Mutations in WDR62, encoding a centrosomal and nuclear protein, in Indian primary microcephaly families with cortical malformations

Primary microcephaly is an autosomal recessive disorder characterized by smaller than normal brain size and mental retardation. It is genetically heterogeneous with seven loci: MCPH1-MCPH7. We have previously reported genetic analysis of 35 families, including the identification of the MCPH7 gene STIL. Of the 35 families, three families showed linkage to the MCPH2 locus. Recent whole-exome sequencing studies have shown that the WDR62 gene, located in the MCPH2 candidate region, is mutated in patients with severe brain malformations. We therefore sequenced the WDR62 gene in our MCPH2 families and identified two novel homozygous protein truncating mutations in two families. Affected individuals in the two families had pachygyria, microlissencephaly, band heterotopias, gyral thickening, and dysplastic cortex. Using immunofluorescence study, we showed that, as with other MCPH proteins, WDR62 localizes to centrosomes in A549, HepG2, and HaCaT cells. In addition, WDR62 was also localized to nucleoli. Bioinformatics analysis predicted two overlapping nuclear localization signals and multiple WD-40 repeats in WDR62. Two other groups have also recently identified WDR62 mutations in MCPH2 families. Our results therefore add further evidence that WDR62 is the MCPH2 gene. The present findings will be helpful in genetic diagnosis of patients linked to the MCPH2 locus

Central nervous system lymphoma: Patterns of incidence in Indian population and effect of steroids on stereotactic biopsy yield

Background: Epidemiology of primary central nervous system lymphoma (PCNSL) world-wide shows an increase in incidence linked to human immunodeficiency virus (HIV) pandemic. Materials and Methods: This retrospective review of case records analyzed the trends of hospital-based incidence of PCNSL over two decades (1991-2010), relation to immune status and effect of steroids on yield of stereotactic biopsy (STB). Results: A total of 76 cases of PCNSL were diagnosed over a period of two decades. Incidence of lymphomas amongst all biopsied lesions showed a gradual increase from 0.18% at the beginning of study period to 0.41% at the end of study period. Only 8.6% (3 of 35 tested) of the PCNSL patients were positive for HIV. The mean age of patients with HIV infection (31.3 ± 3.5 years) was significantly lower compared with those without HIV infection (44.7 ± 10.9 years) (P = 0.033). Diagnosis was obtained by open biopsy in 32 patients (42.1%) and STB in 44 patients (57.9%). Open biopsy yielded a histological confirmation of PCNSL in all cases. Among those who underwent STB, the incidence of negative biopsy with short duration of steroids (≤1 week) was 33.3% and increased to 57.1% with increasing duration of steroid treatment (>1 week). Conclusions: This study documented an increase in hospital based incidence of PCNSL in our institute, independent of HIV association. Steroid intake administration for more than a week prior to biopsy adversely affected the yield of STB in PCNSL

Utility of multiparametric 3-T MRI for glioma characterization

BACKGROUND AND PURPOSE: Accurate grading of cerebral glioma using conventional structural imaging techniques remains challenging due to the relatively poor sensitivity and specificity of these methods. The purpose of this study was to evaluate the relative sensitivity and specificity of structural MRI and MR measurements of perfusion, diffusion, and spectroscopic parameters for glioma grading. A secondary objective was to evaluate a whole-brain MR spectroscopic imaging method for evaluation of brain tumors. MATERIALS AND METHODS: Fifty six patients with radiologically suspected untreated glioma were studied with T1- and T2-weighted MR imaging, DCE-MR imaging, DTI, and volumetric whole-brain MR spectroscopic imaging. ROC analysis was performed using the relative CBV, ADC, FA, and multiple spectroscopic parameters to determine optimum thresholds for tumor grading and to obtain the sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas. Logistic regression was performed to analyze all the parameters together. RESULTS: The relative CBV individually classified glioma as low and high grade with a sensitivity and specificity of 100% and 88% respectively based on a threshold value of 3.34. On combining all parameters under consideration, the classification was achieved with 2% error and sensitivity and specificity of 100% and 96% respectively. CONCLUSION: Individually, CBV measurement provides the greatest diagnostic performance for predicting glioma grade; however, the most accurate classification can be achieved by combining all of the imaging parameters. The whole-brain MR spectroscopic imaging method provided data from of a large fraction of the tumor volumes

Preoperative diffusion-weighted imaging of single brain metastases correlates with patient survival times

Preoperative DWI findings strongly and independently correlate with OS in patients operated for single BM and are related to interstitial fibrosis. Inclusion of DWI parameters into established risk stratification scores for BM patients should be considered