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Podocalyxin, a protein found in cells lining the interior of blood vessels, is key for maintaining the integrity of the blood-brain barrier (BBB) in mice with systemic infection, suggesting its potential as a therapeutic target for neurodegenerative diseases such as multiple sclerosis (MS), a study shows. Disruption of the…

Relapses can be sneaky. They can scythe you down. I’ve been dealing with multiple sclerosis (MS) since 2006 and I only consciously remember two relapses. The first relapse was two years after I had been diagnosed with sclerosis. There was the possible hope from my first neurologist that nothing…

I am in a funk. It took a lot of mental volleying to admit this. I am preconditioned to synonymize feeling down with weakness. This is simply untrue. I am strong. But I am also having a difficult time managing my disease. Both can be true. In my transparency, I…

In mapping the immune system of the brain in mice and humans, scientists in Germany found that microglia — a type of nerve cell located in the central nervous system and responsible for supporting and protecting neurons — share the same core design, but behave differently depending on the specific function each…

Depression and psychological distress symptoms can have a huge effect on the way multiple sclerosis (MS) patients view their well-being, a new study has found. Since depression and psychological distress symptoms can be targeted therapeutically, the study proposes focusing on mental health disorders in MS patients to considerably…

Almost 1 in 5 People Wrongly Diagnosed with MS at Two Specialized Centers in US, Study Finds We know that MS is a difficult disease to diagnose, but is it really possible that 20 percent of the MS diagnoses are wrong? Apparently so. This study reports that…

A protein called Satb1 appears to be the "on switch" that turns a type of T-cell called Th17 from its typical protective role into one that is disease-causing, and key in the development of multiple sclerosis (MS) and other inflammatory autoimmune disorders, a study reports. These findings suggest that Satb1 may be a therapeutic target for autoimmune diseases like MS. The research article, “Satb1 regulates the effector program of encephalitogenic tissue Th17 cells in chronic inflammation,” was published in the journal Nature Communications. Immune cells called T-helper 17 (Th17) cells play a range of roles in immunity, including protecting against infecting pathogens — bacteria, viruses, and other microorganisms that can cause disease. But Th17 cells are also players in the development of such autoimmune diseases as MS, psoriasis, inflammatory bowel disease, and rheumatoid arthritis. This is because Th17 cells can be stimulated to become T-cells that engage in pathogenic, or disease-causing, immune programs. How Th17 cells switch from their typical and helpful immunity role to that of a pathogenic actor has not been resolved, although it is thought critical to treating inflammatory autoimmune diseases. An international team led by researchers at Osaka University and Kyoto University, in Japan, tried to identify the mechanism behind the disease-causing program of Th17 cells. To do so, they built upon previous findings showing that a protein regulator called Satb1 is important in the development of Th17 cell subsets. "We have known for some time that Satb1 is indispensable for the development of T-cells in the thymus. However, how it is involved in the regulation of pathogenic processes of Th17 cells in inflamed tissues had not been examined," Keiko Yasuda, MD, the study's lead author, said in a press release. Researchers used a standard mouse model of MS, called experimental autoimmune encephalomyelitis (EAE) mice. These animals had genetically-modified Th17 cells that lacked Satb1. Researchers tested how Th17 cells lacking Satb1 acted when subject to inflammatory conditions, and how they were stimulated to activate a "pathogenic effector program." Interestingly, these modified mice were resistant to the development of EAE, or MS-like, disease. Researchers saw fewer Th17 cells infiltrating the animals' spinal cord. Also, Th17 cells lacking Satb1 showed poorer production of key pathogenic signaling molecules in autoimmunity, notably one called granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is known to cause localized tissue inflammation in MS and other inflammatory autoimmune diseases. Researchers went on to show that Satb1 can act as a switch between benign and pathogenic Th17 cells, depending on their exposure to healthy or inflammatory conditions. They found molecules that boost the pathogenicity of Th17 cells, such as Bhlhe40, and molecules that promote normal immune function, such as PD-1.  Of note, PD-1 is shut down when Th17 cells engage in their pathogenic effector program. These results showed Satb1 to be a key regulator of Th17 cell pathogenicity in these MS mice. Halting Th17 cells from making Satb1 may offer a way of treatting various autoimmune diseases. “Together, our findings, in addition to providing novel insights into the molecular mechanisms underlying the pathogenic program of tissue Th17 cells in mice, may help design novel immunotherapeutic approaches such as small molecule modifiers of Satb1 for the treatment of autoimmune diseases,” the researchers wrote. Future studies are needed to confirm these results in people. A previous study in people also suggested a link between Satb1 and the pathogenic function of Th17 cells in the central nervous system of MS patients. Overall, "our results suggest that manipulating Satb1 gene expression in Th17 cells could form the basis of novel treatments for various autoimmune diseases caused by Th17 cells. If we can prevent the pathogenic processes of Th17 cells, we may be able to alleviate or even eliminate disease symptoms," concluded Shimon Sakaguchi, PhD, one of the study's senior authors.

