Innovations In Clinical Neuroscience

HOTTOP Multiple Sclerosis DEC 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Hot Topics in Multiple Sclerosis [December 2017] 10 U p d a t e s i n C l i n i c a l P r a c t i c e accumulation of T2 and T1 lesions in the brain. Most research that has measured the cognitive effects of DMTs on MS were interferons (IFNB-1a and IFNB-1b). For example, researchers note an extensive study on the relationship between IFNB- 1a and cognition where 166 patients with RRMS took the Multiple Sclerosis Functional Composite (MSFC). In the Betaferon/Betaseron in Newly Emerging MS for Initial Treatment (BENEFIT) trial, treatment via IFNB-1b was especially effective when administered early in the trial. Additional studies on a variety of other treatments have mostly resulted in inconclusive results, possibly because cognition is not the primary outcome of these studies. In the symptomatic drug portion of the review, the researchers noted that drugs that improve fatigue can often also improve cognition in patients with MS. Of the 26 studies reviewed, 12 showed some level of improvement in cognition, using neuropsychological measures such as the Digit Span, Trail Making Test, Symbol Digital Modalities Test, Selective Reminding Test, and Finger Tapping Test. As of this review, no symptomatic treatment has established itself as having a clear positive effect on cognitive ability. The investigators suggest the need for further research into the possibility of combining pharmacological strategies with other treatments, such as physical exercise. * Access the full study RELAPSING AND PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS Imaging Outcome Measures for Progressive Multiple Sclerosis Trials. Many different imaging biomarkers, including brain lesion count and volume, have been discovered and used in recent years in the clinical trials studying multiple sclerosis (MS). The Progressive MS Alliance recommends that imaging biomarkers be used more frequently in trials because monitoring the biomarkers might take less time and fewer resources than other tools of analysis for the disease. In some cases, studies investigating disease-modifying therapies (DMTs) were unable to conclude that the treatment was effective on overall clinical disability, but they did find a "positive effect on lesion count and volume measures." Researchers also looked at brain atrophy as a biomarker, which has been studied via magnetic resonance imaging (MRI) scans for patients with early stages of MS. They note that brain atrophy doesn't relate to the risk of relapse in MS, which makes it a more valuable biomarker in progressive MS. Advanced MRI techniques, such as magnetization transfer ratio (MTR), diffusion tension imaging (DTI), and magnetic resonance spectroscopy (MRS) have also gained popularity for measuring MS because of their ability to track more specific aspects of the brain. For example, MRS has the ability to measure brain levels of multiple metabolites. Spinal cord atrophy is an especially important biomarker among patients with progressive MS, but this has not been frequently used as a clinical outcome measure for MS because it can be difficult to detect small changes. Another possible outcome measure is position emission tomography (PET), "a quantitative imaging technique that investigates cellular and molecular processes in vivo using positron- emitting molecules, ideally binding a selective target." Finally, optical coherence tomography (OCT) allows for special imaging of the retinas. Retinal nerve fiber layer (RNFL) is thinner in patients with MS compared to healthy subjects. * Access the full study Next-generation Anti-CD20 Monoclonal Antibodies in Autoimmune Disease Treatment. Anti-CD20 monoclonal antibodies (mAbs) continue to play more significant roles in the treatment of autoimmune diseases as researchers reveal the growing importance of B cells. The recent generation of mAbs include ocrelizumab, obinutuzumab, and veltuzumab, which were tested on other diseases beyond multiple sclerosis (MS). Anti-CD20 mAbs have been successful in treating rheumatoid arthritis (RA), but many mAB drugs were additionally tested on patients with MS in clinical trials. The OPERA I and II trials for ocrelizumab were successful in treating patients with relapsing-remitting MS (RRMS) compared to interferon B-1a (IFNB-1a). In both trials, ocrelizumab resulted in nearly 50-percent lower relapse rate than IFNB-1a. The ORATORIO study, on the other hand, measured the ocrelizumab's effect on patients with primary progressive MS (PPMS). Side effects of ocrelizumab included upper respiratory tract infections, infusion-related reactions, and oral herpes. Researchers note, "it is possible that ocrelizumab might benefit PPMS patients with an inflammatory-predominant form of the disease more than the neurodegenerative form." Ocrelizumab has since gained approval from the United States Food and Drug Administration (FDA) for patients with both RRMS and PPMS. Ofatumumab was also tested in multiple clinical trials for patients with MS, where a main side effect was also infusion-related reactions, occurring in 88.5 percent of patients compared to 8.3 percent with the placebo. Anti- CD20 mAbs were also tested on patients with systemic lupus erythematosus and pemphigus. Researchers concluded overall that anti-CD20 mAbs will need to achieve an "excellent safety profile" if they're going to become the future for treating autoimmune diseases. While infusion- related reactions are common, they are frequently mild, and the other common side effects are mostly seen as minor compared to the potential positive results from the drugs. * Access the full study Metabolic Pathways as Possible Therapeutic Targets for Progressive Multiple Sclerosis. The etiology of progressive forms of multiple sclerosis (MS) is still not well understood, and our lack of understanding has a negative

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