A Rare Etiology for Ascending Paralysis in an Infant.

An 11-month-old male infant with ascending paralysis had an unremarkable initial cerebrospinal fluid (CSF) analysis and imaging. Progressive neurological symptoms resulted in repeated CSF sampling, microscopy, and plasma microbial cell-free DNA next-generation sequencing analysis, that in combination with epidemiology, confirmed the diagnosis.

T-cell Lymphoblastic Lymphoma in a Patient With Chromosome 8q21.11 Microdeletion.

The chromosome 8q21.11 deletion syndrome is an extremely rare genetic condition characterized by facial dysmorphic features, Peters anomaly and impaired intellectual development. We report a case of a 2-year-old female with chromosome 8q21.11-q21.2 microdeletion complicated by T-cell lymphoblastic lymphoma. Whole genome single-nucleotide polymorphism microarray detected an interstitial deletion of 8q21.11 to q.21.2, including 16 genes. Autopsy findings revealed a T-cell lymphoblastic lymphoma presenting as an anterior mediastinal mass, encroaching upon the aortic arch, left subclavian artery, left carotid bifurcation and trachea. The genes that may contribute to a neoplastic process are identified (PKIA, IL7, TPD52, PAG1, and FABP5) and discussed in this article.

Monochorionic Triplet Pregnancies With Twin Reversed Arterial Perfusion and Acardiac Triplet: Report of Two Cases and Literature Review.

TRAP pregnancies involving monochorionic triplets are extremely rare, calculated to be 1 in 4.5 million. We report two cases of monochorionic triplet pregnancies with an acardiac triplet. In one case, the mother was a 33-year-old G2P1 who underwent dilation and evacuation at 20 weeks due to poor prognosis. The other case involved a 21-year-old G1P0 mother presenting in advanced preterm labor at 21 weeks who elected expectant management. Seventeen cases of monochorionic triplets with TRAP were identified in the literature. Invasive intervention was performed in 10 cases; 9 cases resulted in the survival of the nonacardiac twins and 1 case resulted in the survival of 1 fetus. Our two cases had common sonographic features which included polyhydramnios of all fetuses. Placental features shared between both cases included being large for gestational age and velamentous insertion of the acardiac twin. The acardiac twins in both of our cases were hydropic and demonstrated developed pelvis and lower extremities. One had an omphalocele. Most case reports in the literature review demonstrate similar findings. Two cases of monochorionic triplets with TRAP and acardiac twin are herein described. Successful treatment by invasive interventions have been described in this condition, highlighting the importance of early diagnosis.

Myocardial Infarction in the Neonate Without Coronary Artery Occlusion and Structurally Normal Heart: A Report of 2 Cases in Twin Pregnancies and Review of the Literature.

Myocardial infarction (MI) is a common diagnosis in the adult population and is associated with coronary artery atherosclerosis. However, it is an unusual diagnosis in the pediatric population, especially in the neonatal period. The authors present 2 autopsy cases of MI in newborn babies of twin pregnancies with normal heart and coronary arteries. The first case is that of a 10-day-old female, monochorionic-diamniotic, twin B born at 29 weeks' gestation. The autopsy revealed diffuse subacute MI in both ventricles, which was compatible with a global hypoxic event during perinatal period. The hypoxic insult was likely caused by maternal HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome as evident in the placental examination, which showed placental infarct and decidual arteriopathy. The second case is that of a 2-day-old term male, dichorionic-diamniotic, twin A with an antenatal history of prolonged rupture of membranes. The hospital course was complicated by neonatal sepsis. The autopsy showed diffuse hemorrhage in the internal organs including the heart, along with myocyte necrosis. The overall findings were consistent with multiorgan dysfunction syndrome resulting from sepsis. Previous reported cases of MI in neonates without coronary artery occlusion were also reviewed and portrayed.

Paroxysmal Nocturnal Dyspnea Secondary to Right Ventricular Myxoma: A Novel Presentation of an Unusual Tumor.

A 14-month-old male presented with paroxysmal nocturnal dyspnea and grade III/VI systolic ejection murmur at the upper left sternal border with an S4 gallop and was subsequently found to have a right ventricular cardiac myxoma. Prior presentations of these tumors have been with exertional syncope and murmur, asymptomatic murmur, or exertional dyspnea; the presentation of such a tumor with paroxysmal nocturnal dyspnea is novel.

Fibroproliferative response to urothelial failure obliterates the ureter lumen in a mouse model of prenatal congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is the most prevalent cause of pediatric chronic kidney disease and end-stage renal disease. The ureteropelvic junction (UPJ) region, where the renal pelvis transitions to the ureter, is the most commonly obstructed site in CON. The underlying causes of congenital UPJ obstructions remain poorly understood, especially when they occur in utero, in part due to the lack of genetic animal models. We previously showed that conditional inactivation of Sec10, a central subunit of the exocyst complex, in the epithelial cells of the ureter and renal collecting system resulted in late gestational bilateral UPJ obstructions with neonatal anuria and death. In this study, we show that without Sec10, the urothelial progenitor cells that line the ureter fail to differentiate into superficial cells, which are responsible for producing uroplakin plaques on the luminal surface. These Sec10-knockout urothelial cells undergo cell death by E17.5 and the urothelial barrier becomes leaky to luminal fluid. Also at E17.5, we measured increased expression of TGFß1 and genes associated with myofibroblast activation, with evidence of stromal remodeling. Our findings support the model that a defective urothelial barrier allows urine to induce a fibrotic wound healing mechanism, which may contribute to human prenatal UPJ obstructions.

