Diagnosed with multiple sclerosis, Maureen Jessen, always wondered why the disease affected her so differently than it did others. Doctor after doctor told her that MS was likely causing her symptoms, so she believed them. Mayo Clinic specialists, however, gave Maureen new insight into her illness — one that had nothing to do with MS.

For 20 years, Maureen Jessen was a poster child for multiple sclerosis (MS). She worked and volunteered at the Hartford, Connecticut, chapter of the National Multiple Sclerosis Society, raised money for research on the neurodegenerative disease, and participated in research studies aimed at learning more about the illness.

Maureen's diagnosis had never been clear-cut, but she followed her neurologist's advice and took prescription medications to treat her MS. When Maureen and her husband relocated from New England to Phoenix in October 2019, she arranged to obtain care at Mayo Clinic in the Center for Multiple Sclerosis and Autoimmune Neurology.

Maureen was aware of the high-caliber care offered at Mayo Clinic, but she never imagined just how comprehensive and patient-centric her experience would be. Maureen's Mayo Clinic MS specialists, Cristina Valencia Sanchez, M.D. Ph.D., and Dean Wingerchuk, M.D., offered personalized care that uncovered the reason why her manifestations of MS didn't align with typical MS symptoms. Maureen didn't have MS.

Maureen actually has a rare, genetic metabolic disorder called cerebrotendinous xanthomatosis, or CTX, which affects the metabolism of cholesterol and bile, and results in systemic neurologic abnormalities.

"My husband and I have joked for years that I was always looking for my Dr. House," says Maureen, referring to the lead character in a popular doctor-detective TV series. "Someday I was going to find my Dr. House, and it's the weirdest thing in the world that here I came to Mayo Clinic in Arizona, and I found him."

Maureen's condition, which is thought to affect only a few hundred people in the world, is not something Mayo Clinic physicians often see. But in Maureen's case, uncovering the correct diagnosis was significant for her care.

"It's a pretty meaningful outcome for her to know what she has," Dr. Wingerchuk says. "I think that's important for her and her family, so she can not only be on treatment for this condition, but also stop potentially harmful treatments for MS. It has a big impact."

Finding the needle in the haystack

Maureen experienced the first symptom of her disease, a slight limp, in 1999. Her neurologist ordered an MRI and saw what he believed was a suspicious spot on her spine. "That started me down that road for MS," Maureen says. "But when they redid MRIs and spinal taps and all of the other tests, they came back negative."

As her symptoms progressed, Maureen's limp became more pronounced, and she developed sensory issues, such as numbness and tingling. "Because there was nothing else to really diagnose me with, they went ahead and diagnosed me with MS," she says.

Several second opinions yielded the same diagnosis. "We decided that it was just kind of a weird MS," Maureen says. "I've run into other people in similar situations, so I thought: "OK. I'm one of a few."

While Maureen's symptoms didn't clearly point to MS, neither did they align with typical presentations of CTX, says Maureen's neurologist and geneticist Radhika Dhamija, M.B.B.S., in Mayo Clinic's Department of Clinical Genomics.

"Her clinical picture is very unusual. It's not like someone missed it. She just had nothing to suggest it initially and carried the incorrect diagnosis of MS for decades."

Radhika Dhamija, M.B.B.S.

In people with CTX, fatty deposits called xanthomas form throughout the body, most commonly growing in the brain and tendons that attach bone to muscle. The xanthomas develop as a result of the body not being able to break down different forms of cholesterol called lipids.

"Her presentation is atypical, even for CTX. Most physicians would not have thought of it," Dr. Dhamija says. "She doesn't have typical manifestations like cataracts, and her cognition is intact. Her MRIs are abnormal now, but they weren't that abnormal before. Her clinical picture is very unusual. It's not like someone missed it. She just had nothing to suggest it initially and carried the incorrect diagnosis of MS for decades."

Before Maureen's Mayo team identified CTX as a possible culprit for her symptoms, they ruled out a number of other illnesses. "We started by looking at common causes of myelopathies, or spinal cord problems," Dr. Valencia Sanchez says. "We looked for vitamin B12 deficiency, copper deficiency, autoimmune-mediated conditions and infections that may cause myelopathy, which were all negative."

