The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

Knobloch syndrome (KS) is a rare disease characterized by severe ocular alterations, including vitreoretinal degeneration associated with retinal detachment and occipital scalp defect. The responsible gene, COL18A1, has been mapped to 21q22.3, and, on the basis of the analysis of one family, we have demonstrated that a mutation affecting only one of the three COL18A1 isoforms causes this phenotype. We report here the results of the screening of both the entire coding region and the exon-intron boundaries of the COL18A1 gene (which includes 43 exons), in eight unrelated patients with KS. Besides 20 polymorphic changes, we identified 6 different pathogenic changes in both alleles of five unrelated patients with KS (three compound heterozygotes and two homozygotes). All are truncating mutations leading to deficiency of one or all collagen XVIII isoforms and endostatin. We have verified that, in exon 41, the deletion c3514-3515delCT, found in three unrelated alleles, is embedded in different haplotypes, suggesting that this mutation has occurred more than once. In addition, our results provide evidence of nonallelic genetic heterogeneity in KS. We also show that the longest human isoform (NC11-728) is expressed in several tissues (including the human eye) and that lack of either the short variant or all of the collagen XVIII isoforms causes similar phenotypes but that those patients who lack all forms present more-severe ocular alterations. Despite the small sample size, we found low endostatin plasma levels in those patients with mutations leading to deficiency of all isoforms; in addition, it seems that absence of all collagen XVIII isoforms causes predisposition to epilepsy.

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Classified according to the latest WHO classification, by a single neuropathologist in a single institution, this large series of pediatric neurological tumors may reflect fairly well their real incidence. Our results obtained in a developing country do not differ substantially from other similar series reported in the literature from the First World.

The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed: P < 0.00001 for CDKN2C, CKS2, EEF1A1, EMP3, PDPN, BNIP2, CA12, CD34, CDC42EP4, PPIE, SNAI2, GDF15 and MMP23b; and NFIA (P: 0.0001), GPS1 (P: 0.0003), LAMA1 (P: 0.002), STIM1 (P: 0.006), and TASP1 (P: 0.01). Five of these genes are located in contiguous loci at 1p31-36 and 2 at 17q24-25 and 8 of them encode surface membrane proteins. PDPN and CD34 protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.

The diagnosis of normal cognition or dementia in the Brazilian Brain Bank of the Aging Brain Study Group (BBBABSG) has relied on postmortem interview with an informant.ObjectivesTo ascertain the sensitivity and specificity of postmortem diagnosis based on informant interview compared against the diagnosis established at a memory clinic.MethodsA prospective study was conducted at the BBBABSG and at the Reference Center for Cognitive Disorders (RCCD), a specialized memory clinic of the Hospital das Clínicas, University of São Paulo Medical School. Control subjects and cognitively impaired subjects were referred from the Hospital das Clínicas to the RCCD where subjects and their informants were assessed. The same informant was then interviewed at the BBBABSG. Specialists’ panel consensus, in each group, determined the final diagnosis of the case, blind to other center’s diagnosis. Data was compared for frequency of diagnostic equivalence. For this study, the diagnosis established at the RCCD was accepted as the gold standard. Sensitivity and specificity were computed.ResultsNinety individuals were included, 45 with dementia and 45 without dementia (26 cognitively normal and 19 cognitively impaired but non-demented). The informant interview at the BBBABSG had a sensitivity of 86.6% and specificity of 84.4% for the diagnosis of dementia, and a sensitivity of 65.3% and specificity of 93.7% for the diagnosis of normal cognition.ConclusionsThe informant interview used at the BBBABSG has a high specificity and sensitivity for the diagnosis of dementia as well as a high specificity for the diagnosis of normal cognition.

Knobloch syndrome is an autosomal recessive disease characterized by the early onset of severe myopia, vitreoretinal degeneration with retinal detachment, macular abnormalities, and midline encephalocele, mainly in the occipital region. Intra and interfamilial variability is present since the encephalocele is not found in all patients, and the degree of myopia is variable. Analysis of the associated malformations suggests alterations during early neuroectodermal morphogenesis. Only 24 cases have been reported. Recently, the gene responsible for the syndrome, mapped to 21q22.3, was identified. The present study reports on four new cases, revealing the existence of neuronal migratory defects associated with the disorder for the first time.

We describe three cases of the rare syndrome of leukoencephalopathy, brain calcifications, and cysts. Conventional MRI, proton spectroscopy, and diffusion-weighted imaging yielded additional information on the disease. Imaging findings favor increased water content rather than a demyelinating process in the pathophysiology of this disease. Clinical features of Coats disease and consanguinity were also encountered.