A role of diffusion tensor imaging in movement disorder surgery

The safe and reversible nature of deep brain stimulation (DBS) has allowed movement disorder neurosurgery to become commonplace throughout the world. Fundamental understanding of individual patient’s anatomy is critical for optimizing the effects and side effects of DBS surgery. Three patients undergoing stereotactic surgery for movement disorders, at the institution’s intraoperative magnetic resonance imaging operating suite, were studied with fiber tractography. Stereotactic targets and fiber tractography were determined on preoperative magnetic resonance imagings using the Schaltenbrand–Wahren atlas for definition in the BrainLab iPlan software (BrainLAB Inc., Feldkirchen, Germany). Subthalamic nucleus, globus pallidus interna, and ventral intermediate nucleus targets were studied. Diffusion tensor imaging parameters used ranged from 2 to 8 mm for volume of interest in the x/y/z planes, fiber length was kept constant at 30 mm, and fractional anisotropy threshold varied from 0.20 to 0.45. Diffusion tensor imaging tractography allowed reliable and reproducible visualization and correlation between frontal eye field, premotor, primary motor, and primary sensory cortices via corticospinal tracts and corticopontocerebellar tracts. There is an apparent increase in the number of cortical regions targeted by the fiber tracts as the region of interest is enlarged. This represents a possible mechanism of the increased effects and side effects observed with higher stimulation voltages. Currently available diffusion tensor imaging techniques allow potential methods to characterize the effects and side effects of DBS. This technology has the potential of being a powerful tool to optimize DBS neurosurgery.     

Comparison study for genotyping of a single-nucleotide polymorphism in the tumor necrosis factor promoter gene.

A variety of methods that address the detection of single-nucleotide polymorphism (SNP) have been used in molecular diagnostics. The allele-specific polymerase chain reaction (ASPCR) has been one of the most extensively studied, including its application in the tumor necrosis factor (TNF)(-308) genotyping. Many studies have demonstrated that the ASPCR sensitivity and specificity depends on various PCR parameters, with mismatches occurring to a degree of 4%. The purpose of our study was to evaluate a comparison of genotyping of the TNF(-308) using an ASPCR and automated sequencing (ASEQ). In a total of 204 DNA samples, their duplicate examination by the ASPCR and ASEQ revealed concordant results in 96.5% and mismatches in 3.5% genotypes. Depending on the target TNF(-308G/G), TNF(-308G/A) , TNF(-308A/A) sequences, this translated into decreased ASPCR sensitivity to a degree of 98.6%, 94.2%, 60.0%, specificity 94.7%, 97.4%, 100.0%, positive predictive values 97.9%, 92.5%, 100.0%, and negative predictive values 96.4%, 98.0%, 99.0%, respectively. Based on these results, we found ASEQ to be more accurate than ASPCR for the TNF(-308) genotyping. By eliminating the need of empirical determination of appropriate PCR conditions for each studied sequence, ASEQ provides a sensitive and reproducible quality-control benchmark for other SNP assays.     

Effects of continuous positive airway pressure treatment on aortic stiffness in patients with resistant hypertension and obstructive sleep apnea: A randomized controlled trial

Resistant hypertension (RHT) is associated with obstructive sleep apnea (OSA) and increased aortic stiffness, measured by carotid‐femoral pulse wave velocity (cf‐PWV). We aimed to evaluate in a randomized controlled trial, the effect of Continuous positive airway pressure (CPAP) treatment on cf‐PWV in comparison with a control group in patients with RHT and moderate‐severe OSA. One‐hundred and sixteen patients were randomized to 6‐month CPAP treatment (56 patients) or no therapy (60 patients), while keeping their antihypertensive treatment unchanged. Carotid‐femoral pulse wave velocity was performed at the beginning and end of the 6‐month period. Intention‐to‐treat intergroup differences in cf‐PWV changes were assessed by a generalized mixed‐effects model with the allocation group as a fixed factor and adjusted for age, sex, changes in mean arterial pressure and the baseline cf‐PWV values. Subgroup sensitivity analyses were performed, excluding patients with low CPAP adherence and low cf‐PWV at baseline. CPAP and control groups had similar clinic‐laboratorial characteristics. Patients had a mean cf‐PWV of 9.4 ± 1.6 m/s and 33% presented cf‐PWV > 10 m/s. During treatment, the control group had a mean increase in cf‐PWV of +0.43 m/s (95% confidence interval [CI], +0.14 to +0.73 m/s; p = .005), whereas the CPAP group had a mean increase of +0.03 m/s (95% CI, ?0.33 to +0.39 m/s; p = .87), resulting in a mean difference in changes between CPAP and control of ?0.40 m/s (95% CI, ?0.82 to +0.02 m/s; p = .059). Subgroup analyses did not change the results. In conclusion, a 6‐month CPAP treatment did not reduce aortic stiffness, measured by cf‐PWV, in patients with RHT and moderate/severe OSA, but treatment may prevent its progression, in contrast to no‐CPAP therapy.     

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Differential effects of countermovement magnitude and volitional effort on vertical jumping

The importance of vertical jumping in sport and rehabilitative medicine is widely recognized. Despite the ample use of jump tests to assess neuromuscular function, the differential effects of muscular activation (volitional effort) and strategy (countermovement magnitude) on jumping performance have not been studied. The present study aimed to investigate the differential effects of countermovement magnitude and volitional effort on vertical jump performance. Ten male participants performed a total of 60 countermovement jumps each with three different countermovement knee angles (50, 70 and 90°) and four effort levels (25, 50, 75 and 100% of maximal effort). Kinematics and Kinetics were recorded using Vicon System together with a force platform. Electromyography of four muscles was recorded. Results show that countermovement magnitude and volitional effort both affect jump performance. These effects were synergistic for jump height (P < 0.001), but antagonistic for peak ground reaction force (P < 0.001). Interestingly, peak jump mechanical power was affected by volitional effort, implying an increase from 31.26 W/kg at 25% to 41.68 W/kg at 100% of volitional effort, but no countermovement magnitude effect was observed for 100% of volitional effort. This suggests that the apparent paradox of larger ground reaction forces in sub-maximal as compared to maximal jumps is due to the different jump strategies. Moreover, these results are relevant for jumping mechanography as a clinical tool, suggesting that peak power can be used to assess neuromuscular performance even when countermovement magnitude varies as a result of age or pathology.     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

PLP1 gene analysis in 88 patients with leukodystrophy

Pelizaeus–Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty‐eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation‐dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array‐CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array‐CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.