Devic's Disease (NMO (neuromyelitis optica)

Devic's Disease and NMO (neuromyelitis optica) are different names for the same condition, which affects the nervous system. It is one of a group of conditions called demyelinating diseases, which include multiple sclerosis, ADEM (acute demyelinating encephalomyelitis) and transverse myelitis.

Devic's / NMO is very rare. The exact figures aren't known but it's certainly much rarer than epilepsy (6 in 1000 people in Europe / North America) and multiple sclerosis (1 in 800 people in Europe / North America)

For more more information on this condition please go to the Devic's Disease and NMO (neuromyelitis optica) page.

Mayo Clinic researchers have identified critical steps leading to myelin destruction in neuromyelitis optica (NMO), a debilitating neurological disease that is commonly misdiagnosed as multiple sclerosis (MS). The findings could lead to better care for the thousands of patients around the world with NMO. The paper was published in the journal, Proceedings of the National Academy of Sciences, USA.

NMO is an inflammatory autoimmune disease of the central nervous system that damages the optic nerves and spinal cord, causing vision loss, weakness, numbness and, sometimes, arm and leg paralysis and loss of bowel and bladder control. NMO was historically misdiagnosed as a severe variant of MS until 2005 when a team led by Vanda A. Lennon, M.D., Ph.D., a Mayo Clinic research immunologist, identified an antibody unique to NMO, and discovered that its unexpected target was the major water channel of the central nervous system (aquaporin-4). A blood test emerging from this discovery has revolutionized the diagnosis of NMO, allowing its distinction from multiple sclerosis and introducing more appropriate treatments.

The NMO antibody targets astrocytes, which are 10 times more numerous in the brain and spinal cord than neurons. In addition to providing nutrients to neurons and supporting the repair and scarring process, other critical functions of astrocytes include regulation of tissue water and electrical activities of neurons, and the stabilizing the protective covering of nerves (myelin). By attacking the water channels on astrocytes, the antibody disrupts all related dynamic functions of the astrocyte and in acute attacks kills many astrocytes.

The new findings advance the understanding of the basic mechanisms of NMO, critical to the ultimate development of optimal treatment or even a cure. Key findings include:

-- The antibody associated with NMO affects two forms of the aquaporin-4 water channel: M1 and M23. M1 more readily escapes from antibodies, but antibody binding to M23 causes aggregation of M23 on the astrocyte surface which amplifies cell damage.

-- As a consequence of antibody interfering with the transfer of water in the brain, water accumulates in the myelin sheath, preventing rapid transmission of nerve messages) and causing breakdown of myelin, a traditional hallmark of MS, thus contributing to the diagnostic confusion.

-- Traditional therapies used to treat MS may actually make NMO worse.

"These findings build on our initial research and greatly advance our understanding of disease development and progression in patients with NMO," Dr. Lennon says. "Only by learning more about NMO can we develop new therapies and new approaches to treat people with this terrible disease."

About Neuromyelitis Optica

Because NMO has only recently been identified as a syndrome distinct from MS, it is difficult to know how many people have it. To date the Mayo Clinic Neuroimmunology Laboratory has detected the antibody in three thousand patients in the United States. Thus NMO is more common than was previously thought. Disease progresses with each new attack, and there is no cure. For most patients, a combination of drug and physical therapy is required to manage NMO, with the focus being on preventing recurrent attacks after treatment of the first attack, thus reducing disability and preventing relapses.

Contributing scientists include: Shannon Hinson, Ph.D.; Claudia Lucchinetti, M.D.; Michael Romero, Ph.D.; Bogdan Popescu, M.D.; James Fryer, M.S. and Tuebingen University (Germany) scientists led by Petra Fallier-Becker, Ph.D.

