SummaryThe pathophysiology of sickle cell disease (SCD) includes vasculopathy as well as anaemia. Elevated plasma homocysteine is a risk factor for vascular disease and may be associated with increased risk of vascular complications in SCD patients. In the present study, microvascular characteristics were assessed in the bulbar conjunctiva of 18 paediatric and 18 adult SCD patients, using the non‐invasive technique of computer‐assisted intravital microscopy. A vasculopathy severity index (SI) was computed to quantify the degree of microvasculopathy in each patient. Plasma homocysteine and several of its determinants [serum folate and vitamin B12, plasma pyridoxal‐5'‐phosphate (vitamin B6 status) and creatinine (kidney function)] were measured. Age was strongly correlated with microvasculopathy in the SCD patients, with the SI increasing about 0·1 unit per one‐year increase in age (P < 0·001). After adjusting for age, gender, B‐vitamin status and creatinine, homocysteine concentration was directly correlated with severity index (P < 0·05). Age and homocysteine concentration were independent predictors of microvasculopathy in SCD patients. It remains to be determined whether lowering homocysteine concentrations using appropriate B‐vitamin supplements (folate and vitamins B12 and B6) ‒ particularly if started early in life ‒ could ameliorate microvasculopathy and its associated complications in SCD patients.

American Journal of Medical Genetics Part AVolume 155, Issue 1 p. fm i-fm iv Table of ContentsFree Access Table of Contents, Volume 155, Number 1, January 2011 First published: 22 February 2011 https://doi.org/10.1002/ajmg.a.33889AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume155, Issue1January 2011Pages fm i-fm iv RelatedInformation

We report on a 5-year-old Caucasian female with multiple anomalies whose deletion, 46,XX,del(21)(q22.11q22.13), was determined by a 105K oligonucleotide-based microarray. This case is a unique deletion that mimicked Fanconi anemia (combination of thrombocytopenia, thumb anomalies, congenital heart defects, borderline small head circumference, strabismus, hydronephrosis, and significant developmental delay) but testing for Fanconi anemia was negative, as was testing for a wide array of genetic/metabolic conditions. Microarray testing done at 5 months failed to demonstrate the interstitial deletion that was found on a newer generation microarray test performed after 3 years of age. When compared to other reported cases of partial monosomy 21q, the unique features of this case include: (1) cleft palate, although high palate is reported in other cases; (2) neonatal thrombocytopenia requiring platelet transfusion; (3) a platelet function defect, reported previously as platelet storage pool defect as part of a familial platelet disorder; and (4) an immune function defect. Similar to other reported patients with terminal 21q deletion, this child had significant developmental delay, and feeding and growth problems. This case also highlights the ability for newer technology microarrays to identify small interstitial deletions previously missed by an earlier version microarray. The advances in the microarray technologies are allowing us to better define new phenotypes and leading to the identification of a diagnosis for many patients who have been previously undiagnosed. Review of the genes involved in these novel deletions allows the caring physician to design surveillance strategies that are custom-designed for these unique patients.

Background HSP90 plays a central role in stabilizing client proteins involved in malignant processes. SNX-2112 is an orally administered potent HSP90 inhibitor that has demonstrated pre-clinical anti-tumor activity in adult malignancies. As many childhood tumors depend upon HSP90 client proteins, we sought to test the pre-clinical efficacy of SNX-2112 in a panel of pediatric cancer cell lines both as a single-agent and in combination with cisplatin (CP). Procedure. Eight cell lines (from osteosarcoma, neuroblastoma, hepatoblastoma, and lymphoma) were studied. Short-and long-term effects of SNX-2112 were assessed by MTT and clonogenic assays. Cell cycling was measured using flow cytometry. Status of HSC70, HSP72, AKT1, C-Raf, and PARP was assessed by immunoblotting. Efficacy of SNX-2112 in combination with CP was assessed using median-effect analysis. Results. Cell lines studied demonstrated sensitivity to SNX-2112 with IC50 values ranging from 10-100 nM. Low dose treatments (12 nM) resulted in a cytostatic response with a minimal increase in sub-G1 content. A higher dose (70 nM) exhibited a more prolonged inhibition and larger sub-G1 accumulation. Observed levels of AKT1 and C-Raf were markedly reduced over time along with an increase in PARP cleavage. In concurrently administered combination treatments, SNX-2112 and CP synergistically inhibited cell growth. Conclusions. SNX-2112 showed marked single-agent activity in pediatric cancer cell lines with downstream effects on HSP90 client proteins. The combination of SNX-2112 and CP showed synergistic activity in two cell lines tested. Further studies of HSP90 inhibitors such as SNX-2112 as a single agent or in combination with chemotherapy are warranted in pediatric cancer. Pediatr Blood Cancer 2012; 58: 885-890. (C) 2011 Wiley Periodicals, Inc.