After eliminating the most common causes of spinal cord disorders, the team started thinking about rarer conditions. One symptom Maureen mentioned during her initial consults — swollen and sore Achilles tendons — gave the team pause.

"The report about the Achilles tendon tears caught our interest because the patient was actually pretty impaired as far as her mobility by the time she was diagnosed with the tears, which is really quite unusual," Dr. Wingerchuk says. "We don't see Achilles tears in people with MS who have mobility problems. That's just not common, so that was another possible clue."

Research into conditions associated with enlarged Achilles pointed the team to CTX. "That is when we decided to refer the patient to Dr. Dhamija in our Neurogenetics Clinic," Dr. Valencia Sanchez says.

Accurate answers lead to targeted therapy

When tests confirmed that Maureen had CTX, she established care with Dr. Dhamija and started taking two medications. One is a prescription cholesterol-lowering medication. The other is a specially formulated drug that prevents the fatty deposits that lead to seizures, loss of sensation in the arms and legs, heart disease and intellectual decline.

Given the rarity of CTX, little information is available about its prognosis and outcome, even when patients are receiving treatment. "It's very hard to know what to expect," Maureen says. "There are definitely cases that show this drug will basically prevent the cholesterol from … creating havoc on your body. So my hope is this drug will prevent all the other things that can cause issues. The hope is it will prevent future disability."

"They can't say, 'You're cured,' because I was diagnosed so late, but we're more hopeful than before. I feel more confident with this."

Maureen Jessen

Although CTX has no cure, the fact that Maureen has a validated diagnosis with a targeted treatment makes her optimistic that the effects of the illness can be halted. "They can't say, 'You're cured,' because I was diagnosed so late, but we're more hopeful than before," says Maureen, who now uses a wheelchair to get around. "I feel more confident with this."

The experience of discovering her rare disease and beginning new treatment has been a whirlwind, but the speed at which Maureen's team discovered and addressed her illness reinforced her belief about Mayo Clinic.

"I was impressed," Maureen says. "Once they knew I had this disease, they got me in —especially because of my heart. They were very concerned about how my heart looked. So on the same day I got the diagnosis, I got tests of my heart, which were negative. My heart is good. When push comes to shove, they make things happen."

For patients like Maureen, whose symptoms don't clearly align with a diagnosis, having a medical team that remains dedicated to finding answers — no matter how obscure the problem — is crucial.

"What concerned us was that the diagnosis of MS appeared to be given by default several times by different doctors despite her not having any typical MS features," Dr. Wingerchuk says. "That's why we questioned the diagnosis in the first place, and I think that's something we do for every patient we see here."

HELPFUL LINKS

• Read about Mayo Clinic's approach to treating rare diseases.
• Learn more about the Department of Clinical Genomics.
• Check out the Center for Individualized Medicine.
• Explore Mayo Clinic.
• Request an appointment.

The post Careful Evaluation, Genetic Testing Offer a New Path Forward appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — The drug eculizumab, a synthetic antibody that inhibits the inflammatory response, significantly reduced the risk of relapse with neuromyelitis optica spectrum disorder (NMOSD). This rare but severe autoimmune inflammatory disorder can cause blindness, paralysis and death. Mayo Clinic researchers and international collaborators report their findings in a randomized, double blind, placebo-controlled study published in the New England Journal of Medicine. Their work also will be presented in the Emerging Science Platform session, part of the American Academy of Neurology's 71st Annual Meeting in Philadelphia May 4–10.

Neuromyelitis optica, also known as Devic's disease, occurs when the body's immune system reacts against otherwise healthy nervous system cells in the optic nerves and spinal cord, and sometimes in the brain. Neuromyelitis optica often is misdiagnosed as multiple sclerosis (MS), but neuromyelitis optica is a distinct condition characterized by more severe attacks and a less complete recovery. A single neuromyelitis optica attack can leave a patient blind or paralyzed. With each relapse, disability can worsen. It affects up to 10 in 100,000 people.

