Mom's Story

A discussion about Mom's Story and MS…

Archive for the tag “brain”

Researchers Funded by National MS Society Pinpoint Direct Damage to Nerve Connections in Mice, Independent of Myelin Damage

Summary
• Researchers have found evidence that microscopic connectors in the brain called “synapses” are directly damaged during the course of MS-like disease in mice, in an area of the brain linked to cognitive function.
• The damage appeared to be unrelated to myelin damage, and was linked to a specific molecule called platelet-activating factor receptor.
• Further research will determine whether treatment that protects synapses in the hippocampus may preserve cognitive function in people with MS. The team is pursuing therapeutic candidates based on these findings.
• This research was funded in part by a National MS Society-American Brain Foundation (American Academy of Neurology) Clinician Scientist Development Award to Dr. Matthew Bellizzi.
• The team (Drs. Bellizzi, Harris Gelbard, and colleagues, from the University of Rochester Medical Center, in New York) has published results in The Journal of Neuroscience. (2016 Jan 27;36(4):1336-46.)
Background: MS involves immune attacks in the brain and spinal cord. During the course of MS, damage occurs to the myelin that surrounds and protects nerve fibers, and nerve cells and their axons are also damaged. Damage to nerve cells in MS has been linked to cognitive impairment, progressive disability and other symptoms.

The causes of nerve damage are not yet well understood, which has limited progress in developing therapies that prevent damage and preserve nerve function (neuroprotection) to slow or stop progressive disability. Some research has shown that microscopic connectors in the brain called “synapses” may be lost in some parts of the brain during the course of MS, but details have been lacking. Synapses are the point of communication between individual nerve cells, and they are critically important for all functions of the nervous system including memory. A team at the University of Rochester has been attempting to determine the extent of damage to nerve cell fibers and synapses in brain, to find ways to protect nerves from damage.

The Study: The team, led by Matthew Bellizzi, MD, PhD, and Harris Gelbard, MD, PhD (University of Rochester), studied mice with the MS-like disease EAE. They measured the density of synapses in an area of the brain called the hippocampus. The hippocampus is involved in memory function. Although myelin was preserved, synaptic density was reduced by 28%, compared with mice that did not have EAE.

In another study, the team grew nerve cells from the hippocampus in laboratory dishes, and then added brain cells called microglia. This made the synapses more vulnerable to damage, and this damage seemed to be dependent on signals from a molecule called platelet-activating factor receptor (PAFR). To test this, the team administered an experimental molecule – BN52021 – that inhibits PAFR. Administering this molecule before EAE developed did not prevent the disease, but preserved synapses.

This research was funded in part by a National MS Society-American Brain Foundation (American Academy of Neurology) Clinician Scientist Development Award to Dr. Matthew Bellizzi. The team published results in The Journal of Neuroscience. (2016 Jan 27;36(4):1336-46.)

Next Steps: Further research will determine whether treatment that preserves synapses in the hippocampus can improve cognitive function in people with MS. According to a press release from the University of Rochester, the researchers are now focused on exploring potential therapeutic candidates based on these findings.

Read more about research to repair damaged tissue in MS
Read more about efforts to understand how MS affects cognitive function
Watch the educational video, Mood & Cognition in MS: [What you can do].

Hearing Loss and MS

Hearing loss is an uncommon symptom of MS. About 6 percent of people who have MS complain of impaired hearing; hearing loss may take place during an acute exacerbation.
In very rare cases, hearing loss has been reported as the first symptom of the disease.
Deafness due to MS is exceedingly rare, and most acute episodes of hearing deficit caused by MS tend to improve.

Hearing loss is usually associated with other symptoms that suggest damage to the brainstem — the part of the nervous system that contains the nerves that help to control vision, hearing, balance and equilibrium.

Hearing deficits caused by MS are thought to be due to inflammation and/or scarring around the eighth cranial nerve (the auditory nerve) as it enters the brainstem, although plaques (abnormal areas that develop on nerves whose myelin has been destroyed) at other sites along the auditory pathways could also contribute to hearing problems.

