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.

The Genetic Landscape of Patent Foramen Ovale: A Systematic Review.

Patent Foramen Ovale (PFO) is a common postnatal defect of cardiac atrial septation. A certain degree of familial aggregation has been reported. Animal studies suggest the involvement of the Notch pathway and other cardiac transcription factors (GATA4, TBX20, NKX2-5) in Foramen Ovale closure. This review evaluates the contribution of genetic alterations in PFO development. We systematically reviewed studies that assessed rare and common variants in subjects with PFO. The protocol was registered with PROSPERO and followed MOOSE guidelines. We systematically searched English studies reporting rates of variants in PFO subjects until the 30th of June 2021. Among 1231 studies, we included four studies: two of them assessed the NKX2-5 gene, the remaining reported variants of chromosome 4q25 and the GATA4 S377G variant, respectively. We did not find any variant associated with PFO, except for the rs2200733 variant of chromosome 4q25 in atrial fibrillation patients. Despite the scarceness of evidence so far, animal studies and other studies that did not fulfil the criteria to be included in the review indicate a robust genetic background in PFO. More research is needed on the genetic determinants of PFO.

Prevalence and grade of RLS in migraine: A prospective study of 251 migraineurs by synchronous test of c-TTE and c-TCD.

BACKGROUND: Right-to left shunt (RLS) is regarded as a risk factor resulting in migraine, but the relevance between the RLS and migraine remains controversial. This paper aims at investigating the prevalence and RLS grade of patent foramen ovale (PFO) in cases of migraine (including migraine with and without aura) and evaluate the relationship between PFO and migraine. METHODS: Synchronous test of contrast transthoracic echocardiography and contrast transcranial Doppler ultrasonography was performed in 251 cases of migraine, which contains 62 cases of migraine with aura (MA) and 189 cases without aura (MO) and 275 healthy adults. Among these cases, 25 cases with migraine and 14 healthy adults were evaluated through transesophageal echocardiography. RESULTS: (1). The prevalence of permanent RLS, total RLS, and large RLS in migraine was 11.16%, 39.04%, and 17.13%, respectively, which was significantly higher than that of the controls (P = .042, <.001, and.001, respectively). (2). Permanent RLS was detected as 7.93% of the cases in MO, 20.96% in MA, and 6.18% in controls. Total RLS was detected as 35.98% of the cases in MO, 48.38% in MA, and 23.64% in controls. Large RLS was detected as 13.76% of the cases in MO, 27.41% in MA, and 7.27% in controls. Compared with controls, the positive rate of total RLS and large RLS in MO increased (P = .004 and.022, respectively), the that of permanent RLS, total RLS, and large RLS in MA also increased (P < .001 for each of the comparisons). The positive rate of permanent RLS and large RLS in MA was remarkably higher than that in MO (P = .005 and.013, respectively). (3) The presence of large-size PFO (≥2.0 mm) of migraine showed higher than that of the controls (P = .048). CONCLUSIONS: PFO is associated with the migraine (especially with aura), when it is permanent RLS, large RLS, and large-size PFO (≥2.0 mm).

Impact of Patent Foramen Ovale Anatomic Features on Right-to-Left Shunt in Patients with Cryptogenic Stroke.

The purpose of this study was to investigate the impact of the morphologic characteristics of patent foramen ovale (PFO) on right-to-left shunt (RLS) in patients with PFO and cryptogenic stroke using transesophageal echocardiography and saline contrast transthoracic echocardiography (c-TTE). Of the 165 patients with PFO stroke, both the height and the length of PFO in the provoked RLS group were smaller than those in the constant RLS group. PFO height, interatrial septum mobility and proportion of atrial septal aneurysms were greater in the severe RLS group than in the mild and moderate RLS groups. Multivariate analysis revealed that PFO height and interatrial septum mobility were independent predictors of severe RLS. Multiple territorial ischemic lesions were more common in the severe RLS or constant RLS group. Our findings indicated that the severity of RLS was related to the anatomic features in PFO, inducing different cerebral ischemia lesion patterns in cryptogenic stroke patients with PFO.

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.

Atrial Cardiopathy and Likely Pathogenic Patent Foramen Ovale in Embolic Stroke of Undetermined Source.

