MS lesions

The Consortium of Multiple Sclerosis Centers has updated guidelines for using magnetic resonance imaging to evaluate people suspected of having multiple sclerosis. Doctors use the MRI guidelines not only to diagnose MS but also to track treatment results. A task force is reviewing the new guidelines before they're published. The working document is called  "Revised Guidelines of the CMSC MRI Protocol for the Diagnosis and Follow-up of MS." The task force, composed of neurologists, radiologists and imaging scientists experienced in MS, met in January 2017 to revise the guidelines. They also updated information about the situations for which standardized brain and spinal cord MRI scans should be used. One change is a recommendation that gadolinium, a contrast agent in scans, be used cautiously. The previous update, published in 2015, included no constraints on the use of gadolinium-based contrast agents. But soon after publication, information emerged showing that gadolinium, although not toxic, accumulates in the brain. This prompted the U.S. Food and Drug Administration to recommend limiting the use of gadolinium to “appropriate clinical circumstances.” To mirror the increased awareness of gadolinium deposits, the new guidelines say: “While there is no known central nervous system toxicity, these agents should be used judiciously, recognizing that gadolinium continues to play an invaluable role in specific circumstances related to the diagnosis and follow-up of individuals with MS.” Since 2009, the Consortium of Multiple Sclerosis Centers has addressed a number of other issues. One is encouraging the use of three-dimensional MRI for brain scans. Another is developing protocols for monitoring severe optic nerve inflammation and progressive multifocal leukoencephalopathy, or PML, a brain disease caused by a virus. The guidelines have been revised to recommend the specific timing of scans for monitoring PML. The update also includes recommendations for the timing of scans on patients receiving disease-modifying drugs. Since 2009, the guidelines have included recommendations on scans of radiologic isolated syndrome, a condition where MS-like MRI lesions are present without symptoms. And they have included provisions on the value of using MRI changes to evaluate treatment effectiveness. The centers' goal "is to standardize the MRI protocol and make these recommendations a useful guideline for neurologists, neuroradiologists, and related healthcare professionals during initial evaluations and during follow-up of patients with MS, and ultimately provide optimum care for those individuals dealing with this unpredictable disease,” June Halper, the centers' chief executive officer, said in a press release.

The 7th Joint ECTRIMS-ACTRIMS Meeting, taking place in Paris this month, is one of the largest scientific conferences focused solely on multiple sclerosis (MS), and the National Multiple Sclerosis Society will be among the many interested parties attending. To get a feeling for meeting highlights and presentations the…

The year’s largest gathering of multiple sclerosis “minds” starts on Oct. 25 in Paris. More than 8,000 neurologists, researchers and others who specialize in treating and curing MS will be attending MSParis2017. It’s a joint meeting of the European and the Americas Committee for Research in Multiple Sclerosis…

Spain’s Oryzon Genomics will offer new data on the preclinical efficacy of ORY-2001, an epigenetic modulator it is developing to treat  multiple sclerosis (MS). Its presentation is set for Oct. 26 at MSParis2017, the joint international meeting of the European and Americas Committees for Treatment and Research in Multiple Sclerosis…

The 7th Joint ECTRIMS-ACTRIMS Meeting, the world’s largest annual international conference devoted to basic and clinical research in multiple sclerosis, will run from Oct. 25 to 28 in Paris — the city of Jean-Martin Charcot, the “Father of Neurology,” who provided the first detailed description of multiple sclerosis (MS)…

Opioid growth factor (OGF) can serve as a new biomarker to determine diagnosis and progression of multiple sclerosis (MS), say researchers at Pennsylvania State University. Their study, “Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone,” appeared in the journal Experimental Biology and…

Researchers at the University of Nottingham and neurologists at Nottingham University Hospitals NHS Trust in England will be working with a team from the Cleveland Clinic in Ohio to better understand the best therapeutic strategy for multiple sclerosis (MS) patients. The $10.6 million international clinical trial was one of five…

