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MRIs reveal multiple sclerosis in pre-symptomatic patients(05/11/14)

A study entitled “Longitudinal Follow-up of a Cohort of Patients with Incidental Abnormal Magnetic Resonance Imaging Findings at Presentation and Their Risk of Developing Multiple Sclerosis” published in the International Journal of MS Care reports that asymptomatic patients accompanied by Magnetic Resonance Images suggestive of MS are more prone to develop MS.

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system. Currently, there is no cure for MS, which affects more than 2.3 million people throughout the world. The disease is characterised by destruction of the myelin layer within nerve cells. This leads to a wide range of neurological symptoms affecting visual, motor, and sensory capabilities. However, individuals at risk of developing MS are frequently asymptomatic. Thus, the diagnostic criteria have been evolving, and magnetic resonance imaging (MRI) is being used increasingly to assess dissemination of central nervous system lesions in time and space. Diagnosing MS, however, has to include at least one clinical event.

In this study, the authors wanted to determine risk factors for developing MS in patients who presented incidental abnormal MRI but did not exhibit typical symptoms of MS.

Researchers evaluated 30 patients from MS clinic at the Henry Ford Hospital with “abnormal brain MRI” but without any clinical manifestations of MS. These patients were followed during a period of up to 5.5 years.

The authors found that patients who had no symptoms and no MRI results suggestive of MS developed MS during the period analysed. On the contrary, asymptomatic patients who exhibited MRI findings indicative of MS, as measured by the Barkhof criteria, were likely to develop MS. These patients were usually accompanied by abnormal Cerebrospinal fluid (CSF) testing results. Thus, in some patients, occurrence of Radiologically Isolated Syndrome (RIS) is an asymptomatic period before the onset of MS.

The authors suggest their findings are helpful for physicians when deciding for further follow-up tests when presented with patients lacking both symptoms and MRI findings suggestive of MS. Further large-scale tests are needed to confirm their observations that RIS increases the risk to develop MS in a later period and determine additional characteristics that may predict the likelihood of developing MS in the future.

Source: © Copyright 2014 BioNews Services LLC (05/11/14)

MRI detects MS progression markers in white matter(16/07/14)

Magnetic resonance imaging shows the combined presence of astrogliosis and axonal damage in white matter, which has cardinal importance in multiple sclerosis (MS) severity, according to an article published in JAMA Neurology.

Researchers from the U.S. and Spain performed a study to evaluate the potential of MR markers of central nervous system injury to predict brain-volume loss and clinical disability among patients with MS.

A total of 59 patients with MS and 43 healthy controls participated in the study. There was also a confirmatory data set that included 220 patients from an independent, large genotype-phenotype research project. Participants were assessed annually over four years for outcomes, which were based on baseline N-acetylaspartate (NAA) level, myo-inositol (mI) in normal-appearing white and gray matter, myelin water fraction in normal-appearing white matter, markers of axonal damage, astrogliosis, and demyelination.

The results showed that mI:NAA could be used as a predictor, based on NAA and mI having significant effects on brain volume. “The ratio was a predictor of brain-volume change in both cohorts (annual slope in the percentage of brain-volume change/unit of increase in the ratio: −1.68; 95 percent CI, −3.05 to −0.30; P = .02 in the preliminary study cohort and −1.08; 95 percent CI, −1.95 to −0.20; P = .02 in the confirmatory study cohort),” the authors wrote.

The mI:NAA ratio predicted clinical disability in the preliminary data set as well, they noted. Also predicted were Multiple Sclerosis Functional Composite evolution, Expanded Disability Status Scale evolution, and Expanded Disability Status Scale sustained progression in the confirmatory data set. However, there was no predictive value shown with myelin water fraction.

The authors concluded that “the mI:NAA ratio in normal-appearing white matter has consistent predictive power on brain atrophy and neurological disability evolution. The combined presence of astrogliosis and axonal damage in white matter has cardinal importance in disease severity.”

Source: Diagnostic Imaging © 1996 – 2014 UBM Medica, LLC (16/07/14)

Measuring brain shrinkage in Multiple Sclerosis(23/06/14)

Sub-Millimeter Imaging of Brain-Free Water for Rapid Volume Assessment in Atrophic Brains.

