MS-Related Memory and Attention Problems Have Signs of Extensive Brain Damage

People with multiple sclerosis (MS) who have cognitive problems, or problems with memory, attention, and concentration, have more damage to areas of the brain involved in cognitive processes than people with MS who do not have cognitive problems, according to a study published in the March 6, 2013, online issue of Neurology, the medical journal of the American Academy of Neurology.

The study used a type of MRI brain scan called diffusion tensor imaging along with regular MRI scans to compare brain measurements in 20 people with MS who had related cognitive problems, 35 people with MS who did not have cognitive problems and 30 healthy participants.

The diffusion tensor images showed that, compared to the healthy control participants, 49 percent of the investigated brain white matter had impaired integrity in those with MS and no cognitive problems, while impaired integrity was evident in 76 percent of the investigated white matter of those with MS and related cognitive problems.

In the people with MS-related cognitive problems, the extra white matter dysfunction was particularly seen in areas important for cognitive skills, such as the thalamus.

"This state-of-the-art imaging technology confirms that cognitive symptoms in MS have a biological basis," said study author Hanneke E. Hulst, MSc, of VU University Medical Center in Amsterdam, the Netherlands.

"The consequence of this discovery is that imaging can now be used to capture a wider spectrum of changes in the brains of people with MS, and will therefore help determine more accurately whether new treatments are helping with all aspects of the disease."

Cognitive problems are common in MS, affecting up to 65 percent of people with the disease.

The study was supported by the Dutch MS Research Foundation.

The above story is reprinted from materials provided by American Academy of Neurology (AAN).

Aberdeen Scientists claim artificial light is key to treating Multiple Sclerosis

Aberdeen scientists have found that artificial sunlight can have a “striking effect” in helping treat sufferers of diseases such as multiple sclerosis.

Researchers from Aberdeen University studied patients in the north of Scotland – which has the highest rate of MS in the UK - who were being treated during winter with artificial UV (ultraviolet)-B light therapy for skin diseases caused by their immune systems acting inappropriately.

The research - published in the Journal of Allergy and Clinical Immunology – shows how UV-B light boosts vitamin D, as well as cells in our body that are responsible for regulating or balancing the immune system. Vitamin D is made in our bodies by UV-B light from the sun.

Some studies have suggested a link between vitamin D deficiency and autoimmune diseases such as MS.

This possible link might also explain the increasing prevalence of autoimmune disease among those living far from the equator, where there are lower levels of winter sun.

Autoimmune diseases - like MS and type 1 diabetes - are diseases where the immune system mistakenly attacks the body’s own tissues or harmless substances that enter the body.

Dr Anthony Ormerod, clinical reader in dermatology at the university, said: “Our study shows that UV-B light, which mimics sunshine, can have a striking effect on the immune system of patients.

“We found that UV-B light boosted the production of vitamin D, and of regulatory T cells, which play an important role keeping our immune systems in check.

“Our findings have important implications for future interventions including the recommendations for healthy lifestyle and a possible role for phototherapy and/or vitamin D supplementation in the prevention or treatment of autoimmune and inflammatory diseases.

“While too much exposure to sunlight is harmful and increases skin cancer risk, these results suggest that subjects in our study would have some benefits from small amounts equivalent to summer exposure in the winter but more work needs to determine the role of sunlight and the role of supplementing the diet with vitamin D.”

Dr Helen Macdonald, senior lecturer in nutrition and translational musculoskeletal research at the university and chair of the National Osteoporosis Society Nutrition and Lifestyle forum, said: “There are risks associated with high levels of both therapies, so it is important that we get the balance right.

“We would also want to stress that we are not advocating sun bed use since this is not the same type of radiation produced by sun beds which already have well-documented health risks.

“The average dose of UV light that the volunteers received was the equivalent to sunlight exposure in Aberdeen over spring and summer and further work is required to determine if lower doses are effective.”

Professor Mark Vickers, chair in applied medicine at the university, added: “Ours is the first study to demonstrate in patients a cause and effect between UV light, vitamin D and systemic immune function in people.”

