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Graphical Abstract

Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology.

Endodermal cysts, also known as neurogenic, neuroenteric, foregut, bronchogenic, respiratory, epithelial, teratomatous, or gastrocytoma cysts, can be found in the central nervous system, predominantly in the subarachnoid space of the cervical and thoracic spinal cord. We describe a child with an endodermal cyst of the third nerve and highlight neuroimaging findings, pathological correlation, clinical course, and patient management.

Graphical Abstract

The current study was designed to evaluate the toxicity and activity of Spartaject™ Busulfan, a microcrystalline preparation of busulfan, following its intrathecal administration into a nude rat model of human neoplastic meningitis. Animals were treated through permanent indwelling subarachnoid catheters. Human glioma D-456 MG growing in the subarachnoid space was treated with 8.1 µmol of intrathecal Spartaject™ Busulfan. Single-dose therapy was also subsequently compared with 4 doses of 8.1 and 2.0 µmol busulfan, respectively, against D-456 MG neoplastic meningitis. Additional experiments evaluated a saline control versus 8.1 µmol×1, 6.2 µmol×4 and 4.1 µmol×4, respectively, against D-456 MG. A single dose of 8.1 µmol of intrathecal Spartaject™ Busulfan resulted in an increase in median survival of 61.7% compared with the saline control. In experiment 2, all busulfan treatments showed increases in median survival of 142.8% (8.1 µmol×1), 52.3% (2.0 µmol×4), and 23% (8.1 µmol×4) (p<0.001 for all groups) compared with the saline control. These results suggest that a narrow therapeutic dose range for both toxicity and activity has been defined for intrathecal busulfan in the treatment of human neoplastic meningitis in athymic nude rats. Although busulfan has only limited activity against solid tumors, the high doses achievable in the CSF following intrathecal administration coupled with the steep dose–response relationships of alkylating agents, provide rationale for further evaluation of this agent.

The catabolism of human tissue plasminogen activator (t-PA) was studied in mice. The clearance of t-PA labeled with iodine 125 was rapid (t1/2). The clearance of phenyl-methylsulfonyl-125l-t-PA, which is active site-inhibited, was identical to the active enzyme. Sodium dodecyl sulfate Polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the vast majority of 125l-t-PA injected into the circulation was present as free enzyme and not in a complex with inhibitors. The clearance of 125l-t-PA was unaltered by large molar excesses of several ligands of known clearance specificities, including macroalbumin, asialoorosomucoid, and diisopropylphosphorylthrombin and was also not altered in the presence of a 1,000-fold molar excess of unlabeled t-PA. Organ distribution studies demonstrated that the early rapid clearance of 125l-t-PA occurred in hepatocytes, followed by a later renal phase of clearance. The clearance of 125l-urokinase (UK) also was studied and was very similar in all aspects to the clearance of 126l-t-PA. These results suggest that both t-PA and UK are cleared from the circulation by unique nonsaturable processes localized in the liver that are independent of the proteinase active site.

In recent years, major advances in the diagnosis and treatment of patients with brain tumors have been seen. Today, evaluation of the central nervous system almost always includes magnetic resonance imaging (MRI). The appearance of a new lesion on the MRI scan of a patient previously treated for a central nervous system (CNS) tumor raises concern for recurrent disease with the need for selection of new, potentially toxic therapy. However, the sensitivity of MRI may allow demonstration of new lesions which are not due to tumor. We now report three patients with medulloblastoma who demonstrated new enhancing lesions on MRI following treatment of their tumors with surgery (3 patients), chemotherapy (2 patients), and radiotherapy (2 patients). Two patients underwent resection of the lesion revealing gliosis. One patient had serial imaging that showed disappearance of the lesions. This suggests that not all new enhancing lesions in previously treated brain tumor patients represent tumor. Histologic proof of a suspicious lesion should be demonstrated prior to initiation of new therapy. Med. Pediatr. Oncol. 28: 127–131 © 1997 Wiley-Liss, Inc.

