CT imaging in adults with neurofibromatosis-1: frequent asymptomatic plexiform lesions

OBJECTIVE: The authors examined the incidence and radiologic characteristics of plexiform neurofibromas in neurofibromatosis-1 (NF-1) to define a cohort at greatest risk for malignant nerve-sheath tumors. BACKGROUND: Plexiform neurofibromas are a frequent complication of NF-1. They can impair function, produce disfigurement, and be the site for the development of malignant nerve-sheath tumors. The incidence and natural history of plexiform neurofibromas is unknown. METHODS: CT imaging of the chest, abdomen, and pelvis was performed in 91 of 125 consecutive adults (age, > or = 16 years) with NF-1. RESULTS: Twenty percent of patients had plexiform neurofibromas of the chest in the paraspinal, mediastinal, or supraclavicular area. Approximately 40% of patients had abnormal abdominal/pelvic scans. The paraspinal, sacral plexus, sciatic notch, and perirectal regions were the most common sites. Most plexiform neurofibromas were asymptomatic. Imaging also revealed a number of tumors, including malignant nerve-sheath tumors, adrenal tumors, carcinoids, and schwannomas. CONCLUSIONS: The frequency of plexiform lesions and other tumors in NF-1 indicates that clinicians should monitor young adults carefully; however, imaging characteristics alone cannot reliably distinguish benign from malignant lesions.     

Dysembryoplastic neuroepithelial tumors in two children with neurofibromatosis type 1

The quality of clinical trials in Japan has been improving through clear protocol preparation, improvements in methodology, coordinating systems, and so forth. In order to further improvement, the following are discussed: 1) dilemmas regarding adherence of treatment determined by protocol, 2) hospital policy and physician's discretion, 3) systems to support randomized controlled trials in hospital, and 4) systems to help obtain informed consent from subjects.     

Thoracic outlet syndrome in children

Thoracic outlet syndrome, although uncommon in children, may be precipitated during rapid growth in adolescence, especially in association with a cervical rib. Four children exhibited the aching, tiredness in the limb, and occasional paresthesia in adolescence. Two had a cervical rib requiring removal, after which the symptoms disappeared. The other two were treated nonoperatively with shoulder-strengthening exercises and avoidance of posturing that elicited the symptoms. It is proposed that in a child, the anatomy of the thoracic outlet is constantly changing with growth and development of the structures that form the thoracic outlet, as well as those that traverse the outlet itself. A conservative approach to these symptoms is warranted in the first instance to allow further growth and remodeling of the thoracic outlet, which may be sufficient to accommodate the nerve roots and brachial plexus and alleviate the symptoms. Excision of the cervical rib in the presence of increasing and chronic symptoms can be quit beneficial.     

Autosomal dominant multiple café-au-lait spots and neurofibromatosis-1: evidence of non-linkage

Multiple café-au-lait spots have been observed in successive generations of several families without any other manifestations of neurofibromatosis (NF) or any other systemic disorder. The café-au-lait spots in these families segregate as an autosomal dominant trait. The relationship (if any) between the gene for this trait and the NF-1 gene has previously been unknown. We describe a family with five individuals spanning four generations with dominantly inherited café-au-lait spots, without any other stigmata of NF-1. Linkage analysis with probes proximal, distal, and within the NF-1 gene indicate that the trait in this family is not linked to NF-1. We propose that this condition be called Familial Café-Au-Lait Spots (FCAL) to distinguish it from the neurofibromatosis syndromes.     

Manifestations of thalamic tumors in children

On the basis of observation of 11 cases of thalamic tumours in children at various age the author discusses differences in symptoms and signs in relation to the same tumours in adults. The first pathological sign was most frequently hemiparesis without, however, typical characteristics of classical spastic hemiparesis. Later on various involuntary movements appeared, most frequently bilaterally. In half of these cases infection, vaccination, cranial trauma or excessive effort were the factors provoking the appearance of first symptoms. Typical symptoms of raised intracranial pressure developed late and were present in some cases only. The course of the disease was chronic, the survival time up to several years. The results of vertebral angiography were of decisive significance for the diagnosis. Carotid angiography showed only internal hydrocephalus without giving any more detailed clues as to the location of the process.     