9565 Background: HSP90 plays a central role in regulating client proteins involved in malignant processes. Currently, geldanamycin derivatives have shown encouraging anti-tumor activity although they may be potentially limited by off-target toxicities. SNX-2112 is an orally administered selective and potent HSP90 inhibitor that has demonstrated preclinical anti-tumor activity in several models. As many childhood tumors are dependent upon HSP90 client proteins, we sought to test the pre-clinical efficacy of SNX-2112 in a panel of pediatric cancer cell lines both as a single-agent and in combination with cisplatin (CP). Methods: Eight pediatric cancer cell lines (derived from osteosarcoma, neuroblastoma, hepatoblastoma, and lymphoma) were studied. Short-term effects of SNX-2112 were assessed by MTT and longer-term effects by clonogenic assays. Efficacy of SNX- 2112 in combination with CP was assessed using median-effect analysis. Cells were exposed to treatment for 72 hours in both. For additional assays, 12nM and 70nM doses of SNX-2112 were used. Status of HSP72, HSC70, B-Raf, AKT1, HER2, PARP, and β-actin was assessed by immunoblotting. Cell cycling was measured using flow cytometry. Results: All cell lines demonstrated sensitivity to SNX-2112 with IC50 values ranging from 20-100nM. Longer-term growth assays indicated an observed IC50 between 10-20nM. Low dose treatments (12nM) resulted in a cytostatic response with a small increase in sub-G1 content, but limited effect on client protein levels. The 70nM dose exhibited a more prolonged inhibition and larger sub-G1 accumulation. Observed levels of AKT1 were markedly reduced over time along with an increase in PARP cleavage. Concomitantly, there was also an increase in B-Raf and HSP72 protein expression. In concurrently administered combination treatments, SNX-2112 acted synergistically with CP to inhibit cell growth. Conclusions: SNX-2112 showed marked single-agent activity in pediatric cancer cell lines with downstream effects on HSP90 client proteins. The combination of SNX-2112 and CP showed synergistic efficacy in two cell lines tested. Further studies of SNX-2112 as a single agent or in combination with CP are warranted in pediatric cancer. No significant financial relationships to disclose.

The conjunctival microcirculation in 14 pediatric and eight adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric [vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits] and dynamic [vessel sludging/sludged flow, boxcar blood (trickled) flow, and abnormal flow velocity] abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs. 6.6 ± 2.4; P = 0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down, or prevent progressive microvascular deterioration.