Currently, the immunosuppressive therapies used to prevent neuromyelitis optica relapses have not been approved by the Food and Drug Administration. Furthermore, 25 to 60 percent of patients receiving these medications continue to have recurring attacks, the authors note.

In the Prevention of Relapses and Evaluation of Eculizumab in NMOSD Treatment (PREVENT) study, 143 adults were enrolled at 70 sites in 18 countries. All patients had aquaporin-4 immunoglobulin G (AQP4-IgG), an antibody associated with most neuromyelitis optica cases. Patients could continue on their prior therapy if desired. In addition, patients were randomly assigned to receive regular doses of a placebo or IV eculizumab.

The study found that treatment with eculizumab reduced the risk of relapse by 94 percent, compared with a placebo. At 48 weeks, nearly 98 percent of patients treated with eculizumab had not relapsed, compared with 63 percent for patients on the placebo.

"This study offers hope to patients, since each attack in NMO can cause loss of visual or motor function," says Sean Pittock, M.D., a Mayo Clinic neurologist and first author. "Stopping attacks can prevent disability and allow patients to maintain function and a better quality of life."

Mayo Clinic is a recognized center of excellence for diagnosing and treating neuromyelitis optica. In 2002, Mayo Clinic researchers led by Claudia Lucchinetti, M.D., the Eugene and Marcia Applebaum Professor of Neurosciences, and colleagues described the unique pathological features of NMO. They proposed that NMO is an autoimmune disease caused by one or more harmful antibodies. In 2004, Vanda Lennon, M.D., Ph.D., Brian Weinshenker, M.D., and Mayo colleagues reported the discovery of the AQP4-IgG biomarker, a blood test that differentiates neuromyelitis optica from MS and similar disorders. The AQP4-IgG antibody was subsequently shown to be able to cause nerve cell damage consistent with what Dr. Lucchinetti and colleagues reported, and AQP4-IgG is now widely considered as the cause of NMO.

"The Mayo Clinic team subsequently demonstrated that when the antibody binds to the water channel AQP4 on nerve cells, a substance called 'complement' is activated and kills the cells, causing significant injury. We thought that if we could block complement activation, then perhaps we could prevent attacks," says Dr. Pittock, director of Mayo Clinic’s Mayo’s Neuroimmunology Laboratory and the Marilyn A. Park and Moon S. Park, M.D., Director of the Center for Multiple Sclerosis and Autoimmune Neurology.

Eculizumab has been used to treat disorders where complement activation causes harm, such as myasthenia gravis, a muscle disease, and paroxysmal nocturnal hemoglobinuria, a genetic disease affecting red blood cells. In an early phase clinical trial, the Mayo team observed a near complete cessation of neuromyelitis optica attacks. Based on those early results, this large multicenter, international study was performed.

"These new study results confirm the important role of complement in neuromyelitis optica and advance our understanding of how the disease works," says Dean Wingerchuk, M.D., a Mayo Clinic neurologist and senior author. "This study provides clear evidence that we can favorably alter the course of this often devastating neurologic disease."

Side effects of eculizumab include risk of meningococcal infections. Study participants were vaccinated against meningococcal infections, and no cases were reported. One person receiving eculizumab died of an infection that was not associated with complement inhibition.

This study only enrolled patients with AQP4-IgG antibodies, so the findings cannot be extrapolated to other inflammatory central nervous system disorders. The long-term effect of eculizumab in patients with neuromyelitis optica requires further study, the authors note.

Coauthors involved in this study are from institutions in Munich, Germany; Sendai, Fukushima City and Koriyama, all in Japan; Goyang, South Korea; Baltimore, Maryland, and Boston, in the U.S.; Oxford, England; Samsun, Turkey; St. Petersburg, Russia; Kuala Lumpur, Malaysia; and Taipei, Taiwan. For a complete list, see the New England Journal of Medicine.

The study was supported by Alexion.

Dr. Pittock reports grants, personal fees and nonfinancial support from Alexion; grants from Grifols S.A. and Autoimmune Encephalitis Alliance; and grants, personal fees, nonfinancial and other support from Viela Bio. Dr. Pittock has patent No. 9,891,219 (application No. 12-573942), "Methods for Treating Neuromyelitis Optica by Administration of Eculizumab to an Individual That Is Aquaporin-4 (AQP4)-IgG Autoantibody Positive." Dr. Wingerchuk reports grants from Alexion and Terumo BCT Inc., and personal fees from Viela Bio, Ono Pharmaceutical Co. Ltd., Celgene Corporation, and Novartis AG.

