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multiple sclerosis

Author Janet Werner, left, and artist Kyle Horne display their finished book, ‘A Pear in an Apple Tree: A Journey with Multiple Sclerosis.’ Photo courtesy Kyle Horne

One of TBR News Media’s very own recently embarked on a life-changing collaboration with a former educator. 

Kyle Horne, a local artist and frequent contributor of political cartoons and editorial illustrations to our newspapers, has partnered with his former teacher, Janet Werner, to create a book about multiple sclerosis. Together, they tell a moving story of overcoming adversity, revealing a powerful, enduring bond between a student and teacher.

A journey with MS

Werner was diagnosed with multiple sclerosis, commonly known as MS, in 1986. At the onset of her symptoms, she recalled a feeling of numbness in her legs and overwhelming fatigue.

“I actually took off for two weeks from work that first year and just slept,” she said. “I got an MRI at the time, and it showed plaque in the brain, which is white lesions. Depending upon where these white lesions are seen in the brain, it could affect your mobility, cognition and eyesight.”

As the years advanced, Werner’s symptoms gradually progressed. During a startling incident one morning, she temporarily lost her eyesight and hearing completely. “What seemed like hours was about 20 minutes,” she said. “I was terrified because it had never happened before.”

Nearly four decades after her initial diagnosis, Werner explained she is “doing pretty well” despite the heightening symptoms with each passing year. She said managing the symptoms requires plenty of rest and an upbeat mentality.

With husband Ernest, “we try to get some exercise, eat correctly and just keep a positive frame of mind,” she said. “Of course, life is very stressful but we try to be positive.”

‘A Pear in an Apple Tree’

Over several years, Werner wrote “A Pear in an Apple Tree: A Journey with Multiple Sclerosis,” saying she was motivated to write the book for various reasons. 

Among them, she noted a lack of public understanding surrounding MS and its symptoms. She also wanted to share her story with those experiencing MS, preparing them for the path ahead and informing them that they are not alone.

“Sometimes with any challenge in your life, you feel like you’re the only one who has this specific condition or challenge, whether it’s MS or cancer and you kind of hide away from the rest of the world,” she said. “That’s not good to do that. I wanted the ‘MSers’ to feel that we’re in this together.”

Werner recalled the moment that gave the book its name. She said she was eating dinner with her husband, struggling with her symptoms that day, when she blurted out, “I feel like a pear in an apple tree, kind of out of place.”

Despite the numerous challenges through the years, Werner said she wrote the book to let others know they have a place with an MS community that also understands their struggles.

A dynamic team

‘You have to educate yourself about the disease and how it affects your body. And then learn to adapt.’

— Janet Werner

The collaboration between Werner and Horne has been decades in the making. A graduate of Deer Park High School, Horne was her student and a member of the school’s Students Against Destructive Decisions Club, which Werner had advised.

“He would invite me to some of his book signings and art shows, and we kept in close contact over the years,” she said. “When I was doing this book, I immediately thought of him because I loved his artwork.”

Horne described the early stages of preparing the book with his former teacher. He was eager to sign onto the project. 

“She came to me with this idea for a book dealing with MS and how it affects her,” Horne said. Although managing symptoms “can be difficult, those challenges have been very helpful in developing her into the person she is today.”

Along with the cover and back cover, Horne prepared several illustrations throughout the book, tying into the themes of each of its chapters. Together, Werner and Horne developed the characters of Ned and Nancy Neuron.

Through the illustrations he prepared for the book, Horne said he learned much about Werner and her experiences with MS, describing a sense of growth and mutual understanding forged throughout their creative journey together.

“I don’t have MS, but I’m able to sympathize more with Janet and the struggles that she’s had,” the artist said. “She has a very strong spirit when it comes to this.”

An optimistic future

Following the success of their first collaboration, Werner and Horne are already working on the next project, a coloring book that adds an interactive component to the story of Ned and Nancy Neuron.

Werner said she remains “very hopeful” that researchers will soon discover a cure for MS. Analyzing the scope of scientific investigation into the condition, she said there is considerable overlap between ongoing MS research and similar autoimmune diseases.

“Research that’s being conducted for, say, AIDS or lupus is also being conducted for MS,” she said. “Stony Brook [University] has an MS center, and their research is going on at a rapid rate. So I am so hopeful.”

