“Flecked retina”—an association with primary hyperoxaluria

A child with hyperoxaluria, probable Type I, was noted to have a "flecked retina" on funduscopic examination at age 2 1/2 months; it persisted throughout his seven years of life. The relationship of the ocular findings to his metabolic disease is discussed.     

ToRCH “co‐infections” are associated with increased risk of abortion in pregnant women

ToRCH infections (toxoplasmosis, rubella, cytomegalovirus and Herpes simplex virus) have long been known to be associated with bad obstetric outcomes. However, little information is available about the impact of ToRCH co‐infections on the outcome of pregnancy. Hence, we tested the IgG and IgM antibodies to Toxoplasma gondii, Rubella, Cytomegalovirus and Herpes Simplex Virus among 81 pregnant women with abortion (case group) and 98 pregnant women with normal delivery (control group). In the single‐infection model, only CMV‐IgM seropositivity was significantly increased in case than control group (25.9% in case and 12.2 % in control, OR = 2.5, P = 0.019). In the co‐infection model, 14 patterns were recognized, but two patterns were significantly increased in the case than the control group. Co‐infection of T. gondii IgG + CMV IgM was 9.1‐fold increased in the case than the control group (8.6% in the case and 1% in control, OR = 9.1; P = 0.024). Also, co‐infection of T. gondii IgG + HSV IgG + CMV IgM was 7.7‐fold increased in case than the control group (7.4% in case and 1 % in control, OR = 7.7; P = 0.04). Although the OR of other co‐infections was higher in the case than the control group, the difference was not statistically significant. These findings indicate that ToRCH co‐infections are associated with increased risk of abortion than single infection. Hence, the rates of co‐infections should be considered in prenatal screening of ToRCH infections.     

The challenge of defining “ultra‐high‐risk” neuroblastoma

Given the biological and clinical heterogeneity of neuroblastoma, risk stratification is vital to determining appropriate treatment. Historically, most patients with high‐risk neuroblastoma (HR‐NBL) have been treated uniformly without further stratification. Attempts have been made to identify factors that can be used to risk stratify these patients and to characterize an “ultra‐high‐risk” (UHR) subpopulation with particularly poor outcome. However, among published data, there is a lack of consensus in the definition of the UHR population and heterogeneity in the endpoints and statistical methods used. This review summarizes our current understanding of stratification of HR‐NBL and discusses the complex issues in defining UHR neuroblastoma.     

Multifactorial analysis of opsoclonus‐myoclonus syndrome etiology (“Tumor” vs. “No tumor”) in a cohort of 356 US children

1 Background

Pediatric opsoclonus‐myoclonus syndrome (OMS) presents a paradox of etiopathogenesis: A neuroblastic tumor (NB) is found in only one half of the cases, the others are ascribed to infections or designated as idiopathic.

2 Method

From an IRB‐approved observational study of 356 US children with OMS, secondary analysis of “etiology” and related factors was performed on a well‐characterized cohort. The “Tumor” (n = 173) and “No Tumor” groups (n = 183), as defined radiologically, were compared according to multiple factors considered potentially differentiating. Data were analyzed retrospectively using parametric and nonparametric tests as indicated.

3 Results

Patients with NB were not distinguishable by prodromal symptoms, OMS onset age, gender, race/ethnicity, OMS severity, rank order of neurological sign appearance, or geographic distribution. Various CSF immunologic biomarker abnormalities of OMS did not vary in the presence or absence of a detectable tumor: frequency of six lymphocyte subsets, or concentrations of 18 cytokines/chemokines, cytokine antagonists, chemokine receptors, cell adhesion molecules, or neuronal/glial markers. Prior responsiveness to conventional immunotherapy was not contingent on tumor/no tumor designation.

4 Conclusions

Multiple convergent factors provide compelling empirical evidence and rationalize the concept that OMS is one neurological disorder, regardless of apparent etiology. Limitations to the current clinical etiologic classifications as paraneoplastic, parainfectious/post‐infectious, and idiopathic etiology require antigen‐based biological solutions to tease out the molecular pathophysiology of viral/tumoral mechanisms. Systematic studies, regardless of presumed etiology, will be necessary to find the highest‐yield combination of imaging approaches, screening for infectious agents, and new biomarkers. Two testable hypotheses for future research are presented.