Central Versus Extraventricular Neurocytoma in Children: A Clinicopathologic Comparison and Review of the Literature.

BACKGROUND: Central neurocytomas (CN) are rare pediatric CNS tumors most often with a benign clinical course. Occasionally, these tumors occur outside the ventricles and are called extraventricular neurocytomas (EVN). We present a retrospective institutional analysis of children with neurocytoma with prolonged follow-up. PROCEDURE: Twelve patients were diagnosed with neurocytoma at our institution between 1993 and 2004. RESULTS: Six patients were male and the median age at diagnosis was 12 years (1.5 to 16 y). Seven patients had CN and 5 had EVN. Presenting symptoms included headaches (67%), vomiting (50%), nausea (33%), seizures (33%), and mental status changes (25%). Obstructive hydrocephalus was present at diagnosis in 42% of the cases. Younger age and seizures were more common in patients with EVN. Gross total resection (GTR) was achieved in 42% (5/12) of the patients. Patients with GTR received no adjuvant therapy upfront; 1 patient subsequently had recurrence with leptomeningeal disease. Patients with subtotal resection received additional treatment: 1 underwent reoperation (GTR), 2 patients received focal radiation, 2 patients received adjuvant chemotherapy, and 2 patients received craniospinal irradiation followed by chemotherapy. The 20-year overall survival for this cohort was 83% with event free survival of 56%. Overall survival for CNs was 100%, versus 40% for EVN. Event free survival for CNs was 57% and 53% for the EVNs. An MIB-1 fraction >2% was associated with worse prognosis. CONCLUSIONS: Neurocytomas are rare brain tumors in children usually cured with GTR. Adjuvant focal radiation therapy and/or chemotherapy may improve disease control in cases with subtotal resection, but case-by-case analysis should be done. EVNs might be associated with worse outcome due to a higher proliferative index.

Serotype-specific dengue virus circulation and dengue disease in Bangkok, Thailand from 1973 to 1999.

Dengue virus circulation and association with epidemics and severe dengue disease were studied in hospitalized children with suspected dengue at the Queen Sirikit National Institute of Child Health in Bangkok, Thailand, from 1973 to 1999. Dengue serology was performed on all patients and viral isolation attempted on laboratory-confirmed patients. Acute dengue was diagnosed in 15,569 children and virus isolated from 4,846. DEN-3 was the most frequent serotype in primary dengue (49% of all isolates), DEN-2 in secondary and in dengue hemorrhagic fever (37% and 35%, respectively). The predominant dengue serotype varied by year: DEN-1 from 1990-92, DEN-2 from 1973-86 and 1988-89; DEN-3 in 1987 and 1995-99; and DEN-4 from 1993-94. Only DEN-3 was associated with severe outbreak years. Our findings illustrate the uniqueness of each serotype in producing epidemics and severe disease and underscore the importance of long-term surveillance of dengue serotypes in understanding the epidemiology of these viruses.

Evidence that rodents are a reservoir of hepatitis E virus for humans in Nepal.

Hepatitis E virus (HEV) is an important cause of enterically transmitted hepatitis in developing countries. Sporadic autochthonous cases of hepatitis E have been reported recently in the United States and other industrialized countries. The source of HEV infection in these cases is unknown; zoonotic transmission has been suggested. Antibodies to HEV have been detected in many animals in areas where HEV is endemic and in domestic swine and rats in the United States. There is evidence supporting HEV transmission between swine and humans. Nevertheless, HEV has not been detected in wild rodents. We tested murid rodents and house shrews trapped in Nepal's Kathmandu Valley, where hepatitis E is hyperendemic, for HEV infection. The most commonly trapped species was Rattus rattus brunneusculus. Serum samples from 675 animals were tested for immunoglobulin G against HEV by enzyme-linked immunosorbent assay; 78 (12%) were positive, indicating acute or past infection. Antibody prevalence was higher among R. rattus brunneusculus and Bandicota bengalensis than in Suncus murinus. Forty-four specimens from 78 antibody-positive animals had sufficient residual volume for detection of HEV RNA (viremia) by reverse transcription-PCR. PCR amplification detected four animals (9%; three were R. rattus brunneusculus and one was B. bengalensis) with viremia. Phylogenetic analysis of the four genome sequences (405 bp in the capsid gene) recovered showed that they were identical, most closely related to two human isolates from Nepal (95 and 96% nucleotide homology, respectively), and distinct from HEV sequences isolated elsewhere. These data prove that certain peridomestic rodents acquire HEV in the wild and suggest that cross-species transmission occurs, with rodents serving as a virus reservoir for humans.

Clinical and epidemiological relevance of quantitating hepatitis E virus-specific immunoglobulin M.

Diagnosis of acute hepatitis E by detection of hepatitis E virus (HEV)-specific immunoglobulin M (IgM) is an established procedure. We investigated whether quantitation of HEV IgM and its ratio to HEV total Ig furnished more information than conventional IgM tests that are interpreted as positive or negative. A previously described indirect immunoassay for total Ig against a baculovirus-expressed HEV capsid protein was modified to quantitate HEV-specific IgM in Walter Reed (WR) antibody units by using a reference antiserum and the four-parameter logistic model. A receiver-operating characteristics curve derived from 197 true-positive specimens and 449 true-negative specimens identified 30 WR units/ml as an optimum cut point. The median HEV IgM level in 36 patients with acute hepatitis E fell from 3,000 to 100 WR units/ml over 6 months, suggesting that 100 WR units/ml would be a more appropriate cut point for distinguishing recent from remote IgM responses. Among three hepatitis E case series, determination of the HEV IgM-to-total-Ig ratio in acute-phase serum revealed that most patients had high ratios consistent with primary infections whereas a few had low ratios, suggesting that they had sustained reinfections that elicited anamnestic antibody responses. The diagnostic utility of the new IgM test was similar to that of a commercially available test that uses different HEV antigens. In conclusion, we found that HEV IgM can be detected specifically in >95% of acute hepatitis E cases defined by detection of the virus genome in serum and that quantitation of HEV IgM and its ratio to total Ig provides insight into infection timing and prior immunity.

Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay.

We developed a quantitative enzyme immunoassay (EIA) for antibody to hepatitis E virus (HEV) by using truncated HEV capsid protein expressed in the baculovirus system to improve seroepidemiology, to contribute to hepatitis E diagnosis, and to enable vaccine evaluations. Five antigen lots were characterized; we used a reference antiserum to standardize antigen potency. We defined Walter Reed antibody units (WR U) with a reference antiserum by using the four-parameter logistic model, established other reference pools as assay standards, and determined the conversion factor: 1 WR U/ml = 0.125 World Health Organization unit (WHO U) per ml. The EIA performed consistently; median intra- and inter-test coefficients of variation were 9 and 12%, respectively. The accurate minimum detection limit with serum diluted 1:1,000 was 5.6 WR U/ml; the test could detect reliably a fourfold antibody change. In six people followed from health to onset of hepatitis E, the geometric mean antibody level rose from 7.1 WR U/ml to 1,924.6 WR U/ml. We used the presence of 56- and 180-kDa bands by Western blotting as a confirmatory test and to define true-negative and -positive serum specimens. A receiver-operating characteristics plot identified 30 WR U/ml as an optimum cut-point (sensitivity, 86%; specificity, 89%). The EIA detected antibody more sensitively than a commercially available test. The EIA was transferred to another laboratory, where four operators matched reference laboratory results for a panel of unknowns. Quantitation of antibody to HEV and confirmation of its specificity by Western blotting make HEV serology more meaningful.