Posts Tagged ‘multiple sclerosis’


The Dr. Peter Stys lab within the Hotchkiss Brain Institute at the Cumming School of Medicine, University of Calgary, is equipped with highly specialized microscopes used for researching multiple sclerosis, Alzheimer’s and other neurodegenerative disease. In this customized lab, the researchers can’t wear white lab coats, they have to wear dark clothing. Photons could reflect off light clothing and interfere with the experiments. From left: Megan Morgan, research assistant, and Craig Brideau, engineering scientist. Photo by Pauline Zulueta, Cumming School of Medicine

By Kelly Johnston, Cumming School of Medicine

Ridiculous. That’s how Andrew Caprariello says his colleagues described his theory about multiple sclerosis (MS) back when he was doing his PhD in Ohio.

Caprariello’s passion to explore controversial new theories about MS propelled him to seek out a postdoctoral fellowship with a like-minded thinker, whom he found in University of Calgary’s Dr. Peter Stys, a member of the Hotchkiss Brain Institute at the Cumming School of Medicine (CSM).

The collaboration paid off. Caprariello, Stys and their colleagues have scientific proof published in the Proceedings of the National Academy of Sciences (PNAS) that their somewhat radical theory has merit. “I’ve always wondered ‘what if’ MS starts in the brain and the immune attacks are a consequence of the brain damage,” says Caprariello, PhD, and lead author on the study.

Currently, MS is considered to be a progressive autoimmune disease. Brain inflammation happens when the body’s immune system attacks a protective material around nerve fibers in the brain called myelin. Conventional thinking is that rogue immune cells initially enter the brain and cause myelin damage that starts MS.

“In the field, the controversy about what starts MS has been brewing for more than a decade. In medical school, I was taught years ago that the immune attack initiates the disease. End of story,” says Stys, a neurologist and professor in the Department of Clinical Neurosciences at the CSM. “However, our findings show there may be something happening deeper and earlier that damages the myelin and then later triggers the immune attacks.”

To test the theory, the research team designed a mouse model of MS that begins with a mild myelin injury. In this way, researchers could mirror what they believe to be the earliest stages of the disease.

“Our experiments show, at least in this animal model, that a subtle early biochemical injury to myelin secondarily triggers an immune response that leads to additional damage due to inflammation. It looks very much like an MS plaque on MRI and tissue examination,” says Stys. “This does not prove that human MS advances in the same way, but provides compelling evidence that MS could also begin this way.”

With that result, the researchers started to investigate treatments to stop the degeneration of the myelin to see if that could reduce, or stop, the secondary autoimmune response.

“We collaborated with researchers at the University of Toronto and found that by targeting a treatment that would protect the myelin to stop the deterioration, the immune attack stopped and the inflammation in the brain never occurred,” says Stys. “This research opens a whole new line of thinking about this disease. Most of the science and treatment for MS has been targeted at the immune system, and while anti-inflammatory medications can be very effective, they have very limited benefit in the later progressive stages of the disease when most disability happens.”

It can be very hard to find funding to investigate an unconventional theory. The research team was funded by the Brain and Mental Health Strategic Research Fund, established by the Office of the Vice-President (Research) at UCalgary to support innovative, interdisciplinary studies within the Brain and Mental Health research strategy.

“We chose high-risk, novel projects for these funds to support discoveries by teams who did not have the chance to work together through conventional funding sources,” said Ed McCauley, PhD, vice-president (research). “The MS study shows the potential of brain and mental health scholars to expand capacity by tapping into new approaches for conducting research. Their work also exemplifies the type of interdisciplinary research that is propelling the University of Calgary as an international leader in brain and mental health research.”

http://www.ucalgary.ca/utoday/issue/2018-05-04/ucalgary-scientists-discover-new-way-battle-multiple-sclerosis

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A single genetic mutation may increase a person’s risk of developing a rare, severe form of multiple sclerosis (MS) by roughly 60 percent, according to a study published recently in the journal Neuron.

That’s an unusually straightforward result for a complex disease like MS, which has previously been traced to hundreds of mutations that each increases the risk of developing the disease only slightly.

“That’s why our finding is unprecedented,” Carles Vilariño-Güell, Ph.D., an assistant professor of medical genetics at The University of British Columbia and one of the paper’s senior authors, told Healthline.

His team found the mutation by combing through a database of Canadians with MS who had donated blood samples as part of the Canadian Collaborative Project on Genetic Susceptibility to MS.

Some of these samples belonged to a family that was disproportionately diagnosed with the disease. Four first cousins and two parents developed MS.

The team isolated a common mutation from their DNA, and looked for that mutation in other individuals in the database.

That’s how they found a second family similarly afflicted. Three first cousins and two parents were diagnosed with MS.