BACKGROUND: Atrial cardiopathy and likely pathogenic patent foramen ovale (PFO) are two potential embolic sources in patients with embolic stroke of undetermined source (ESUS). The relationship between these two mechanisms among ESUS patients remains unclear. METHODS: Atrial cardiopathy was defined as increased left atrial diameter index (> 23 mm/m2) or left atrial volume index (> 34 mL/m2), or PR prolongation (≥ 200 ms), or presence of supraventricular extrasystoles in the electrocardiograms performed during hospitalization for the index stoke. The presence of PFO was assessed by transthoracic echocardiography with microbubble test or by transesophageal echocardiography. The presence of PFO was considered as likely pathogenic if the Risk of Paradoxical Embolism score was 7 to 10. RESULTS: Among 367 ESUS patients with available information about the presence of PFO and the presence of atrial cardiopathy (median age: 61 years, 40.6% women), likely pathogenic PFO was diagnosed in 62 (16.9%) and atrial cardiopathy in 122 (33.2%). Only 4 patients (1.1%) had both likely pathogenic PFO and atrial cardiopathy. The prevalence of atrial cardiopathy was lower in patients with likely pathogenic PFO (6.5%) compared with patients with likely incidental PFO (31.2%) or without PFO (40.6%) (Pearson's chi-square test: 26.08, p < 0.001; adjusted odds ratio [OR]: 0.28, 95% confidence interval [CI]: 0.09-0.86). The prevalence of likely pathogenic PFO was lower in patients with atrial cardiopathy compared with patients without atrial cardiopathy (3.3% vs. 23.7%, respectively [Pearson's chi-square test: 24.13, p < 0.001; adjusted OR: 0.2, 95% CI: 0.02-0.6]). CONCLUSION: The presence of atrial cardiopathy is inversely related to the presence of likely pathogenic PFO in patients with ESUS.

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)

Role of transoesophageal echocardiography in detecting patent foramen ovale in stroke patients aged ≤60 years: A retrospective study.

BACKGROUND: The underlying aetiology of ischaemic strokes is unknown in as many as 50% of cases. Patent foramen ovale (PFO) has become an increasingly recognised cause of ischaemic strokes in young patients. The present study aimed (1) to assess the frequency of transoesophageal echocardiography (TOE) performed and the proportion of PFOs detected in patients aged ≤60 years and (2) examine the effect of PFO closure on reducing stroke reoccurrence. METHODS: This was a retrospective clinical audit based on de-identified, secure medical records of the Canberra Hospital, Australia. A review of records was conducted on discharged patients aged 18-60 years admitted to the stroke unit following an ischaemic stroke episode between January 1, 2015, and December 31, 2018. RESULTS: A total of 214 acute ischaemic stroke patients were admitted to the stroke unit (mean age, 49.2 ± 9.7 years). Concerning aetiology, 47.2% were cryptogenic in origin, whereas 52.8% had a stroke of a determined cause. 12 patients were diagnosed with a PFO and 7 venous thromboembolic events were identified, 1 in the cryptogenic group and 6 in the determined cause group. 91.7% of PFOs were diagnosed in patients with a cryptogenic stroke. Trans-thoracic echocardiography (TTE) was performed in 37.3% of patients and had detected 4 PFOs (sensitivity 27.3%, specificity 92.5%). TOE was performed in 26.2% of patients and had detected 11 PFOs (sensitivity 90.0%, specificity 100%). The number needed to treat to prevent the occurrence of an ischaemic stroke through PFO closure was estimated at 30. CONCLUSIONS: An inverse association between age and PFO presence was found in patients aged 18-60 years. Additionally, TOE was superior to TTE for detecting PFO, particularly in those with stroke of an undetermined cause. Our results suggest an increased need for TOE as a routine imaging procedure for acute ischaemic stroke patients aged ≤60.

An unusual presentation of developmental anomalies of the cardiovascular system including tetralogy of fallot, double outlet right ventricle, patent foramen ovale and persistent right aortic arch in a Friesian calf.

BACKGROUND: Congenital heart diseases are occasionally encountered in the bovine species. Ventricular septal defects (VSD) and atrial septal defects (ASD) are reported to be the most common; however, a vast collection have been reported [1, 2]. Congenital heart diseases is thought to represent less than 3% of all congenital abnormalities in calves [3]. Various cardiac anomalies arise due to defective embryologic development such as defects of the septae or the cardiac chambers [2]. The exact aetiology of these congenial heart anomalies remains to be fully elucidated [4]. VSDs appear to be the most common congenital cardiac anomaly in calves. Other diseases can be subdivided into cyanotic (e.g. ASD or patent ductus arteriosus) and non-cyanotic (e.g. tetralogy of fallot or eisenmengers complex) [5, 6]. An exceptional presentation of an array of congenital anomalies was identified in a Friesian heifer calf. To the authors' knowledge this concurrent collection of congenital abnormalities has never been reported in this species. CASE PRESENTATION: A 3-day old Friesian heifer presented with a history since birth of regurgitation post feeding. The main finding on clinical examination was tachypnoea with a holosystolic murmur. Echocardiography identified a VSD, patent foramen ovale (PFO) (both with left to right blood flow) and tricuspid insufficiency. The calf was subsequently euthanised and underwent gross post-mortem examination. A persistent right aortic arch (PRAA) was identified. The cardiac anomalies identified on the echocardiogram were confirmed along with additional abnormalities; double outlet right ventricle (DORV), partial transposition of the great vessels, pulmonic stenosis, hypoplasia of the right branch of the pulmonary artery and right ventricular hypertrophy. The final diagnosis was Tetralogy of Fallot with DORV, PFO and PRAA. The lungs appeared oedematous and congested due to cardiac malfunction and cranioventral aspiration pneumonia. Free serous fluid was identified in the thoracic cavity. Unilateral renal agenesis of the left kidney was an incidental finding but is of note due to its coexistence with the cardiac abnormalities. CONCLUSIONS: This is an unusual case as it features numerous congenital abnormalities that appeared to negate each other allowing capability with life. To the authors' knowledge, this collection of concurrent cardiac anomalies has not been previously reported in bovines.