Source: Mayo Clinic (02/12/11)

Thousands of Neuromyelitis Optica (NMO) patients are potentially being misdiagnosed with Multiple Sclerosis (MS), according to Mayo Clinic Neurologist Sean Pittock, M.D., largely due to lack of awareness of NMO within the medical community. Dr. Pittock shared this finding with more than 50 of the world’s leading doctors and medical researchers – from Harvard to Oxford – who gathered at the 2009 NMO Roundtable Conference, sponsored by the Guthy-Jackson Charitable Foundation.

NMO is a rare and debilitating disease that attacks the optic nerves and spinal cord, often causing vision loss, paralysis of legs and arms, and sensory disturbances. The Guthy-Jackson Charitable Foundation has brought together these researchers to help find a cure for this rare disease.

Dr. Pittock came to his conclusion based on ongoing research at the Mayo Clinic. Of the 1,200 blood samples that are sent to Mayo Clinic’s neuroimmunology laboratory for NMO antibody (NMO-IgG) testing each month, approximately 70 new patients test positive for NMO, which is surprisingly high considering it is believed to be a rare disease. Of the 70 patients who have the NMO antibody, Dr. Pittock has found that a majority were previously thought to have MS.

Making the distinction between MS and NMO has been greatly assisted by Mayo Clinic’s recent discovery of this NMO antibody. In fact, this is the first biomarker that has shown to be sensitive and specific for any central nervous system (CNS), inflammatory demyelinating disease.

“It’s important to differentiate NMO from MS as these disorders are treated differently,” says Dr. Pittock. “The identification of this novel antibody marker will hopefully assist neurologists in making a correct diagnosis of NMO, rather than MS.”

Dr. Pittock believes that part of the reason for the lack of awareness of NMO is that there was no biomarker until recently, and traditionally, NMO was considered by many in the medical and research communities to be a form of MS, a difficult disease to diagnose. Recent clinical and pathological studies now support the concept that NMO is a distinct disease from MS.

“It’s important for the neurologists to be aware that NMO is associated with symptoms other than optic neuritis and transverse myelitis. NMO patients can have intractable hiccups, nausea, vomiting as well as problems with thermoregulation,” says Bruce Cree, M.D., Ph.D., M.C.R. of the University of California San Francisco Multiple Sclerosis Center. “It is important to test for presence of the anti-aquaporin 4 antibody, in the setting of neurological illness presenting with these symptoms as well as optic neuritis and myelitis, even in patients who have abnormal brain MRI findings. Some of these abnormalities can appear to be identical to those seen in MS, whereas others are more distinct of NMO.”

At the conference, Mayo Clinic Neurologist Dean Wingerchuk, M.D., also reported that the prevalence and incidence of NMO have not been firmly established. Based on current data, in aggregate, it suggests that there are likely more than 4,000 people with NMO in the United States.

That is why the Guthy-Jackson Charitable Foundation is launching a significant medical education campaign to ensure that doctors nationwide are aware of the differences between MS and NMO. Doing so will help patients get the appropriate treatments and will help more researchers collect the best data in their pursuit of a cure.

Cosmetics trailblazer Victoria Jackson established the foundation in July 2008, one month after her daughter’s diagnosis. The foundation’s approach is to provide bureaucracy-free funding to researchers willing to share data to help find a cure.

“I am on this mission for my daughter, and for the thousands of other families who have seen their world turned upside down by NMO,” says Jackson. “Through our work at the foundation, more and more, we are hearing from NMO patients who have been previously diagnosed with MS.”

While the first two days of the conference focused on research, the third day will take an emotional turn. Today, the conference, for the first time, will host a patient session dedicated to those affected by NMO, enabling them to engage in a dialogue with the medical community and to share personal stories with others affected by the same disease. Most of the patients will be meeting other people diagnosed with NMO for the first time.

Patients who attend the conference also will be enrolled in the newly-established Guthy-Jackson Repository for NMO to collect much-needed blood samples. This innovative repository is critical to future research.

“For me, this has been a very lonely journey. NMO needed a voice and a face to make it real for the rest of the world. It has that now,” says Candace Coffee, a young woman who was diagnosed more than six years ago. “Those of us struggling everyday with NMO, feeling the weight of its effect on our lives, finally have an advocate.”