Because hearing deficits are so uncommon in MS, people with MS who do develop hearing loss should have their hearing thoroughly evaluated to rule out other causes.

Finding an audiologist or speech-language therapist:
The American Academy of Audiology provides an online search tool to locate audiologists who are members of the Academy. The American Speech-Language-Hearing Association (ASHA) provides an online search tool to locate certified speech-language pathologists (SLPs) and audiologists.

American Academy of Audiology
11480 Commerce Park Drive, Suite 220 Reston, VA 20191
Phone: 800-222-2336, website or email

American Speech-Language-Hearing Association (ASHA)
2200 Research Boulevard
Rockville, MD 20850-3289
Phone: 800-638-8255, website

Study authors find brain lesion, taste problem link

A new study finds that the more lesions spotted on an MRI, the worse the taste function of the patient with multiple sclerosis. They also found that women did better men on taste measures.

The researchers, led by Richard Doty, director of the University of Pennsylvania’s Smell and Taste Center, administered a standard taste test (sweet, sour, bitter, and salty) to 73 MS patients and 73 controls subjects, along with MRI of 52 brain regions known to be affected by MS in both groups. They found that the disease significantly influenced the ability to identify tastes, especially salty and sweet. Fifteen to 32 percent of MS patients – which is nearly twice as high as previous studies found – had taste scores below the 5th percentile of controls. What’s more, taste scores were inversely correlated with lesion amounts and volumes in the large sectors of the frontal and temporal lobes, the higher regions of the brain, identified on the MRI.

Regardless of subject group, women outperformed men on taste measures, which mirrors what previous taste studies have found. It is likely because women have more taste papillae and taste buds than men, the researchers said.

“It appears that a sizable number of these patients exhibit taste deficits, more so than originally thought. This suggests that altered taste function, though less noticeable than changes in vision, is a relatively common feature in MS. Future studies investigating the relationship between taste and MS may help better diagnose and understand the disease, as well as better manage symptoms,” Doty said.

The findings were reported in the Journal of Neurology.

MRI Study Yields Clues to the Development of Primary-Progressive MS

Summary

  • In a study of 453 people described as having radiologically isolated syndrome (specific areas of damage on MRI scans with no accompanying symptoms), about 12% eventually developed primary-progressive MS. This mirrors the frequency of primary-progressive MS seen in other studies of people with MS.
  • Those who developed primary-progressive MS were more likely to be men, were significantly older, and were more likely to have MS-like lesions in the spinal cord compared to those who went on to develop clinically isolated syndrome (CIS) or relapsing-remitting MS.
  • This study provides a rare glimpse of a very early stage of disease even before progression begins, and provides additional evidence of the value of research into radiologically isolated syndrome. Finding a way to identify and track primary-progressive MS earlier may help to improve access to care for those who have it.
  • The team (Dr. Orhun Kantarci, Mayo Clinic and Foundation, and national and international collaborators) published their findings in Annals of Neurology (published online, December 29, 2015).

Background: Diagnosing MS can be challenging, and it often happens in stages. The term “clinically isolated syndrome” (CIS) is used to describe a first episode of neurologic symptoms  that lasts at least 24 hours and is caused by inflammation and demyelination in one or more sites in the brain and spinal cord. Individuals who experience a CIS may or may not go on to develop definite MS. However, clinical trials of specific disease-modifying therapies have led to approvals for their use to treat CIS.

Some people have specific, “clinically silent” lesions (areas of inflamed or damaged tissue) on MRI, meaning that they are experiencing no symptoms and only have imaging findings. There has been growing research on this phenomenon, called “radiologically isolated syndrome (RIS),” which like CIS may or may not go on to develop into definite MS. There is debate as to whether people with RIS would benefit from early treatment with disease-modifying therapies.