Researchers have taken the first steps towards the development of a gene therapy for multiple sclerosis — a treatment that boosted anti-inflammatory immune processes and reversed severe paralysis in mouse models of the disease. The University of Florida Health research team said it was optimistic that the therapy can work…

Structural changes of the eye retina are a common feature among multiple sclerosis patients with a clinical history of optic neuritis, a Danish study finds. Loss of the myelin protective layer of optic nerve cells due to inflammation causes optic neuritis. About 20 percent of MS have it, and optic neuritis is a symptom of disease progression in about 40 percent of patients. In most cases, symptoms persist, leading to visual impairment or blindness, along with pain. Non-invasive optical coherence tomography can help evaluate neurodegeneration of optic nerve cells. This imaging technique allows a three-dimensional evaluation of internal eye structures, including the thickness of the retina nerve fiber layer. Previous studies have shown that MS patients may present progressive RNFL loss, but this can also be caused by optic neuritis. The use of OCT has been proposed to distinguish MS subtypes and evaluate disease activity. However, little clinical data is available to validate OCT's accuracy and potential as a diagnostic tool. To find out more, a Danish research team conducted a long-term evaluation of structural and functional visual outcomes in MS patients with and without a history of optic neuritis. Researchers observed that patients with a history of optic neuritis had significantly more RNFL thickness loss than those without optic neuritis. They linked reduced RNFL thickness with a 1.56 times higher risk of optic neuritis development. Nevertheless, the team did not find any association between optic neuritis and functional impairment of visual acuity or color vision. Use of high-resolution OCT devices coupled with up-do-date analysis software can improve the diagnostic efficacy of this imaging technique in MS patients, said researchers, who urged more studies to address the relevance of structural changes in MS.

Striking similarities between patients with multiple sclerosis and a type of schizophrenia suggest the disorders are related, according to a review of a number of studies. Dr. Boris M. Arneth wrote the article, “Multiple Sclerosis and Schizophrenia.” It was published in the International Journal of Molecular Sciences. MS…

Brain donation for multiple sclerosis research optimizes the chances that a cure might be discovered. It might result in a vaccine or other preemptive strike to prevent the disability from starting in the first place. As addressed in a previous column, there is a shortage…

A new and potentially important mechanism in the development of autoimmune diseases like multiple sclerosis was discovered by scientists at the University of Freiburg, Germany. They identify a protein, called Caveolin-1, that is essential to immune cells called B-cells working as intended to protect a person from pathogens or — in its absence…

Multiple sclerosis damages human brains, so MS researchers often study mice brains. How can multiple sclerosis be cured or prevented without studies of human brains? Researchers need the anatomical bequests of MS brains. Harvard Brain Tissue Resource Center Harvard University specifically collects and studies brains (and brain tissue),…