Pediatric DermatologyVolume 26, Issue 1 p. 121-126 Congenital, Single System, Single Site, Langerhans Cell Histiocytosis: A New Case, Observations from the Literature, and Management Considerations Theodore Zwerdling M.D., Theodore Zwerdling M.D. Section Hematology/Oncology, Department of Pediatrics, University of California, Davis Medical Center, Sacramento, CaliforniaSearch for more papers by this authorThomas Konia M.D., Thomas Konia M.D. Department of Pathology, University of California, Davis Medical Center, Sacramento, CaliforniaSearch for more papers by this authorMarc Silverstein M.D., Marc Silverstein M.D. Department of Dermatology, University of California, Davis Medical Center, Sacramento, CaliforniaSearch for more papers by this author Theodore Zwerdling M.D., Theodore Zwerdling M.D. Section Hematology/Oncology, Department of Pediatrics, University of California, Davis Medical Center, Sacramento, CaliforniaSearch for more papers by this authorThomas Konia M.D., Thomas Konia M.D. Department of Pathology, University of California, Davis Medical Center, Sacramento, CaliforniaSearch for more papers by this authorMarc Silverstein M.D., Marc Silverstein M.D. Department of Dermatology, University of California, Davis Medical Center, Sacramento, CaliforniaSearch for more papers by this author First published: 16 February 2009 https://doi.org/10.1111/j.1525-1470.2008.00852.xCitations: 6 Address correspondence to Ted Zwerdling, M.D., Director, Section Hematology/Oncology, University of California, Davis Medical Center, 2516 Stockton Boulevard, Sacramento, CA 95817, or e-mail: [email protected]. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Favara BE, Feller AC, Pauli M et al. Contemporary classification of histiocytic disorders. The WHO Committee On Histiocytic/Reticulum Cell Proliferations. Reclassification Working Group of the Histiocyte Society. Pediatr Oncol 1997; 29: 157–166. 2 Hashimoto K, Pritzker MS. Electron microscopic study of reticulohistiocytoma: an unusual case of congenital self-healing reticulohistiocytosis. Arch Dermatol 1973; 107: 263–270. 3 Minkov M, Prosch H, Steiner M et al. Langerhans cell histiocytosis in neonates. Pediatr Blood Cancer 2005; 45: 802–807. 4 Bernstein EF, Resnik KS, Loose JH et al. Solitary congenital self-healing reticulohistiocytosis. Br J Dermatol 1993; 129: 449–454. 5 Chun SI, Song MS. Congential self-healing reticulohistiocytosis. Yonsei Med J 1992; 33: 194–198. 6 Berger TG, Lane AT, Headington JT et al. A solitary variant of congenital self-healing reticulohistiocytosis: solitary Hashimoto-Pritzker disease. Pediatr Dermatol 1986; 3: 230–236. 7 Taieb A, De Mascarel A, Surleve-Bazeille JE et al. Solitary Langerhans cell histiocytoma. Arch Dermatol 1986; 122: 1033–1037. 8 Jordaan HF, Drusinsky SF. Congenital self-healing reticulocytosis: report of a case. Pediatr Dermatol 1986; 3: 473–475. 9 Masouye I, Chavaz P, Salomon D et al. Solitary Langerhans cell histiocytoma: an unusual form of Hashimoto-Pritzker histiocytosis? Pediatr Dermatol 1990; 7: 299–302. 10 Ikeda M, Yamamoto Y, Kitagawa N et al. Solitary nodular Langerhans cell histiocytosis. Br J Dermatol 1993; 128: 220–222. 11 Tay YK, Friednas MM, Weston WL et al. Solitary congenital nodule in an infant. Arch Dermatol 1998; 143: 625–630. 12 Ofuji S, Tachibana S, Kanato M et al. Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker): a case report with a solitary lesion. J Dermatol 1987; 14: 182–184. 13 Michel JL, Gentil-Perret A, Gebska E et al. Histioctomes congenitaux: 2 cas. Ann Derm Venereol 2000; 127: 624–628. 14 Weiss T, Weber L, Scharffetter-Kochanek K et al. Solitary cutaneous dendritic cell tumor in a child: role of dendritic cell markers for the diagnosis of skin Langerhans cell histiocytosis. J Am Acad Dermtol 2005; 53: 838–844. 15 Levisohn D, Seidel D, Phelps A et al. Solitary congenital indeterminate cell histiocytoma. Arch Dermatol 1993; 129: 81–85. 16 Boullie MC, Thomine E, Fessard C et al. Histiocytose auto-involutive De Hashimot-Pritzker. Revue de la literature a propos deux observations. Ann Pediatr (Paris) 1988; 35: 339–344. 17 Jang KA, Ahn SJ, Choi JH et al. Histiocytic disorders with spontaneous regression in infancy. Pediatr Dermatol 2000; 17: 364–368. 18 Shy SW, Lee WH, Chang YC et al. A solitary congenital self-healing histiocytosis report of a case and review of the literature. Path Res Pract 1996; 192: 869–874. 19 Divaris DXG, Ling FCK, Prentice RSA. Congenital self-healing histiocytosis report of two cases with histochemical and ultrastructural studies. Am J Dermatopathol 1991; 13: 481–487. 20 Munn SE, Pembroke AC. Solitary congenital self-healing reticulo-histiocytosis (Hashimoto-Pritzker disease). Ann Derm Venereol 1998; 125(Suppl. 1): S13–S226. 21 Weitzman S, Jaffe R. Uncommon histiocytic disorders: the non-Langerhans cell histiocytoses. Pediatr Blood Cancer 2005; 45: 256–264. 22 Schmitz L, Favara BE. Langerhans cell histiocytosis in neonates. 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A lack of Birbeck granules in Langerhans cells is associated with a naturally occuring point mutation in the human Langerin gene. J Invest Dermatol 2005; 124: 714–717. Citing Literature Volume26, Issue1January/February 2009Pages 121-126 ReferencesRelatedInformation