Primary-progressive multiple sclerosis is a relatively rare form of MS, with about 10% of all people with MS receiving this diagnosis. It is characterized by steady worsening of neurologic functioning, without any distinct relapses (also called attacks or exacerbations) or periods of remission.

The Study:  This team examined data from 453 people with RIS collected from 22 investigators in five countries; a database of 210 people with MS in Olmsted County, Minnesota; and a cohort of 754 people with progressive MS.

Of the 453 people with RIS, 128 (28%) went on to develop a first neurological event consistent with CIS or relapsing MS. Of these, 15 (11.7%) developed primary-progressive MS. Those who developed primary-progressive MS were more commonly men, and older at diagnosis by approximately 10 years, than the 113 people who developed CIS/MS. The frequency of primary-progressive MS and age comparisons were similar to those identified in other groups of MS. Of the 15 who went on to develop primary-progressive MS, 12 had MRI scans of the spinal cord, and all 12 had lesions in the spinal cord, compared with 64% of those who developed CIS/MS.

The team (Dr. Orhun Kantarci, Mayo Clinic and Foundation, and national and international collaborators) published their findings in Annals of Neurology (published online, December 29, 2015).

Conclusions: This study provides a rare glimpse of a very early stage of disease even before progression begins, and provides additional evidence of the value of research into radiologically isolated syndrome. Finding a way to identify and track primary-progressive MS earlier may help to improve access to care for those who have it.

Read more about primary-progressive MS

– See more at: http://mjnickum-mynewbook.blogspot.com/#sthash.AQU8pdwj.dpuf

Study suggests possible inside-out origin for MS

A new study suggests an inside-out theory of multiple sclerosis in which the disease may be triggered by the death of brain cells that make the insulation around nerve fibers, according to a new study from Northwestern Medicine and the University of Chicago researchers. Creating a mouse-model of progressive MS, scientists also used a specially developed nanoparticle that prevented MS even after the death of those brain cells.
The new study shows the possibility that MS can begin from the inside out, in which damage to oligodendrocytes in the central nervous system can trigger an immune response directly. Oligodendrocytes can possibly be destroyed by developmental abnormalities, viruses, bacterial toxins or environmental pollutants. Oligodendrocytes are responsible for the maintenance of myelin. If they die, the myelin sheath falls apart. The death of these cells can activate the autoimmune response against myelin, which is the main feature of MS. The inside-out hypothesis suggests that when myelin falls apart, the immune system interprets the products of its degradation as foreign bodies or antigens, erroneously viewing them as invaders and beginning a full-scale attack on myelin, initiating MS.
“Protecting oligodendrocytes in susceptible individuals might help delay or prevent MS from initiating. It’s likely that therapeutic strategies that intervene early in the disease process will have greater impact,” said Brian Popko, the Jack Miller Professor of Neurological Disorders at the University of Chicago and one of the lead investigators in the study.
The scientists also developed the first mouse model of the progressive form of the autoimmune disease, which will enable the testing of new drugs against progressive MS. In the study, nanoparticles creating tolerance to the myelin antigen were administered and prevented progressive MS from developing. The nanoparticles are being developed for clinical trials that could lead to new treatments – without the side effects of current therapies – in adults.
The study was published in Nature Neuroscience.

MS Trial Alert: Investigators Nationwide Recruiting People with MS for Phase I Study to Determine Safety of Experimental Antibody in Treating Relapse

Summary: Investigators nationwide are recruiting 30 people with MS for a phase I study to determine the safety and tolerability of rHIgM22, an experimental antibody. Participants may remain on their current therapy throughout the study. The study is enrolling participants experiencing a clinical acute relapse (new or worsening neurological symptoms attributable to MS preceded by a stable or improving neurological state of at least 30 days) and with at least one new, active lesion (damaged area) on MRI scans. The study is funded by Acorda Therapeutics, Inc.