Gao KC, Nair G, Cortese IC, Koretsky A, Reich DS.

Abstract

INTRODUCTION: Cerebral atrophy occurs in healthy aging, and in disease processes such as multiple sclerosis (MS), it correlates with disability accumulation. Imaging measurements of brain atrophy are commonly based on tissue segmentation, which is susceptible to classification errors and inconsistencies. High-resolution imaging techniques with strong contrast between brain parenchyma and cerebrospinal fluid (CSF) might allow fully automated, rapid, threshold-based determination of the free water in the brain. We hypothesized that total brain-free-water (BFW) volume and BFW volume expressed as a normalized fraction of the intracranial volume ("BFW fraction"), determined from heavily T2-weighted images, would be useful surrogates for cerebral atrophy and therefore would correlate with clinical measures of disability in MS.

METHODS: Whole brains of 83 MS cases and 7 healthy volunteers were imaged with a 4.7-min, heavily T2-weighted sequence on a 3T MRI scanner, acquiring 650-μm isotropic voxels. MS cases were clinically assessed on Expanded Disability Status Scale (EDSS), Scripps Neurological Rating Scale (SNRS), Paced Auditory Serial Addition Test (PASAT), 9-Hole Peg Test (9HP), Symbol Digit Modalities Test (SDMT), and 25-Foot Walk. Twelve of the MS cases were rescanned within an average of 1.8months to assess reproducibility. Automated calculations of BFW volume and BFW fraction were correlated with clinical measures of disability upon adjusting for age and sex. Results were compared to data from T1-based approaches (SIENAX and Lesion-TOADS).

RESULTS AND DISCUSSION: BFW volume was automatically derived from heavily T2-weighted images with no need for separate skull stripping. BFW volume and fraction had mean scan-rescan coefficients of variation of 1.5% and 1.9%, respectively, similar to the T1-based approaches tested here. BFW fraction more strongly correlated with clinical measures than T1-derived results. Among those clinical measures, modality-specific disability scores, such as SDMT and 9HPT, were more strongly associated with BFW fraction than composite measures, such as EDSS and SNRS.

CONCLUSION: The BFW method robustly estimates cerebral atrophy in an automated, fast, and reliable manner, and as such may prove a useful addition to imaging protocols for clinical practice and trials.

Sources: Neuroimage. 2014 Jun 16. pii: S1053-8119(14)00491-1. doi: 10.1016/j.neuroimage.2014.06.014. [Epub ahead of print] & Pubmed PMID: 24945671 (23/06/14)

Could brain imaging help treat MS-related depression?(17/06/14)

Magnetic resonance imaging (MRI) can predict responses to depression treatment in patients with multiple sclerosis (MS), according to Anthony Feinstein, Professor at the Department of Psychiatry of the Sunnybrook Health Sciences Centre & the University of Toronto. In the presentation “Depression in MS: Is brain imaging helpful?” at this year’s 2014 CMSC ACTRIMS Annual Meeting in Dallas, the researcher argued that continuing to image and document brain function will help in the diagnosis and treatment of depression associated with the disease.

Feinstein believes that imaging the brain enables clinicians “to appreciate the structural brain changes” that occur in depressed MS patients in order to study the links between these changes and alterations in mood. In addition to improving diagnosis and treatment by observing lesion changes in the brain over time, Feinstein also stated the importance of MRI in determining “how the structural brain changes linked to depression differ from those seen in pseudobulbar affect.”

The pseudobulbar affect is a neurologic disorder characterized by involuntary and uncontrolled episodes of crying, without sadness, or laughing, without happiness. Although it affects up to 10% of MS patients, imaging the variance and location of the lesions in the brain can determine the pattern of the affect. The lifetime prevalence of the disease in patients with MS may be as high as 50 percent. During the annual meeting, Dr. Feinstein presented a study that analysed 115,071 Canadians that revealed a 12-month prevalence of depression in MS patients higher that in healthy subjects. Between the ages of 18 and 45 years old, the 12 month prevalence was 25.7%. Moreover, the rates have increased in relation to other neurological disorders.

