Opsoclonus-myoclonus and anti-Hu positive limbic encephalitis in a patient with neuroblastoma.

Opsoclonus-myoclonus syndrome (OMS) is seen in 2-3% of children with neuroblastoma and is believed to be caused by an autoimmune process elicited by the tumor. Although long-term neurologic sequelae are common in children with OMS, limbic encephalitis has not previously been reported. We report a child who developed limbic encephalitis associated with anti-Hu antibodies, 6 years after her initial diagnosis of neuroblastoma and OMS. This case demonstrates that patients with neuroblastoma and OMS are at risk for developing new paraneoplastic symptoms years after their original diagnosis and emphasizes the need for careful long-term follow-up.

Highly variable recurrence of tsunamis in the 7,400 years before the 2004 Indian Ocean tsunami.

The devastating 2004 Indian Ocean tsunami caught millions of coastal residents and the scientific community off-guard. Subsequent research in the Indian Ocean basin has identified prehistoric tsunamis, but the timing and recurrence intervals of such events are uncertain. Here we present an extraordinary 7,400 year stratigraphic sequence of prehistoric tsunami deposits from a coastal cave in Aceh, Indonesia. This record demonstrates that at least 11 prehistoric tsunamis struck the Aceh coast between 7,400 and 2,900 years ago. The average time period between tsunamis is about 450 years with intervals ranging from a long, dormant period of over 2,000 years, to multiple tsunamis within the span of a century. Although there is evidence that the likelihood of another tsunamigenic earthquake in Aceh province is high, these variable recurrence intervals suggest that long dormant periods may follow Sunda megathrust ruptures as large as that of the 2004 Indian Ocean tsunami.

Initial endoscopic management of pineal region tumors and associated hydrocephalus: clinical series and literature review.

OBJECT: The authors report their experience in six patients with pineal tumors and associated hydrocephalus who underwent an endoscopic biopsy procedure and third ventriculocisternostomy (ETVC) in a single sitting. METHODS: The ETVC was successfully performed without complication in all patients; however, a ventriculoperitoneal shunt was eventually required in four. Histological diagnosis was successfully established in four patients. The authors also reviewed the literature to assess reports involving ETVC and tumor biopsy sampling in patients with pineal tumors and hydrocephalus. A total of 54 cases, including those in this study, have been reported. Fifteen percent of the patients eventually required placement of a ventricular shunt. The transient complication rate was 15% with no death. A positive tissue diagnosis was established in 89% of the cases overall. CONCLUSIONS: The authors conclude that the endoscopic management of patients with pineal region masses and hydrocephalus may be a preferred initial strategy.

Early postinduction intensification therapy improves survival for children and adolescents with high-risk acute lymphoblastic leukemia: a report from the Children's Oncology Group.

Longer and more intensive postinduction intensification (PII) improved the outcome of children and adolescents with "higher risk" acute lymphoblastic leukemia (ALL) and a slow marrow response to induction therapy. In the Children's Cancer Group study (CCG-1961), we tested longer versus more intensive PII, using a 2 x 2 factorial design for children with higher risk ALL and a rapid marrow response to induction therapy. Between November 1996 and May 2002, 2078 children and adolescents with newly diagnosed ALL (1 to 9 years old with white blood count 50 000/mm3 or more, or 10 years of age or older with any white blood count) were enrolled. After induction, 1299 patients with marrow blasts less than or equal to 25% on day 7 of induction (rapid early responders) were randomized to standard or longer duration (n = 651 + 648) and standard or increased intensity (n = 649 + 650) PII. Stronger intensity PII improved event-free survival (81% vs 72%, P < .001) and survival (89% vs 83%, P = .003) at 5 years. Differences were most apparent after 2 years from diagnosis. Longer duration PII provided no benefit. Stronger intensity but not prolonged duration PII improved outcome for patients with higher-risk ALL. This study is registered at http://clinicaltrials.gov as NCT00002812.

Intradural spinal Wilm's tumor metastasis: case report.

OBJECTIVE: Wilm's tumor metastasis to the central nervous system (especially the spine) is rare. We present a case of a lumbosacral intradural drop metastasis in a male child with a remote history of intracerebral Wilm's tumor metastases. CLINICAL PRESENTATION: A 7-year-old boy with known metastatic Wilm's tumor was discovered to have left frontal and parietal metastases. He subsequently underwent craniotomy and gross total resections of those lesions. Four years later, he developed low back pain and lower extremity weakness and was found to have an intradural lumbosacral lesion without intracranial recurrence. INTERVENTION: The patient underwent lumbar laminectomy for resection of the intradural lesion. The tumor was found to be in the subarachnoid space and displaced the nerve roots of the cauda equina to the periphery of the thecal sac. The nerve roots were matted and encased within tumor tissue, thereby limiting the surgery to biopsy only. Postoperatively, the patient received radiation to the lesion. Unfortunately, follow-up imaging 4 months later revealed little tumor regression, and the patient's neurological condition did not improve significantly. CONCLUSION: Spinal intradural Wilm's tumor metastases are rare. This is the only reported case in the literature of a probable drop metastasis from an intracerebral source. Although the optimal treatment for intra- or extradural Wilm's tumor spine metastases is not known, our patient did not make significant neurological improvement with radiation therapy.

