Cutaneous and leptomeningeal vascular malformations are hallmarks of the Sturge-Weber Syndrome (SWS), resulting in chronic ischemic tissue damage. The mechanisms underlying the pathobiology of these progressive lesions are unknown. Aberrant expression of angiogenic factors has been implicated in the genesis and maintenance of vascular malformations. To assess the role of angiogenesis in SWS vascular lesions we determined the expression of key angiogenic factors by immunohistochemistry and in situ hybridization in 8 SWS patients (age: 8 months to 18 years). We observed increased expression of vascular endothelial growth factor (VEGF), its cognate receptors VEGFR-1, VEGFR-2, and neuropilin (NP)-1 as well as Tie2 in leptomeningeal SWS blood vessels. Intriguingly, these factors are known to be transcriptionally induced by hypoxia-inducible factor (HIF). The HIF system has emerged as the key regulatory system of responses to hypoxia. Immunohistochemical analysis demonstrated markedly elevated nuclear HIF-1alpha and HIF-2alpha protein levels in SWS vessels. Concomitantly, SWS vessels revealed signs of enhanced endothelial cell (EC) turnover as evidenced by increased EC proliferation and apoptosis. Thus, in terms of angiogenesis, vascular malformations in SWS are not static lesions but constitute dynamic structures. Our observation of a dysregulated HIF-alpha expression in SWS vessels are in agreement with recent findings that EC-specific HIF activation provides a setting which supports and sustains angiogenesis and could be of potential use for developing therapeutic strategies to treat these currently incurable lesions.

Capillary hemangiomas are rare benign vascular tumors that tend to occur in children. Whereas the majority of hemangiomas may regress spontaneously, those associated with functional sequelae or severe symptoms may require treatment. Two patients with capillary hemangiomas of the cavernous sinus that caused neurological symptoms were treated with fractionated stereotactic radiation therapy. Both hemangiomas had shown a progressive increase in size during observation before radiation therapy; both tumors regressed after radiotherapy. Up to the time of the last follow-up evaluation both patients experienced symptomatic relief after radiation. One patient's tumor remains in complete remission and the second tumor continues to demonstrate minor residual contrast enhancement without progression.The authors conclude that fractionated stereotactic radiation therapy is a useful treatment modality in the management of symptomatic capillary hemangiomas when these tumors arise in regions of the brain or skull base in which a complete resection cannot be accomplished.

The 30 choroid plexus tumors recorded in a large pediatric tumor registry were reviewed. The 22 choroid plexus papillomas and 8 choroid plexus carcinomas represented 2.1% of all brain tumors in the registry. The patients (19 boys, 11 girls) were aged 3 months to 12 years (mean: 2 years 9 months). All tumors and four samples of normal choroid plexus were examined with conventional histology, 9 tumors were examined with electron microscopy and 24 using immunohistochemical techniques with antisera against glial fibrillary acidic protein, S-100 protein, epidermal cytokeratin, internal organ cytokeratin and carcinoembryonic antigen. Seven of the tumors (1 carcinoma and 6 papillomas) had some positive cells with antiserum against glial fibrillary acidic protein. Twenty-seven of the tumors (90%) and all normal choroid plexus samples were positive with antiserum to S-100 protein. Some tumor cells from both types of tumor and the normal choroid plexus reacted positively with internal organ cytokeratin antiserum, but all tissue samples were nonreactive with epidermal cytokeratin antiserum. Ultrastructurally, both papillomas and carcinomas displayed cytoplasmic intermediate filaments. Transmission and/or scanning electron microscopy revealed cilia in all choroid plexus papillomas. Frequently, the cilia had an abnormal arrangement, varying from 5 + 0 to 8 + 1. This study demonstrates that tumor cells of choroid plexus origin are characterized by the presence of S-100 protein and internal organ cytokeratin antiserum. Cilia, either normal or abnormal, are consistently identified in papillomas but rarely and with difficulty in carcinomas. Carcinoembryonic antigen is seen in choroid plexus carcinomas but not papillomas.

Although the occurrence of Wernicke's encephalopathy (WE) in patients on dialysis is frequently alluded to, review of the literature reveals only 3 described cases. We describe 5 patients on dialysis who developed WE in the absence of alcoholism or other predisposing factors. The clinical diagnoses included uremic encephalopathy (2 patients), dysequilibrium syndrome (1), dialysis dementia (1), and brainstem hemorrhage (1). At postmortem examination, classic findings of WE were evident. The rarity of WE in patients on dialysis may in part be explained by studies indicating a genetic defect in transketolase activity. Patients on dialysis are also potentially at risk for thiamine deficiency because of anorexia, vomiting, and intravenous alimentation. Other factors altering thiamine requirements, such as glucose load or infections, may also contribute. Preventable and potentially curable, WE should be suspected in all patients on dialysis who have an unexplained neurological picture.