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, comprehensive care to everyone who needs healing. Learn more about Mayo Clinic. Visit the Mayo Clinic News Network.

Media contact:

• Susan Barber Lindquist, Mayo Clinic Public Affairs, 507-284-5005, newsbureau@mayo.edu

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Kratom: Unsafe and ineffective
Kratom is an herbal extract that comes from the leaves of an evergreen tree grown in Southeast Asia. It's sold as an energy booster, mood enhancer, pain reliever and antidote for opioid withdrawal. At one time, some researchers believed that kratom might be a safe alternative to opioids and other prescription pain medications. However, studies on the effects of kratom have identified many safety concerns and no clear benefits. Here's what you need to know.

EXPERT ANSWERS
Are there any new treatments for MS?
There is no cure for multiple sclerosis (MS), but there has been progress in developing new drugs to treat it, and research is ongoing to develop new and better disease-modifying therapies. Although initial research shows promise, the benefits, side effects and long-term safety of these new drugs will become clear with additional investigation. Learn more from Dr. Dean Wingerchuk, a Mayo Clinic neurologist.

Wondering what you can do to improve your heart health?
Are you wanting to improve your heart health but don't think you have the motivation to take the necessary steps? Even small, basic changes in your diet, exercise routine and sleep habits can make a big difference. Learn more from Dr. Francisco Lopez-Jimenez, a Mayo Clinic cardiologist.

PLUS ADDITIONAL HIGHLIGHTS
How to be happy: Tips for cultivating contentment
Post-traumatic stress disorder
Tetanus
Video: 'Allergy or Irritant? The Truth About Your Rash'

HEALTHY RECIPES
Sweet potatoes and roasted bananas
Shrimp and grits
Dijon Parmesan crusted salmon
Seafood gumbo

HEALTH TIP OF THE WEEK
Vitamin C: Can it prevent colds?
Vitamin C supplements won't prevent colds. However, if you regularly take vitamin C, it may shorten the duration of cold symptoms. Starting a vitamin C supplement after you develop a cold will not shorten the duration of your symptoms.

Need practical advice on diet and exercise? Want creative solutions for stress and other lifestyle issues? Discover more healthy lifestyle topics at mayoclinic.org.

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His recent article in Neurology raises the possibility that handheld gadgets may be to blame. Because of that, he says physicians may need to include smartphone use in their patient history reviews.  To listen click the link below.

Transient smartphone blindness

The post Transient smartphone blindness: Mayo Clinic Radio Health Minute appeared first on Mayo Clinic News Network.

His recent article in Neurology raises the possibility that handheld gadgets may be to blame. Because of that, he says physicians may need to include smartphone use in their patient history reviews. Here’s Dennis Douda.

Watch: The Mayo Clinic Minute

Journalists: A broadcast-quality video pkg (0:59) is in the downloads. Read the script.

The post Mayo Clinic Minute: It’s only temporary – smartphone blindness appeared first on Mayo Clinic News Network.

Multiple sclerosis (MS)

"It tends to strike people in early adulthood," explains Mayo Clinic neurologist Dr. Dean Wingerchuk. "Most people develop initial symptoms in their twenties or thirties, when they’re in the primes of their lives."

While there is no cure for MS, there are drug treatments, including a recently approved medication for a type of MS called primary progressive.

Meanwhile, research continues into how lifestyle can affect MS management.

In this Mayo Clinic Minute, Dr. Wingerchuk explains what’s already known and which lifestyle questions are still being investigated. Jeff Olsen reports.

Watch: The Mayo Clinic Minute

Journalists: Broadcast-quality video pkg (1:00) is in the downloads. Read the script.

The post Mayo Clinic Minute: Can lifestyle changes help with MS? appeared first on Mayo Clinic News Network.

