Oral vs IV Steroids for Acute Optic Neuritis

MedicalResearch.com Interview with:

Sarah A. Morrow MD, MS, FRCPC Associate Professor of Neurology Department of Clinical Neurological Sciences University of Western Ontario (Western)

Dr. Morrow

Sarah A. Morrow MD, MS, FRCPC
Associate Professor of Neurology
Department of Clinical Neurological Sciences
University of Western Ontario (Western)

MedicalResearch.com: What is the background for this study?

Response: Acute demyelinating optic neuritis, which presents with loss of vision and painful eye movements, is common in multiple sclerosis (MS) occurring 50% of persons with MS. High dose (≥ 1g) corticosteroids administered through an IV became the standard of practice after the landmark Optic Neuritis Treatment Trial as IV administration. However, in that study the IV dose of corticosteroids was much higher (1 gram daily) than the oral dose (1 mg/kg). Thus, it is not clear if IV administration is still better if equivalent doses are used orally. Oral administration is much more convenient for patients and less expensive, and previous studies showed that it is preferred by patients.

In this study, we asked the following question: are high dose (≥ 1000mg) IV corticosteroids superior to equivalent doses of oral corticosteroids for the acute treatment of optic neuritis?

We randomly assigned fifty-five cases of acute optic neuritis to 1000mg IV methylprednisolone or 1250mg oral prednisone daily for three days and compared recovery of their vision over the next 6 months.  Continue reading

Multiple Sclerosis: Rituximab Had Better Short and Medium Term Outcomes

MedicalResearch.com Interview with:
Fredrik Piehl MD PhD, prof. of Neurology

Neuroimmunology Unit. Dept Clinical Neuroscience
Neurology Dept.
Karolinska University Hospital (Solna)
Stockholm

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In recent years we have seen a drastic increase in treatment options for relapsing-remitting multiple sclerosis (RRMS). However, it is difficult to deduce long term performance of different drugs based only on data from randomized controlled trials, since such trials are performed in selected patients without major co-morbidities and perhaps also enriched for those with a milder disease course. In addition, most trials only last for two years and lack relevant comparators. This lack of knowledge makes it difficult to predict if a drug will work or not for a given patient, in turn leading to frequent treatment switches but also different treatment practices across countries, regions or even between centers. This is also the case in Sweden, but with the additional aspect that some regions have opted to treat most newly diagnosed RRMS patients with rituximab (Rituxan/Mabthera), a drug not formally approved for RRMS, but with extensive safety data from other indications.

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Multiple Sclerosis: Functional Changes After Inflammation May Partly Explain Clinico-Radiological Paradox

MedicalResearch.com Interview with:
Netta Levin MD PhD
fMRI lab
Neurology Department
Hadassah Hebrew University Medical Center
Jerusalem 

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, manifesting with episodes of local inflammatory processes, called relapses. The most useful surrogate laboratory test for MS is magnetic resonance imaging (MRI), in which dissemination of demyelinating lesions in space and time are the hallmark of the disease. However, there is a discrepancy between the lesion load – the number, size, and location of the lesions – and the clinical state of the patients, reflected in their disability. This discrepancy is known as the “clinico-radiological paradox” and suggests that something other than the well-known mechanisms of demyelination, remyelination, and axonal loss may tip the scale of recovery from an acute episode. Global effects of the local damage and compensatory mechanisms were suggested as an explanation to this paradox.

In this study, we compared the visual system of patients with clinically isolated syndrome optic neuritis (ON) to patients with clinically isolated episodes in other functional systems, exploring changes, both anatomical and functional, caused to the system following the demyelinating episode. Optic neuritis was deemed a good in vivo model for studying the pathophysiology of tissue damage and repair in MS due to its characteristic clinical manifestation and to the visual pathways’ amenability to investigation using various techniques. To assess anatomical wiring ,i.e the white matter fibers themselves , we used diffusion tensor imaging (DTI). To assess functional networking as reflected by signal synchronization between distinct brain regions, we used resting state fMRI.

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Intestinal Microbiome Alterations May Trigger Immune Reactions Inducing Multiple Sclerosis

MedicalResearch.com Interview with:

Kouichi Ito, PhD Associate Professor Department of Neurology Robert Wood Johnson Medical School Rutgers

Dr. Kouichi Ito

Kouichi Ito, PhD
Associate Professor
Department of Neurology
Robert Wood Johnson Medical School
Rutgers

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), and breakdown of immune tolerance to CNS proteins has been suggested to initiate CNS autoimmunity. Although the mechanism underlying the breakdown of immune tolerance to CNS proteins is still unknown, gut microbiota has been suggested to be involved in disease initiation and progression.

