKGROUND: Intramedullary abscess of the spinal cord is a rare entity, especially in the setting of an intracardiac shunt, which, to our knowledge, has not been described in the literature. Here we present a case of an intramedullary spinal cord abscess in a patient with a patent foramen ovale. METHODS: The article includes a chart review and description of a clinical case presentation. RESULTS: A 59-year-old man was admitted with rapidly progressive quadriparesis. Magnetic resonance imaging of the cervical spine demonstrated a large intramedullary mass extending from the level of C3 to C7. The patient was taken to the operating room for biopsy and surgical evacuation of the mass. Intraoperative pathology was consistent with abscess, and subsequent cultures grew Streptococcus viridans. On further workup, the patient was found to have a patent foramen ovale with right-to-left flow. Postoperatively, the strength improved significantly in all extremities with residual weakness. CONCLUSION: This is the first published case of an intramedullary spinal cord abscess in the setting of an intracardiac right-to-left shunt. Although intramedullary spinal cord abscess is rare, there are certain predisposing conditions that increase the risk of its occurrence.