Ocrevus (ocrelizumab), a new drug to treat multiple sclerosis (MS),  has been approved by the U.S. Food and Drug Administration (FDA). The National Multiple Sclerosis Society says it's a "game changer" and Dr. Dean Wingerchuk, a Mayo Clinic neurologist, says, "The approval of ocrelizumab is an important milestone — both for people with MS and MS research."

In a statement released on Wednesday, March 29, Dr. Billy Dunn, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research says, “This therapy not only provides another treatment option for those with relapsing MS, but, for the first time, provides an approved therapy for those with primary progressive MS.”

MS is a potentially disabling disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body. Eventually, the disease can cause the nerves to deteriorate or become permanently damaged.

According to Dr. Wingerchuk there are an estimated 400,000 people in the U.S. who have MS, which means that roughly 1 in every 700 Americans have the disease. "It tends to strike people in early adulthood, so most people develop their first symptoms in their twenties or thirties, really when they’re in the primes of their lives." Dr. Wingerchuk is encouraged by the news about ocrelizumab:

"It is the first treatment shown to benefit primary progressive disease and will hopefully be a springboard to more effective drugs for treating this disabling type of MS.  It also convincingly reduces activity and disability from relapsing MS, giving people with that form of the disease another powerful option. It is relatively safe but there are some important safety signals, including risks of cancer and infection, that will need close monitoring when the drug is used in usual practice." — Dr. Wingerchuk

Watch: Dr. Wingerchuk discusses symptoms, treatment and research.

Journalists: Broadcast-quality sound bites with Dr. Wingerchuk are in the downloads.

Dr. Wingerchuk concludes by saying, "I want to emphasize how much effort and how many resources are being poured into this disease, and for people and their families to know that we’ve got a lot of really brilliant people throughout the world who are doing their best to try to crack the mystery that’s MS and put a stop to it."

Mayo Clinic in Arizona participated in the ocrelizumab trial and received funds to support trial operations. Dr. Wingerchuk did not receive any personal compensation from the sponsor.

The post New drug for MS is milestone for patients, research appeared first on Mayo Clinic News Network.

The paper states that many people with newly diagnosed or early stage MS are overwhelmed by the combination of uncertain prognosis and the often-unsettling prospect of starting preventive measures that are used indefinitely. However, the authors say that patients and physicians can benefit from an awareness of recent and emerging developments.

“MS is the second most common disabling disease of young adults - it is a lifelong disease with an unpredictable clinical course for the most part,” said Dean Wingerchuk, M.D., Mayo Clinic neurologist and co-author of the review. “That means that people are challenged with making decisions about treatment. It’s important for both the patient and physicians to be aware of current and emerging therapies  to make appropriate decisions going forward.”

Journalists: Sound bites with Dr. Wingerchuk are available in the downloads.

Dr. Wingerchuk said that MS research has been prolific and that scientific advances in understanding the relapsing form of the disease have led to the recent development of several new treatments. There are currently 10 new approved MS therapies including the approval of three oral therapies since 2010. Dr. Wingerchuk added that there are many more promising treatments in the pipeline including exciting therapies that may promote repair of the nervous system. And it is likely that current and future therapies will eventually be used as part of a “personalized medicine” approach, with individual treatment decisions guided by predictive biomarkers and pharmacogenomics in addition to the patient’s own preferences.

“While current therapies provide both immediate options and hope for people there is still a lack of therapies that convincingly slow or halt progressive forms of the disease,” the paper says. “Fortunately, clinical investigators worldwide and organizations such as the National Multiple Sclerosis Society have focused their attention on these problems, promising even greater advances toward and beyond the horizon of the next decade.”

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About Mayo Clinic
Recognizing 150 years of serving humanity in 2014, Mayo Clinic is a nonprofit worldwide leader in medical care, research and education for people from all walks of life. For more information, visit 150years.mayoclinic.org, www.mayoclinic.org and newsnetwork.mayoclinic.org.

MEDIA CONTACT:
Jim McVeigh, Mayo Clinic Public Affairs, 480-301-4222, mcveigh.jim@mayo.edu

The post Advancements in Multiple Sclerosis Research Hold Promise for Patients appeared first on Mayo Clinic News Network.