Chemotherapy with the "8 in 1" protocol for malignant brain tumors in children: a population-based study in Finland

We evaluated the outcome of 68 children with malignant brain tumors treated with the "8 in 1" chemotherapy protocol in Finland from 1986 to 1993, comparing 5-year survival rates with those for a historical control group (from 1975 to 1985). For all malignant brain tumors, overall survival was 43% (vs 28% in the control group; P <0.05), and progression-free survival (PFS) was 43% (vs 23%; P <0.05). For medulloblastoma and primitive neuroectodermal tumor, survival was 63% (vs 35%; P <0.05), and the corresponding PFS was 59% (vs 35%; P = 0.15). For high-grade glioma, both the survival rate and the PFS were 27% (vs 17%; P = NS). Thus the outcome was significantly better for our "8 in 1" -treated patients than for the historical controls, especially among the children with primitive neuroectodermal tumor and medulloblastoma. In contrast, those with high-grade gliomas and brain stem tumors seem to have received little benefit; different, more effective treatments are needed for these patients.     

Use of extendable total femoral replacements in children with malignant bone tumors

Although rarely required, extendable reconstruction devices for replacing the entire femur offer children with malignant bone tumors the opportunity of a nearly normal development by overcoming an expected leg length discrepancy. Femoral integrity can be restored, allowing most patients to walk without the use of aids. There are no data available to provide evidence regarding long term results and morbidity in such patients. Six patients (range 2-12 years of age), three with osteogenic osteosarcoma and three with Ewing's sarcoma, were treated between 1988 and 1996 with custom made Stanmore extendable prosthetic total femoral replacements. One patient died 12 months after surgery because of complications relating to pulmonary metastasis. The remaining five patients were observed between 2.7 and 8.9 years (average, 5 years). No tumor recurrence has been recorded and no amputation has been performed. All surviving patients underwent an average of 9.4 operative procedures (range, 4-16 procedures) including 6.4 extension procedures (range, 3-10 procedures), and one prosthetic revision (range, 0-3 procedures). Five revisions in two patients were necessary because of infection, loosening of the prosthesis, mismatch between femoral head and acetabulum, or full extension of the extending mechanism. The functional results were measured in accordance with the Musculoskeletal Tumor Society rating score, with an average result of 77.3%. Total femoral replacement in a growing individual achieves good functional results yet has various risks for an uncertain outcome. Careful selection of the patient and realistic appraisal of the long term prospects are essential for successful treatment.     

Orbital tumors in children. Transcranial surgical approach

From March 1980 to December 1995, at the Department of Neurosurgery of the Instituto Nacional de Pediatría (INP), 23 patients were treated for orbital tumors. In this communication, the authors report on the clinical presentation, age, radiological findings, visual-evoked potentials, type of surgery, histological diagnosis, and results. Two kinds of surgical techniques were employed: craniotomy with orbital roof removal (NAFZIGER) and fronto-orbitotomy. Eleven patients had optic nerve gliomas, 3 had fibrous osseous dysplasia, 2 meningiomas, neurofibromas, Langerhans cells histiocytosis, and 1 case of Anaplastic astrocytoma, Teratoma, primitive Neuroectodermal tumor, germinoma with areas of choriocarcinoma. The results were evaluated for the quality of life in regard to the Karnofsky scale, tumor recurrence and postoperative visual-evoked potentials. It is important to note the very variable histological kinds of lesions found in this series that can be approached surgically with cranio orbitotomy with good results.     

Benign and malignant smooth muscle tumors containing Epstein-Barr virus in children with AIDS

Smooth muscle tumors (leiomyosarcomas) are the second most prevalent malignancy of children with the acquired immunodeficiency syndrome (AIDS). We have investigated the tumors, plasma, and peripheral white blood cells of eight children with AIDS with smooth muscle tumors for evidence of tumor association with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV). Very low levels of HIV were found in the tumors of the AIDS patients, probably resulting from blood-borne carriage of virus. These smooth muscle tumors had very high quantities of EBV in all the tumor cells by in situ hybridization, with an average of 4.5 EBV genomes per cell by quantitative polymerase chain reaction amplification. Increased amounts of EBV were found in the peripheral blood cells of two AIDS patients before the time of tumor diagnosis. EBV clonality studies demonstrated different monoclonal EBV infection of two separate colonic tumors from one patient, and dual or mixed monoclonal EBV infection in another patient. The muscle cells of leiomyomas and leiomyosarcomas of patients with AIDS demonstrated prominent staining with antibodies to the EBV receptor. The uniform distribution and striking amount of EBV in the tumor cells demonstrates that EBV is capable of infecting smooth muscle cells and that these cells support EBV replication. Clonal EBV proliferation suggests that EBV infection occurs at an early stage of tumor development. These findings indicate that EBV has a causal role in the oncogenesis of leiomyosarcomas of patients with AIDS.     