Systemic and placental α-klotho: Effects of preeclampsia in the last trimester of gestation.

INTRODUCTION: α-klotho is an anti-aging protein, potentially important in preeclampsia (PE). Produced by kidney, brain and placenta, and by mRNA splicing is both a full-length membrane-bound and a truncated soluble protein in the circulation. The membrane-bound protein is an obligate co-receptor for fibroblast growth factor 23 (FGF23) and its action on receptor (FGFR), but ADAM proteinases also cause its shedding. The aims of this study were to investigate levels of maternal plasma, placental, and fetal membrane α-Klotho and their association with placental accelerated villous maturation (AVM) in PE. In addition, placental and membrane levels of ADAM17 and FGFR were measured in the same patients. METHODS: Maternal blood, placenta and fetal membranes from 61 women (31 with PE and 30 controls) between 32 and 40 weeks gestation were collected. Plasma α-klotho was measured by ELISA, and quantitative immunohistochemistry used for α-klotho, ADAM17 and FGFR1 in tissues. Placental AVM was histologically assessed. RESULTS: Maternal plasma levels of α-Klotho were higher in PE compared to controls (p = 0.01) and patients with the highest levels had significantly less AVM (p = 0.03). α-Klotho, ADAM17, and FGFR were all present in syncytiotrophoblast and cytotrophoblast of membranes. Between 32 and 40 weeks gestation, all placental levels decreased in controls respectively (p = 0.04, p = 0.004, p = 0.05), but not in PE. Fetal membrane levels were unchanged. DISCUSSION: Maternal plasma α-Klotho was increased in PE and its levels associated with reduced placental AVM. Changes in placental α-Klotho, ADAM17, and FGFR suggest their involvement in the pathophysiology of PE.

Reduced immune cell infiltration and increased pro-inflammatory mediators in the brain of Type 2 diabetic mouse model infected with West Nile virus.

BACKGROUND: Diabetes is a significant risk factor for developing West Nile virus (WNV)-associated encephalitis (WNVE) in humans, the leading cause of arboviral encephalitis in the United States. Using a diabetic mouse model (db/db), we recently demonstrated that diabetes enhanced WNV replication and the susceptibility of mice to WNVE. Herein, we have examined immunological events in the brain of wild type (WT) and db/db mice after WNV infection. We hypothesized that WNV-induced migration of protective leukocytes into the brain is attenuated in the presence of diabetes, leading to a high viral load in the brain and severe disease in diabetic mice. METHODS: Nine-week old C57BL/6 WT and db/db mice were infected with WNV. Leukocyte infiltration, expression of cell adhesion molecules (CAM), neuroinflammatory responses, activation of astrocytes, and neuronal death were analyzed using immunohistochemistry, qRT-PCR, flow cytometry, and western blot. RESULTS: We demonstrate that infiltration of CD45+ leukocytes and CD8+T cells was significantly reduced in the brains of db/db mice, which was correlated with attenuated expression of CAM such as E-selectin and ICAM-1. WNV infection in db/db mice was associated with an enhanced inflammatory response in the brain. mRNA and protein levels of key chemokines such as CXCL10, CXCL1, CCL2, CCL5, CCL3, and G-CSF, and cytokines such as IL-1ß, TNF, IL-6, IFNγ, and IL-1α were significantly elevated in the brains of db/db mice compared to WT mice. Elevated levels of cytokines also correlated with increased astrocytes activation and neuronal damage in the brains of db/db mice. CONCLUSION: These data suggest that reduced leukocytes recruitment, in part, due to lower levels of CAM results in failure to clear WNV infection from the brain leading to increased production of inflammatory molecules, which mediates increased neuronal death and mortality in db/db mice. This is the first study to elucidate the expression of CAM and their correlation with the migration of leukocytes, specifically cytotoxic CD8+ T cells, in increasing disease severity in the diabetic mouse model.

Appendicitis as the presenting manifestation of Kawasaki disease.

In cases of Kawasaki's disease (KD) presenting as acute surgical abdomen, rarely has the presence of acute appendicitis been found. We report two cases of histologically confirmed acute appendicitis in the presence of KD and a review of the literature as it pertains to acute abdomen and atypical presentations of KD.

Pericardial effusion and cardiac tamponade in neonates: sudden unexpected death associated with total parenteral nutrition via central venous catheterization.