Rationale: Although the body repairs some damage to nerve-insulating myelin that occurs in MS, this repair is insufficient. One strategy under study is to stimulate the body’s own internal repair capabilities. With funding from the Hilton Foundation, NIH, the National MS Society and others, Moses Rodriguez, MD, and colleagues (Mayo Clinic Foundation) identified a human antibody – rHIgM22 – that targets and attaches to myelin-making cells. When given to mice with an experimental MS-like disease, rHIgM22 promotes myelin repair. This antibody was well tolerated in another phase I study (trial NCT01803867, as listed on clinicaltrials.gov) in 55 people with all types of MS. (Abstract #P4.339, Annual Meeting of the American Academy of Neurology 2015)

Eligibility and Details: Men and women between the ages of 18 and 70 with a diagnosis of MS are eligible. The study is enrolling participants with a clinical acute relapse; an MRI will be performed to confirm that there is an active lesion (damaged area). There are detailed exclusion criteria related to laboratory, cardiac, immune and other factors. For more information on these criteria, please use the contact information below.

Participants will remain on their current therapy throughout the study. Upon entering the study with an acute relapse, subjects will receive high-dose oral steroids for five days, a standard treatment for an acute relapse. Following completion of the oral steroids for the acute relapse the subjects will receive either a single dose of rHIgM22 or placebo.

Investigators are testing 2 dose levels. For each dose, 10 participants are being randomly assigned to receive active treatment (rHIgM22) and 5 are being randomly assigned to receive inactive placebo, both via a single intravenous infusion. Blood samples will be collected from participants before and at specified times for up to 48 hours after dosing, so participants must agree to remain in the hospital for that time. Participants are being followed for 180 days after dosing, which includes return visits to the clinic and MRI scans.

The primary outcome of the study is to determine the safety and tolerability of rHIgM22 in people with MS. Adverse events are being monitored throughout the study. The investigators will also evaluate how this experimental treatment is absorbed in the body, and how the immune and nervous systems react to it. Phase I studies are the first of three stages of clinical trials that determine whether an exploratory treatment is safe and beneficial.

Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact Kevin Cronin, Manager Corporate Communications, kcronin@acorda.com, 914-326-5279, or visit the trial’s listing on clinicaltrials.gov to find the site nearest you.

Sites are recruiting in the following cities:

Aurora, CO
Centennial, CO (Denver metro-area)
Dallas, TX
Indianapolis, IN
Long Beach, CA
Rochester, NY
Sacramento, CA
Saint Louis, MO
San Francisco, CA
Seattle, WA
Stanford, CA
Teaneck, NJ (NY metro area)

Download a brochure that discusses issues to think about when considering enrolling in an MS clinical trial (PDF).

Study reveals brain network responsible for cognitive changes in multiple sclerosis

An estimated 2.3 million individuals are living with multiple sclerosis (MS) worldwide. Approximately half of all individuals with MS experience changes in cognition such as impaired concentration, attention, memory, and judgment. The underlying brain basis for these deleterious effects has been largely elusive. New findings published yesterday in Neuropsychology reveal that decreased connectivity between network-specific brain regions are to blame for the central deficit common to the various cognitive changes associated with MS, slowed cognitive speed.
In the first study of its kind, researchers at the Center for BrainHealth at The University of Texas at Dallas and The University of Texas Southwestern Medical Center found that, compared to healthy controls, individuals with MS exhibit weaker brain connections between the dorsolateral prefrontal cortex and posterior brain regions. The change amounts to a breakdown in communication between the part of the brain responsible for executing goal-directed thought and action and the regions responsible for carrying out tasks related to cognitive speed such as visual processing, motor execution, and object recognition. The researchers believe that the diminished connections are likely the result of decreased white matter surrounding the neurons in the brain.

“Our study is the first to really zero in on the physiology of cognitive speed, the central cognitive deficit in MS,” explained Center for BrainHealth principal investigator Bart Rypma, Ph.D., who also holds the Meadows Foundation Chair at UT Dallas. “While white matter is essential to efficient network communication, white matter degradation is symptomatic of MS. This study really highlights how tightly coupled connectivity is to performance and illuminates the larger, emerging picture of white matter’s importance in human cognitive performance.”

