“You know, Doctor, it happened so fast. One minute I was fine, the next I felt a stabbing pain in my eye! Now we are here in the ED with you.”
Solving mysteries is often an emergency medicine practice's main focus. This patient experienced a sudden onset of severe eye pain with no history of eye disease. It's the famed mystery diagnosis, and it drags on as test after test comes up negative. All the while you're thinking of the old adage, When you hear hoofbeats behind you, don't expect to see a zebra. But sometimes it might be a zebra, just as it was in this case: neuromyelitis optica (NMO).
You may remember learning about NMO in medical school. It was likely mentioned at some point by your neurology professor and may have been referred to as Devic's disease (Eugene Devic, MD, 1858–1930). Ring any bells? If not, don't feel bad. It's considered so rare that most clinicians may never see a case of NMO during their careers.
NMO is often misdiagnosed as multiple sclerosis, and until recently, it was thought to be a type of MS. Recent discoveries indicate that NMO and MS are distinct diseases. NMO is an autoimmune disease of the central nervous system, and is most commonly characterized by inflammation and demyelination of the spinal cord and optic nerves, causing any of the following symptoms:
- Rapid onset of eye pain or loss of vision (optic neuritis).
- Limb weakness, numbness, or partial paralysis (transverse myelitis).
- Shooting pain or tingling in the neck, back, or abdomen.
- Loss of bowel and bladder control.
- Prolonged nausea, vomiting, or hiccups (often the earliest symptoms of the disease).
Traditionally spinal cord lesions seen in NMO are longer than in MS, but this is not always the case. Physicians treating NMO stress the importance for those diagnosed with MS to discuss these symptoms with their doctors to help consider NMO in their differential diagnosis, especially if they aren't doing well on their MS regimen.
Unlike other autoimmune diseases, NMO may have a clinical advantage in that people can be tested for NMO with the NMO IgG antibody test. A simple blood test is easily ordered by emergency physicians, neurologists, or primary care physicians. Most NMO IgG tests list a 5–10 percent chance of a false-positive result or a 20–30 percent chance of a false-negative result. The NMO antibody is directed at the AQP4 water channel found in the CNS, especially in the spinal cord and optic nerves. By binding, an inflammatory reaction is initiated that clinically, often rapidly, can lead to blindness and paralysis.
The treatments for NMO and MS can be very different, and recent reports suggest that some agents used to treat MS may be ineffective for NMO or actually make NMO symptoms and disease worse. Early detection and treatment for NMO help ensure best outcomes and are keys to decreasing morbidity in these patients.
The mainstay for acute attacks, as established in the clinical literature, still appears to be intravenous high-dose steroid infusions, and patients sometimes require plasmapheresis in severe recalcitrant attacks. The key is that attacks must be treated rapidly to avoid loss of function.
NMO also shares symptoms with other conditions, including unexplained transverse myelitis, acute disseminatedencephalomyelitis, unexplained optic neuritis, Leber's hereditary optic neuropathy, and optico spinal MS (mostly described in Japan). Some patients with NMO also have associated autoimmune diseases such as Sjögren's syndrome, systemic lupus erythematosus, and mixed connective tissue disease.
The prevalence and incidence of NMO have not been firmly established, according to Mayo Clinic neurologist Dean Wingerchuk, MD. “It has a worldwide distribution, and reported risk factors include females and [those with a] non-Caucasian racial background,” he said. “Previous population-based studies of clinically diagnosed NMO [patients] have indicated prevalence rates from 0.32 to 4.4 cases per 100,000 population. The data suggested a likelihood of more than 4,000 people with NMO in the United States and possibly more than 10,000.”
The National Institutes of Health classifies NMO as a rare orphan disease because of its lower incidence and prevalence, which means significant amounts of government funds are not assigned to researching it. Finding a clinician who knows how to treat the disease has proven extremely difficult for the NMO patient community as well.
But change is occurring: NMO research has been galvanized like never before because of one teenage girl's positive NMO IgG test results. This extraordinary young woman is Alexandra (Ali) Guthy, the daughter of Victoria Jackson and Bill Guthy.
Immediately after Ali's diagnosis in 2008, her parents formed the Guthy-Jackson Charitable Foundation, a nonprofit dedicated to funding biomedical research to understand the pathophysiology and biochemistry of NMO and to discovering a cure. The foundation is now a leading source of funding for NMO research in the United States, and its portfolio includes investigators from Stanford, Harvard, UC-Denver, UC-San Francisco, the Mayo Clinic, and many more.
The foundation is also mapping NMO clinicians worldwide on its website, a valuable resource for potential referrals. The site currently lists more than 70 NMO clinicians in the United States alone. More information about the foundation is available at www.guthyjacksonfoundation.org.