Despite the decades she has spent with MS, Werner shares a message of resolve in the face of hardship.

“I think you have to keep fighting,” she said. “You cannot give up. If you’re faced with a challenge, you have to educate yourself about the disease and how it affects your body. And then learn to adapt.”

Horne said the collaboration with Werner has been a personal experience as well. Learning about MS, he said, has informed his outlook on his own life.

“I have a condition known as ulcerative colitis, also known as Crohn’s disease,” Horne said. “Understanding the perspective of another chronic illness, and from a different person, has come to help with my own process and working through my own things.”

He added, “When it comes to something like this it can be very scary at times, but it also can be very rewarding knowing the perseverance of getting through a struggle like that.”

To learn more about MS, visit www.nationalmssociety.org. To purchase “A Pear in an Apple Tree,” visit www.allbook-books.com.

Maurizio Del Poeta. File photo from SBU

By Daniel Dunaief

Sometimes, fixing one problem creates another.

People with multiple sclerosis have been taking a medication called fingolimod for a few years. The medicine calms immune systems that attack the myelin around nerve cells. Fingolimid decreases the lymphocyte number in the bloodstream by trapping them in the lymph nodes.

In a few cases, however, the drug can reduce the immune system enough that it allows opportunistic infections to develop. Cryptococcosis, which is a fungal infection often spread through the inhalation of bird droppings or from specific trees such as eucalyptus, is one of these infections, and it can be fatal if it’s not caught or treated properly, especially for people who have weakened immune systems.

Swiss pharmaceutical giant Novartis contacted Stony Brook University fungal expert Maurizio Del Poeta, a professor in the Department of Molecular Genetics & Microbiology, to understand how this drug opens the door to this opportunistic and problematic infection. He is also exploring other forms of this drug to determine if tweaking it can allow the benefits without opening the door to problematic infections.

Most of the human population has been exposed to this fungus. In a study in the Bronx, over 75 percent of children older than 2 years of age had developed an antibody against Cryptococcus neoformans, which means they have been exposed to it. It is unknown whether these people harbor the fungus or if they have just mounted an immune reaction. Exposure may be continuous, but infections may only occur if a person is immunocompromised.

Fingolimid “inhibits a type of immunity” that involves the movement of lymphocytes from organs into the bloodstream,” Del Poeta said. “Because of this, there are certain infections that can develop.”

Through a spokeswoman, Novartis explained that the company was “happy to have started a scientific collaboration” with Del Poeta to understand the role of a specific pathway in cryptococcus infections.

Cryptococcal meningitis is one of several infections that can develop. Others include herpes meningitis and disseminated varicella zoster. Before starting fingolimid, patients need to receive immunization for varicella zoster virus. At this point, doctors do not have a vaccine for cryptococcosis.

To study the way this drug and its derivatives work, Del Poeta recently received a $2.5 million grant over a five-year period from the National Institutes of Health.

Yusuf Hannun, the director of the Cancer Center at SBU, was confident Del Poeta would continue to be successful in his ongoing research.

Del Poeta “does very important and innovative work on fungal pathogenesis and he is a leader in the field,” Hannun wrote in an email. “His work will enhance our understanding of the molecular mechanisms.”

Fingolimid mimics a natural lipid. Years ago, Del Poeta showed that this sphingolipid, which is on the external surface of the membrane, is important to contain cryptococcosis in the lung. If its level decreases, the fungus can move from the lung to the brain.

While people with multiple sclerosis have developed signs of this infection, it is also prevalent in areas like sub-Saharan Africa, where people with AIDS battle cryptococcosis. About 40 percent of this HIV population develops this fungal infection, Del Poeta said. About 500,000 people die of cryptococcosis every year.

In certain areas of the United States, such as the Pacific Northwest, this fungus is also endemic. On Vancouver Island, about 19 people died from Cryptococcus gattii infections between 1999 and 2007. Most of those patients were immunocompromised.

When the fungus migrates from the lung to the brain, it is “very difficult, if not impossible in most cases, to eradicate,” Del Poeta explained in an email. If the diagnosis is made early enough before the infection spreads to the brain, the recovery rate is high, he suggested. In people whose immune systems are not compromised by drugs or disease, “death is rare.” 

Del Poeta plans to study the interaction between the drug and the fungal infection through a mouse model of the disease. The mouse model mimics the human disease and will provide insights on how to control the infection, particularly when the fungus reaches the brain.

