Genetic polymorphisms of EGF 5'-UTR and NAT2 857G/A associated with glioma in a case control study of Malaysian patients.

Studies of genetic mutations that have been used in predicting glioma prognosis have revealed a complex relationship between clinical and genetic factors. Epidermal growth factor (EGF) and the NAT2 gene play a central role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production, and the mutations in the NAT2 gene have been postulated as a risk factor for cancer. We investigated EGF and the NAT2 gene in 13 glioma tissue samples and 12 normal controls. In the EGF 5'-UTR 61G polymorphism, the heterozygote GA was the most common genotype in the glioma patients. In the NAT2 polymorphism at nucleotide position 857G/A, the G allele and the GG genotype were the most prevalent forms in both the glioma and normal samples. We did not find any homozygous AA genotypes in the glioma patients. Based on this preliminary evidence, the EGF 5'-UTR at position 61 and the NAT2 SNP at position 857 polymorphisms are associated with increased risk for glioma.

Three-dimensional anatomical accuracy of cranial models created by rapid prototyping techniques validated using a neuronavigation station.

In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7®.

Deep brain stimulation of the pedunculopontine nucleus in Parkinson's disease. Preliminary experience at Oxford.

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinson's disease and related disorders. Here, we summarize our non-human primate and neuroimaging research of relevance to our surgical targeting of the PPN. We also describe our clinical experience of PPN DBS with greatest motor improvements achieved by stimulation at low frequencies.

Topography of cortical and subcortical connections of the human pedunculopontine and subthalamic nuclei.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is the most common surgical therapy for Parkinson' s disease (PD). DBS of the pedunculopontine nucleus (PPN) is emerging as a promising surgical therapy for PD as well. In order to better characterize these nuclei in humans, we determined the anatomical connections of the PPN and STN and the topography of these connections using probabilistic diffusion tractography. Diffusion tractography was carried out in eight healthy adult subjects using diffusion data acquired at 1.5 T MRI (60 directions, b=1000 s/mm(2), 2 x 2 x 2 mm(3) voxels). The major connections that we identified from single seed voxels within STN or PPN were present in at least half the subjects and the topography of these connections within a 36-voxel region surrounding the initial seed voxel was then examined. Both the PPN and STN showed connections with the cortex, basal ganglia, cerebellum, and down the spinal cord, largely matching connections demonstrated in primates. The topography of motor and associative brain areas in the human STN was strikingly similar to that shown in animals. PPN Topography has not been extensively demonstrated in animals, but we showed significant topography of cortical and subcortical connections in the human PPN. In addition to demonstrating the usefulness of PDT in determining the connections and topography of small grey matter structures in vivo, these results allow for inference of optimal DBS target locations and add to our understanding of the role of these nuclei in PD.