The neurotransmitter glutamate triggers most brain signals by activating proteins on the surface of neurons called glutamate receptors. Columbia University Medical Center researchers have taken the first 3D images of the AMPA-subtype glutamate receptors involved in several brain activities, including memory and learning. By increasing scientists' understanding of how the receptors work, the images could offer insight into the role that faulty receptors play in the development of neurodegenerative disorders such as multiple sclerosis, Alzheimer’s, and Parkinson’s. And that insight could lead to therapies. “With our new findings, we can now, for the first time, visualize how the neurotransmitter glutamate opens glutamate receptor ion channels,” Dr. Alexander Sobolevsky, an associate professor of biochemistry and molecular biophysics at Columbia, said in a news release. “This is the fundamental process that directly affects learning and memory, and finding its structural determinants has been the primary goal of molecular neuroscience since the ‘90s," added Sobolevsky, the senior author of the study. For the brain to work properly, neurons need to communicate with each other. To do that, they use neurotransmitters, small compounds that pass from one cell to a receptor on another cell. Glutamate is the neurotransmitter involved in many of these communications, and glutamate receptors are the structures that gather up many of the signals. Several types of glutamate receptors participate in cognitive functions. AMPA receptors – a subgroup of glutamate receptors – are known for their fast activity, opening and closing in less than a millisecond. Because they work so fast, they are involved in rapid brain responses, such as rapid perception and reaction to the surrounding environment. For years, researchers have tried to understand how AMPA receptors work. In previous studies, Sobolevsky's team learned how the receptors regulated both the speed and strength of cell communications. In the recent study, the researchers used advanced imaging techniques developed by Dr. Joachim Frank to record the actions of the AMPA receptors. Frank, a professor of biochemistry and molecular biophysics, and biological sciences, was a co-author of the study. The images showed that AMPA receptors open in the presence of glutamate or a similar signaling compound. The mechanism can be compared to a camera’s iris, or aperture. The signaling particles pass through the opening, triggering electrical signals necessary for brain activity. “These new fundamental discoveries have implications for our understanding of neurotransmission by glutamate, our brain’s major neurotransmitter,” said Edward C. Twomey, a Ph.D. candidate who was the first author of the study. “Understanding these processes will impact future studies on glutamate receptor signaling in neurodegenerative diseases as well as drug design.”

A new study draws a reverse link between the number of MRI scans of multiple sclerosis patients who are on interferon-beta 1a and doctors declaring there is evidence of the patients’ disease worsening. When doctors looked at one scan, rather than multiple ones, they were more likely to say that…

(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this first of two columns about terms starting with the letter “G.”) When it comes to multiple sclerosis, mastering an understanding of the disease means you need to…

A herpes virus that lies dormant in many people can hinder the repair of the neuron-protecting myelin sheath whose deterioration causes multiple sclerosis, a study reports. The finding about the HHV-6 virus may help explain differences in the symptoms and progression of the disease from person to person, researchers said.

B-cells of patients with relapsing-remitting multiple sclerosis (RRMS) secrete substances that are toxic to both neurons and neuron-protecting myelin-forming cells, causing both kinds to die, according to a study. Despite analyses of numerous inflammatory and other factors believed to drive MS processes, researchers were unable to identify the molecules that are toxic, however. Dr. Robert Lisak of Wayne State University in Detroit, Dr. Amit Bar-Or of McGill University in Montreal and their teams are now working on identifying the factor, and learning if the process is also involved in progressive MS. Their study, “B-cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro,” was published in the Journal of Neuroimmunology. It demonstrated that B-cells gathered from the blood of RRMS patients killed lab-grown neurons and oligodendrocyte cells, which form myelin, a protecting coating for nerve cells. Deterioration of the myelin coating and the death of neurons are hallmarks of MS. An earlier study the team conducted indicated that B-cells from MS patients could kill oligodendrocytes. But since the experiments involved only three patients and three controls, the team scaled up their experiments to include 13 patients and an equal number of controls. Both rat and human neurons died when mixed with MS-derived B-cells. In contrast, B-cells from healthy people had little or no impact on the survival of the brain cells. Researchers also discovered that the secreted toxic molecules had no impact on other types of central nervous system cells — astrocytes and microglia. The toxins killed only neurons and myelin-producing cells. The B-cells triggered a process called apoptosis, or programmed cell death, researchers said. This is basically a suicide program. It tells a cell to die when exposed to stressful factors or toxins. The process differs from cell disintegration. Despite thoroughly screening about 40 inflammation-related substances, researchers were unable to identify any factors that caused the cells to die. The National MS Society and the Research Foundation of the MS Society of Canada funded the research, which the U.S. society highlighted in a news release. In the newest phase of the study, researchers will try to learn more about the processes underlying neuron and myelin-related cell deaths and identify the factors responsible. In addition to testing B-cells from progressive MS patients, the team will examine patients with other autoimmune conditions to see if the process is unique to MS or not. Researchers increasingly realize that B-cells are important to MS processes. This observation was underscored by U.S. regulators' approval of the B-cell depleting therapy Ocrevus (ocrelizumab) at treatment for both relapsing and primary progressive MS.