Some of the derivatives Novartis has developed do not cause a fungal infection. Del Poeta is working with Novartis to study other forms of fingolimid that do not reactivate cryptococcosis. Del Poeta said Novartis is currently in Phase III clinical trials for another drug for multiple sclerosis. The new drug acts on a different receptor.

“We think the reason the fingolimid reactivates cryptococcosis is that it is blocking one receptor, which is important for the containment” of the fungus. The other drug doesn’t allow the disease-bearing agent to escape.

“This is a hypothesis,” Del Poeta said. He is waiting to corroborate the cell culture data in animal models.

Del Poeta has been working with Novartis for over three years. The Stony Brook scientist used some preliminary studies on the way fingolimid analogs behave as part of the research grant application to the NIH that led to the current grant.

Del Poeta said he is excited about the possibility of contributing to this area.

“Not only will this work contribute to the field of MS, but it will also have a contribution to the field of cryptococcosis,” he said. “This will have important implications for MS patients [and] for the entire HIV population.” He said he believes patients may have some other defect. If he is able to discover what that is, he may be able to protect them from a cryptococcosis infection.

Ultimately, Del Poeta hopes this work leads to a broader understanding of fungal infections that could apply to other pathogens as well.

Mycobacterium tuberculosis causes a granuloma very similar to the one caused by the cryptococcosis and we could potentially study whether the same molecular mechanisms involved in the control of the infection in the lung are similar between the two infections,” he explained in an email.

In Europe, lipoic acid is classified as a drug, unlike in the United States, where it is a supplement.
Lipoic acid may have a significant effect on multiple chronic diseases

By David Dunaief, M.D.

Lipoic acid, also known as alpha lipoic acid and thioctic acid, is a noteworthy supplement. I am not a big believer in lots of supplements for several reasons: Diet contributes thousands more nutrients that work symbiotically; in the United States, supplements are not regulated by the FDA, thus there is no official oversight; and research tends to be scant and not well-controlled.

Dr. David Dunaief

So why would I write about lipoic acid? It is a supplement that has scientific data available from randomized controlled trials, which are the gold standard of studies. In Europe, lipoic acid is classified as a drug, unlike the United States, where it is a supplement (1).

Lipoic acid is an antioxidant, helping to prevent free radical damage to cells and tissues, but also is a chelating agent, potentially removing heavy metals from the body. Lipoic acid is involved in generating energy for cells; it is an important cofactor for the mitochondria, the cell’s powerhouse. It may also boost glutathione production, a powerful antioxidant in the liver (1). We produce small amounts of lipoic acid in our bodies naturally. Lipoic acid may be important in chronic diseases, including Alzheimer’s, multiple sclerosis and diabetic peripheral neuropathy. Let’s look at the evidence.

Diabetic peripheral neuropathy

Diabetic peripheral neuropathy, or diabetic neuropathy, involves oxidative stress and occurs in up to half the population with diabetes. One in five patients, when diagnosed, will already have peripheral neuropathy. The most common type is distal symmetric polyneuropathy — damage to nerves on both sides of the body in similar locations. It causes burning pain, numbness, weakness and pins and needles in the extremities (2).

The best studies with lipoic acid focus on peripheral neuropathy with diabetes. In a double-blinded, randomized controlled trial (SYDNEY I), results showed that the total treatment score had improved significantly more for those receiving 600 mg lipoic acid by intravenous therapy compared to the placebo group (3). Also, individual symptoms of numbness, burning pain and prickling significantly improved in the group treated with lipoic acid compared to placebo.

The study involved 120 diabetes patients with stage 2 neuropathy. Its weakness was its duration; it was a very short trial, about three weeks. The author concluded that this therapy would be a good adjunct for those suffering diabetic neuropathy.

In a follow-up to this study (SYDNEY II), the design and the results were the same (4). In other words, in a second double-blinded, placebo-controlled trial, the lipoic acid treatment group showed significantly better results than the placebo group. There were 180 patients with a similarly short duration of five weeks.

Why include this study? There were several important differences. One was that lipoic acid was given in oral supplements, rather than intravenously. Thus, this is a more practical approach. Another difference is that there were three doses tested for lipoic acid: 600, 1,200 and 1,800 mg. Interestingly, all of them had similar efficacy. However, the higher doses had more side effects of nausea, vomiting and vertigo, again without increased effectiveness. This suggests that an oral dose of 600 mg lipoic acid may help treat diabetic peripheral neuropathy.