To investigate the etiology of Multiple Sclerosis, we have created humanized transgenic mice expressing MHC class II and T cell receptor genes isolated from an Multiple Sclerosis patient and showed that gut dysbiosis, alteration in intestinal microbial composition, can induce gut leakiness and subsequently trigger the development of neurological deficits through activation of complement C3 and reduction of CBLB and Foxp3 genes.

This study suggests that gut dysbiosis is one of the possible etiological factors for Multiple Sclerosis.

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IQuity Developing RNA-Based Disease Activity Test for Multiple Sclerosis

MedicalResearch.com Interview with:

Dr. Chase Spurlock, Ph.D. Executive Officer at IQuity, Inc Nashville, Tennessee

Dr. Chase Spurlock

Dr. Chase Spurlock, Ph.D.
Executive Officer at IQuity, Inc
Nashville, Tennessee

IQuity is working to further develop RNA technologies that can be used to diagnose and treat Multiple Sclerosis. IQuity hopes to develop a ‘disease activity test’, which would help physicians determine when a patient is likely to relapse so that treatments can be timed for best effect.

 

MedicalResearch.com: What is the background for IQuity? What are its goals and mission?

Response: IQuity, Inc. is a biotechnology company that focuses on the research and development of innovative specialty diagnostic technology, specifically for autoimmune diseases. Our research has shown that autoimmune patients have distinct RNA expression patterns in their blood, and we have figured out how to leverage machine learning methods to analyze these RNA expression patterns and test for the presence of diseases like multiple sclerosis, IBS/IBD (Crohn’s and ulcerative colitis) and fibromyalgia. We collected patient samples from around the globe to match their RNA profiles against healthy and sick patient profiles we identified through our previous research. These tests led to the development of IQIsolate, our technology that informs the suite of tests which, when used even at the earliest onset of symptoms, can give providers information to rule in or rule out a suspected autoimmune disease with more than 90% accuracy.

Our mission is to relentlessly pursue innovation in specialized diagnostic and analytic technology, identifying complicated autoimmune and autoimmune-related diseases at the earliest signs of symptoms. We strive to enable providers to diagnose early and treat sooner in the disease progression to improve long-term outcomes, lower the overall cost of lifelong autoimmune diseases and minimize the uncertainty and fear patients experience during prolonged diagnosis periods.

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Multiple Sclerosis Patients Show Cognitive Benefit From Remotely Supervised Transcranial Direct Current Stimulation

MedicalResearch.com Interview with:

Leigh E. Charvet, PhD Associate Professor, Department of Neurology Department of Neurology New York University Langone Medical Center New York, NY

Dr. Charvet

Leigh E. Charvet, PhD
Associate Professor, Department of Neurology
Department of Neurology
New York University Langone Medical Center
New York, NY

MedicalResearch.com: What is the background for transcranial direct current stimulation? What are the main findings of this study in multiple sclerosis patients?

Response: The application of tDCS is a relatively recent therapeutic development that utilizes low amplitude direct currents to induce changes in cortical excitability. When paired with a rehabilitation activity, it may improve learning rates and outcomes.

Multiple repeated sessions are needed for both tDCS and cognitive training sessions to see a benefit. Because it is not feasible to have participants come to clinic daily for treatments, we developed a method to deliver tDCS paired with cognitive training (using computer-based training games) to patients at home. Our protocol uses a telemedicine platform with videoconferencing to assist study participants with all the procedures and to ensure safety and consistency across treatment sessions.

When testing our methods, we enrolled 25 participants with multiple sclerosis (MS) completed 10 sessions of tDCS (2.0 mA x 20 minutes, dorsolateral prefrontal cortex, left anodal) using the remotely-supervised telerehabilitation protocol. This group was compared to n=20 MS participants who completed 10 sessions of cognitive training only (also through remote supervision).

We administered cognitive testing measures at baseline and study end. We found that both the tDCS and cognitive training only group had similar and slight improvements on composites of standard neuropsychological measures and basic attention. However, the tDCS group had a significantly greater gain on computer-based measures of complex attention and on a measure of intra-individual variability in response times.

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Long Term Fampridine (AMPYRA) Improves Gait Function in Multiple Sclerosis

MedicalResearch.com Interview with:

Linard Filli, PhD Gait Research Lab Department of Neurology University Hospital Zurich Zürich

Dr. Linard Filli

Linard Filli, PhD
Gait Research Lab
Department of Neurology
University Hospital Zurich
Zürich

MedicalResearch.com: What is the background for this study?

Response: Gait dysfunction is common in patients with multiple sclerosis (MS) and is perceived as the most restricting of symptoms. Fampridine (4-aminopyridine, dalfampridine), a blocker of voltage-gated potassium channels, is currently the only approved medication for the symptomatic treatment of walking disorders in patients in both the early and late phases of  multiple sclerosis.