Having so many cases of MS within a family is rare. The disease is not considered truly heritable, although a person’s risk does increase if a parent or sibling has the disease.

The families shared another rare trait. Most had the more severe version of the disease known as primary progressive MS, which makes up 10 to 15 percent of all MS cases.

Treatments for primary progressive MS have so far eluded scientists, although there are promising clinical trials underway of a drug called Ocrelizumab.


Future Research

The study found the mutation only in a handful of people, all of whom were diagnosed with a rare form of the disease.

Therefore, the researchers don’t suggest they have found the genetic basis of MS.

But they do think they’ve discovered a way to study how the disease progresses in the body and what drugs could be developed to slow or even stop it

Bruce Bebo, Ph.D., vice president of research at the National Multiple Sclerosis Society, agrees.

“Studying the genetics of a very rare form that is inherited can give us clues about pathways involved in MS in the general population,” he told Healthline.

The mutation appears to disable a regulatory gene called NR1H3, which codes for a protein that helps regulate the inflammation and the metabolism of lipids.

The researchers now plan to engineer a similar mutation in mice so they can study the outcome of a disabled NR1H3 gene and test potential new drugs in an animal model.

And because the NR1H3 pathway has already been implicated in diseases like atherosclerosis and heart disease, there are already drugs in clinical trials for safety that could be repurposed for treating MS, Vilariño-Güell said.

“Understanding the genetics of MS could help us get closer to individualizing therapy to people for better outcomes,” Bebo said.

Getting Personal with Treatment

People with a disease like MS, which appears in so many different ways and can be linked to so many different genetic components, could benefit by personalized medicine.

If the mechanism of each disease causing mutation or group of mutations is pinpointed, scientists could potentially design more effective, targeted treatments rather than the standard one-size-fits-all therapies.

That means tracking down the many different genetic hotspots that are linked to MS.

Overall, genetic predisposition accounts for only about a third of a person’s risk of developing the disease, Bebo said. Within that category only about half the genes responsible can be identified.

Researchers don’t know where the other half of that genetic risk comes from, Bebo said, but it makes sense that it would include rare mutations like this one that help explain risk in a small fraction of MS patients.

And there could be many different versions of these mutations.

“Odds are if you look at a different family the genetic risk would probably be something different than this,” Bebo said.

Speeding Through the Genome

The Canadian database has been available since the late 1990s, but only recently has the team had access to exome sequencing, a powerful, efficient tool that makes searching for tiny genetic changes easier.

This technique sequences only the DNA that codes for proteins — leaving the other 98 percent behind. It’s like speed reading the genome.

Exome sequencing has been particularly helpful for finding so-called “Mendelian” diseases — diseases that can be traced to a single, heritable mutation just like Gregor Mendel’s purple and white pea flowers. Cystic fibrosis and sickle cell anemia are two examples of these diseases.

With this discovery, the researchers say that have found a Mendelian form of MS.

That doesn’t mean the discovery won’t be beneficial for the 85 percent of people diagnosed with relapsing remitting MS. In many of those patients, the disease eventually changes course and becomes progressive.

Whatever is learned about primary progressive MS — a condition that doesn’t respond to treatments for other types of MS — could also potentially help those with secondary progressive MS, the researchers say.

http://www.healthline.com/health-news/form-of-ms-could-be-caused-by-single-genetic-mutation#5


Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two.

A pioneering new stem cell treatment is reversing and then halting the potentially crippling effects of multiple sclerosis.

Patients embarking on a ground-breaking trial of the new treatment have found they can walk again and that the disease even appears to be stopped in its tracks.

Holly Drewry, 25, from Sheffield, was wheelchair bound after the birth of her daughter Isla, now two. But Miss Drewry claims the new treatment has transformed her life.

She told the BBC’s Panorama programme: “I couldn’t walk steadily. I couldn’t trust myself holding her (Isla) in case I fell. Being a new mum I wanted to do it all properly but my MS was stopping me from doing it.

“It is scary because you think, when is it going to end?”

The treatment is being carried out at Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London and involves use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient’s own blood.

Miss Drewry had the treatment in Sheffield. She said: “I started seeing changes within days of the stem cells being put in.

“I walked out of the hospital. I walked into my house and hugged Isla. I cried and cried. It was a bit overwhelming. It was a miracle.”

Her treatment has now been reviewed and her condition found to have been dramatically halted. She will need to be monitored for years but the hope is that her transplant will be a permanent fix.

She is now planning to get married.

For other patients, the results have been equally dramatic. Steven Storey was a marathon runner and triathlete before he was struck down with the disease and left completely paralysed: “I couldn’t flicker a muscle,” he said.

But within nine days of the treatment he could move his toe and after 10 months managed a mile-long swim in the Lake District. He has also managed to ride a bike and walk again.

“It was great. I felt I was back,” he said.