A gene mutation may explain the uncontrolled, inflammatory immune response seen in autoimmune and chronic inflammatory diseases like multiple sclerosis, scientists at the Research Institute of the McGill University Health Centre (RI-MUHC) report. It's a discovery that, they said, appears to be "a big step in the right direction." According to the study, published in the journal Science Immunology, alterations in the FOXP3 gene affect specific immune cells called regulatory T-cells, or Tregs. Those mutations hamper Tregs in performing a crucial regulatory role, leading to a loss of control over the immune system’s response to a perceived threat. “We discovered that this mutation in the FOXP3 gene affects the Treg cell’s ability to dampen the immune response, which results in the immune system overreacting and causing inflammation,” Ciriaco Piccirillo, the study's lead author and an immunologist in the Infectious Diseases and Immunity, Global Health Program, at the RI-MUHC, said in a news release. Tregs are known to be the immune system players responsible for keeping other immune cells under control, preventing them from attacking the host’s own tissues, while maintaining a proper immune response against harmful agents. The normal activity of Treg cells is essential for preventing excessive immune reactions. The FOXP3 gene is also well-known, and documented, to be essential for proper Treg cell function. However, the mechanisms by which FOXP3 gene is involved in Treg cell activities are still poorly understood. In the study, “Suppression by human FOXP3+ regulatory T cells requires FOXP3-TIP60 interactions,” the research team — in collaboration with researchers at University of Pennsylvania, University of Washington School of Medicine, and Teikyo University School of Medicine in Japan — evaluated the impact of a FOXP3 gene mutation in autoimmunity response. Taking advantage of cutting-edge technology, the team studied samples from two patients carrying a common FOXP3 gene mutation, which caused a genetic immune disorder called IPEX. Interestingly, the researchers found that this genetic variant did not reduce the number of Treg cells or the levels of FOXP3 protein. Instead, the mutation altered the way Tregs could suppress other immune cells to prevent overactivation. “What was unique about this case of IPEX was that the patient’s Treg cells were fully functional apart from one crucial element: its ability to shut down the inflammatory response,” said Piccirillo. “Understanding this specific mutation has allowed us to shed light on how many milder forms of chronic inflammatory diseases or autoimmune diseases could be linked to alterations in FOXP3 functions,” added Khalid Bin Dhuban, the study's first author and a postdoctoral fellow in Piccirillo’s laboratory. The team developed a compound capable of restoring Treg cells' ability to control the immune system in the presence of this specific FOXP3 gene mutation. Tested in animal models of colitis and arthritis, two chronic inflammatory diseases, the compound reduced inflammation and restored normal Treg function. Researchers now plan to develop similar drugs that may be of use in other diseases where Treg cells are known to be defective, including multiple sclerosis, type 1 diabetes, and lupus. "Currently, we have to shut down the whole immune system with aggressive suppressive therapies in various autoimmune and inflammatory diseases," said Piccirillo. “Our goal is to increase the activity of these Treg cells in certain settings, such as autoimmune diseases, but we want to turn it down in other settings, such as cancer.” “This discovery gives us key insights on how Treg cells are born and how they can be regulated,” Piccirillo added. “With this discovery, we are taking a big step in the right direction.”