“Feeling depressed mood most of the day, markedly diminished interest or pleasure in all activities, appetite change with significant weight loss or gain, psychomotor agitation or retardation, fatigue or loss of energy nearly every day, worthlessness, excessive, inappropriate guilt, having insomnia or hypersomnia nearly every day, diminished ability to think or concentrate or recurrent thoughts of death five or more times during the same two week period” may be evidence of depression, according to Dr. Feinstein.

Dr. Feinstein believes that adequately managing depression in disorders like MS cannot be overstated, since it not only impacts the clinical condition of the patient, but also the quality of life and cognitive function. A quarter of MS patients contemplate suicide, and the major factors for it include depression, social isolation, and alcohol abuse.

A new automated imaging technique was recently successfully used in a trial with women who suffered both from MS and depression. The study, led by Cedars-Sinai neurologist Nancy Sicotte‘s multicenter research team, was able to identify shrinkage of a mood-regulating brain structure. The results revealed that patients with MS and symptoms of “depressive affect” – such as depressed mood and loss of interest — feature a reduced size of the right hippocampus.

At the University of Calgary’s Hotchkiss Brain Institute, new techniques are also being studied to improve diagnosis and treatment using MRI by sensing small changes in patterns of the MS patients’ brains. Using an algorithm, the researchers hope to find a parameter called MRI texture heterogeneity and clearly identify patterns and changes in the tissue.

Source: Multiple Sclerosis News Today © Copyright 2014 BioNews Services, LLC (17/06/14)

Researchers develop better way to track MS(10/06/14)

What if an MRI scan could detect damage caused by Multiple Sclerosis at an early stage?

Researchers at Western University have developed a way to better track MS progression in patients by looking at damage in brain areas common to all MS patients.

The technique is called Quantitative Susceptibility Magnetic Resonance Imaging (MRI).

While MRI scans are a vital part of diagnosing Multiple Sclerosis, they are often not conclusive until a patient is relatively late in the progression of the disease. However, the brain changes long before symptoms begin.

MRIs are able to detect spots on the brain, but using Quantitative Susceptibility MRI data, doctors can see damage areas of the brain that otherwise would go unnoticed until symptoms were farther advanced.

Currently a standard MRI will detect lesions in the brain but, until now, there was no correlation between lesions and the extent of a patient's disability. While lesions can appear or disappear over time, the damage caused is still apparent in QS image testing even after the patient's first episode.

Research leader at UWO, Ravi Menon, noted the changes are subtle – on the parts per billion level – but by using QS they are able to measure when tissues begin to degenerate or as iron accumulates in the brain. Iron accumulation happens naturally as a person ages, however, Menon explained that for an MS patient, they have levels that are likened to that of a person three years older.

Early detection and treatment can stop or slow down the disease.

Menon said if every current MS patient were diagnosed early and treated with low doses of prescription drugs the number of cases would drop four to five fold. He estimated about $100 billion dollars would be saved in drug costs alone.

The next stage, he said, is to have QS work on a single subject.

The university is equipped with a 7T MRI machine – the only one in Canada - but the tests were performed on the less sensitive 3T machine, meaning they can be reproduced in any hospital in the country.

That, Menon said, is a sign of hope.

The QS test group consisted of 25 patients with recurring or remitted MS or clinically isolated syndrome, which leads to the disease, as well as 15 age and sex-matched participants. The QS mapping showed the same damage areas in brains of all MS patients.

The progression of Multiple Sclerosis is measured using an Extended Disability Status Score, and QS results from the MS patients correlated to individual scores very well.

The diagnostic benefits of QS imaging has great potential, as some patients have to wait between six months to twenty years for their MS to become apparent.

For those with low disability scores or those who have not been diagnosed, the difference is life-changing. The wait, Menon said, is the hardest part for many patients. Early detection and treatment of MS can save much heartache for patients waiting on diagnosis, as well as save lives and long term healthcare costs.

Source: thelondoner.ca © 2014 Londoner (10/06/14)

Spinal cord size in relation to MRIs and disability in MS(12/05/14)

Mean upper cervical cord area (MUCCA) measurement in long-standing multiple sclerosis: Relation to brain findings and clinical disability.

