Voxel-based analysis of MTR images: a method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis

PURPOSE: To determine whether voxel-based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS). MATERIALS AND METHODS: We acquired GM MTR maps in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS), and 18 sex- and age-matched healthy controls. We evaluated the clinical status of the patients using the MS functional composite score and the expanded disability status scale. A two-sample t-test (P <0.0001, k=20, uncorrected for height threshold) was used to compare GM MTR maps from patients and controls on a voxel-by-voxel basis. We then extracted data from regions with t-values above the statistical threshold to verify the significance of differences using a nonparametric Mann-Whitney U-test. RESULTS: A between-groups comparison of GM maps revealed large abnormalities in the basal ganglia, including the bilateral thalamus, bilateral lenticular nucleus, bilateral head of caudate, and protuberance, and smaller abnormalities in the right insula, right BA 4, and left BA 40. The MTR measured in the left caudate and right insula was inversely correlated with duration following the first clinical event. CONCLUSION: These results suggest that although MS is a multifocal demyelinating disease that affects white matter (WM), a pattern of tissue damage is present inside the GM involving predominantly basal ganglia at the earliest stage of the disease.     

In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain

The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor alpha (TGFalpha) into forebrain structures. Only in animals with both lesion and infusion of TGFalpha was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFalpha infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFalpha infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases.     

Aspects of the nurse tutor-student nurse relationship

This paper is focused on selected items from an exploratory study of nurse tutor-student nurse role-relationships. Aspects of the teacher-student and counsellor-client dimensions of the relationship are reported. The research was conducted from a sociological perspective using role theory as the organizing theoretical framework. An 'ideal type' tutor-student relationship was proposed from the findings. There was concensus between tutors and students that tutors acted in a caring way towards students but many constraints were identified which inhibited students with problems from seeking help from tutors and prevented tutors from offering all the help which they wished to give to students.     

Revealing the human mutome

Chen JM, Férec C, Cooper DN. Revealing the human mutome. The number of known mutations in human nuclear genes, underlying or associated with human inherited disease, has now exceeded 100,000 in more than 3700 different genes (Human Gene Mutation Database). However, for a variety of reasons, this figure is likely to represent only a small proportion of the clinically relevant genetic variants that remain to be identified in the human genome (the ‘mutome’). With the advent of next‐generation sequencing, we are currently witnessing a revolution in medical genetics. In particular, whole‐genome sequencing (WGS) has the potential to identify all disease‐causing or disease‐associated DNA variants in a given individual. Here, we use examples of recent advances in our understanding of mutational/pathogenic mechanisms to guide our thinking about possible locations outwith gene‐coding sequences for those disease‐causing or disease‐associated variants that are likely so often to have been overlooked because of the inadequacy of current mutation screening protocols. Such considerations are important not only for improving mutation‐screening strategies but also for enhancing the interpretation of findings derived from genome‐wide association studies, whole‐exome sequencing and WGS. An improved understanding of the human mutome will not only lead to the development of improved diagnostic testing procedures but should also improve our understanding of human genome biology.     

Apolipoprotein E epsilon4 influences on episodic recall and brain structures in aging pilots

The apolipoprotein (APOE) epsilon4 allele is associated with cognitive deficits and hippocampal atrophy in nondemented middle-aged and older adults. It is not known to what extent this genetic risk factor for Alzheimer's disease (AD) impacts performance in late middle-aged and older workers in cognitively demanding occupations. This cross-sectional analysis examines brain-cognitive-genetic relationships in actively flying general aviation pilots, half of whom are APOE epsilon4 carriers. Fifty pilots were studied with structural MRI and memory tasks. Average visual paired associate memory recall performance was lower in APOE epsilon4 carriers than non-carriers. Memory performance correlated positively with hippocampal volume, but no structural differences were found in hippocampal or frontal volumes with respect to APOE epsilon4 allele. These results were evident in healthy professionals without any presenting memory problems and without selection for a family history of AD. These findings point to basic memory testing as a sensitive tool for detecting APOE epsilon4-related influences on memory in aging workers.     

DTI at long diffusion time improves fiber tracking

While diffusion‐tensor‐imaging tractography provides remarkable in vivo anatomical connectivity of the central nervous system, the majority of DTI studies to date are predominantly limited to tracking large white‐matter fibers. This study investigated DTI tractography using long diffusion time (t_diff) to improve tracking of thinner fibers in fixed rhesus monkey brains. Stimulated Echo Acquisition Mode (STEAM) sequence on a 3T Siemens TRIO was modified to include a diffusion module. DTI was acquired using STEAM with t_diff of 48 and 192 ms with matched signal‐to‐noise ratios (SNR). Comparisons were also made with the conventional double‐spin echo (DSE) at a short t_diff of 45 ms. Not only did the fractional anisotropy increase significantly with the use of long diffusion time, but directional entropy measures indicated that there was an increased coherence amongst neighboring tensors. Further, the magnitude of the major eigenvector was larger at the t_diff = 192 ms as compared to the short t_diff. Probabilistic connectivity maps at long t_diff showed larger areas of connectivity with the use of long diffusion time, which traversed deeper into areas of low anisotropy. With tractography, it was found that the length of the fibers, increased by almost 10% in the callosal fibers that branch into the paracentral gyrus, the precentral gyrus and the post central gyrus. A similar increase of about 20% was observed in the fibers of the internal capsule. These findings offer encouraging data that DTI at long diffusion time could improve tract tracing of small fibers in areas of low fractional anisotropy (FA), such as at the interfaces of white matter and grey matter. Copyright © 2010 John Wiley & Sons, Ltd.