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A new technique that will enable doctors to ‘see’ things happening at the molecular level using standard MR imaging techniques has been developed by Oxford scientists. The technique has initially been directed towards MS, but long-term it has the potential to be used for a vast range of health problems.
Oxford University researchers have developed a marker that attaches itself to particular molecules involved in inflammation. As a result, these molecules ‘light up’ on MRI scans.
The ‘VCAM-1’ molecule plays a key role in inflammation, which contributes to many diseases, including multiple sclerosis, arthritis, inflammatory bowel disease and atherosclerosis (a hardening and narrowing of the arteries which can lead to heart attack and stroke).
By injecting into the body markers that attach themselves to VCAM-1 molecules, and which are visible under MRI scanning, the researchers were able to see on a scan exactly where the molecules were in operation, and in what quantities. The ultimate goal is to facilitate earlier diagnosis, guide treatment and provide more precise monitoring of disease progression.
The team has developed the technique with a view to using it in multiple sclerosis (MS), an autoimmune disease that affects the central nervous system. In MS the body’s own immune system, through inflammation, attacks the fatty tissue surrounding nerve fibres (myelin), which helps nerves carry signals, leading to a range of problems with vision and movement.
Compared to conventional MRI techniques, the new technique has the potential to reveal disease activity much earlier and, crucially, before tissue destruction has occurred. Earlier intervention with drug treatments guided by this information may alter disease progression.
Reference: McAteer, M et al. (2007) In vivo magnetic resonance imaging of acute brain inflammation using microparticles of iron oxide. Nature Medicine, published online 23 September 2007
Read abstract/source full text of article: http://www.nature.com/nm/journal/vaop/ncurrent/abs/nm1631.html
Magnetic resonance spectroscopic imaging (MRSI) studies were performed on 58 people with primary progressive multiple sclerosis over a period of 3 years in order to investigate the efficacy of glatiramer acetate (Copaxone©) as treatment for this form of MS.
Researchers found the difference between the normal appearing tissues and lesion-containing regions in those being treated with Copaxone© was not significantly different from those treated with a placebo.
Reference: Balasrinivasa, R. et al. (2007) Longitudinal magnetic resonance spectroscopic imaging of primary progressive multiple sclerosis patients treated with glatiramer acetate: multicenter study. Multiple Sclerosis 19 Sep 2007.
Read abstract/source full text of article: http://highwire.stanford.edu/cgi/medline/pmid;17881390
This study observes that brain atrophy is more closely associated with cognitive impairment in MS than are conventional MRI lesion measures.
They note that enlargement of the third ventricle of the brain shows a particularly strong correlation with cognitive impairment, suggesting clinical relevance of damage to surrounding structures, such as the thalamus.
In this study, researchers tested the hypothesis that the volume of the brain’s thalamus volume is lower in MS than in normal subjects, and that thalamic atrophy in MS correlates with cognitive function.
They studied 79 people with MS and 16 without. A subgroup of 31 MS subjects underwent cognitive testing.
They found in particular that normalised thalamic volume was 16.8% lower in the MS group vs controls andthat cognitive performance was moderately to strongly related to thalamic volume in the MS group.
They concluded that thalamic atrophy is a clinically relevant biomarker of the neurodegenerative disease process in multiple sclerosis.
Reference: Houtchens, M. et al. (2007) Thalamic atrophy and cognition in multiple sclerosis. Neurology 18 Sep 2007 69(12): p. 1213.
Read abstract/source full text of article: http://highwire.stanford.edu/cgi/medline/pmid;17875909
Researchers examined the relationship between low-contrast letter acuity* and brain MRI abnormalities in people with MS.
They determined lesion volume and brain parenchymal fraction (used to measure whole brain atrophy). Magnetisation transfer ratio histograms were examined and vision testing was performed binocularly using low-contrast letter acuity and high-contrast visual acuity.