Iodine-123-MIBG SPECT versus planar imaging in children with neural crest tumors

Iodine-123-metaiodobenzylguanidine (MIBG) SPECT was compared with 123I-MIBG planar imaging in 35 studies of 25 children with neural crest tumors. METHODS: Iodine-123-MIBG (0.070-0.140 mCi/kg intravenously) was followed at 24 hr by wholebody planar imaging and triple-detector, high-resolution thoraco-abdominal SPECT. At 48 hr, thoracoabdominal planar imaging was performed whenever a high-tissue background or gut activity interfered with the interpretation of the 24-hr planar images. SPECT views included a cine loop presentation of multiple volume-rendered projections. Two reviewers enumerated the number of abnormal sites on the planar and SPECT studies and rated the certainty of interpretation for each study on a scale from 0.1 (low certainty) to 1.0 (high). RESULTS: Abnormal uptake was noted on planar or SPECT imaging in 13 studies (seven patients). The average number of abnormal sites detected per study for all 35 studies was 2.7 for planar imaging and 2.9 for SPECT (p = not significant) (and 7.2 and 8.4 for planar and SPECT, respectively, for the 13 abnormal studies.) The certainty ratings for all 35 studies were 0.74 for planar studies, 0.82 for SPECT (p = 0.05, chi-square, compared with planar) and 0.86 for planar and SPECT combined (p = 0.01 compared with planar alone). On volume-rendered images, gut activity was seen as diffuse and/or linear intraluminal activity. CONCLUSION: When 123I-MIBG SPECT is used, the number of lesions detected is not increased, but there is a significant improvement in the certainty of interpretation over planar imaging.     

Preliminary results of treatment of solid tumors in children with non-standard radiotherapy]

Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.     

Occipitocervical fusion with C1 laminectomy in children

STUDY DESIGN: Eight children in whom atlantoaxial dislocation had developed underwent occipitocervical fusion using a rectangular rod. The postoperative results are presented, and the postoperative growth and deformation of the cervical spine were determined radiographically. OBJECTIVES: To investigate in a relatively long-term follow-up study whether occipitocervical fusion affects the growth of the cervical spine and induces spinal deformation. SUMMARY OF BACKGROUND DATA: It has been reported that children who have undergone C1-C2 posterior fusion are likely to develop abnormal curvature or deformation of the cervical spine as a result of a disturbance of growth of the fused vertebrae. There have been no studies, however, to confirm that these changes occur after occipitocervical fusion in children. METHODS: The subjects were one boy and seven girls who had undergone occipitocervical posterior fusion during childhood. The average age at the time of surgery was 8.3 years, and the average follow-up period was 5.9 years. The following were assessed radiographically: redislocation of the atlas, bone union, changes in the curvature of the cervical spine, the height and width of the vertebral bodies, and the anteroposterior diameter of the spinal canal. RESULTS: Solid bone union was achieved in all patients with maintenance of the reduced position at the time of surgery. None of the patients exhibited abnormal curvature of the cervical spine. The rate of increase in height of the C2 vertebral body was significantly less than that of vertebral bodies below C3. The rate of increase in width of the vertebral body and the anteroposterior diameter of the spinal canal of the C2 vertebral body and vertebral bodies below C3 did not differ significantly. CONCLUSIONS: Occipitocervical fusion with a rectangular rod is useful for treating atlantoaxial dislocation in children and yields excellent results because of the firm internal fixation it achieves. This surgery induced no apparent postoperative spinal deformations.     

Classification and grading of low-grade astrocytic tumors in children

This article reviews current perspectives in the classification and grading of astrocytomas in children and calls attention to several histologically distinct groups of low-grade tumors that characteristically arise during childhood. Recognition of these tumors and the range of histological features that they may exhibit is essential for making rational assessments regarding their expected behavior and, more importantly, for guiding therapeutic intervention. For example, pleomorphic xanthoastrocytoma, which may exhibit "anaplastic" features, generally carries a relatively favorable prognosis and should not be classified with other high-grade gliomas, such as anaplastic astrocytoma and glioblastoma multiforme. Similarly, the finding of anaplastic features, such as vascular proliferation or necrosis, in pilocytic astrocytomas does not automatically portend the unfavorable prognosis that such features would imply for "diffuse" astrocytomas. Increased appreciation of the morphological diversity of astrocytomas in children should help to improve the management of children with low-grade astrocytic tumors by avoiding potentially dangerous overtreatment of otherwise indolent lesions.