Dementia and Alzheimer’s

In a recent randomized, placebo-controlled trial involving Alzheimer’s patients, results were significantly better for lipoic acid (600-mg oral dose) in combination with fish oil, compared to fish oil alone or to placebo (5). The amount of fish oil used was 3 grams daily containing 675 mg docosahexaenoic acid and 975 mg eicosapentaenoic acid of the triglyceride formulation.

The duration of this pilot study was 12 months with 39 patients, and the primary end point was a change in an oxidative stress biomarker, which did not show statistical significance. However, and very importantly, the secondary end point was significant: slowing the progression of cognitive and functional decline with the combination of fish oil and lipoic acid. Minimental status and instrumental activities of daily living declined less in the combination treatment group. This was encouraging, although we need larger trials.

However, another study showed 900 mg lipoic acid in combination with 800 IU daily of vitamin E (alpha tocopherol strain) and 500 mg vitamin C actually mildly reduced an oxidative stress biomarker but had a negative impact on Alzheimer’s disease by increasing cognitive decline on a minimental status exam (6). What we don’t know is whether the combination of supplements in this study produced the disappointing effects or if an individual supplement was the cause. It is unclear since the supplements were tested in combination. The study duration was 16 weeks and involved 78 moderate to severe Alzheimer’s patients.

Multiple sclerosis

In a study involving rats, giving them high doses of lipoic acid resulted in slowing of the progression of multiple sclerosis-type disease (7). The mechanism by which this may have occurred involved blocking the number of inflammatory white blood cells allowed to enter the cerebrospinal fluid in the brain and spinal cord by reducing the enzymatic activity of factors such as matrix metalloproteinases.

I know this sounds confusing, but the important point is that this may relate to a human trial with 30 patients that showed reduction in the enzyme MMP (8). Thus, it could potentially slow the progression of multiple sclerosis. This is purely connecting the dots. We need a large-scale trial that looks at clinical outcomes of progression in MS, not just enzyme levels. The oral dose used in this study was 1,200 to 2,400 mg lipoic acid per day.

Interestingly, the 1,200-mg dose used in the human trial was comparable to the high dose that showed slowed progression in the rat study (9). This only whets the appetite and suggests potential. So, we have lots of data. What do we know? In diabetic neuropathy, 600 mg oral lipoic acid may be beneficial. However, in Alzheimer’s the jury is still out, although 600 mg lipoic acid in combination with fish oil has potential to slow the cognitive decline in Alzheimer’s disease. It also may have a role in multiple sclerosis with an oral dose of 1,200 mg, though this is early data.

Always discuss the options with your physician before taking a supplement; in the wrong combinations and doses, supplements potentially may be harmful. The good news is that it has a relatively clean safety profile. If you do take lipoic acid, know that food interferes with its absorption, so it should be taken on an empty stomach (1).

References: (1) lpi.oregonstate.edu. (2) emedicine.medscape.com. (3) Diabetes Care. 2003;26:770-776. (4) Diabetes Care. 2006;29:2365-2370. (5) J Alzheimer’s Dis. 2014;38:111-120. (6) Arch Neurol. 2012;69:836-841. (7) J Neuroimmunol. 2002;131:104-114. (8) Mult Scler. 2005;11:159-165. (9) Mult Scler. 2010;16:387-397.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.

Vitamin D levels may play an important role in the treatment of multiple sclerosis.

By David Dunaief, M.D.

David Dunaief, M.D.
David Dunaief, M.D.

Medicine has made great strides in the treatment of multiple sclerosis over the last few decades. Multiple sclerosis (MS) is an autoimmune disease where there is underlying inflammation and the immune system attacks its own tissue. This causes demyelination, or breakdown of the myelin sheath, a protective covering on the nerves in the central nervous system (CNS). The result is a number of debilitating effects, such as cognitive impairment, numbness and weakness in the limbs, fatigue, memory problems, inflammation of the optic nerve causing vision loss and eye pain (optic neuritis) and mobility difficulties.

There are several forms of MS. The two most common are relapsing-remitting and primary-progressive. Relapsing-remitting has intermittent flare-ups and occurs about 85 to 90 percent of the time. Primary-progressive (steady) occurs about 10 percent of the time. Relapsing-remitting may eventually become secondary-progressive MS, which is much harder to control, although dietary factors may play a role.