BACKGROUND: Total parenteral nutrition (TPN) via central venous catheter (CVC) is used routinely to provide adequate nutrition for neonates, especially those with very low birth weights (VLBWN). Pericardial effusion and cardiac tamponade (PCE/CT) is a potentially life-threatening CVC complication. DESIGN: This autopsy study presents the gross and histopathologic findings in 5 neonates receiving continuous TPN via CVCs, who suddenly and unexpectedly died from PCECT. RESULTS: The study population included five neonates (age 4-29 days, 3 males, 2 females, 4 VLBWN neonates, 1 full-term neonate). Chemical analysis of the milky-white PCE fluid showed high triglyceride levels (717-777 mg/dL) consistent with intralipid. Right atrial microscopic examination with the four VLBWNs showed interstitial edema and dilated lymphatics (n=4), atrial thrombus (n=1), and focal fibrinous epicardial exudate (n=1). The full-term neonate RA revealed focal myocyte coagulative necrosis, acute organizing hemorrhage, focal collagen deposition, myocardial hypertrophy, and endocardial thickening. CONCLUSIONS: Right atria in PCE/CT demonstrated marked interstitial edema and dilated fine vascular channels. Endocardial injury with permeation of hyperosmotic TPN fluid into the interstitium and egress into the pericardial sac is hypothesized as the etiology of PCE/CT. Recognition of PCE and impending CT in neonates with CVCs for TPN with expedient intervention may avoid sudden unexpected deaths.

Relaxin, its receptor (RXFP1), and insulin-like peptide 4 expression through gestation and in placenta accreta.

This study was designed to show whether placental relaxin (RLN), its receptor (RXFP1), or insulin-like peptide 4 (INSL4) might have altered expression in patients with placenta accreta. The baseline expression of their genes through gestation (n = 34) was quantitated in the placental basal plate (BP) and villous trophoblast (TR), and compared to their expression in placenta accreta (n = 6). The proteins were also immunolocalized and quantitated in the accreta tissues. The messenger RNAs (mRNAs) of matrix metalloproteinase 9, -2, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were also measured. Results demonstrated that the BP and TR expressed low levels of RLN/RXFP1 and INSL4 through gestation. In accreta, increased RLN gene and protein in BP were associated with antepartum bleeding whereas INSL4 expression decreased throughout the TR. There were no changes in mRNAs for MMPs, but TIMP-1 was increased only in the invasive TR.

Placental mesenchymal dysplasia.

Placental mesenchymal dysplasia is a benign condition that can be confused with a molar pregnancy by ultrasound scanning and gross examination. Conservative management should be considered with a normal-appearing singleton fetus and a cystic-appearing placenta. We present a case of placental mesenchymal dysplasia with a favorable outcome.

Treatment of Gorham-Stout disease with zoledronic acid and interferon-α: a case report and literature review.

Gorham-Stout disease is a rare disease characterized by osteolysis, angiomatosis, and soft-tissue swelling. It is a diagnosis of exclusion and has an unknown etiology. Chylothorax is a common complication of the disease that is associated with a high mortality rate. There is no standard of treatment. We report a case of a 16-year-old female with Gorham-Stout disease and recurrent pleural effusions who was successfully treated with concurrent zoledronic acid and peg-interferon α-2b.

Two cases of primary yolk sac tumor of the liver in childhood: case reports and literature review.

Primary yolk sac tumor of the liver is an extremely rare neoplasm, with fewer than 20 cases reported. We evaluated 2 pediatric cases (21-month-old and 23-month-old female patients), who presented with liver masses and markedly raised serum alpha-fetoprotein (AFP). One patient received a partial hepatectomy and another patient underwent a liver biopsy, both of which showed characteristic features of yolk sac tumor, with tumor cells staining strongly positive for AFP. There was no evidence of an extrahepatic primary source. Both of our patients have been healthy, without evidence of recurrent tumor, and their AFP level remains in the normal range after their chemotherapeutic treatments.

Placental mesenchymal dysplasia.

CONTEXT: Placental mesenchymal dysplasia is characterized by placentomegaly and may be mistaken for molar pregnancy both clinically and macroscopically because of the presence of "grapelike vesicles." It may be associated with a completely normal fetus, a fetus with growth restriction, or a fetus with features of Beckwith-Wiedemann syndrome. OBJECTIVE: To review the etiology, molecular pathology, gross and microscopic features, clinical presentation, complications, and differential diagnosis of placental mesenchymal dysplasia. DATA SOURCES: The PubMed and the Medline databases were systematically searched for articles between 1970 and 2006. The following keywords were used: placental mesenchymal dysplasia, mesenchymal hyperplasia, molar pregnancy, pseudomolar pregnancy, Beckwith-Wiedemann syndrome, and placentomegaly. Relevant references from review articles were also searched. CONCLUSIONS: Placental mesenchymal dysplasia should be considered in the differential diagnosis when the ultrasonographic findings show a cystic placenta. Close attention should be paid to fetal morphology for early recognition of fetal complications and to prevent unnecessary termination of pregnancy in cases associated with a normal fetus.