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.

Case report - azygos vein drainage into the left atrium in a dog with cor triatriatum dexter and a patent foramen ovale.

A 2-year-old Airedale terrier was presented with exercise intolerance since birth and newly developed chylous pleural effusion. Imaging procedures including echocardiography, cardiac magnetic resonance imaging, computed tomography, and selective angiography revealed an aberrant connection of the azygos vein and the left atrium, a membrane in the right atrium consistent with cor triatriatum dexter, and a patent foramen ovale with right-to-left shunt. Balloon dilation of the membrane in the right atrium seemed to result in transient improvement of exercise tolerance compared with the previous 2 years. When chylothorax relapsed after three months, the dog was euthanized. Necropsy confirmed the azygos vein to left atrial connection, the patent foramen ovale, and the cor triatriatum dexter.

Diving physiopathology: the end of certainties? Food for thought.

Our understanding of decompression physiopathology has slowly improved during this last decade and some uncertainties have disappeared. A better understanding of anatomy and functional aspects of patent foramen ovale (PFO) have slowly resulted in a more liberal approach toward the medical fitness to dive for those bearing a PFO. Circulating vascular gas emboli (VGE) are considered the key actors in development of decompression sickness and can be considered as markers of decompression stress indicating induction of pathophysiological processes not necessarily leading to occurrence of disease symptoms. During the last decade, it has appeared possible to influence post-dive VGE by a so-called "preconditioning" as a pre-dive denitrogenation, exercise or some pharmacological agents. In the text we have deeply examined all the scientific evidence about this complicated but challenging theme. Finally, the role of the "normobaric oxygen paradox" has been clarified and it is not surprising that it could be involved in neuroprotection and cardioprotection. However, the best level of inspired oxygen and the exact time frame to achieve optimal effect is still not known. The aim of this paper was to reflect upon the most actual uncertainties and distil out of them a coherent, balanced advice towards the researchers involved in gas-bubbles-related pathologies.

Entrapped paradoxical thromboembolism.

A 67-year-old obese woman (BMI 38.3) was found at autopsy to have deep venous thrombosis of the left calf with bilateral peripheral and saddle pulmonary thromboemboli and a 165 mm long segment of paradoxical thromboembolus wedged between the right and left atria through a patent foramen ovale. Death was due to acute right-sided decompensation caused by obstruction of the pulmonary outflow tract from bilateral pulmonary thromboemboli. Paradoxical thromboemboli pass from the venous system into the systemic circulation through intracardiac or intrapulmonary shunts causing ischemic injury to the brain, heart, intestines, kidneys and limbs. Very rarely, as in this case, they may become entrapped in a patent foramen ovale. Due to its entrapment the paradoxical embolism did not play a role in the lethal episode.

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.

Complex Congenital Heart Malformation Including Transposition of the Great Vessels, Presenting as Sudden Unexplained Infant Death.

Transposition of the great vessels (TGV) is a common congenital heart defect that is difficult to diagnose before birth. Antenatal diagnosis is associated with increased survival. Unusual features such as anomalous pulmonary artery origin may delay cyanosis, decreasing clinical suspicion. A three-week old female infant who had never been cyanotic presented for forensic autopsy due to onset of unresponsiveness at home. History included risk factors for TGV and signs of heart enlargement that were not recognized during life. Cardiac pathology consultation identified D-type TGV with additional rare anomalies. TGV may present as sudden unexplained infant death (SUID) for forensic autopsy if variant features prevent development of cyanosis. Cardiac pathology consultation is helpful in clarifying these features.

Clinical and imaging characteristics of PFO-related stroke with different amounts of right-to-left shunt.

