Summary: Structural abnormalities in white matter, even before the onset of inflammation, may serve as a new therapeutic target for multiple sclerosis (MS). The study, focusing on ‘normal-appearing white matter’, identified early changes in myelin, an insulating substance around nerve fibers.
In MS patients, myelin was found to wrap less tightly around nerve fibers, impairing signal transmission and resulting in symptoms such as impaired mobility and vision.
Future research will focus on ways to enhance the wrapping of myelin, potentially preventing new lesions and providing a novel approach to MS treatment.
- The research discovered that myelin, which insulates nerve fibers, wraps less tightly around these fibers in MS patients, even before the development of lesions.
- Loosely wrapped myelin impairs signal transmission in the central nervous system, leading to MS symptoms such as impaired mobility and vision.
- Future studies will aim to enhance the wrapping of myelin around nerve fibers, which could potentially prevent the formation of new lesions in MS patients.
Patients with multiple sclerosis show structural abnormalities in their white matter even before MS inflammation develops.
This is the conclusion of a new study by the Netherlands Institute for Neuroscience (NIN) in Amsterdam and the Max Planck Institute for Multidisciplinary Sciences in Göttingen (MPI). Could this finding be a target for a new treatment to prevent MS inflammation?
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. In early, as well as advanced progressive MS, lesions arise along with substantial inflammatory activity.
Lesions are the inflammatory sites where the myelin is broken down and taken up by microglial cells (our brain’s immune cells). But do we see something in the tissue even before these inflammation spots appear?
To answer this question, Aletta van den Bosch of the research team of Inge Huitinga (NIN) and Wiebke Moebius (MPI) looked into human post-mortem brains of MS patients and controls that have been donated to the Dutch Brain Bank. Their focus was particularly on the so-called ‘normal-appearing white matter’.
As the name suggests, these are areas where lesions have not formed yet, and so still appear normal. How is it possible that people with MS develop lesions here later and people without MS do not?
The team took a detailed look at myelin to see if there are early changes in people with MS. Myelin is an insulating white, fatty substance that is wrapped up to 150 times around the nerve fibers.
At regular distances from each other there are interruptions of the myelin, these are the Nodes of Ranvier.
During the transmission of electrical signals, the signal jumps from one Node or Ranvier to the next, allowing a myelin-containing fiber to transmit a signal 100 times faster than without myelin.
In people with MS, myelin is damaged and signal transmission in the central nervous system is disrupted, which can impair functions such as walking and vision. What kinds of changes in brain tissue can we observe in the early stages of MS?
Aletta van den Bosch: “To be able to study myelin properly, we looked at the optic nerve. In this area, all nerve fibers and their myelin follow the same direction very nicely, so that we can visualize the myelin well. We did this by using electron microscopy. With this technique we zoomed in 5,000 to 30,000 times on a cross-section of a nerve-fiber.
“In MS, myelin was found to be less tightly wrapped around the nerve-fiber. This means that the fiber is not properly insulated which has major consequences: the signal can’t be transmitted as fast as it used to be.
“We saw that where myelin was less attached to the fiber, there was a disruption of the nodes of Ranvier combined with increased levels of T-cells and activated microglia. Furthermore, there were more mitochondria.
“Mitochondria are the energy factories of the cell, so this phenomenon may indicate that more energy is needed for signal movement and maintenance of the fibers.”
“Although mitochondria are generally good for energy production, they also produce many by-products, such as oxygen radicals. We suspect this to be an amplifying factor for myelin breakdown: the myelin is already in a bad state, more mitochondria develop to provide more energy, which then makes conditions even worse.
“The theory is that a threshold value is needed to initiate the breakdown. It is also possible that the body recognizes the detached myelin as ‘abnormal’, which could be the start of breakdown by immune cells.”
“We haven’t been able to look at human tissue in such detail before, meaning that almost all the research so far has been done in laboratory animals. Although this is very valuable research, it could sometimes be more difficult to translate the results directly to humans.
“This is the first glimpse into what happens at the ultrastructural level in people with MS and what exactly leads to the lesions. You need very good tissue to do this which is why the brain bank is so crucial for our research.”
“The next step is to see if we can prevent the myelin from winding so loosely around nerve endings.
“First, we want to experiment in culture dishes to see if we can make the wrapping of myelin stronger. Subsequently, we will have perform tests in laboratory animals, and eventually we will be able to take the step to humans.
“It would be great if we could find something to prevent myelin detachment. While this will not prevent the damage of the lesions that are already there, it might prevent the development of new lesions. This would provide a whole new target for MS treatment.”
