Correlation between cerebral blood volume measurements by perfusion-weighted magnetic resonance imaging and two-year progression-free survival in gliomas.

Our goal was to determine whether relative cerebral blood volume (rCBV) can serve as an adjunct to histopathologic grading in the assessment of gliomas, with the hypothesis that rCBV can predict two-year survival. We evaluated 29 newly diagnosed gliomas (13 WHO grade II, seven grade III, nine grade IV; 17 astrocytomas, 12 oligodendroglial tumors). Dynamic susceptibility-weighted contrast-enhanced perfusion MR images and CBV maps were obtained. rCBVmax measurements (maximum tumor CBV/contralateral normal tissue CBV) and progression-free survival (PFS) were recorded. Receiver operating characteristic curves and Kaplan-Meier survival curves were calculated for rCBVmax and histologic grade. rCBVmax measurements differed between gliomas without (2.38 +/- 1.22) and with progression (5.57 +/- 2.84) over two years. The optimal rCBVmax cut-off value to predict progression was 2.95. rCBVmax < 2.95 was a significant predictor of two-year PFS, almost as accurate as WHO grade II. In the pure astrocytoma subgroup, the optimal rCBVmax cut-off value to predict progression was 2.85. In this group rCBVmax < 2.85 was a significant predictor of two-year PFS, an even better predictor of two-year PFS than WHO grade II. rCBVmax can be used to predict two-year PFS in patients with gliomas, independent of pathologic findings, especially in tumors without oligodendroglial components.

Atypical cystic meningioma of the trigeminal nerve in a pediatric patient.

SUMMARY: We report an unusual case of atypical cystic meningioma of the trigeminal nerve proved by histology in a 15-year-old white girl. A review of the literature showed that this is only the second reported case of a meningioma of the trigeminal nerve without dural attachment and the first occurrence in a pediatric patient.

Idiopathic hypertrophic spinal pachymeningitis: report of two cases with typical MR imaging findings.

SUMMARY: Two patients with a chronic progressive myelopathy were successfully surgically treated and idiopathic hypertrophic spinal pachymeningitis (IHSP) was found on histology. In both patients, an extensive extramedullary mass of low T2 signal with peripheral contrast enhancement was compressing the spinal cord on MR imaging. This imaging appearance in patients with chronic progressive myelopathy should suggest the diagnosis of IHSP.

Apparent diffusion coefficients for differentiation of cerebellar tumors in children.

BACKGROUND AND PURPOSE: Diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps provide information at MR imaging that may reflect cell attenuation and integrity. We hypothesized that cerebellar tumors in children can be differentiated by their ADC values. METHODS: Brain MR imaging studies that included ADC maps were retrospectively reviewed in 32 patients with histologically proved cerebellar neoplasm. There were 17 juvenile pilocytic astrocytomas (JPA), 8 medulloblastomas, 5 ependymomas, and 2 rhabdoid (atypical teratoid/rhabdoid tumor [AT/RT]) tumors. Absolute ADC values of contrast-enhancing solid tumor regions and ADC ratios (ADC of solid tumor to ADC of normal-appearing white matter) were compared with the histologic diagnosis. ADC values and ratios of JPAs, medulloblastomas, and ependymomas were compared by using a 2-tailed t test and one-way analysis of variance (ANOVA). RESULTS: ADC values were significantly higher in pilocytic astrocytomas (1.65 +/- 0.27) (mean +/- SD) than in ependymomas (1.10 +/- 0.11) (P = .0003) and medulloblastomas (0.66 +/- 0.15) (P < .0001). Ependymomas demonstrated significantly higher ADC values than medulloblastomas (P = .0005). The observed differences were statistically significant on ANOVA (P < .001). ADC ratios were also significantly different among these 3 tumor types. AT/RT ADC values were similar to medulloblastoma. The range of ADC values and ratios within JPAs and ependymomas did not overlap with that of medulloblastomas. CONCLUSION: Assessment of ADC values of enhancing solid tumor is a simple and reliable technique for preoperative differentiation of cerebellar tumors in pediatric patients. Our cutoff values of >1.4 x 10(3) mm(2)/s for JPA and <0.9 x 10(3) mm(2)/s for medulloblastoma were 100% specific.

