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First blood test to diagnose paralyzing, blinding disease

15.12.2004


Misdiagnosis of a severely paralyzing disease can now be averted due to a blood test developed by Mayo Clinic researchers and their Japanese collaborators. Often misdiagnosed as multiple sclerosis, neuromyelitis optica (NMO) also causes blindness in many sufferers. The findings of this international collaborative effort appear in the current issue of The Lancet.



The finding will help doctors correctly treat NMO -- also known as Devic’s syndrome -- sooner and more effectively. In some countries, misdiagnosis may be as high as 30 percent. Early diagnosis is important because NMO is best treated differently than multiple sclerosis. Treatment requires immune suppressive medications in the first instance, rather than the immune modulatory treatments typically prescribed for MS. Therefore, a patient who has NMO, but is misdiagnosed with MS, may not receive optimal care at the earliest possible time.

NMO affects the optic nerves and spinal cord -- and within five years causes half of affected patients to lose vision in at least one eye. Many lose the ability to walk independently. The prognosis for loss of sight and permanent paralysis is much worse for patients who have NMO than for those who have MS. MS is not confined to optic nerve and spinal cord involvement. However, the symptoms of the two diseases overlap, and optic nerve and spinal cord involvement occur in both. NMO is particularly difficult to distinguish from MS in the early phases of the disease.


"Early diagnosis and treatment are of paramount importance to reduce the severity of the course of NMO," says Vanda A. Lennon, M.D., Ph.D., Mayo Clinic neuroimmunologist who led the international research team. In addition to colleagues at Mayo Clinic locations in Rochester, Minn., and Scottsdale, Ariz., the team is composed of scientists from Tohoku University School of Medicine in Sendai, Japan. "With this biomarker, physicians are in a much better position to start optimal therapies sooner, and hopefully, lessen the impact of the disease," Dr. Lennon says. "This is really a very exciting development."

About NMO

Neuromyelitis optica is a debilitating inflammatory disease that destroys the protective myelin sheath around the optic nerve and spinal cord. This ultimately leads to impaired vision -- including blindness -- impaired mobility and loss of bladder and bowel control. Its cause is unknown, and prognosis is generally poor -- though early diagnosis can help. If diagnosed correctly before the myelin sheath is too damaged, plasma exchange therapy and immunosuppressive medications such as azathioprine and corticosteroids can be effective in stopping the damage and restoring nerve function.

It’s not clear how many people have NMO, though it’s generally regarded as rare in the United States. However, one Mayo Clinic physician in Rochester has seen approximately 50 cases in the last three years, and an equal number of variants of NMO, such as recurrent transverse myelitis and recurrent optic neuritis. Ninety percent are women aged 30-60.

By some estimates, one of four African Americans diagnosed with MS may actually have NMO instead. NMO is considerably more common in Japan and Asia, where its prevalence is about three per 100,000 citizens. In Japan, roughly one-third of patients diagnosed with MS-like illness may actually have NMO.

Without the new blood test, classic NMO can only be distinguished from MS by the extensive spinal cord lesions it inflicts spanning three or more segments of the bony spine, and by lack of MS-type lesions found by magnetic resonance imaging of the brain.

About the Investigation

Blood samples were taken from patients in the United States and Japan and evaluated for the presence of a newly identified central-nervous system autoantibody. All antibodies are circulating proteins produced by the immune system. Unlike antibodies of healthy persons which attack invading disease organisms, an autoantibody attacks normal body constituents by a poorly understood error in immune function. This new autoantibody (named NMO-IgG) was discovered in the Mayo Clinic Neuroimmunology Laboratory in the course of analyzing 85,000 blood samples. However, the significance of the antibody was not initially appreciated. Based on a study of one group of patients with clinically recognized NMO, the researchers discovered that this "unclassified" antibody was common among these patients and therefore useful as a diagnostic biomarker for NMO.

The results show that 73 percent of a group of North American patients with NMO had the biomarker. Of 22 patients with similar symptoms, but who ultimately were shown to have MS rather than NMO, only two (9 percent) had tested positive for NMO-IgG. Statistically, this means the new test is sufficiently powerful to discriminate between patients who present with similar symptoms, but whose subsequent disease course shows that they have different disorders, MS or NMO. It is the first diagnostic tool ever to do this. Results were similar among the Japanese patients studied.

In addition to Dr. Lennon, the Mayo Clinic research team included Thomas Kryzer, Claudia Lucchinetti, M.D., Sean Pittock, M.D., Dean Wingerchuk, M.D., and Brian Weinshenker, M.D. Collaborators from Tohoku University School of Medicine included Kazuo Fujihara, M.D., and Ichiro Nakashima, M.D. Their work was supported by the Mayo Foundation.

Bob Nellis | EurekAlert!
Further information:
http://www.mayo.edu
http://www.lancet.org

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