About this multiple sclerosis research news
Author: Eline Feenstra
Contact: Eline Feenstra – KNAW
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Ultrastructural Axon–Myelin Unit Alterations in Multiple Sclerosis Correlate with Inflammation” by Alleta van den Bosch et al. Annals of Neurology
Ultrastructural Axon–Myelin Unit Alterations in Multiple Sclerosis Correlate with Inflammation
Changes in the normal-appearing white matter (NAWM) in multiple sclerosis (MS) may contribute to disease progression. Here, we systematically quantified ultrastructural and subcellular characteristics of the axon–myelin unit in MS NAWM and determined how this correlates with low-grade inflammation.
Human brain tissue obtained with short postmortem delay and fixation at autopsy enables systematic quantification of ultrastructural characteristics. In this study, we performed high-resolution immunohis tochemistry and quantitative transmission electron microscopy to study inflammation and ultrastructural characteristics of the axon–myelin unit in MS NAWM (n=8) and control white matter (WM) in the optic nerve.
In the MS NAWM, there were more activated and phagocytic microglia cells (HLA+P2RY12−and Iba1+CD68+) and more T cells (CD3+) compared to control WM, mainly located in the perivascular space. In MS NAWM compared to control WM, there were, as expected, longer paranodes and juxtaparanodes and larger overlap between paranodes and juxtaparanodes. There was less compact myelin wrapping, a lower g-ratio, and a higher frequency of axonal mitochondria. Changes in myelin and axonal mitochondrial frequency correlated positively with the number of active and phagocytic microglia and lymphocytes in the optic nerve.
These data suggest that in MS NAWM myelin detachment and uncompact myelin wrapping occurs, potassium channels are unmasked at the nodes of Ranvier, and axonal energy demand is increased, or mitochondrial transport is stagnated, accompanied by increased presence of activated and phagocytic microglia and T cells. These subclinical alterations to the axon–myelin unit in MS NAWM may contribute to disease progression. ANN NEUROL 2023;93:856–870
What is the most common demyelinating event in patients with MS? ›
The initial symptom of MS is optic neuritis (ON) in 14% to 23% of patients, and more than 50% experience a clinical episode of ON during their lifetime. The most common manifestation is visual loss in one eye that evolves over a few days.What is the hallmark of multiple sclerosis? ›
The hallmark of MS pathology is the focal demyelinated lesion, or “plaque,” present in the white matter of the optic nerves, brain, and spinal cord.Does MS cause inflammation of the brain? ›
Longbrake says MS brain lesions are caused by inflammatory damage to nerves. This damage leads to neurologic deficits like weakness, numbness, or memory problems. Inflammation of the central nervous system is linked to the initial appearance of the disease as well as relapses.What are MS plaques made of? ›
PATHOLOGY OF MS. The pathology is characterized by multifocal lesions, the MS plaques. The usual evolution of the MS plaque is as follows: in the acute phase (active plaque), activated mononuclear cells, including lymphocytes, microglia, and macrophages destroy myelin and, to a variable degree, oligodendrocytes.How do you treat demyelination of the brain? ›
A variety of drug therapies are recommended depending on your specific disorder. Strategies to treat symptoms include medications to improve walking, spams, bladder dysfunction and others. Physical therapy, occupational therapy and cognitive behavioral therapy can also help manage symptoms.What is the most common clinical manifestation of multiple sclerosis? ›
- vision problems.
- numbness and tingling.
- muscle spasms, stiffness and weakness.
- mobility problems.
- problems with thinking, learning and planning.
- depression and anxiety.
Sjogren's syndrome is an autoimmune disease that can mimic some of the symptoms of MS such as fatigue and joint pain.How do you get rid of MS inflammation? ›
People with multiple sclerosis can incorporate natural therapies into their health protocol in order to reduce inflammatory chemicals and reduce blood-brain-barrier disruption. Some of the most potent natural therapies to achieve these goals include resveratrol, vitamin D, fish oil, and a healthy diet.What does MS inflammation feel like? ›
These pain sensations feel like burning, stabbing, sharp and squeezing sensations. In MS you can experience acute neuropathic pain and chronic neuropathic pain. Acute Neuropathic Pain is sometimes an initial symptom of MS or may be part of an MS relapse. Acute means it has a rapid onset and is of short duration.What mineral deficiency causes multiple sclerosis? ›
There have been studies that suggest Vitamin D deficiency may play a role in immune system function and the development of auto immune disorders such as Multiple Sclerosis.