Contrasting effects of anti-adhesion molecule therapy in experimental allergic encephalomyelitis and Theiler's murine encephalomyelitis.

An augmentation of experimental allergic encephalomyelitis (EAE) was observed when monoclonal antibody (mAb) to intercellular adhesion molecule 1 (ICAM-1) was administered after adoptive transfer. Clinical disease was more severe in the ICAM-1 specific mAb-treated EAE mice and included prominent ataxia compared to the PBS-treated controls or Theiler's murine encephalomyelitis virus (TMEV) infected mice treated with ICAM-1 specific mAb. Neuropathologic evaluation demonstrated a distinctly different distribution of lesions in the anti-ICAM-1-treated EAE mice which featured prominent demyelination and inflammation in the cerebellum, brainstem and cerebrum. These structures were minimally involved in the control mice and mAb treatment did not alter the neuropathology in TMEV-infected mice. These results indicate that anti-ICAM-1 can alter trafficking of lymphocytes and mononuclear cells in EAE but not TMEV-induced demyelinating disease.

Successful therapy in a child with a congenital peripheral medulloepithelioma and disruption of hindquarter development.

PURPOSE: Medulloepithelioma is an embryonal multipotential neuroepithelial tumor with a striking potential for divergent differentiation. It is usually intraocular or intracerebral and associated with a good prognosis only if completely surgically excised. Data regarding therapy in children with incompletely resected tumors are limited. PATIENT AND METHODS: A girl was born with a large, peripheral, congenital medulloepithelioma associated with complete absence of the left hindquarter and anus. Plain film, ultrasonography, and magnetic resonance imaging demonstrated complete absence of the left kidney and hemipelvis. A subtotal resection of the mass and reconstruction of the tumor-related anatomical defects were performed. RESULTS: Pathologic examination showed neuroglia and pseudostratified neuroectoderm diagnostic of medulloepithelioma. She was treated with multiagent chemotherapy including vincristine, cisplatin, cyclophosphamide, carboplatin, and etoposide. She is now 50 months of age and developing normally without recurrent disease. CONCLUSIONS: A child with an incompletely resected congenital peripheral medulloepithelioma who has experienced long-term disease-free survival after treatment with chemotherapy is described. This report supports a role for adjuvant chemotherapy in the treatment of children with peripheral medulloepithelioma.

Tissue and cell-type specific expression of the tuberous sclerosis gene, TSC2, in human tissues.

TSC2 is a gene on chromosome 16p13.3 associated with the autosomal dominant neurocutaneous disorder, tuberous sclerosis complex (TSC). By using a partial nucleotide sequence from the cloned TSC2 and polymerase chain reaction methodology, we constructed a digoxigenin-labeled complementary DNA probe to examine TSC2 gene expression in autopsy- or biopsy-derived human tissues by in situ hybridization. TSC2 messenger RNA was widely expressed in various cell types throughout the body, including epithelia, lymphocytes, and cells with endocrine functions, e.g., adrenal cortex and anterior pituitary. It was prominently and selectively (within the central nervous system) expressed in pyramidal cells of the cerebral cortex and other motor neurons, e.g., in spinal cord and brainstem nuclei. Visceral TSC2 expression was comparable in autopsy tissues from patients with and without TSC; TSC2 messenger RNA expression was most prominent in cells with a rapid mitotic rate and turnover, e.g., epithelia and lymphocytes, with central nervous system pyramidal cells and other neurons being an obvious exception, and/or in cells with important secretory/transport functions. This widespread expression of the TSC2 gene supports the view that it encodes a protein vital to cell growth and metabolism or one that functions as a tumor/growth suppressor.

Localization of tuberous sclerosis 2 mRNA and its protein product tuberin in normal human brain and in cerebral lesions of patients with tuberous sclerosis.