Abstract

BACKGROUND: The majority of patients with multiple sclerosis (MS) present with spinal cord pathology. Spinal cord atrophy is thought to be a marker of disease severity, but in long-disease duration its relation to brain pathology and clinical disability is largely unknown.

OBJECTIVE:Our aim was to investigate mean upper cervical cord area (MUCCA) in patients with long-standing MS and assess its relation to brain magnetic resonance imaging (MRI) measures and clinical disability.

METHODS: MUCCA was measured in 196 MS patients and 55 healthy controls using 3DT1-weighted cervical images obtained at 3T MRI. Clinical disability was measured using the Expanded Disability Status Scale (EDSS), Nine-Hole-Peg test (9-HPT), and 25 feet Timed Walk Test (TWT). Stepwise linear regression was performed to assess the association between MUCCA and MRI measures, and between MUCCA and clinical disability.

RESULTS: MUCCA was smaller (mean 11.7%) in MS patients compared with healthy controls (72.56±9.82 and 82.24±7.80 mm2 respectively; p<0.001), most prominently in male patients. MUCCA was associated with normalized brain volume, and number of cervical cord lesions. MUCCA was independently associated with EDSS, TWT, and 9-HPT.

CONCLUSION: MUCCA was reduced in MS patients compared with healthy controls. It provides a relevant marker for clinical disability in long-standing disease, independent of other MRI measures.

Daams M, Weiler F, Steenwijk MD, Hahn HK, Geurts JJ, Vrenken H, van Schijndel RA, Balk LJ, Tewarie PK, Tillema JM, Killestein J, Uitdehaag BM, Barkhof F.

Source: Mult Scler. 2014 May 8. [Epub ahead of print] & Pubmed PMID: 24812042 (12/05/14)

Neuroimaging study sheds light on mechanisms of cognitive fatigue in MS(04/11/13)

A new study by Kessler Foundation scientists sheds light on the mechanisms underlying cognitive fatigue in individuals with multiple sclerosis. Cognitive fatigue is fatigue resulting from mental work rather than from physical labor. Genova H et al: Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging" was published on Nov. 1 in PlosOne. This is the first study to use neuroimaging to investigate aspects of cognitive fatigue. The study was funded by grants from the National MS Society and Kessler Foundation.

The study investigated the neural correlates of cognitive fatigue in MS utilizing three neuroimaging approaches: functional magnetic resonance imaging (fMRI), which allows researchers to look at where in the brain activation is associated with a task or an experience; diffusion tensor imaging (DTI), which allows researchers to look at the health of the brain's white matter; and voxel-based morphometry (VBM), which allows researchers to investigate structural changes in the brain. These three approaches were used to examine how likely it is for an individual to report fatigue ("trait" fatigue), as well as the fatigue an individual feels in the moment ("state" fatigue). This study is the first to use neuroimaging to investigate these two, separable aspects of fatigue.

"We looked specifically at the relationship between individuals 'self-reported fatigue and objective measures of cognitive fatigue using state-of-the-art neuroimaging," explained Helen M. Genova, Ph.D., research scientist in Neuropsychology & Neuroscience Research at Kessler Foundation. "The importance of this work lies in the fact that it demonstrates that the subjective feeling of fatigue can be related to brain activation in specific brain regions. This provides us with an objective measure of fatigue, which will have incalculable value as we begin to test interventions designed to alleviate fatigue."

In Experiment 1, patients were scanned during performance of a task designed to induce cognitive fatigue. Investigators looked at the brain activation associated with "state" fatigue. In Experiment 2, DTI was used to examine where in the brain white matter damage correlated with increased "trait" fatigue in individuals with MS, as assessed by the Fatigue Severity Scale (FSS). The findings of Experiments 1 and 2 support the role of a striato-thalamic-frontal cortical system in fatigue, suggesting a "fatigue-network" in MS.

"Identifying a network of fatigue-related brain regions could reframe the current construct of cognitive fatigue and help define the pathophysiology of this multifaceted yet elusive symptom of MS," said John DeLuca, Ph.D., VP of Research & Training at Kessler Foundation. "Replication of these findings with larger sample sizes will be an important next step."

Source: Science Codex (04/11/13)