A naturally occurring compound, a neurosteroid called allopregnanolone, prevents the activation of the TLR4 protein in macrophages  — a type of immune cell — and in the brain, new research in animal models found. This effect blocks an inflammatory response in cells, and may lead to new treatments for…

It’s finally official: Around 900,000 Americans and quite possibly more than that have multiple sclerosis (MS) — easily double the long-accepted figure of 400,000. Since MS News Today first reported on this finding in November 2017, the National Multiple Sclerosis Society (NMSS) study, which reached that conclusion, has…

Blood levels of a nerve cell-derived component known as neurofilament light chain (NfL) could be used as a biomarker of disease severity and treatment response in patients with relapsing-remitting multiple sclerosis (RRMS), a new study shows. The research article, “Blood neurofilament light chain as a biomarker of MS…

Editor’s note: “Need to Know” is a series inspired by common forum questions and comments from readers. Have a comment or question about multiple sclerosis? Visit our forum. This week’s question is inspired by the forum topic, “Are you a parent caregiver of a child with…

Early-life use of antibiotics disrupts gut microbiota in a rat model of multiple sclerosis (MS) and provokes nervous system autoimmunity, ultimately aggravating disease severity, new research shows. Results also indicate early-life antibiotic use may have unfavorable consequences on regulation of the immune system. The research article, “…

Almost one in five patients diagnosed with multiple sclerosis (MS) and referred to one of two MS-specialized centers in the U.S. were found to not have the disease, a study at those two centers reported. Migraine was the most common correct diagnosis eventually given these people. The retrospective study…