Source: Business Wire ©2009 Business Wire (12/11/09)

Researchers at the Mayo Clinic in Rochester, Minnesota, say that they have uncovered a neurotransmitter defect that may trigger Devic’s disease, a potentially blinding neurological disorder that is often confused with multiple sclerosis.

In their study report, published in the online edition of the Journal of Experimental Medicine, the researchers say that their finding may result in new treatment options for the devastating disease.

Individuals with Devics disease often experience rapid visual loss, paralysis, and loss of leg, bladder, and bowel sensation. Some lose their sight permanently.

This disease can be diagnosed by the presence of a specific self-attacking immune proteinan autoantibody referred to as NMO-IgGin the blood.
However, it has remained unclear to date as to how that protein damages nerves and contributes to disease symptoms.

Research leader Dr. Vanda Lennon has now found that NMO-IgG sets off a chain of events that leads to a toxic build-up of a neurotransmitter called glutamate.

The researcher says that NMO-IgG binds to a protein that normally sops up excess glutamate from the space between brain cells.

In its presence, adds the researcher, this sponge-like action is blocked, allowing glutamate to accumulate.

And too much glutamate can kill the cells that produce myelin, the protein that coats and protects neurons.

The study suggests that glutamate-induced damage to nerve cells and their insulating myelin coats might account for the neurological symptoms associated with Devic’’s disease.

If the groups” results are confirmed in vivo, drug development could be very straightforward.

Therapeutic trials for glutamate blockers, created to treat other neurodegenerative diseases like Lou Gehrig’’s disease (or ALS), are already underway.

Source: Thaindian news (07/10/08)

A pilot study of the central nervous system disease afflicting the eye nerve will be funded with $44,000 of the $220,000 total. The remainder will pay for postdoctoral fellowship research related to the study.

Dr. Brian Weinshenker, a Mayo neurologist, said Dr. Vanda Lennon and colleagues at Mayo showed a test can tell whether someone has neuromyelitis optica, a "very severe" MS-like condition that causes inflammation of the optic and spinal nerves.

Attacks of NMO, or Devic's disease (named after the doctor who first described it), can cause blindness, paralysis in arms and legs or death.

Most patients with the condition have "immune antibodies" in their blood that target a neurologic protein called aquaporin-4, says a statement from the MS Society.

There's no reliable test for MS.

But a test for neuromyelitis optica called NMO-IgG detects the antibody and is positive in 70 percent of patients with NMO and "virtually never in MS or other diseases."

Weinshenker said the test has helped properly diagnose patients who in the past were misdiagnosed. He saw two people last week who just learned they have neuromyelitis.

"It's very under-recognized, because these patients were diagnosed elsewhere with multiple sclerosis," Weinshenker said.

He estimates, with a rough guess based on Olmsted County numbers, that about 1 to 2 percent of patients wrongly diagnosed with MS actually have neuromyelitis optica instead, although those numbers are higher in some demographics.

Notably, the treatment for MS doesn't work as a treatment for neuromyelitis optica.

About 80 percent of people with the neuromyelitis have northern European ancestry, whereas 98 percent of people with MS do, Weinshenker said.

The antibody test has been a major advance in diagnosing who has neuromyelitis, he said. But some people mistaken for MS patients are testing positive for neuromyelitis optica instead, despite lack of eye symptoms.

Now, Weinshenker, said, his research team wants to take the next step.

"We very strongly suspect the antibody isn't just a test, but is actually causing the disease," he said. The next question, if that is true, will be why people with Devic's disease produce the antibody.

"I was seeing these cases even before I came to Mayo, and many more cases when I came to Mayo," Weinshenker said.

"The research may ultimately lead to a specific therapy that targets the actual immune response to aquaporin-4, and may provide insights into treating MS as well," the MS Society says.

Source: Post-Bulletin Copyright 2008 Post-Bulletin Company (03/03/08)

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