Pediatric frequent relapsing nephrotic syndrome with multiple cerebral infarctions accompanied by patent foramen ovale and cerebral venous sinus thrombosis: a case report.

BACKGROUND: Idiopathic nephrotic syndrome (NS) presents as a hypercoagulable state, of which thromboembolism (TE) is a well-known life-threatening complication. Although TE is more likely to occur in venous vessels than arterial vessels, arterial TE is important because it may cause after-effects, including tissue necrosis and cerebral infarction (CI); therefore, prompt diagnosis and appropriate treatment are required. We report a pediatric NS case with multiple CIs. CASE PRESENTATION: A 14-year-7-month-old Japanese girl was diagnosed with frequent relapsing NS, accompanied by headache and disturbance of consciousness during the second relapse. Brain magnetic resonance imaging (MRI) and four-dimensional computed tomography revealed multiple CIs, vasogenic edema, and cerebral venous sinus thrombosis (CVST). The patient had no underlying thrombophilia other than hypercoagulability due to NS and prednisolone (PSL), and no cardiac arrhythmia; however, a right-to-left shunt through the patent foramen ovale (PFO) was observed with the Valsalva maneuver by echocardiography. Therefore, we assumed that a potential cause of multiple CIs might be an embolic stroke, caused by thrombosis formed from a hypercoagulable state due to NS and PSL treatment and reached through PFO. Antiplatelet and anticoagulant therapies were administered for TE. She was treated with PSL and mycophenolate mofetil (MMF) for NS. Rituximab (RTX) was administered to prevent NS relapse after complete remission (CR). She underwent transcatheter PFO closure at age 14 years and 9 months because we considered that the right-to-left shunt through the PFO would be one of the risks for recurrent cerebral embolism when NS relapses. One year after the onset of CIs, an MRI indicated that the CVST had resolved, leaving no neurological sequelae due to CI; therefore, anticoagulant therapy was discontinued. And then she has been in CR for NS with only MMF therapy. CONCLUSIONS: CI is a serious complication in patients with NS. The pathogenesis of multiple CIs is various, including right-to-left shunt through PFO, in addition to the hypercoagulability due to NS. It is important to investigate and manage underlying risks such as PFO, besides preventing the relapses of NS by aggressive treatments using MMF and RTX, in patients with NS.

Genetic background of Japanese patients with pediatric hypertrophic and restrictive cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) and restrictive cardiomyopathy (RCM) present a high risk for sudden cardiac death in pediatric patients. The aim of this study was to identify disease-associated genetic variants in Japanese patients with pediatric HCM and RCM. We analyzed 67 cardiomyopathy-associated genes in 46 HCM and 7 RCM patients diagnosed before 16 years of age using a next-generation sequencing system. We found that 78% of HCM and 71% of RCM patients carried disease-associated genetic variants. Disease-associated genetic variants were identified in 80% of HCM patients with a family history and in 77% of HCM patients with no apparent family history (NFH). MYH7 and/or MYBPC3 variants comprised 76% of HCM-associated variants, whereas troponin complex-encoding genes comprised 75% of the RCM-associated variants. In addition, 91% of HCM patients with implantable cardioverter-defibrillators and infant cases had NFH, and the 88% of HCM patients carrying disease-associated genetic variants were males who carried MYH7 or MYBPC3 variants. Moreover, two disease-associated LAMP2, one DES and one FHOD3 variants, were identified in HCM patients. In this study, pediatric HCM and RCM patients were found to carry disease-associated genetic variants at a high rate. Most of the variants were in MYH7 or MYPBC3 for HCM and TNNT2 or TNNI3 for RCM.

Extremely enlarged right atrial appendage in paediatric idiopathic pulmonary hypertension.

We report an extremely rare case of a right atrial appendage aneurysm in idiopathic pulmonary arterial hypertension (PAH) identified at autopsy. The female patient was diagnosed with idiopathic PAH at the age of 7. Despite intensive treatment, she expired due to cardiac failure at the age of 18. At autopsy, initial thoracotomy revealed an extremely enlarged intrapericardial balloon-like chamber with characteristic horizontal stripes, which turned out to be a markedly dilated right atrial appendage. The histology of the lungs was compatible with idiopathic PAH. In cor pulmonale which may complicate PAH, the occurrence of a right atrial appendage aneurysm is extremely rare, although right ventricular dilatation is common. Improved prognosis and rare paediatric occurrence of idiopathic PAH may have disclosed the unprecedented flexibility and expandability of the atrial appendage in children.

Clinical implication of main pulmonary artery Windkessel size after banding operation.

BACKGROUND: The Windkessel model, proposed in 1895 by O. Frank, successfully explained systemic and abnormal pulmonary hemodynamics of congenital cardiac defects. The model is essentially a functional one and describes only hemodynamics, not anatomical or geographic structures. Because pulmonary arterial banding (PAB) adds a substantial resistance proximal to arterioles, it provides an ideal anatomical structure of the Windkessel model, namely, an elastic reservoir of much dilated main pulmonary artery (mPA) followed by a substantial artificial resistance of banding. METHODS: The pulmonary artery (PA) Windkessel size (WS) of 10 patients, several months to years after PAB, were estimated both in peak systole (WSs) and minimum diastole (WSd), as the product of Windkessel compliance and proximal to distal pulmonary arterial pressure difference at each cardiac phase. They were compared to cineangiogram-determined corresponding volumes (Vs, Vd) of PA proximal to the band or mPA. RESULT: WSs and WSd correlated well with Vs and Vd, respectively, with the correlation coefficient of 0.91 and 0.62, indicating that the Windkessel in these patients corresponds to mPA. Among five patients whose resistance at the band comprised more than half of the whole PA resistance, the coefficients proved even better. CONCLUSION: Much bigger secondarily developed Windkessel, as placed proximal to the band on top of a substantial resistance at PAB, contributed much to alleviate the stress downstream at the periphery caused by greatly increased systolic stroke volume into mPA in these cardiac defects.