INTRODUCTION: Right-to-left shunt (RLS) induced by a patent foramen ovale (PFO) is associated with an increased risk of cryptogenic stroke (CS). However, little is known about the relationship between the amount of RLS and the stroke pattern. In this study, we aimed to evaluate the distinct clinical features of PFO-related CS in different RLS degrees resulting from PFO. METHODS: This is a cohort study of 222 CS patients admitted to the Tongji Hospital from 1st May 2014 to 31st April 2017. All patients underwent contrast transcranial Doppler examination. And then, 121 (54.5%) were classified as non-RLS group, while 76 (34.2%) were classified as mild RLS group and 25 (11.3%) were large RLS group according to the number of micro-emboli signals. The groups were compared with respect to their clinical and neuroimaging characteristics. RESULTS: In terms of risk factors of stroke, the prevalence of hypertension was lower in mild group (p = 0.002). Regarding the infarct patterns in different CS patients, we found that the multiple cortical lesions were more frequently observed (p<0.001) with increasing RLS in DWI. Moreover, there was a rising trend in the proportion of small lesions (≤1 cm) with an increasing RLS (p < 0.01). And as RLS increased, the posterior circulation was more likely to be influenced (p < 0.05). In addition, the serum cholesterol concentration was lower in the large RLS group, compared to the non-RLS group (p = 0.003) and mild RLS group (p = 0.008). While the mean platelet volume (MPV) in mild group was significantly higher than that of non-RLS group (p = 0.013). CONCLUSION: Patients with larger RLS show more infarction in posterior circulation, higher frequency of small lesions or multiple cortical lesions. The results of our study indicate that the infarct patterns might be a clue of PFO-related stroke.

Variant morphology and arterial supply of diaphragmatic crura with probe patent foramen ovale.

Crura are the posterior pillars of the tendino-muscular partition between thoracic and abdominal cavity. This study highlights bilaterally an unfamiliar morphology of diaphragmatic crura with uncommon origin of inferior phrenic artery and accompanying atrial septal defect in a 63-years-old female cadaver with scoliosis. An attempt is made to portray the clinical implications of these variations. In addition authors have discussed the embryological and genetic basis of these variations. In the recent few decades, surgical correction of scoliosis involving intervention with the crura has gained pace. Knowledge about the normal as well as variant crural morphology is imperative for the surgeons to decide the correct approach during spinal corrective surgeries and for radiologist to prevent any diagnostic pitfall. Familiarity about the variant origin of inferior phrenic artery may prevent complications during treatment of pathological conditions related to inferior phrenic artery. Preoperative awareness about the coexisting atrial septal defect is vital for anesthesiologists promoting them to administer cardioprotective anesthetic drugs. To the best of our knowledge, description of such a combination of variations in anatomical literature is rare and scarcely reported. Awareness of these anatomical variations is relevant for operating surgeons, radiologists, anesthesiologists and anatomists.

Ictus criptogénico. Un no diagnóstico / Cryptogenic stroke. A non-diagnosis

El ictus criptogénico se define como aquel para el que no encontramos una etiología. Sin embargo, existe cierta heterogeneidad en los criterios para definir un ictus criptogénico entre las diferentes clasificaciones etiológicas de uso habitual. Los avances en sistemas de monitorización y detección de fuentes cardioembólicas, el avance de las técnicas de neuroimagen para la caracterización de la placa de ateroma, así como la mayor evidencia de la implicación del foramen oval permeable en el riesgo de ictus en pacientes jóvenes, hacen que cada vez menos ictus queden sin un diagnóstico etiológico. Realizamos una revisión crítica del concepto de ictus criptogénico como un «no diagnóstico», resaltando la importancia de realizar un estudio diagnóstico completo, evitando simplificaciones que pueden llevar a agrupar diferentes entidades que, aunque no identificadas, podrían subyacer al ictus criptogénico y, por tanto, a aplicar el mismo tratamiento preventivo a todas ellas, con resultados inciertos

The term cryptogenic stroke refers to a stroke for which there is no specific attributable cause after a comprehensive evaluation. However, there are differences between the diagnostic criteria of etiological classifications used in clinical practice. An improvement in diagnostic tools such advances in monitoring for atrial fibrillation, advances in vascular imaging and evidence regarding the implication of patent foramen oval on the risk of stroke specially in young patients are reducing the proportion of stroke patients without etiological diagnosis. We carried out a critical review of the current concept of cryptogenic stroke, as a non-diagnosis, avoiding the simplification of it and reviewing the different entities that could fall under this diagnosis and reviewing the different entities that could fall under this diagnosis; and therefore avoid the same treatment for differents entities with uncertains results