They found that people with lower (worse) low-contrast letter acuity and high-contrast visual acuity scores had greater T2 lesion volumes. A 3mm increase in lesion volume corresponded, on average, to a 1-line worsening of low-contrast acuity on the eye chart, whereas 1-line worsening of high-contrast acuity corresponded to a 5.5mm increase.
They concluded that low-contrast letter acuity scores correlate well with brain MRI lesion burden in MS, supporting validity for this vision test as a candidate for clinical trials.
* Low-contrast letter acuity testing involves the perception of light grey letters of progressively smaller sizes on a white or retro-illuminated background. The level of contrast can be changed by using charts with letters that are more or less grey. This method of testing is reliable, and scores are reduced (worse) in people with MS.
Reference: Wu,G. Et al. (2007) Relation of vision to global and regional brain MRI in multiple sclerosis. Neurology 19 Sep 2007.
Read abstract/source full text of article: http://highwire.stanford.edu/cgi/medline/pmid;17881718
This review summarises the existing knowledge regarding the effects of physical exercise in people with MS.
Recommendations are given regarding exercise prescription for PwMS and for future study directions.
The review observes that previously PwMS were advised not to participate in physical exercise. But during recent years, it has been increasingly acknowledged that exercise benefits them.
They suggest that to date the effects of exercise have been studied only in moderately impaired people MS with an EDSS score of less than 7. But they say evidence exists for recommending participation in endurance training at low to moderate intensity, as people with MS can both tolerate and benefit from this training.
Also, resistance training of moderate intensity seems to be well tolerated and to have beneficial effects. Only two studies have evaluated the effects of combined resistance- and endurance training, making solid conclusions regarding this training modality impossible.
Reference: Dalgas, U. , Stenager, E. and Ingemann-Hansen, T. (2007) Multiple sclerosis and physical exercise: recommendations for the application of resistance-, endurance- and combined training. Multiple Sclerosis 19 Sep 2007.
Read abstract/source full text of article: http://highwire.stanford.edu/cgi/medline/pmid;17881393
This study notes that the presence of demyelinated plaques in the central nervous system is the hallmark of MS and that some plaques remyelinate, but others do not, leaving permanent damage.
They suggest that one possibility is the lack of migration of oligodendrocyte cells* to the lesion. They suspect that the guidance molecules Semaphorin 3A and 3F — already known to direct oligodendroglial migration — may also be active in controlling this migration in MS, and hence may determine the ability of plaques to remyelinate.
In an experimental model of demyelination, they demonstrate a local source of these molecules around active demyelinating lesions, but not chronic plaques. They also provide evidence for their up-regulation at a distance from the lesion, in the neuronal cell bodies corresponding to the demyelinated axons.
They propose that both of these mechanisms influence remyelination.
* Oligodendrocytes main function is the myelination of nerve axons exclusively in the central nervous system.
Reference: Williams, A. et al. (2007) Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain 11 Sep 2007.
Read abstract/source full text of article: http://highwire.stanford.edu/cgi/medline/pmid;17855378
Canadian researchers set out to determine the incidence of MS in a longitudinal surveillance over 35 years and to estimate the prevalence rate in Saskatoon, in the province of Saskatchewan, on January 1, 2005.
They used a population-based registry established in 1969, and identified cases that continued through o 2005 from medical records, physicians, neurologists, community and provincial resources. People with definite and probable MS were included. The rates were age- and sex-adjusted to the US, European, and world 2000 populations.
They found that the incidence and prevalence rates adjusted to the standardised populations were statistically higher than the longitudinal European studies and similar to North American studies.
The study confirms a high risk of MS in Saskatoon, and these rates seem to be stable over the past 35 years.
Reference: Hader W. and Yee, I. (2007) Incidence and prevalence of multiple sclerosis in Saskatoon, Saskatchewan. Neurology 18 Sep 2007 69(12):p. 1224.
Read abstract/source full text of article: http://highwire.stanford.edu/cgi/medline/pmid;17875910