MSBase and icometrix have joined efforts in a large-scale project to identify imaging markers of multiple sclerosis (MS) that could help diagnose the disease in its early stages. The combination of magnetic resonance imaging (MRI) information collected from MS patients with clinical information from the MSBase Registry can offer new insights in disease progression, potentially leading to new predictive tools for MS. It may also promote more standardized use of imaging measures in clinical practice. With more than 52,000 MS patients, the MSBase Registry is an international database committed to collecting patients’ information as well as sharing, tracking and evaluating overall outcome data in MS and other neurological conditions. Until now, the MSBase Registry included only descriptive information regarding patients' imaging analysis results, with no access to full imaging data. This joint, large-scale project will include MRI scan data routinely acquired in clinical setting taking advantage of icometrix’s software platform, MSmetrix. “We wish to unlock the power of MRI for personalized monitoring in MS," Helmut Butzkueven, director of MSBase, said in a press release. "The MSBase Scientific Leadership group has selected MRI integration as the top strategic priority for MSBase. We believe that already conducted MRI scans represent an enormous missed opportunity, because advanced measurements to assess change over time from these scans are not currently in practical use.” Butzkueven said MSBase "will test the predictive power of this unlocking of MRI data in the first phase," with a total of 10,000 MRI data points in at least 3,000 MS patients from all over the world. The project is expected to identify disease progression markers that could help detect early signs of MS by MRI evaluation. This investigator-initiated collaboration between icometrix and the MSBase Foundation is being supported by three global pharmaceutical giants: Novartis, Biogen and Roche. “MRI measures play an essential part in the complex puzzle of MS,” said Danny Bar Zohar, global head of neuroscience development at Novartis. “Partnering with MS Base and icometrix in this exciting project will bring the acquisition of high-quality real world data to the next level, ultimately improving the outcome of people living with MS.”

During a routine exam with my neurologist recently, I asked her a question I’d never thought to ask before: “Why do you order regular MRIs of my brain, but not of my spine?” Interestingly, within a few days of my exam, a Harvard Med School study was…

Physical disability may have no link to brain lesion volume in some patients with multiple sclerosis (MS), concludes a recent study led by Dr. Rohit Bakshi, a neurology and radiology professor at Harvard Medical School. The study, “Characterizing Clinical and MRI Dissociation in Patients with Multiple Sclerosis,” appeared in the Journal…

Researchers managed to change the immune system — replacing inflammation with immune tolerance — in a mouse model of multiple sclerosis (MS) using so-called quantum dots, or nano-sized particles carrying pieces of myelin. Experiments with this advanced technological solution may help researchers design MS therapies that are based on promoting regulatory T-cells rather…

Editor’s note: Patient columnist Laura Kolaczkowski attended the 31st annual Consortium of Multiple Sclerosis Centers conference in New Orleans. The information in this article was taken from an interview session with the physicians.   The use of gadolinium, which is the contrast agent often used during MRIs for multiple…

How multiple sclerosis affects the “social brain,” which governs the ability to understand how others think and feel — a skill called social cognition — is linked to specific types of brain damage that occur in MS: both lesions and microscopic changes taking place in the brain’s white matter, a research team…

(Photo by Andreea Antonovici) A few months ago, I wrote about a bicycle that mimics the symptoms of multiple sclerosis. Now, I’ve discovered that there’s an “MS House” that allows a healthy person to experience some of what life is like for someone who lives with MS.

(Editor’s note: Tamara Sellman continues her occasional series on the MS alphabet with this second of two parts on terms starting with the letter “D.”) When it comes to multiple sclerosis, mastering an understanding of the disease means you need to mind your Ps and…

Multiple sclerosis patients who start Rituxan (rituximab) treatment are three times more likely to have unchanged or improved brain-scan readings than worse ones, according to a study. Holy Name Medical Center researchers presented the findings at the Consortium of Multiple Sclerosis Centers annual meeting in New Orleans, May 24-27. The presentation…

Researchers from the New York Stem Cell Foundation (NYSCF) have developed a method to produce brain immune cells, called microglia, from human stem cells. That can help scientists uncover biological mechanisms involved in multiple sclerosis (MS) and other neurological conditions. “NYSCF’s mission is to bring cures to patients faster,” Susan L.

MS brain inflammation is a result of interactions between processes in the brain and the rest of the body, with interferon-gamma (IFN-gamma) being a key player, according to a detailed analysis of cytokines in the spinal fluid and serum of MS patients. Russia’s Kazan Federal University found that IFN-gamma activates other…