Post-transplant lymphoproliferative disorder subtypes correlate with different recurring chromosomal abnormalities.

Although cytogenetic analysis advanced the understanding of the pathogenesis of primary non-Hodgkin lymphoma and led to improved clinical management, there have been no large cytogenetic studies of post-transplant lymphoproliferative disorder (PTLD). We examined the karyotypes of 36 PTLD cases and correlated them with clinical, laboratory, and pathologic findings. The cases included 2 early lesions, 13 polymorphic PTLDs, and 21 monomorphic PTLDs (18 B-cell and 3 T-cell proliferations). Cytogenetic abnormalities were identified in 72% of monomorphic B-cell PTLDs and in all T-cell PTLDs, but in only 15% of polymorphic PTLDs and in no early lesions. The most frequent clonal abnormalities in monomorphic PTLD were trisomies 9 and/or 11 (5 cases), followed by rearrangements of 8q24.1 (4 cases), 3q27 (2 cases), and 14q32 (2 cases). MYC rearrangement (8q24.1) and T-cell-associated chromosomal abnormalities correlated with poor outcome and short survival. PTLD with trisomy 9 and/or 11 developed early after transplant, presenting as Epstein-Barr virus-positive large B-cell lymphoma with prolonged survival.

Thrombocytopenia in children with severe iron deficiency.

PURPOSE: Thrombocytopenia has been reported in some children with severe iron deficiency anemia, but the validity of the association and the mechanism of the thrombocytopenia are not well established. Six children with severe iron deficiency and thrombocytopenia are described, and the literature is reviewed. PATIENTS AND METHODS: Clinical, hematologic, and morphologic data were collected and analyzed for six patients referred for evaluation of severe microcytic anemia and thrombocytopenia. RESULTS: The children ranged in age from 14 months to 17 years (median age 27 months) and were otherwise healthy. The iron deficiency was nutritional in four patients younger than 3 years of age and resulted from menstrual blood loss in two teenage girls. The mean initial hemoglobin was 2.5 g/dL (range 1.6-4.7) and the mean initial platelet count was 64 x 109/L (range 11-102). Bone marrow examinations were performed in three patients and showed increased numbers of megakaryocytes. After treatment with therapeutic doses of oral iron, all the patients showed rapid increases in their platelet counts. CONCLUSIONS: These observations validate and extend previous reports of an association between severe iron deficiency and thrombocytopenia. The increased numbers of megakaryocytes and the extremely rapid increase in platelet counts after initiation of iron therapy suggest an essential role for iron in a late stage of thrombopoiesis.

Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease.

Allogeneic bone marrow transplantation (BMT) from HLA-identical siblings is an accepted treatment for both thalassemia and sickle cell disease (SCD). However, it is associated with decided risk of both transplant-related mortality (TRM) and chronic graft-versus-host disease (GVHD). We analyzed 44 patients (median age, 5 years; range, 1-20 years) given an allogeneic related cord blood transplant for either thalassemia (n = 33) or SCD (n = 11). Thirty children were given cyclosporin A (CsA) alone as GVHD prophylaxis, 10 received CsA and methotrexate (MTX), and 4 patients received other combinations of immunosuppressive drugs. The median number of nucleated cells infused was 4.0 x 10(7)/kg (range, 1.2-10 x 10(7)/kg). No patient died and 36 of 44 children remain free of disease, with a median follow-up of 24 months (range, 4-76 months). Only one patient with SCD did not have sustained donor engraftment as compared with 7 of the 33 patients with thalassemia. Three of these 8 patients had sustained donor engraftment after BMT from the same donor. Four patients experienced grade 2 acute GVHD; only 2 of the 36 patients at risk developed limited chronic GVHD. The 2-year probability of event-free survival is 79% and 90% for patients with thalassemia and SCD, respectively. Use of MTX for GVHD prophylaxis was associated with a greater risk of treatment failure. Related CBT for hemoglobinopathies offers a good probability of success and is associated with a low risk of GVHD. Optimization of transplantation strategies could further improve these results.

The 2002 Denali fault earthquake, Alaska: a large magnitude, slip-partitioned event.

The MW (moment magnitude) 7.9 Denali fault earthquake on 3 November 2002 was associated with 340 kilometers of surface rupture and was the largest strike-slip earthquake in North America in almost 150 years. It illuminates earthquake mechanics and hazards of large strike-slip faults. It began with thrusting on the previously unrecognized Susitna Glacier fault, continued with right-slip on the Denali fault, then took a right step and continued with right-slip on the Totschunda fault. There is good correlation between geologically observed and geophysically inferred moment release. The earthquake produced unusually strong distal effects in the rupture propagation direction, including triggered seismicity.