Collaborating with Elliot Frohman, M.D., Ph.D., director of the Multiple Sclerosis Program and Clinical Center at UT Southwestern, the study recruited 29 participants with relapsing-remitting MS and 23 age- and sex- matched healthy controls. Participants underwent functional magnetic resonance imaging (fMRI) while completing a measure of cognitive processing speed. Participants were given 4 seconds to view a nine-item key of number and symbol pairs (for example ‘+’ above the number 3) and one number-symbol pair probe. Participants were asked to indicate with a left or right thumb button press whether or not the probe appeared in the key.

While accuracy was similar for both healthy controls and individuals with MS, response times for individuals with MS were much slower. Analysis of the fMRI data revealed that while completing this measure, MS patients showed weaker functional connections with dorsolateral prefrontal cortex.

“These findings reveal a diffuse pattern of disconnectivity with executive areas of the brain,” explained the study’s lead author, Nicholas Hubbard, a doctoral candidate at the Center for BrainHealth working with Dr. Rypma. “Importantly, these decreases in connectivity predicted MS-related cognitive slowing both in and out of the fMRI environment suggesting that these results were not specific to our task, but rather were able to generalize to other situations where cognitive speed is required.”

This research supports the need for therapies that target white matter structures and white matter proliferation. Rypma and Hubbard are currently conducting research to further explore the physiology of white matter to better understand cognitive speed reductions not only in MS, but also in healthy aging individuals.

New Discovery

Brain and central nervous system (Shutterstock)

Brain and central nervous system (Shutterstock)
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Researchers have discovered tiny vessels connecting the brain to the immune system – which could profoundly alter the treatment of autism, Alzheimer’s disease, and multiple sclerosis.
The team at the University of Virginia School of Medicine found the brain – like every other tissue – is connected to the immune system through lymphatic vessels, although these had never been detected despite a thorough mapping of the body.
“I really did not believe there are structures in the body that we are not aware of. I thought the body was mapped,” said Jonathan Kipnis, a neuroscience professor and director of the university’s Center for Brain Immunology and Glia. “I thought that these discoveries ended somewhere around the middle of the last century — but apparently they have not.”
The vessels are “well hidden” along a major blood vessel that travels down into the sinuses, the researchers said, and were discovered only after devising a new way to examine the membrane covering the brain on a single microscope slide.
Antoine Louveau, one of the researchers, noticed vessel-like patterns in the immune cells on his slides, and tests revealed they were lymphatic vessels.
“The first time these guys showed me the basic result, I just said one sentence: ‘They’ll have to change the textbooks,’” said Kevin Lee, chair of the university’s neuroscience department.
The discovery could radically alter the study and treatment of neurological diseases because brain diseases can now be understood mechanically instead of abstractly, researchers said.
“It changes entirely the way we perceive the neuro-immune interaction,” Kipnis said. “We always perceived it before as something esoteric that can’t be studied – but now we can ask mechanistic questions.”
For example, Kipnis said scientists already understand that Alzheimer’s disease is the result of protein accumulations in the brain, but the discovery suggests the lymphatic vessels – which change with age – simply don’t remove them efficiently enough.
The findings have been published in the journal Nature, and the researchers said they could radically alter the way scientists understand the central nervous system’s relationship with the immune system.