Tuberous sclerosis (TSC), an autosomal dominant disorder, is characterized by malformations, hamartomas and tumors in various organs including the brain. TSC is genetically linked to two loci: TSC1 on chromosome 9q34 and TSC2 on 16p13.3. TSC2 has been cloned, sequenced and encodes a protein (tuberin) which functions as a tumor suppressor. We have analyzed the distribution of TSC2 mRNA and tuberin in the brains of TSC patients and non-affected individuals using both autopsy and biopsy material. High levels of transcript and protein expression were observed in choroid plexus epithelium, ependymal cells, most brainstem and spinal cord motor neurons, Purkinje cells and the external granule cell layer of the cerebellum in both TSC and control cases. Individual balloon cells from TSC patients showed very faint expression while other glia showed no expression of either transcript or tuberin. Neocortical and hippocampal neurons expressed high levels of TSC2 transcript, but only modest levels of tuberin. The internal granule cell layer of the cerebellum expressed abundant transcript but low levels of tuberin. These observations suggest either that tuberin expression is controlled at the level of both transcription and translation or the antibody and in-situ hybridization recognize different splice variants of the TSC2 gene. In TSC patients, dysmorphic cytomegalic neurons expressed high levels of tuberin and transcript, particularly when in an 'ectopic' location. Individual cells within subependymal giant cell astrocytomas (SEGAs) and hamartomas from TSC patients expressed moderate to high levels of TSC2 transcript and tuberin. While the TSC2 transcript is widely expressed primarily within neurons, tuberin is demonstrable primarily within dysplastic/cytomegalic cells of the cortex and subependymal hamartomas/SEGAs. CNS expression of tuberin is unique in that primarily non-dividing cells express it in this location, whereas extra-CNS expression of tuberin is mainly found in actively proliferating cell types such as epithelium.

Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions.

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and hamartomatous lesions. Although hamartomas can occur in almost any organ, they are most common in the brain, kidney, heart, and skin. Allelic loss or loss of heterozygosity (LOH) in TSC lesions has previously been reported on chromosomes 16p13 and 9q34, the locations of the TSC2 and TSC1 genes, respectively, suggesting that the TSC genes act as tumor-suppressor genes. In our study, 87 lesions from 47 TSC patients were analyzed for LOH in the TSC1 and TSC2 chromosomal regions. Three findings resulted from this analysis. First, we confirmed that the TSC1 critical region is distal to D9S149. Second, we found LOH more frequently on chromosome 16p13 than on 9q34. Of the 28 patients with angiomyolipomas or rhabdomyomas, 16p13 LOH was detected in lesions from 12 (57%) of 21 informative patients, while 9q34 LOH was detected in lesions from only 1 patient (4%). This could indicate that TSC2 tumors are more likely than TSC1 tumors to require surgical resection or that TSC2 is more common than TSC1 in our patient population. It is also possible that small regions of 9q34 LOH were missed. Lastly, LOH was found in 56% of renal angiomyolipomas and cardiac rhabdomyormas but in only 4% of TSC brain lesions. This suggests that brain lesions can result from different pathogenic mechanisms than kidney and heart lesions.

Augmentation of adoptively transferred experimental allergic encephalomyelitis by administration of a monoclonal antibody specific for LFA-1 alpha.

We investigated the effect of an anti-leukocyte function antigen 1 (LFA-1 alpha) monoclonal antibody, M17/4.2, on murine relapsing experimental allergic encephalomyelitis (EAE). In vitro investigations demonstrated that M17/4.2 inhibited proliferation with concanavalin A or myelin basic protein. Control mice treated with phosphate buffered saline (PBS) developed a mild to moderate disease at 7-10 days followed by a long-term relapsing clinical course. With administration of M17/4.2, the time of disease onset was unchanged; however, the severity of the disease was greatly augmented, resulting in early mortality. The pathology correlated well with the clinical course. M17/4.2 mice showed more inflammation and demyelination than PBS or anti-CD4 treated mice. Therefore, this anti-LFA-1 specific monoclonal antibody augmented EAE.