The 22-year-old woman gripped the thick, battered notebook on her lap. It contained her medical records dating back to when she first got sick 18 years earlier. Her parents had always been the ones to bring the notebook to her medical visits. But she had just moved to New York City to go to nursing school, and this was the first time she was seeing a doctor without them. She had an appointment to meet a new physician at the N.Y.U. Langone Multiple Sclerosis Comprehensive Care Center with the hope that he would help her manage the illness she’d been dealing with for as long as she could remember. And maybe even figure out a mystery that none of the many doctors she’d seen had been able to solve: What exactly was wrong with her?
Dr. Josef Maxwell Gutman, a postgraduate fellow at the center, introduced himself and sat down. She wasn’t sure if she really remembered when she first got sick, the woman told the young doctor, or if she had heard the story so many times that she’d created the memories. When she was 4, she awakened in the early hours of the morning and found she couldn’t move or feel her legs. She rolled off the bed and dragged herself, Army-style, to her parents’ room. Her mother still remembers the terror she felt seeing her child this way. The girl was taken to the emergency room, the first of many such visits.
She was admitted to the hospital and during that first day became confused and began to speak in baby talk — something she hadn’t done for years. The M.R.I.s of her brain and spine were dotted with cloudy blotches that indicated swelling and inflammation. She was diagnosed with a rare autoimmune disorder known as acute disseminated encephalomyelitis (ADEM). In ADEM, antibodies mistakenly attack the myelin sheath that protects the nerves in the brain and spinal cord, and in this case it was affecting the girl’s legs. ADEM is seen mostly in young children who have recently had an infection, and the girl was recovering from a bad cold when this happened. Once her doctors felt certain that she didn’t have an infection in her brain, she was given steroids. Within 24 hours she was no longer confused and was able to walk. She was discharged on a two-week course of prednisone.
Ten days later, the child suddenly lost her vision. Her world looked blurry, she told her mother, as if she had Vaseline smeared over her eyes. Another hospitalization. Another M.R.I. In this one, the clouds previously seen in her brain were fading, but the nerves that connected her eyes to her brain were swollen. She had optic neuritis (ON) — another inflammatory condition, also often seen after an illness. Unlike ADEM, ON can sometimes be the first symptom of a chronic autoimmune disease. She was given more intravenous steroids. And because ON is caused by an immune system gone so wild that it attacks itself, she was treated with intravenous gamma globulins — antibodies collected from thousands of donors. Why this is helpful in autoimmune disorders is not well understood, but the flood of new antibodies seems to dilute those mistakenly attacking their own body. When her vision returned, she was discharged from the hospital, this time on weeks of steroids.
Specialist After Specialist
Over the next six years, the girl was hospitalized with ON about once every year. Each time she was given steroids, and her vision returned to normal. Throughout it all, her parents worked hard to make sure she had as normal a life as possible. She went to theater camp; she did after-school sports. But she also saw many specialists. Some wondered whether she might have multiple sclerosis, one of the chronic diseases sometimes preceded by optic neuritis. But she seemed young for that, and the spinal taps never showed the proteins that were characteristic of M.S. Without a diagnosis, there was no treatment beyond the steroids at the time of each attack.
When she turned 10, it all just stopped. She thought maybe her illness, whatever it had been, was over. She’d nearly forgotten about it when, not long after her 15th birthday, it came back with a vengeance. Two or three times a year, she would awaken to find that her vision, usually in her right eye, was gone. Each time she would be given a long course of steroids, and her vision would return. Over and over again.
She saw doctors at the children’s hospital in Washington, D.C., and the one in Philadelphia. She went to the Mayo Clinic in Rochester, Minn., and to Johns Hopkins in Baltimore. She was given another unusual diagnosis — neuromyelitis optica (NMO), an inflammatory disease that attacks the eyes and the spinal cord — but neither the doctors nor her family were sure it was right. As was the case with M.S., this disease often carries a characteristic protein in the spinal fluid, and that protein wasn’t to be found. Plus, her vision returned after each episode, while most with NMO permanently lose some or all vision after just a couple of attacks. Did she have some kinder, gentler version of NMO? Or was it something else altogether? No one could tell her. She was started on an immune-suppressing therapy known as rituximab but continued to have two or three episodes a year.
After hearing her long and complicated history, Gutman examined her, paying particular attention to her eyes. They looked normal. But the vision in her right eye was worse than 20/200 on his testing. When he shined a bright light into the left eye, both pupils contracted as they should, to limit the light and protect the eyes. When he shined the light into her right eye, neither pupil changed. Clearly these many bouts of optic neuritis had taken their toll.
A New Blood Test
Gutman wondered whether she might have a newly described disorder involving an antibody that attacks a protein in the brain and the spinal cord known as the myelin oligodendrocyte glycoprotein, or MOG. This protein is part of the equipment that creates and sustains the myelin sheath surrounding each nerve. The antibody that attacks MOG is somehow less destructive than that found in NMO. She had been tested for it before, and the results were negative. Gutman had recently read about a new test, created at the Mayo Clinic, that was supposed to be better, but it wasn’t available commercially. The patient had gone to Mayo in 2010, long before there was a MOG antibody test, and blood was taken. Maybe Mayo still had some stored away.
After the patient left, Gutman sat down and quickly drafted a note to Dr. Andrew McKeon, head of the neuroimmunology lab at Mayo, to ask whether they still had samples of his patient’s blood. Could they use their new test to look for MOG antibodies? He mentally crossed his fingers and went home.
Early the next morning, he got his answer. McKeon wrote that they did still have her blood and, after receiving Gutman’s email, ran the test. Gutman immediately called the patient with the news. The young woman held her breath. Would she finally have an answer? Yes. They had found antibodies to the MOG protein in her blood. She had what was now known as MOG antibody disease, or MOGAD. MOGAD is rare, thought to affect 1 in 50,000 people, often starting in childhood.
For the patient, the relief at having an answer was immediate. After so much uncertainty, she finally knew what had been causing her blindness all these years. And this brought its own comfort, even though her symptoms and the treatment did not immediately change. Eventually she was weaned off the rituximab, and at this point she is maintained on the monthly antibody infusions, which have kept her bouts of optic neuritis in check.
The patient, now 30, finished her training as a nurse. She has little vision in her right eye, and her peripheral vision is so poor in her left eye that she can’t drive or ride a bike. But she is glad to be able to work full time with a researcher who is trying to get a better understanding of her disease, managing trials of two experimental treatments for it. And she is trying to raise awareness about this rare disorder, just in case it isn’t quite as rare we think.