A protein called MMP-9 could be a predictive marker of progressive multifocal leukoencephalopathy development in patients with relapsing-remitting multiple sclerosis (RRMS) who are being treated with Tysabri (natalizumab), a study suggests. The study, “Dynamic changes of MMP-9 plasma levels correlate with JCV reactivation and immune activation in natalizumab-treated multiple sclerosis patients,” was published in the journal Nature Scientific Reports. Brain inflammation in multiple sclerosis patients occurs when immune cells breach the blood-brain barrier. This layer of cells protect the brain and its supporting fluids, such as cerebral spinal fluid (CSF), from dangerous agents circulating in blood. How easily immune cells can break through the blood-brain barrier depends on its porousness. For instance, it is known that decreasing the activity of matrix metalloproteinases (MMP) increases the protective layer’s permeability. Matrix metalloproteinases are a family of proteins responsible for the degradation of collagen and other proteins in the extracellular matrix, which provides structural and biochemical support to surrounding cells. One metalloproteinase, called MMP-9, has been extensively studied in multiple sclerosis. MMP-9 levels are elevated in the CSF of multiple sclerosis patients and considered a potential biomarker of disease activity and possible therapeutic target. Tysabri (marketed by Biogen) is one of the most effective treatments for RRMS currently available. It works by blocking the entry of immune cells into the brain. Tysabri is known to decrease MMP-9 levels in the CSF and serum in RRMS patients. However, Tysabri has been associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML). This rare and often fatal viral disease, caused by the John Cunningham virus (JCV), is characterized by progressive damage and/or inflammation at multiple sites in the brain. The reduced migration of immune cells across the blood-brain barrier induced by Tysabri is thought to be the cause of this increased PML risk. Whether MMP-9 is involved in this process has not been studied. To look at this, a team led by researchers from Sapienza University and Aldo Moro University in Italy investigated MMP plasma levels following Tysabri treatment in the context of JCV. The team specifically looked at how levels of MMP-9 were linked to disease-related processes. Samples from 34 RRMS patients being treated with Tysabri (intravenous dose of 300 mg every four weeks) were analyzed. As expected, results showed that MMP-9 plasma levels stabilized within one year of Tysabri treatment (up to 12 Tysabri infusions), although they began to steadily rise afterward (between 12 and 24 infusions). These increased MMP-9 plasma levels were not associated with clinical relapses in RRMS patients. "MMP-9 levels increased in plasma accordingly with [Tysabri] infusion number," the researchers wrote. In comparing JCV-positive and JCV-negative samples, the researchers observed an increase in MMP-9 plasma levels in JCV-positive samples. This result suggested that JCV circulation in peripheral blood could be implicated in the increase of MMP-9 levels. Interestingly, increased MMP-9 plasma levels were found to be correlated with immune cell activation. "Our findings suggest a potential pathogenic role of MMP-9 in the development of progressive multifocal leukoencephalopathy during [Tysabri] treatment, and its possible use as a marker of JCV reactivation,” the researchers wrote. Future studies are nonetheless needed to confirm these findings in larger groups of RRMS patients.

Multiple sclerosis (MS) can make our bodies experience pain, become weak, and easily fatigue. We can find it difficult just to walk. These challenges can steal our motivation to be active. But without regular activity, we become sedentary, which can increase weakness and fatigue symptoms that cause additional health…

Issues with social cognition can occur in relapsing-remitting multiple sclerosis (RRMS) patients even without the presence of cognitive impairment, and are related to damage in a specific brain region known as the amygdala, a study reports. The study, “Social cognition deficits and the role of…

OK, I’ve used a typical tabloid headline to draw you into a column about dealing with lymphedema. Well, the topic is not exactly sexy! Though my calves are now extremely toasty due to being effectively embalmed. Lymphedema has been plaguing me for years now. There seems to be…

Warning the reporter accompanying him not to take any pictures, veteran horticulturalist Michael Castleman punches an electronic code and unlocks the door to Room 209, nicknamed the “Mother Room.” Photography is indeed forbidden inside this living vault, which contains 20 phenotypes of cannabis plants thriving under the glare of 25…

The RhoE protein has been identified as being important for axons’  myelination and extension in the central nervous system, two processes that go awry in diseases like multiple sclerosis (MS). The findings stem from Pilar Madrigal’s doctoral thesis, “Role of the small GTPase RhoE in myelination and axonal tracts development.”…

Life never lets me forget its fragility. Sometimes my challenges seem like mountains to be scaled. Adversity has become the elephant in the room; it is ever present even when I refuse to acknowledge it. A few weeks ago, I faced what could potentially have been a medical crisis.