Mr Storey celebrated his first transplant birthday with his daughters. His treatment has been reviewed and, like Miss Drewry, there was no evidence of active disease.

The treatment – which effectively ‘reboots’ the immune systems – is the first to reverse the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.

Stem cells are so effective because they can become any cell in the body based on their environment.

Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.

Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, said: “Since we started treating patients three years ago, some of the results we have seen have been miraculous.

“This is not a word I would use lightly, but we have seen profound neurological improvements.”

During the treatment, the patient’s stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.

The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.

Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.

However specialists warn that patients need to be fit to benefit from the new treatment.

The research has been published in the Journal of the American Medical Association.

http://www.telegraph.co.uk/news/health/news/12104774/Miraculous-results-from-new-MS-treatment.html

Thanks to Steve Weihing for bringing this to the It’s Interesting community.

Coffee lovers may live longer than those who don’t imbibe — with lower risks of early death from heart disease and neurological conditions such as Parkinson’s disease, a large U.S. study finds.

Researchers said the study, published online Nov. 16 in Circulation, adds to a large body of evidence on the good side of coffee.

People often think of coffee-drinking as a bad habit that they need to break, said study leader Dr. Frank Hu, a professor of nutrition and epidemiology at Harvard School of Public Health in Boston.

But, Hu said, many studies have linked moderate coffee intake to lower risks of developing various diseases — from heart disease and diabetes, to liver cancer, to neurological diseases such as Parkinson’s, multiple sclerosis and Alzheimer’s.

His team’s study, funded by the U.S. National Institutes of Health, adds another layer of evidence. It found that coffee drinkers were not only less likely to develop certain diseases — they also tended to live longer.

Over 30 years, nonsmokers who drank three to five cups of coffee a day were 15 percent less likely to die of any cause, versus nondrinkers. Specifically, they had lower rates of death from heart disease, stroke, neurological conditions and suicide.

Both regular coffee and decaf were linked to longer survival, the study found.

None of that proves coffee, itself, extends people’s lives or directly protects against certain diseases, Hu said. Other factors might explain the connection.

But, Hu added, his team did account for many of those factors. And the coffee benefit remained.

The findings are based on more than 200,000 U.S. doctors, nurses and other health professionals who were surveyed repeatedly over almost three decades. During that time, almost 32,000 study participants died.

It turned out that people who drank one to five cups of coffee at the outset had lower odds of dying during the study period when other lifestyle habits and certain health problems, such as high blood pressure and diabetes, were taken into account.

The relationship grew stronger when the researchers looked only at nonsmokers: Those who drank three to five cups of coffee a day were 15 percent less likely to die during the study period, compared with adults who didn’t drink coffee. Lower risks were even seen among the heaviest coffee drinkers (more than five cups a day), who had a 12 percent lower death risk than nondrinkers.

“The body of evidence does suggest coffee can fit into a healthy lifestyle,” Hu said.

That evidence, Hu noted, has already been incorporated into the latest U.S. dietary guidelines, which say that a healthy diet can include up to three to five cups of coffee a day.

But overall lifestyle is key, Hu said. That is, there’s a difference between a person who gets little sleep, then uses coffee to function during the day, and a person who sleeps well, exercises, and eats a balanced diet that includes some coffee.

Alice Lichtenstein, a spokesperson for the American Heart Association, agreed.

“This doesn’t mean you should start drinking coffee in the hopes of getting health benefits,” said Lichtenstein, who is also a professor of nutrition science and policy at Tufts University in Boston.

But, she added, the new findings build on years of evidence that coffee is not the bad guy many believe it is. “There’s this lingering idea that coffee must be bad for you because it’s enjoyable,” Lichtenstein said. “It’s almost like we’ve been trying to find something wrong with it.”

There are caveats, though. “You do need to be careful about what you’re putting in your coffee,” Lichtenstein pointed out. Some milk is fine, she said, but watch the sugar and heavy cream.

And why would coffee be related to health benefits? It’s not clear from this study, Hu said, but other research has suggested that compounds in coffee can reduce inflammation, act as antioxidants, and improve blood sugar regulation, among other things.

Also, when it comes to some neurological conditions, such as Parkinson’s disease, Hu said, there’s evidence that caffeine offers benefits.

SOURCES: Frank Hu, M.D., Ph.D., professor, nutrition and epidemiology, Harvard School of Public Health, Boston; Alice Lichtenstein, D.Sc., professor, nutrition science and policy, Tufts University, Boston; Nov. 16, 2015, Circulation, online

Read more at http://www.philly.com/philly/health/HealthDay705311_20151116_Coffee_Drinkers_May_Live_Longer.html#rPogcDb2tVXwEFwz.99

brain

The many documented cases of strange delusions and neurological syndromes can offer a window into how bizarre the brain can be.