What mineral deficiency causes MS? ›
They found that people who naturally had lower levels of vitamin D (because of their genetics) were more likely to develop MS.Is MS caused by heavy metals? ›
One group of toxic agents that could produce many features of MS are the potentially toxic elements (PTEs), formerly referred to as “heavy metals”, that include elements such as mercury, lead, and cadmium27.What is the first indicator of MS? ›
One of the more obvious first signs of MS is a problem with vision, known as optic neuritis. This is often because it's a more concrete symptom as opposed to vaguer neurological symptoms like numbness and tingling.What are the cardinal signs of multiple sclerosis? ›
Multiple sclerosis (MS) is a disease of the central nervous system that can affect the brain, spinal cord and optic nerves. Common symptoms include fatigue, bladder and bowel problems, sexual problems, pain, cognitive and mood changes such as depression, muscular changes and visual changes.What foods increase myelin? ›
The myelin sheath is mostly made of fat, but certain fats work better as building materials. Healthy fats can help grease the gears. Unsaturated fats found in foods like nuts, seeds, salmon, tuna, avocado, and vegetable oils help nerve cells communicate more quickly.Can myelin be restored in MS? ›
Myelin is repaired or replaced by special cells in the brain called oligodendrocytes. These cells are made from a type of stem cell found in the brain, called oligodendrocyte precursor cells (OPCs). And then the damage can be repaired.What type of cell would be the most likely target of multiple sclerosis? ›
In multiple sclerosis, immune cells target a certain cell type called oligodendrocytes, which are only located in the central nervous system (the brain and spinal cord). Oligodendrocytes are special types of neurons (or brain cells), which produce something called myelin.What is the most common pattern of MS attacks? ›
Attacks strike approximately every 12 to 18 months. This pattern is common when patients first develop MS and through the early years of their disease, and is referred to as relapsing-remitting MS.What does MS feel like in feet? ›
Erythromelalgia is a painful MS symptom that affects the feet. The feet may feel tight or swollen and have a burning sensation. Some remedies for hot feet include: wearing pressure socks.What can be mistaken for multiple sclerosis? ›
- Epstein-Barr Virus.
- Vitamin B12 Deficiency.
- Nerve Damage.
- Eye Problems.
- Lupus and Other Autoimmune Diseases.
- Parkinson's Disease.
What neurological disorder mimics MS? ›
These include fibromyalgia and vitamin B12 deficiency, muscular dystrophy (MD), amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), migraine, hypo-thyroidism, hypertension, Beçhets, Arnold-Chiari deformity, and mitochondrial disorders, although your neurologist can usually rule them out quite easily.What disease is almost like MS? ›
Devic's disease/NMO most often affects only the optic nerve and spinal cord at first. With MS, changes in memory, reasoning, problem solving and depression are also common. Vision loss with MS usually affects one eye at a time, but Devic's disease/NMO may affect both eyes at the same time.Why is Benadryl great for multiple sclerosis? ›
Diphenhydramine, sold as Benadryl, is a type of antihistamine that can help reduce the likelihood or severity of an allergic reaction to a multiple sclerosis (MS) infusion treatment. Antihistamines block histamines, chemicals made by white blood cells that cause allergy symptoms such as itchy skin, rash, and hives.What is the best vitamin for MS? ›
Vitamins that seem of particular interest to people with MS include vitamin D, the antioxidant vitamins, vitamin B6 and vitamin B12. Vitamin D Vitamin D is a hormone, or chemical messenger, in the body.What vitamins should you avoid with MS? ›
High doses of other vitamins can antagonize your immune-modulating, immunosuppressive therapies used to manage MS. Supplements that stimulate the immune system should be avoided in high doses. Those include selenium, zinc, B1, B2, folic acid, B6, vitamin A, biotin, magnesium, copper, and manganese.When should you suspect multiple sclerosis? ›
People should consider the diagnosis of MS if they have one or more of these symptoms: vision loss in one or both eyes. acute paralysis in the legs or along one side of the body. acute numbness and tingling in a limb.What type of inflammation is multiple sclerosis? ›
Multiple sclerosis (MS) is a chronic, inflammatory disease of unknown etiology that involves an immune-mediated attack on the central nervous system. Myelin and the oligodendrocytes that form myelin appear to be the primary targets of the inflammatory attack, although the axons themselves are also damaged.Where does inflammation occur in multiple sclerosis? ›
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which leads to the development of focal inflammatory lesions with secondary axonal damage.How much vitamin D should I take for multiple sclerosis? ›
Vitamin D sources and supplements
Mattson tends to recommend 1,000 to 2,000 IU per day to people with MS, even if levels are normal, to boost the protective factor against MS activity. “If vitamin D levels are low, I tend to recommend 2,000 units per day.
One study noted young people with MS who took a calcium, vitamin D, and magnesium supplement had a reduced number of relapses. The study authors theorized that magnesium could play a role in the growth and stability of myelin.