Genetic variants that enhance the activity of the NLRP3 inflammasome or the interleukin-1 beta cytokine are linked to higher severity and progression of multiple sclerosis, a study suggests. Previous studies with mouse models of MS have shown that a complex of innate immune system receptors and sensors, known as the inflammasome, is likely a player promoting the immune system’s attack on the central nervous system in MS and, consequently, the loss of myelin. Follow-up studies showed that people carrying mutations that enhance the function of the NLRP3 inflammasome — one of the three components of the inflammasome complex — had a worse prognosis, once again supporting the role of the inflammasome in MS. Once activated, the inflammasome triggers an enzyme called caspase-1 that promotes the production of two very powerful proinflammatory cytokines called interleukin (IL)-1 beta and IL-18. To further evaluate the role of the inflammasome in MS, a team led by researchers at the Universidade de Sao Paulo in Brazil analyzed the genetic sequence of five inflammasome genes — NLRP1, NLRP3, NLRC4, IL-1 beta, and IL-18 — in blood samples retrieved from 264 patients diagnosed with MS or other demyelinating diseases. They also analyzed 233 healthy individuals used as controls. The team specifically looked at eight variations in certain nucleotides (the building blocks of DNA), called single nucleotide polymorphisms (SNPs). Previous studies reported a link between SNPs in inflammasome-related genes and certain forms of MS. Results showed that SNPs associated with low serum levels of IL-18 were significantly less frequent in MS patients than in controls. In contrast, variants that enhance the function of NLRP3 and IL-1 beta were associated with severity and progression of MS, as measured by the Expanded Disability Status Scale. These results suggest that the "activation of NLRP3 inflammasome could represent a risk factor for MS clinical presentation,” the researchers wrote. A particular variant in the NLRC4 gene was less frequent in patients whose disease progressed rapidly compared with those who had a slower disease, an intriguing observation, according to researchers, suggestive of a “protection effect of this variant against a bad prognosis.” Carriers of this variant also responded better to treatment with interferon-beta. Regarding MS type, the genetic variant that promotes the function of the IL-1 beta gene was significantly more frequent in progressive forms of MS than in relapsing-remitting MS, strengthening once again the negative effects of IL-1 beta in the disease. An analysis of inflammasome activity in blood monocytes, a group of immune cells, showed that the inflammasome is permanently activated in MS compared with healthy controls. "This study emphasizes that a constitutive activation of NLRP3 inflammasome, principally through IL-1 beta production, represents a risk factor for both the development of MS and the progression to severe forms of the disease. On the other hand, low IL-18 production and/or NLRC4 activation were beneficial for MS patients,” the team concluded.

People with multiple sclerosis may be twice as likely to develop deep-vein blood clots, a condition known as venous thromboembolism, than healthy people do, a study reports. But data linking the two is limited, and its researchers say further work is needed to understand if MS is directly related to…

I’ve often wondered if there may be a connection between fibromyalgia, multiple sclerosis (MS), and other neurological conditions. Back in the early 1990s, my doctor suspected fibromyalgia as the culprit for my fatigue, aches, and pains. At the time, doctors diagnosed fibromyalgia by the use of tender points.

Awareness of certain symptoms, particularly gait disorders and depression, could be critical for reducing the time it takes to diagnose multiple sclerosis after a patient first contacts a healthcare provider, research shows. In the past 30 years, there has been a major decrease in the time from the…

If MS was just about MS, it wouldn’t be easy, but it would be a lot easier. It’s different for all of us. For me, MS means ambulation is practically impossible. I could manage a few yards, but the risk of falling and spending the day as an upside-down beetle…

Reducing body temperature during physical exercise can help rewire the brain and improve motor control in patients with multiple sclerosis (MS), a new research study at Canada’s Memorial University shows. Physical exercise can have several benefits for patients with MS, including improved strength and reduced symptoms of fatigue and…

Anxiety and depression are associated with lower cognitive abilities in patients with multiple sclerosis (MS) other and immune-mediated inflammatory diseases such as inflammatory bowel disease (IBD) and rheumatoid arthritis, a study shows. These findings indicate the importance of managing symptoms of anxiety and depression in MS, as…

“If I were you two, I think I’d plan for the worst,” Amy, my physiatrist, said to my wife and me as we sat in the examination room. It was just after 11 a.m. on Friday, Jan. 18. January has become one of two pivotal months in terms of…

“Oh no, not again.” My mind races and time slows as I crumble to the floor. Every downward movement is magnified, and so too is the pain of my twisted left foot and leg. They have become the resting place for my slumping body. My fuzzy and confused mind…

Herbicide Called Linuron Seen to Trigger Inflammatory Signals Linked to MS in Study This is only a mouse study, but this herbicide has been banned in Europe because of health concerns. Its effects seem worthy of further investigation. The herbicide linuron, commonly used with other herbicides, insecticides,…