Receptor may hold key to Multiple Sclerosis treatment

This image shows the A2A adenosine receptor (in red) abundantly expressed in the central nervous system (CNS). The blue colour identifies the nuclei of cells in the CNS.

A receptor recently discovered to control the movement of immune cells across central nervous system barriers (including the blood-brain barrier) may hold the key to treating multiple sclerosis (MS), a neuroinflammatory disease of the central nervous system.
 

In MS, immune cells enter the central nervous system and attack and destroy the myelin sheath surrounding the axons of nerve cells in the brain and spinal cord, resulting in blindness, paralysis, incontinence and many more symptoms.

The research, appearing last month online and in print June 1 in the Journal of Immunology, reveals how the A2A adenosine receptor expressed on blood-brain barrier cells acts as a gateway, allowing immune cells to enter the brain, where they can cause havoc in people with MS.

The blood-brain barrier is composed of specialized cells that selectively prevent substances from passing from the bloodstream into the brain.

"We found that expression of this A2A adenosine receptor is important for regulating the entry of cells into the brain; whereby its activation allows immune cell entry and its inhibition blocks entry," said Margaret Bynoe, associate professor of immunology at Cornell's College of Veterinary Medicine and senior author of the paper, which was also selected as a featured publication in the "In This Issue" section of the journal, where the top 10 percent of manuscripts are featured. Jeffrey Mills, a postdoctoral associate in Bynoe's lab, is the paper's lead author.

In this study, the researchers used mice where the A2A adenosine receptor was knocked out and then infused those mice with normal immune cells from wild-type mice expressing the A2A adenosine receptor.

This produced chimeric mice expressing the A2A receptor on immune cells, but not on blood-brain barrier cells.

Without A2A receptor on blood-brain barrier cells, the normal immune cells failed to effectively infiltrate the central nervous system, and thus, these mice were protected and developed less severe symptoms of MS-like disease.

"The absence of the A2A receptor on blood-brain barrier cells is similar to the effect of pharmacologically blocking the receptor with antagonists [drugs], which also protected mice from MS-like disease," Bynoe said.

"The implications of these findings are that, potentially, modulation of this receptor can be beneficial for future treatment of MS," she added.

Journal reference: Journal of Immunology  

Provided by Cornell University

Multiple sclerosis starts in brain’s outer layers

Researchers at the Mayo Clinic and Cleveland Clinic have reversed the traditional understanding of how multiple sclerosis (MS) begins and travels in the brain.

The common view is that the disease starts in the centre of the brain, in the white matter mostly found there, and then moves toward the outer layers, such as the cortex.

But this study, which is unique because it focused on the brain tissues of patients in the very early stages of MS, shows the opposite: that it moves from the outside in.

It begins in the “subarachnoid space,” which surrounds the brain, cushions it and is filled with cerebrospinal fluid. From there it moves into the white matter. This animation shows how the two hypotheses differ.

The findings are also significant because they support the hypothesis that inflammation, not neurodegeneration, is a main driver of the disease.

The authors conclude that it is “overwhelmingly likely” that MS is fundamentally an inflammatory disease, and not a neurodegenerative disease similar to Alzheimer’s.

Researchers are not entirely sure exactly causes MS, but the prevailing theory is that it is an autoimmune disease in which the body’s own immune system attacks and destroys its own myelin, a fatty substance essential to the nervous system. It protects the crucial nerve fibres enable different sections of the brain to communicate.

When myelin is damaged (as in MS), messages between the brain and the body are delayed or blocked, leading to MS symptoms such as blindness, numbness, paralysis, and thinking and memory difficulties.

“Our study shows the cortex is involved early in MS and may even be the initial target of disease,” co-lead author of the study and Mayo Clinic neurologist Dr. Claudia F. Lucchinetti stated.

“Inflammation in the cortex must be considered when investigating the causes and progression of MS”, she says. She and her co-author, Dr. Richard Ransohoff of the Cleveland Clinic, published the results of their study in the New England Journal of Medicine.