Neurological manifestations in infantile osteopetrosis are common and varied, and not always attributable to the skeletal pathology. An unusual association of osteopetrosis with neuronal storage of ceroid lipofuscin is reported in two infant brothers born of nonconsanguinous parents. The first child became symptomatic at age 5 days with weight loss and vomiting. He had poor head control, hypertonia, and persistent fisting, and died at age 2 months. In the second infant, the diagnosis of osteopetrosis was confirmed at age 2 days. His neurological symptoms inlcuded blindness, deafness, and recurrent seizures. The infant died at 7 months of age. In both cases, autopsy confirmed the diffuse bony sclerosis with hepatosplenomegaly and extramedullary hematopoiesis. Neuropathological examination revealed cerebral atrophy with ventricular dilation, neuronal loss, and astrogliosis. The most striking finding was widespread accumultion of neuronal ceroid lipofuscin associated with formation of axonal spheroids. The optic nerves were compressed at the optic foramina and showed loss of myelinated axons and gliosis. Rapid Golgi impregnations of neurons from the calcarine cortex in the second infant were analyzed quantitatively, showing a reduction in the total dendritic length and number of branches. The primary defect in osteopetrosis is thought to be a lysosomal dysfunction involving the monocyte cell line from which osteoclasts are derived. Thus, the association in two brothers of osteopetrosis with accumulation of neuronal ceroid lipofuscin may not be fortuitous. The neuronal storage disorder in this instance probably reflects lysosomal dysfunction.

Fourteen pure oligodendrogliomas were studied by light- and electronmicroscopy and immunohistochemistry to examine glial fibrillary acidic protein (GFAP) positivity in the tumors. To compare the immunohistochemical staining patterns of neoplastic oligodendroglia and immature oligodendroglia, myelination glia in the white matter of eight normal brains from children under 6 months of age were studied. The tumors possessed light microscopic and ultrastructural features characteristic of oligodendrogliomas. Microtubules were found in the cytoplasm of nine tumors on electronmicroscopy. In one, intermediate filaments and microtubules were observed in occasional tumor cells with polygonal crystalline structures in the cytoplasm. Using the peroxidase-antiperoxidase technique, all specimens were stained for GFAP, vimentin, S-100 and neuron-specific enolase (NSE). In nine tumors, variable numbers of cells with an oligodendroglial morphology reacted positively for GFAP. All tumors were positive for S-100 and negative for vimentin and NSE. The myelination glia in the eight normal brains stained positively for GFAP but not for vimentin. Vimentin is expressed by developing, reactive and neoplastic astrocytes. Thus, GFAP positivity combined with vimentin negativity in both neoplastic and immature oligodendroglia suggests that GFAP positivity in oligodendrogliomas may reflect the transient expression of this intermediate filament by immature oligodendroglia.

The authors review the cases of 60 children (aged 5 months to 18 years) with thalamic tumors who were seen at The Hospital for Sick Children between 1951 and 1983. The diagnosis of thalamic tumor was based on neuroradiological studies; 33 children were first seen in the pre-computerized tomography (CT) era and 27 since the advent of CT scanning. Histological diagnosis was obtained in 37 patients at the time of operation. A further four tumors were verified histologically at autopsy. Thirty-six patients required cerebrospinal fluid shunt placement. Sixteen patients had no surgery on their tumor, three underwent needle biopsy, 20 underwent open biopsy, and 21 had partial resection. Forty-four patients were irradiated. All 20 patients with malignant tumors died, with a mean survival time of 1.1 years. Of 19 patients with benign tumors, 11 died, with a mean survival time of 5.3 years, and eight are still alive after a mean period of 7.2 years since diagnosis. Based on this series, the authors recommend open biopsy of thalamic tumors (and resection if deemed safe), followed by radiation in selected cases.

A primary cerebellar rhabdomyosarcoma (RMS) in a six and a half year old boy is reported. Microscopy of the surgical material revealed lobules of closely packed cells with a high mitotic rate, pleomorphic hyperchromatic nuclei and scant cytoplasm. At their periphery, the lobules merged with rounded cells with similar nuclei but more abundant cytoplasm. These areas were surrounded by interlacing fascicles of strap cells, which were occasionally multinucleated and showed cross striations. Electron microscopy (EM) revealed the primitive nature of the closely packed cells; however, occasional intermediate size filaments were present within their cytoplasm and focal basement membrane accumulation was observed. Cells with more abundant cytoplasm had large accumulations of thick and thin filaments while strap cells showed well-developed cross striations. Immunohistochemical studies (peroxidase-antiperoxidase technique) showed vimentin in the primitive cells and desmin, myoglobin and adenosine triphosphatase as the tumor cells appeared more differentiated. Immunoreaction with antibodies against glial fibrillary acidic protein, S-100 protein and neurofilament protein were negative. Electron microscopic and immunohistochemical studies in this case demonstrated that this was an exclusively mesenchymal tumor with rhabdomyoblastic differentiation and that the pattern of differentiation follows that seen in normal myogenesis.