Effect of early optic canal unroofing on the outcome of visual functions in surgery for meningiomas of the tuberculum sellae and planum sphenoidale.

OBJECTIVE: The aim of this study was to evaluate the effect of early optic canal unroofing on visual function in patients with meningiomas of the tuberculum sellae and planum sphenoidale. METHODS: We retrospectively reviewed the clinical records of 20 consecutive patients with tuberculum sellae meningiomas and two patients with planum sphenoidale meningiomas who were admitted to our institution from 1999 to 2007. Factors that may influence postoperative visual functions were analyzed, including patient's age and sex, duration of preoperative visual symptoms, preoperative visual acuity, tumor size, tumor consistency, tumor extension into the optic canal, tumor adhesion to the optic nerve, timing of optic canal unroofing, and tumor resection rate. RESULTS: The mean patient age was 52.9 +/- 13.7 years (range, 27-73 yr); 18 patients were women and four were men. The mean maximum tumor size was 2.3 +/- 0.7 cm (range, 1.5-3.5 cm). Visual symptoms were present preoperatively in 19 patients, and three patients were asymptomatic. The mean duration of visual symptoms was 12.0 +/- 16.4 months (range, 0-72 mo). Tumor resection was evaluated according to Simpson's grade, and Grade II was achieved in 14, Grade III in two, and Grade IV in six (two patients were recurrent cases). Tumors were extended into the optic canal in 15 patients, and severe adhesion to the optic nerve was observed in nine patients. Tumor consistency was soft in eight patients, intermediate in eight patients, and hard in six patients. The optic canal was unroofed early before dissection or manipulation of tumor in nine patients (early group) and after dissection of tumor in seven patients (late group), and optic canal unroofing was not performed in six patients (none group; no canal extension in two and intentional incomplete resection in four patients). Visual symptoms were improved in 10 patients, unchanged in seven patients, and worsened in five patients (transient in two and permanent in three). Logistic regression analysis revealed that early optic canal unroofing was an independent factor for postoperative improvement of visual symptoms. CONCLUSION: Early optic canal unroofing may increase the possibility of improved preoperative visual symptoms in surgical resection of tuberculum sellae meningiomas and planum sphenoidale meningiomas.

Model-based linkage analyses confirm chromosome 19q13.3 as a susceptibility locus for intracranial aneurysm.

BACKGROUND AND PURPOSE: In previous studies of familial intracranial aneurysm (IA), parametric linkage analyses have been undertaken for five unrelated families, four providing maximum logarithm of odds (LOD) scores with dominant models and one with a recessive model. Each family was linked to a distinct locus, indicating locus heterogeneity. This study aimed to examine whether Japanese IA families consistent with autosomal-dominant mode of inheritance support linkage to these loci. METHODS: We performed genomewide linkage analysis using the GENEHUNTER program. Affected-only parametric linkage analysis was used for 41 affected members in nine unrelated IA families with dominant models, which were selected from 29 families used for a nonparametric (model-free) linkage analysis in our previous study. RESULTS: We failed to support the linkage to previously reported autosomal-dominant loci. Instead, we found linkage to chromosome 19q13.3 with a maximum multipoint LOD score of 4.10. The LOD-1 interval (regions with LOD scores of >1) was 8.0 cM between D19S198 and D19S902. CONCLUSIONS: A genomewide scan for IA families with dominant models in Japan confirmed the locus at chromosome 19q13.3, which has also been reported as a candidate locus in a Finnish population.

Combination of linkage and association studies for brain arteriovenous malformation.

BACKGROUND AND PURPOSE: Genetic factors for brain arteriovenous malformation are unexplored because of the low incidence of familial cases, albeit local and familial clustering. We used a combination of a linkage study and an association study to explore the genetic background. METHODS: A genome-wide linkage analysis was performed in 12 patients from 6 unrelated families using the GENEHUNTER program. A genome-wide association analysis of 26 cases and 30 controls was performed using a GeneChip 10K mapping array. Significance levels for linkage and single single-nucleotide polymorphism association analyses were set at P<0.05 and P<0.0001, respectively. Genotyping was also performed using 58 960 single-nucleotide polymorphisms for 2 sets of discordant twins. RESULTS: The linkage analysis revealed 7 candidate regions, with the highest logarithm of odds score of 1.88 (P=0.002) at chromosome 6q25. A significant association was observed for 4 single-nucleotide polymorphisms and 2 haplotypes, but none of them overlapped with candidate linkage regions. Genotyping of the twins showed no genetic heterogeneity. CONCLUSIONS: The present study failed to identify genetic factors for arteriovenous malformation although the low statistical power may have resulted in such evidence being missed.

Search on chromosome 17 centromere reveals TNFRSF13B as a susceptibility gene for intracranial aneurysm: a preliminary study.

BACKGROUND: Our previous studies have shown a significant linkage of intracranial aneurysms (IAs) to chromosome 17. METHODS AND RESULTS: Nine genes (TNFRSF13B, M-RIP, COPS3, RAI1, SREBF1, GRAP, MAPK7, MFAP4, and AKAP10) were selected from 108 genes that are located between D17S1857 and D17S1871 by excluding 99 genes that were pseudogenes, hypothetical genes, or well-characterized genes but not likely associated with IA. Direct sequencing of all coding and regulatory regions in 58 cases (29 pedigree probands and 29 unrelated nonpedigree cases) was performed. Deleterious changes were found only in TNFRSF13B, K154X, and c.585 to 586insA in exon4. The association of IA with TNFRSF13B was further studied in 304 unrelated cases and 332 control subjects. Rare nonsynonymous changes, a splicing acceptor site change and a frame shift, were found in unrelated cases (2.3%; 14 of 608) more frequently than in control subjects (0.8%; 5 of 664; P=0.035). The association study using single-nucleotide polymorphisms in an unrelated case-control cohort revealed a protective haplotype (odds ratio 0.69, 95% confidence interval 0.52 to 0.92, P=0.012) compared with the major haplotype after adjustment for covariates. CONCLUSIONS: We propose that TNFRSF13B is one of the susceptibility genes for IA.

Association analysis of common variants of ELN, NOS2A, APOE and ACE2 to intracranial aneurysm.

BACKGROUND AND PURPOSE: Previous studies have shown positive evidence of linkage of the intracranial aneurysm (IA) at chromosome 7q11, 17cen, 19q13, and Xp22. These regions contain elastin (ELN), nitric oxide synthetase 2A (NOS2A), apolipoprotein E (APOE), and angiotensin-I converting enzyme 2 (ACE2), which are considered to be promising candidate genes for IA. We aimed to examine the association of single-nucleotide polymorphisms (SNPs) with IA in these candidate genes. METHODS: To identify polymorphisms in NOS2A and ACE2, all exons and exon-intron boundaries were screened by direct sequencing in 30 randomly selected controls. The program tagSNPs was used to select an optimal set of haplotype-tagging SNPs. For ELN and APOE, SNPs were selected from previous reports. These selected SNPs were then genotyped in 362 cases with IA and 332 residential area matched controls. THESIAS software was used to investigate the association of alleles and haplotypes with IA by adjusting with covariates. RESULTS: We genotyped 8 SNPs in ELN, 8 SNPs in NOS2A, 3 epsilon alleles in APOE and 1 SNP in ACE2. No alleles or haplotypes of 4 candidate genes revealed any significant association with IA. CONCLUSIONS: Investigated polymorphisms in this study were not associated with IA.