We report on a 5-year-old male with expressive language delay, developmental delay, short stature, and facial anomalies consistent with Floating-Harbor syndrome (FHS). In addition, he developed an intramedullary ganglioglioma. This is the first reported case of a tumor associated with FHS, and may represent an as yet undefined genetic link between spinal cord tumors and FHS, adding this syndrome to the growing list of disorders with a predisposition for tumor development.

Currently, a combination of technologies is typically required to assess the malignancy of cancer cells. These methods often lack the specificity and sensitivity necessary for early, accurate diagnosis. Here we demonstrate using clinical samples the application of laser trapping Raman spectroscopy as a novel approach that provides intrinsic biochemical markers for the noninvasive detection of individual cancer cells. The Raman spectra of live, hematopoietic cells provide reliable molecular fingerprints that reflect their biochemical composition and biology. Populations of normal T and B lymphocytes from four healthy individuals and cells from three leukemia patients were analyzed, and multiple intrinsic Raman markers associated with DNA and protein vibrational modes have been identified that exhibit excellent discriminating power for cancer cell identification. A combination of two multivariate statistical methods, principal component analysis (PCA) and linear discriminant analysis (LDA), was used to confirm the significance of these markers for identifying cancer cells and classifying the data. The results indicate that, on average, 95% of the normal cells and 90% of the patient cells were accurately classified into their respective cell types. We also provide evidence that these markers are unique to cancer cells and not purely a function of differences in their cellular activation.

Pica is defined as the compulsive ingestion of particular food items or substances not fit as food or of no nutritional value. Organic causes of pica include iron deficiency, lead encephalopathy, pregnancy, and zinc deficiency.1 Patients with pica have been shown to have decreased iron and zinc absorption compared with control subjects; subsequent zinc supplementation results in pica elimination.2 The most common forms of pica include geophagia (ingestion of clay, sand, and dirt), pagophagia (ice), trichophagia (hair), and amylophagia (laundry starch).3 Pica occurs frequently in children with sickle cell disease, with one study reporting a prevalence of almost 34%.1 A potentially devastating complication of pica is the development of a gastric bezoar, with consequent gastrointestinal sequelae such as gastric ulceration, bleeding and perforation, intussusception, and small bowel obstruction.4 Pancreatitis has been reported rarely. Trichobezoar, which results from the ingestion of hair or carpet fibers, is the most common bezoar in the pediatric age group.5 Patients commonly present with recurrent abdominal pain and a palpable abdominal mass.

Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific, slow, biologically perturbing, or a combination thereof. Here, we show that single-cell micro-Raman spectroscopy averts these shortcomings and can be used to discriminate between unfixed normal human lymphocytes and transformed Jurkat and Raji lymphocyte cell lines based on their biomolecular Raman signatures. We demonstrate that single-cell Raman spectra provide a highly reproducible biomolecular fingerprint of each cell type. Characteristic peaks, mostly due to different DNA and protein concentrations, allow for discerning normal lymphocytes from transformed lymphocytes with high confidence (p << 0.05). Spectra are also compared and analyzed by principal component analysis to demonstrate that normal and transformed cells form distinct clusters that can be defined using just two principal components. The method is shown to have a sensitivity of 98.3% for cancer detection, with 97.2% of the cells being correctly classified as belonging to the normal or transformed type. These results demonstrate the potential application of confocal micro-Raman spectroscopy as a clinical tool for single cancer cell detection based on intrinsic biomolecular signatures, therefore eliminating the need for exogenous fluorescent labeling.

BACKGROUND. Docetaxel, which is an antitubulin agent, has demonstrable activity against murine and human tumors. The current study was designed to determine response rates to docetaxel in various strata of recurrent solid tumors of childhood and to assess toxicity in a group of patients who were assigned to receive it.METHODS. Docetaxel was given at a dose of 125 mg/m(2) once every 21 days as a 1-hour intravenous infusion for a maximum of 12 courses. From January 1997 to November 2001, 109 male patients and 68 female patients (total, 177 patients) were enrolled, and 173 patients were eligible. The median patient age at entry was 13 years (range, 1-27 yrs). One hundred sixty patients were evaluable for response.RESULTS. There were no deaths attributable to study drug. Hematologic toxicity was common during therapy. Dermatologic, neurologic, pulmonary, and infectious side effects as well as edema were significant. One patient each had acute myeloid leukemia, acute lymphoid leukemia, and high-grade glioma reported as secondary malignancies. One patient with osteosarcoma and.1 patient with rhabdomyosarcoma achieved a complete response. Partial responses were observed in patients with Ewing sarcoma (3 patients), osteosarcoma (I patient), squamous cell carcinoma (1 patient), and medulloblastoma (1 patient). Seventeen patients had stable disease. The 1-year and 5-year overall survival rates for the 160 evaluable patients were 24% (standard error = 4%) and 6% (standard error = 2%), respectively.CONCLUSIONS. Docetaxel demonstrated activity in patients with recurrent Ewing sarcoma but was found to be ineffective for treating the other types of recurrent solid tumors that were studied.

New lesions that occur while patients are receiving treatment for malignant tumors may represent not only difficulties in arriving at the correct diagnosis, but also impact on subsequent therapeutic options. We encountered a patient developing new pulmonary lesions during and after receiving treatment for Stage II Wilms tumor (WT). The presence of mature rhabdomyoblasts in multiple biopsy specimens allowed rational decisions to be made regarding subsequent therapy. This and other published experiences suggest that patients with WT may develop choristomas or have tumors, which undergo cytodifferentiation. Methodologies are now available allowing differentiation of these two processes. © 2005 Wiley‐Liss, Inc.

Historically, the concept of palliative care has been limited to hospice and end-of-life services. Recently, palliative care has been expanded to emphasize its integration throughout an illness. We suggest that palliative care provides an opportunity to prevent illness. Palliative care providers can effectively reduce the risk of illness in families by employing methods and strategies of preventive medicine. We illustrate three such cases. Patients and survivors may benefit from appropriate recognition and referral to prevent potential medical, social, and psychological problems. For preventive medicine to become fully exploited by palliative care providers, curricula will need to be developed. Risk assessment indicators of heritable and acquired conditions will define core functions of this educational process. Relevant topics should encompass basic preventive medicine methods, methods to disseminate assigned risk to the palliative care team, and referral mechanisms to specialists with expertise in the identified area(s) of concern. Opportunities to integrate preventive care into end-of-life services will create a new dimension for comprehensive palliative care.