Releasable tissue plasminogen activator (t-PA) and the fast inhibitor of t-PA were measured in 18 controls and a pedigree with venous thrombosis. The functional assay was performed by a technique that destroys the t-PA inhibitor when blood is drawn. It was found that activator and inhibitor levels varied widely in the control group. One patient demonstrated inhibitor levels, on two different occasions, of 2.82 and 3.54 IU of t-PA per milliliter of plasma, as compared with a releasable activator level of 1.87 IU/mL. The t-PA antigen levels of this patient and the remainder of the pedigree were essentially normal for all seven subjects. Thus, it is suggested that the previously reported fibrinolytic disorder in this pedigree represents an imbalance between activator and inhibitor levels rather than an actual deficiency of t-PA.(Arch Intern Med 1986;146:188-191)

DNA derived from medulloblastoma biopsies was analyzed to determine if deletions of the 17p region, mutations of theTP53 gene, or amplification of the c-myc, N-myc, EGFR (epidermal growth factor receptor), orMDM2 (murine double-minute-2) genes was indicative of a poor prognosis. Loss of heterozygosity for 17p, observed in 8/28 (29%) paired samples, was associated with a shortened survival period (p=0.045 by the logrank test).TP53 mutations occurred in 2/46 (4.3%) tumor samples. c-myc Amplification was seen in 3/43 (6.9%) cases, while none of the tumors contained amplified N-myc, EGFR, orMDM2 genes. These results demonstrate that, while only rare medulloblastomas containTP53 gene mutations or amplification of the c-myc gene, loss of heterozygosity on chromosome 17p is indicative of a significantly worse prognosis among patients with these tumors. Further, these results provide a strong impetus for a prospective analysis of loss of heterozygosity in a cooperative group setting, which would include tumor staging, a selection of treatment modalities, and multivariate analyses.

Seventeen patients less than or equal to 20 years of age with newly diagnosed (n = 10) or recurrent (n = 7) malignant gliomas (anaplastic astrocytoma and glioblastoma multiforme) were treated with cyclophosphamide in association with hematopoietic cytokines (GM-CSF or G-CSF). Cyclophosphamide was given at a dose of 2 g/m² daily for 2 days at 4-week intervals. Toxicity consisted of grade IV neutropenia and thrombocytopenia in 95% and 48% of cycles, respectively. There were no cyclophosphamide-related cardiac, pulmonary, or urothelial toxicities observed. Four of 10 patients with newly diagnosed disease demonstrated responses (three complete and one partial responses; one CR was only of 2 months duration). None of the seven patients with recurrent tumors demonstrated a response. We conclude that high-dose cyclophosphamide warrants further evaluation in children with newly diagnosed malignant glioma. Med. Pediatr. Oncol. 30:75–80, 1998. © 1998 Wiley-Liss, Inc.

Gangliocytomas are rare CNS tumors that occur in children and young adults. We present a case of a cerebellar gangliocytoma with invasion of the cervical spinal cord demonstrated on MR. Radiographic differentiation of gangliocytomas from other ganglion cell tumors—ganglioglioma, dysplastic gangliocytoma of Lhermitte-Duclos, and desmoplastic infantile ganglioglioma—is discussed.

Heart transplantation is considered nowadays the gold standard in the therapy of chronic and terminal heart insufficiency. Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or acute rejection. All these factors can potentially lead to multiorgan failure. Pharmacological and mechanical support for these patients is limited and often related to side effects. Ca2sensitizers have been proposed to increase cardiac contractility without altering intracellular Ca2levels, thus avoiding the side effects of Ca2overload. We report two cases of heart transplanted patients suffering from acute graft failure in the early postoperative period who recovered after intravenous administration of levosimendan, a Ca2sensitizer.

We report development of an intracranial epidermoid cyst 2 years after a depressed skull fracture. The epidermoid cyst is presumed to be the result of introduction of epidermal elements at the time of trauma. Posttraumatic intracranial epidermoid cysts are rare and appear to be less common than those occurring in the spine.