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Multiple Treatment Options Now Available for Multiple Sclerosis

MedicalResearch.com Interview with:

Tomas Kalincik, MD, PhD, PGCertBiostat Neurologist and Senior Research Fellow Melbourne Brain Centre | Department of Medicine | University of Melbourne Department of Neurology | Royal Melbourne Hospital Melbourne | Victoria | Australia

Dr. Tomas Kalincik

Tomas Kalincik, MD, PhD, PGCertBiostat
Neurologist and Senior Research Fellow
Melbourne Brain Centre | Department of Medicine | University of Melbourne
Department of Neurology | Royal Melbourne Hospital
Melbourne | Victoria | Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multiple sclerosis is a disease predominantly of young adults, with the peak of incidence in the 3rd and 4th decades. It is the most common cause of neurological disability in young adults. Only in Australia, 23,000 people are living with MS, with MS representing an annual cost of almost 1 billion $AU to the Australian society. It is a disease that presents with broad range of neurological symptoms and signs, which are typically temporary (these are called relapses) that with time can lead to permanent neurological disability. While there is currently no cure for MS, with appropriate therapy, its symptoms can be controlled and the disability progression slowed down.

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CSF Biomarker May Signal Progression of Clinically Isolated Syndrome to MS

MedicalResearch.com Interview with:

Prof Rogier Q Hintzen Neurologist/immunologist Head MS Centre ErasMS Dept of Neurology Erasmus MC, PB 2040 Rotterdam

Prof Rogier Q Hintzen

Prof Rogier Q Hintzen
Neurologist/immunologist
Head MS Centre ErasMS
Dept of Neurology
Erasmus MC, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Years ago, we identified soluble (s) CD27 as a biomarker for T cell activation in body fluids, as part of my PhD study. (J Immunol. 1991 Jul 1;147(1):29-35.)
As we presume the neuropathology seen in MS is guided by T cells we were interested to be able to quantify the activity of such cells in a given patient.
Cerebrospinal fluid (CSF) is as close as we can get to the site of the disease process in MS, therefore we focus on biomarkers in this compartment.
We found clearly elevated levels of sCD27 in CSF of Multiple Sclerosis patients versus non-inflammatory controls.

In this study we investigated whether at the moment of first attack of suspected Multiple Sclerosis, quantification of CSF sCD27 can predict further progression in to a diagnosis of MS and whether sCD27 levels are correlated with later attack frequency. Indeed, we found that high sCD27 measured at this early stage predicts a more rapid diagnosis of Multiple Sclerosis and a more aggressive disease course.

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Mutliple Sclerosis: Ocrelizumab Lowers Rate of Disease Progression and Disability

MedicalResearch.com Interview with:

Jerry S. Wolinsky, MD Emeritus Professor in Neurology McGovern Medical School part of UTHealth | The University of Texas Health Science Center at Houston Houston’s Health University Department of Neurology Houston, Texas 77030

Dr. Jerry Wolinsky,

Jerry S. Wolinsky, MD
Emeritus Professor in Neurology
McGovern Medical School
The University of Texas Health Science Center at Houston
Houston’s Health University
Department of Neurology
Houston, Texas 77030

MedicalResearch.com: What is the background for this study?

Response: Multiple sclerosis (MS) clinically is a very heterogeneous disease. It presents in considerably different ways and has a very poorly predictable clinical course. In an attempt to better communicate between experts in the field, there have been multiple attempts to categorize “typical” courses of the disease. How we think about the disease is in part driven by these somewhat artificial categories that lump our patients into those with relapsing forms of the disease (relapsing remitting with or without accumulating clinical disability, and secondary progressive with accumulating disability eventually occurring even in the absence of apparent clinical episodes of the disease), and primary progressive MS, where patients are slowly or sometimes rather rapidly accumulating disability in the absence of prior clinical relapses.

However, the distinctions between multiple sclerosis patients are not always as clear as the definitions would suggest, and it is certain that patients with primary progressive multiple sclerosis sometimes have clinical relapses after years of never having had relapses, and show MRI evidence of having accumulated many lesions in the brain over the course of their disease. Until now, none of the drugs that have shown benefit for relapsing disease have been able to convincingly show clinical benefit for patients with primary progressive disease, and for that matter have shown variable results when attempted in patients categorized as having secondary progressive courses. While some of our currently approved drugs have shown hints of benefit when tried in major clinical trials in primary progressive MS, the results were not been robust enough to seek regulatory approval.

The Oratorio study design was based on lessons learned from prior trials in primary progressive and relapsing forms of MS, as well as the recognition that B cells might play an important role in the immunopathogenesis of disease based on a considerable amount of preclinical work and observations in patients with multiple sclerosis.

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