We report four young women who developed acute psychiatric symptoms, seizures, memory deficits, decreased level of consciousness, and central hypoventilation associated with ovarian teratoma (OT) and cerebrospinal fluid (CSF) inflammatory abnormalities. Three patients recovered with treatment of the tumor or immunosuppression and one died of the disorder. Five other OT patients with a similar syndrome and response to treatment have been reported. Our patients' serum or CSF showed immunolabeling of antigens that were expressed at the cytoplasmic membrane of hippocampal neurons and processes and readily accessed by antibodies in live neurons. Immunoprobing of a hippocampal-expression library resulted in the isolation of EFA6A, a protein that interacts with a member of the two-pore-domain potassium channel family and is involved in the regulation of the dendritic development of hippocampal neurons. EFA6A-purified antibodies reproduced the hippocampal immunolabeling of all patients' antibodies and colocalized with them at the plasma membrane. These findings indicate that in a young woman with acute psychiatric symptoms, seizures, and central hypoventilation, a paraneoplastic immune-mediated syndrome should be considered. Recognition of this disorder is important because despite the severity of the symptoms, patients usually recover. The location and function of the isolated antigen suggest that the disorder is directly mediated by antibodies.

Raman spectroscopy is a laser-based analytical technique that enables chemical characterization of molecules in a sample. It is based on the inelastic scattering of photons by molecular bond vibrations. A Raman spectrum obtained from single cells is an intrinsic molecular fingerprint of the sample, revealing detailed information about DNA, RNA, protein, lipid, and carbohydrate content as well as macromolecular conformations. This technique is rapid, non-invasive and non-destructive. We have demonstrated that single-cell laser tweezers Raman spectroscopy (LTRS) reliably discriminates between normal human T- and B-lymphocytes and their transformed, Jurkat-T and Raji-B, counterparts. Herein the same technique is used to discern normal human T- and B-cells from T- and preB-leukemia cells. Also, demonstrated are Raman spectra changes that result from the activation of normal T-cells with a combination of TPA and ionomycin, and normal B-cells by cross linkage of surface immunoglobulin. T- and B-cells were isolated from healthy volunteers. T- and preB-leukemia cells were isolated from patient samples. Spectra are both compared directly and analyzed by principal component analysis. Significant Raman spectra differences in characteristic DNA and protein signals discriminate between normal cells and their leukemia counterparts. Human leukemia cells were indistinguishable from Jurkat-T and Raji-B cells. Changes in spectra that result from cell activation and proliferation only partially account for the spectra changes of leukemia cells. These data demonstrate the utility of LTRS to discern normal lymphocytes from both transformed cells and leukemia cells.

PURPOSE:To review the diagnosis, treatment, and long-term outcome of children and adolescents with meningiomas diagnosed by a single institution and compare these findings with other published data. PATIENTS AND METHODS:A 25-year retrospective analysis of 18 patients with meningioma diagnosed at Children's Hospital Medical Center, Cincinnati, Ohio was performed. A literature review of published reports was undertaken to compare evaluation. treatment, and outcome for similar patients. RESULTS:Patients ranged from ages 19 months to 17 years at diagnosis. The most common symptoms were headache (5) and seizures (5), although most patients had multiple symptoms. The brain was the primary location of tumor in 17 patients, with the remaining tumor located in the spine. Comorbid diagnoses were common, including developmental delay, balanced chromosomal translocation, type I diabetes mellitus, neurofibromatosis, Klinefelter syndrome, and seizures. Eleven patients had gross total resection performed. Four patients had malignant meningiomas. Two patients were treated with radiotherapy only, one had chemotherapy only, and two underwent both. Karyotype abnormalities most commonly involved chromosome 22, but other abnormalities were present. Sixteen patients remain alive and two patients, having had malignant tumors, are dead of disease. Long-term sequelae include seizures, diabetes insipidus, blindness, neuropsychologic abnormalities, and multiple surgical procedures. Only three patients are self-described as being without problems. CONCLUSIONS:Based on this study and a literature review, the roles of surgery, radiation, and chemotherapy remain unclear. Long-term outcome for patients with meningiomas, especially as it relates to cognitive function, is rarely reported. This group of patients has a high incidence of morbidity associated not only with treatment but also with preexisting diseases. These data indicate the need for a national cooperative group study to better understand the evaluation, treatment, and outcome for children and adolescents who are treated for meningiomas.