Diagnosis and progression

MS is diagnosed in several ways. The ophthalmologist may be the first to diagnose the disease with a retinal exam (looking at the back of the eye). If you have eye pain or sudden vision loss in one eye, it is important to see your ophthalmologist. Another tool in diagnosis is an MRI of the CNS. This looks for lesions caused by the breakdown of the myelin sheath. The MRI can also be used to determine the risk of progression from a solitary CNS lesion to a full-blown MS diagnosis. This is accomplished by examining the corpus callosum, a structure deep within the brain, according to a presentation at the European Neurologic Society (1). Approximately half of patients with one isolated lesion will progress to clinically definite MS within six years. An MRI may be able to predict changes in this portion of the brain within two years. Patients with a family history of MS should discuss this diagnostic with a neurologist.


Interferon beta is the mainstay of treatment for MS for good reason. Data shows that it reduces recurrence in relapsing-remitting MS and also the number of brain lesions.However, in a study, interferon beta failed to stop the progression to disability in the long term (2). Many MS patients will experience disability over 20 years. Ultimately, what does this mean? Patients should continue therapy; however, they should have realistic expectations. This study was retrospective, looking back at previously collected data — not the strongest of studies.

In an RCT, higher levels of vitamin D in the blood showed a trend toward reduced disability in timed tandem walking and in disability accumulation.

Vitamin D impact

Vitamin D may play a key role in reducing flare-ups in relapsing-remitting MS. There have been several studies that showed this benefit with vitamin D supplements and/or with interferon beta. In one study, interferon beta had very interesting results showing that it may help increase the absorption of vitamin D from the sun (3). This was a randomized controlled trial (RCT), the gold standard of studies, involving 178 patients. The study’s authors suggest that interferon beta’s effectiveness at reducing the frequency of relapsing-remitting MS flare-ups may have to do with its effect on the metabolizing of vitamin D. In those who did not have higher blood levels of vitamin D, interferon beta actually increased the risk of flare-ups.

Physicians should monitor blood levels of vitamin D to make sure they are adequate. It may be beneficial for MS patients to get 15 to 20 minutes of sun exposure without sunscreen per day. However, patients with a history of high risk of skin cancer should not be in the sun without protective clothing and sunscreen.

In a prospective (forward-looking) observational study, patients with higher levels of vitamin D, even in those without interferon beta treatment, had reduced risk of relapsing-remitting MS flare-ups (4). The patients with higher levels had 40 ng/ml, and those with lower levels had 20 ng/ml. Patients’ blood samples were assessed every eight weeks for a mean duration of 1.7 years. The relationship with vitamin D was linear — as the blood level increased two-fold, the risk of flare-ups decreased by 27 percent.

In an RCT, higher levels of vitamin D in the blood showed a trend toward reduced disability in timed tandem walking and in disability accumulation (5). The results did not reach statistical significance, but approached it. A much larger RCT needs to be performed to test for significance.

Diet and lifestyle

Interestingly, a study found that caffeine, alcohol and fish — fatty or lean — intake may result in delay of secondary progression of relapsing-remitting MS (6). This observational study involved 1,372 patients. The reduction in risk of disability was as follows: Moderate daily alcohol intake resulted in a 39 percent reduction; daily coffee consumption showed a 40 percent reduction; and fish two or more times a week showed a 40 percent reduction.

All of these results were compared to patients who did not consume these items. However, the same effect was not shown in primary-progressive MS patients: Fatty fish actually increased risk of progression, compared to lean fish. With MS, vitamin D blood levels may be critically important. They are one of the easier fixes, although it may take higher doses of vitamin D supplementation to reach sufficient levels, once low.

While food (fish with bones, for example) provides vitamin D, it falls short of the amount needed by an MS patient. Interferon beta and vitamin D supplementation may have added effects. Lifestyle changes or additions also have tantalizingly appealing possibilities.

References: (1) Abstract O-293; June 2012. (2) JAMA. 2012;308:247-256. (3) Neurology. 2012;79:208-210. (4) Neurology. 2012;79:254-260. (5) J Neurol Neurosurg Psychiatry. 2012;83(5):565-571. (6) Eur J Neurol. 2012 Apr;19(4):616-624.

Dr. Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com or consult your personal physician.