It may seem that hallucinations are random images that appear to some individuals, or that delusions are thoughts that arise without purpose. However, in some cases, a specific brain pathway may create a particular image or delusion, and different people may experience the same hallucination.

In recent decades, with advances in brain science, researchers have started to unravel the causes of some of these conditions, while others have remained a mystery.

Here is a look at seven odd hallucinations, which show that anything is possible when the brain takes a break from reality.

1. Alice-in-Wonderland syndrome
This neurological syndrome is characterized by bizarre, distorted perceptions of time and space, similar to what Alice experienced in Lewis Carroll’s “Alice’s Adventures in Wonderland.”

Patients with Alice-in-Wonderland syndrome describe seeing objects or parts of their bodies as smaller or bigger than their actual sizes, or in an altered shape. These individuals may also perceive time differently.

The rare syndrome seems to be caused by some viral infections, epilepsy, migraine headaches and brain tumors. Studies have also suggested that abnormal activity in parts of the visual cortex that handle information about the shape and size of objects might cause the hallucinations.

It’s also been suggested that Carroll himself experienced the condition during migraine headaches and used them as inspiration for writing the tale of Alice’s strange dream.

English psychiatrist John Todd first described the condition in an article published in the Canadian Medical Association Journal in 1955, and that’s why the condition is also called Todd’s syndrome. However, an earlier reference to the condition appears in a 1952 article by American neurologist Caro Lippman. The doctor describes a patient who reported feeling short and wide as she walked, and referenced “Alice’s Adventures in Wonderland” to explain her body image illusions.

2. Walking Corpse Syndrome
This delusion, also called Cotard’s Syndrome, is a rare mental illness in which patients believe they are dead, are dying or have lost their internal organs.

French neurologist Jules Cotard first described the condition in 1880, finding it in a woman who had depression and also symptoms of psychosis. The patient believed she didn’t have a brain or intestines, and didn’t need to eat. She died of starvation.

Other cases of Cotard’s syndrome have been reported in people with a range of psychiatric and neurological problems, including schizophrenia, traumatic brain injury and multiple sclerosis.

In a recent case report of Cotard’s syndrome, researchers described a previously healthy 73-year-old woman who went to the emergency room insisting that she was “going to die and going to hell.” Eventually, doctors found the patient had bleeding in her brain due to a stroke. After she received treatment in the hospital, her delusion resolved within a week, according to the report published in January 2014 in the journal of Neuropsychiatry.

3. Charles Bonnet syndrome
People who have lost their sight may develop Charles Bonnet syndrome, which involves having vivid, complex visual hallucinations of things that aren’t really there.

People with this syndrome usually hallucinate people’s faces, cartoons, colored patterns and objects. It is thought the condition occurs because the brain’s visual system is no longer receiving visual information from the eye or part of the retina, and begins making up its own images.

Charles Bonnet syndrome occurs in between 10 and 40% of older adults who have significant vision loss, according to studies.

4. Clinical lycanthropy
In this extremely rare psychiatric condition, patients believe they are turning into wolves or other animals. They may perceive their own bodies differently, and insist they are growing the fur, sharp teeth and claws of a wolf.

Cases have also been reported of people with delusional beliefs about turning into dogs, pigs, frogs and snakes.

The condition usually occurs in combination with another disorder, such as schizophrenia, bipolar disorder or severe depression, according to a review study published in the March issue of the journal History of Psychiatry in 2014.

5. Capgras delusion
Patients with Capgras delusion believe that an imposter has replaced a person they feel close to, such as a friend or spouse. The delusion has been reported in patients with schizophrenia, Alzheimer’s disease, advanced Parkinson’s disease, dementia and brain lesions.

One brain imaging study suggested the condition may involve reduced neural activity in the brain system that processes information about faces and emotional responses.

6. Othello syndrome
Named after Shakespeare’s character, Othello syndrome involves a paranoid belief that the sufferer’s partner is cheating. People with this condition experience strong obsessive thoughts and may show aggression and violence.

In one recent case report, doctors described a 46-year-old married man in the African country Burkina Faso who had a stroke, which left him unable to communicate and paralyzed in half of his body. The patient gradually recovered from his paralysis and speaking problems, but developed a persistent delusional jealousy and aggression toward his wife, accusing her of cheating with an unidentified man.

7. Ekbom’s syndrome
Patients with Ekbom’s syndrome, also known as delusional parasitosis or delusional infestations, strongly believe they are infested with parasites that are crawling under their skin. Patients report sensations of itching and being bitten, and sometimes, in an effort to get rid of the pathogens, they may hurt themselves, which can result in wounds and actual infections.

It’s unknown what causes these delusions, but studies have linked the condition with structural changes in the brain, and some patients have improved when treated with antipsychotic medications.

http://www.livescience.com/46477-oddest-hallucinations.html