If you’re suddenly experiencing blurred vision, numb limbs, relentless vomiting, or hiccups that last for days on end, you probably—no, you definitely—want to know what’s going on, stat. But getting an accurate diagnosis for these unsettling symptoms isn't always straight forward. While they’re the classic signs of the autoimmune disease neuromyelitis optica spectrum disorder (NMOSD), they can ring true for other conditions, too. So, it may take some sleuthing work before your doctor can put all the pieces together and get you on the right treatment path. Here’s why:
1. NMOSD is super rare—only 15,000 people in the U.S. have it. So your doctor might not suspect it at first.
NMOSD, a.k.a. Devic’s disease, accounts for just 2% of all demyelinating diseases—those that damage the myelin sheath, the protective covering on your nerves—so there’s a good chance your primary care physician has never had a single patient with the disease. NMOSD attacks myelin on the optic nerve (which carries visual info from the eyes to the brain), the spinal cord, and sometimes the brainstem, leading to a wide range of symptoms that affect vision, balance, and even bladder and bowel function.
“Symptoms develop over a period of a few days and peak within a week to 10 days,” says Elias Sotirchos, M.D., director of the Neuromyelitis Optica Clinic at Johns Hopkins University in Baltimore. But if you were to google your symptoms (and we suspect you already have), you’ll see that there’s a lot of overlap with other conditions including multiple sclerosis (MS), lupus, and even a brain tumor. So, before your doc lands on an NMOSD diagnosis, he may consider—and potentially try to rule out—these other, more common issues first.
2. Some tissues may appear normal during an exam.
If you have blurry vision and throbbing eye pain—which can happen because NMOSD often causes a condition called optic neuritis (ON), leading to inflammation of the optic nerve—you’d expect your doc to find some evidence of it when looking into your eyes during a regular eye exam. But with NMOSD, that’s not always the case.
“Optic disc swelling may not be present,” says Dr. Sotirchos. Getting an ON diagnosis, then, comes from other parts of an eye exam, a thorough patient history, and an optical coherence tomography (OCT) scan. This non-invasive diagnostic test can help spot swelling and damage of nerves in the back of the eye, and can also help nail an ON diagnosis, he adds. An MRI can also be done to ID which part of the nerve is involved.
3. If you do get an ON diagnosis, multiple sclerosis (MS) may be suspected first.
ON happens in about half of all MS cases. About 20% of the time, it’s one of the first symptoms of that condition, according to research published in the journal Eye and Brain. So, if you go to your doctor with sudden vision loss or pain behind one or both eyes, your doctor may initially suspect MS.
And to confuse matters more, NMOSD was once considered a variant of MS, not a completely separate disease. “Up until about 15 years ago, if a patient came in with [these symptoms], they would be diagnosed with MS,” says Patricia Coyle, M.D., interim chair of the department of neurology at Stony Brook University in Stony Brook, NY.
4. If you have weakness or numbness in your limbs, injury to the spinal cord must first be ruled out.
Waking up to one or both limbs feeling weak, numb, or even paralyzed can be pretty scary. Or maybe you can’t control your bladder, or urinate at all. These are things that can happen with you have transverse myelitis (TM). TM is diagnosed through a medical history and a neurological exam, as well as an MRI to look for spinal cord lesions that are typical with TM.
But your physician isn’t finished there. He has to figure out why you have it. TM can signal NMOSD or MS, but it can also stem from other autoimmune disorders, vascular causes, and infections, as well as compression from a mass or even unexplained injury. So these other possibilities may need to be considered—and then rejected—before NMOSD emerges as the likely cause of your TM symptoms.
5. Seemingly benign symptoms like hiccups or vomiting (even if severe) may initially be dismissed.
If your brainstem is the target of an NMOSD attack—a rare occurrence in an already rare disease—your symptoms, while intense, may not immediately point to this condition.
NMOSD brainstem attacks aren’t as common as ON and TM. They happen in just 10% of cases. Nausea and vomiting might be dismissed as the flu or even food poisoning. It’s only after you’ve been throwing up for days—or even weeks—that your doctor may start looking for other causes.
Hiccups are usually benign and can be triggered from carbonated beverages, alcohol, stress, eating too much, or swallowing air. But when they linger for more than 48 hours, your doctor may suspect nerve damage or irritation caused by reflux or even a cyst or tumor, central nervous system conditions including MS and stroke, as well as metabolic diseases (such as diabetes and kidney disease) before determining they’re actually the result of an NMOSD attack.
6. Bloodwork to identify NMOSD-specific antibodies can take weeks to come back.
Fortunately, there are some highly specific blood tests that can tell docs if you have NMOSD. Back in 2004, researchers discovered that about 75% of people with NMOSD have antibodies in their blood called aquaporin-4 antibodies (AQP4-IgG). These antibodies target water channels (aquaporins) located on astrocytes, a type of cell in the central nervous system. “We now realize that NMOSD is [usually] an immune attack on aquaporin-4,” says Dr. Coyle.
About 20% of people with NMOSD don’t have AQP4-IgG, but they may have another kind of antibody: myelin oligodendrocyte glycoprotein (MOG-IgG), a protein in the outer layer of the myelin sheath. Identifying these two antibodies have helped docs get to an NMOSD diagnosis faster than before (and rule out MS in one fell swoop).
Even so, getting your results can take weeks, leaving you, well, a bundle of nerves. And a small percentage of people with NMOSD won’t have either antibody, even though they have all the classic NMOSD symptoms. If this happens to you, after your bloodwork comes back your doctor may schedule more tests, including a spinal tap and an MRI.
7. You might test positive for lupus, confusing matters more.
There is some association between NMOSD and the autoimmune disorder lupus. Some people with NMOSD will test positive for antibodies associated with lupus, even if they don’t have any signs of that condition, says Dr. Sotrichos. “The overlap between NMO and lupus likely has to do with a shared genetic tendency to developing these two autoimmune diseases,” he says.
Interestingly, those who do have lupus and symptoms of ON and TM often carry AQP4-1gG antibodies—as many as 60%, suggests a study in Lupus. “People with lupus with transverse myelitis, optic neuritis, or other neurological symptoms consistent with NMOSD should be tested for AQP4-IgG at that time,” Dr. Sotirchos advises. In most cases, those who are positive for AQP4-IgG have actual signs of NMOSD, suggesting it may be co-existing with lupus.
8. Once you get a diagnosis, it will likely be years before your doctors can tell you definitively which type you have.
As if this rare disease isn’t complex enough, there are two types: relapsing, which is when you get repeated attacks with months or even years of remission in between, and monophasic, a single attack that lasts for at least a month or two. Your doctor won’t know which one you have right away, but your bloodwork holds some clues: AQP4-IgG-positive NMOSD is typically treated as relapsing.
Those with MOG-IgG antibodies may have a monophasic attack, but it’s a wait-and-see game. “If patients [with MOG-IgA antibodies] are followed long enough, the vast majority will have a relapse,” says Dr. Sotirchos. So, doctors treat most cases as if they are the relapsing type.
Now that you have an official diagnosis of NMOSD, you might sigh with relief to finally have a name for what you’ve been experiencing—even as you battle worry, or even fear. Deep breath. Know that in the past few years powerful new treatment options have emerged to reduce the likelihood of another attack occurring—to help keep you symptom-free in the future.