Writing Mom’s Story

I began writing the story in late 2007. Actually, I began the story in February 1978. Immediately after getting out of bed that February morning, I couldn’t stand. The room was whirling, my stomach was churning. I sat on the edge of t he bed until my head cleared a little and I could stand. I tried to dress, but wasn’t able to bend down without the room spinning again and the nausea returning. I made a doctor’s appointment. He couldn’t find anything and treated me with Dramamine for a mild middle ear inflammation. It cleared after about a week and I put the occurrence in the back of my mind. In August of the same year, I awoke one morning with a gray spot in the vision of my left eye. It enlarged over the morning. By afternoon, my vision in my left eye was limited to the extreme outer edges. Being Saturday, I went to the Emergency Room, convinced I was going blind. An Ophthalmologist happened to be on duty. He diagnosed the problem immediately as optic neuritis and prescribed prednisone. That cleared in about eight weeks.
Fast forward to 1989. I had been a “normal volunteer” at the National Institutes of Health for several years. I was asked if I would volunteer for an MRI. They said it’s easy if you’re not claustrophobic, no needles, only some noise. I said I would be glad to do it. They were right, lots of noise but no other discomforts. About a week later, a physician called to tell me that they found something strange on my brain. I went back to the physician and came away with a definite diagnosis of multiple sclerosis (MS). I launched a search for information, this being pre-internet, I went to libraries and contacted the National Multiple Sclerosis Society (www.nmss.org ).
By June of 2006 I had retired on disability from my position as a Science Librarian and worked from home as an editor and writer. I attended a meeting of the Outdoor Writers Association of America (www.owaa.org ). I was interested in writing for children by this time and I attended a session given by the renowned children’s author, Kathleen Kudlinski (www.kathleenkudlinski.com ). Her one piece of advice (among others) that I took away from her presentation was: “Write what you know.”
In October 2007, after spending over a year researching and learning about writing for children, I asked myself, “What do I know?” It came to me quickly, I know about MS. I have been interested in health issues and have read quite extensively, especially about plagues and infectious diseases. But also about MS, I have an extensive library about the disease and I have reviewed books on the subject for Library Journal.

Now in it’s second edition.

New Study Yields Clues to How Nervous System Damage Occurs in MS

Understanding the damage that occurs to the brain and spinal cord during multiple sclerosis is key to finding ways to stopping MS progression. A new study by researchers in Austria provides new clues to the type and extent of nervous system damage in MS, opening new paths for further exploration that could eventually lead to better treatments to stop MS in its tracks. Lukas Haider, MD, Josa Frischer, MD and colleagues (Medical University of Vienna) report their findings in the Journal of Neurology, Neurosurgery and Psychiatry (Published Online June 4, 2014). The study was supported by the Austrian Science Fund.

Background: MS involves immune system attacks to the brain and spinal cord. The “white matter” in the brain consists of nerve fibers, which transmit messages to, from, and throughout the brain, and myelin. Myelin, the fatty substance that surrounds and protects nerve fibers, is white in color and is a major target of the immune system in MS. The “gray matter” in the brain includes the nerve cells and several associated structures. Recent research suggests that the gray matter is also damaged by MS, may be damaged early in the disease process, and has been linked to cognitive symptoms and disease progression.

The Study: Dr. Haider’s team studied the distribution of lesions – areas of damage – in brain tissue obtained from 75 people with MS via autopsy, as well as 12 controls without MS. Using a series of sophisticated laboratory techniques, they found that damage to gray matter was most prominent in the area of the brain known as the “basal ganglia,” an area associated with motor abilities, learning, cognition, and emotion.

Both white and gray matter damage were found in people with all types of MS. The extent of gray matter damage was similar in people with all types of MS, but white matter damage was more extensive in people with progressive MS. These findings indicate that there are important differences in the mechanisms by which white and gray matter damage develops, and these differences are apparent as well when damage develops in different parts of the brain.

The team also found elevated levels of iron in gray matter lesions, which appears to be liberated from myelin-making cells during injury and which may mean that these levels play a role in nerve cell degeneration in MS. Iron has been implicated in amplifying oxidative injury (a process wherein “free radicals,” normal byproducts of bodily processes, cause tissue injury).

Conclusion: This study provides some new information on nervous system damage caused by MS. More research, which is currently underway by investigators worldwide, is needed to understand the timing of the damage and to determine how this knowledge can be translated to new approaches to stopping MS progression.

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