What vitamin and mineral deficiencies mimic MS? ›
Vitamin B12 deficiency or Copper Deficiency
A vitamin B12 deficiency can cause MS-like symptoms, says Conway. These symptoms can include fatigue, mental confusion, and numbness and tingling in the hands and feet.
While zinc deficiency causes brain cells to die, high levels can also be neurotoxic. Obtaining an equilibrium, or homeostasis, may be essential to improving clinical outcomes in people with MS.Can vitamin D reverse MS? ›
Higher levels of vitamin D are associated with reduced risk for developing multiple sclerosis (MS), and with reduced clinical activity in established MS, including decreased risk of relapse and reduction in disease activity on brain MRI [1, 2].Can B12 deficiency be misdiagnosed as MS? ›
A vitamin B12 deficiency can cause neurological symptoms that mimic those of multiple sclerosis (MS). Symptoms of both conditions include muscle weakness, difficulty walking, cognitive dysfunction, and sensory disturbances.What toxins cause multiple sclerosis? ›
Clostridium perfringens and epsilon toxin may explain many of these mysteries.” An environmental trigger is required for MS to occur in a genetically susceptible individual, and the abundance of epsilon toxin-producing Clostridium perfringens in people with MS suggests it could be the culprit.What is the strongest known risk factor for MS? ›
While the genetics governing MS risk are still not completely understood, some 200 genes are thought to possibly contribute — even in small ways — to MS development. The strongest genetic risk factor is a particular variant of the HLA-DRB1 gene, called HLA-DRB1*15:01.What is the biggest cause of MS? ›
Multiple sclerosis is caused by your immune system mistakenly attacking the brain and nerves. It's not clear why this happens but it may be a combination of genetic and environmental factors.What is the first demyelinating event? ›
The first episode of clinically eloquent CNS inflammatory demyelination is frequently the first clinical manifestation of multiple sclerosis. This may occur on a background of sub-clinical disease that has been present for many years prior.What are active demyelinating lesions in multiple sclerosis? ›
Demyelination and multiple sclerosis
In MS, demyelination occurs in the white matter of the brain and in the spinal cord. Lesions or “plaques” then form where myelin is under attack by the immune system. Many of these plaques, or scar tissue, occur throughout the brain over the course of years.
Fatigue. Fatigue is one of the most common symptom of MS, reported by at least 75% of patients with the disease. Fatigue is described as an overwhelming feeling of lassitude or lack of physical or mental energy that interferes with activities.
Can you have demyelination and not have MS? ›
Antinuclear antibodies (ANA) or antiphospholipid antibodies (aPL) can also occur in MS. Thus a number of patients with systemic autoimmune disease and demyelinating lesion can be misdiagnosed for MS.Does demyelination always mean MS? ›
Does demyelination always mean MS? MS is the most common demyelinating disorder that affects the central nervous system (CNS), comprised of the brain, spinal cord, and optic nerves. It is not the only condition characterized by CNS demyelination, however.What are the three demyelinating diseases? ›
- Multiple sclerosis. Aetiology, pathogenesis and epidemiology. ...
- Acute‐disseminated encephalomyelitis. Aetiology, pathogenesis and epidemiology. ...
- Acute haemorrhagic leucoencephalitis. This rare, usually fatal, disease is thought to be a hyperacute variant of ADEM.
T cells and B cells in MS
T cells become activated in the lymph system and, in MS, enter the central nervous system through blood vessels. Once there, T cells release chemicals that cause inflammation and damage. This results in damage to myelin, nerve fibers and the cells that make myelin.
When a damaged nerve “short circuits,” it can cause a sharp pain or a burning or squeezing sensation. A common pain in MS is what's known as Lhermitte's sign. “This occurs when there's a lesion on the cervical spine, the neck area of the spinal cord,” says Dr. Scherz.Can demyelination be anything other than MS? ›
Demyelinating disorders of the central nervous system (CNS) that affect the brain and spine have a variety of etiologies and can be separated into primary such as multiple sclerosis (MS) and other idiopathic inflammatory-demyelinating diseases (IIDDs) and secondary (e.g., infectious, ischemic, metabolic, or toxic) ...What is the most common form of multiple sclerosis MS at the time of diagnosis? ›
Relapsing-Remitting MS (RRMS)
The most common type of MS is called RRMS. It is defined by temporary periods called relapses, flare-ups or exacerbations, when new symptoms appear.
- muscle cramps and stiffness.
- tremor (shaking)
- loss of coordination and balance.
- trouble with talking and swallowing.
Cognitive impairment—a decline in the ability to think quickly and clearly and to remember easily—affects up to 75 percent of people with MS. These cognitive changes may appear at the same time as the physical symptoms or they may develop gradually over time.