Marie Newbrough had been living a wonderful life in Colorado Springs with her husband and two beautiful daughters when in the course of a day in June 2016, the unthinkable happened: Newbrough went blind in her left eye.
For weeks prior, Newbrough had struggled with odd vision problems. Her field of view was filled with speckles and weird, dark curtains closing in. Then, one day, everything in her left eye went black.
Newbrough, who had been on a new job for only 10 days and was 37 years old at the time, went to her primary care doctor, who sent her to a retina specialist, who didn’t see anything wrong with the retina and ordered an MRI. In the meantime, her vision went dark quickly in the left eye and she had an emergency MRI. She found a neurologist who thought Newbrough might have multiple sclerosis (MS). The neurologist prescribed IV steroids and eventually admitted her to a hospital. Unfortunately, she got progressively worse, not better. The diagnosis and treatment was for viral meningitis, but this was incorrect and didn’t explain her blindness or various other symptoms. The neurologist told Newbrough she “was a mystery”.
Her fingers and toes were tingly and numb; her hair was rapidly falling out and nerve pain was spreading along the entire right side of her body. After hospitalizations and follow-up visits with doctors, Newbrough had no answers.
A doctor in Colorado Springs referred her to Dr. Jeffrey Bennett at UCHealth University of Colorado Hospital on the Anschutz Medical Campus in Aurora. Within a few hours, Bennett explained to Newbrough that he suspected neuromyelitis optica (NMO), a rare autoimmune disease that is often mistaken for multiple sclerosis. A blood test would later confirm his diagnosis. He explained that therapies needed to be started immediately to stop the progression of vision loss and prevent future attacks on the nervous system.
For Newbrough, the diagnosis brought some temporary relief. At least he didn’t say she had a brain tumor. As she learned more, though, Newbrough learned that NMO is extremely rare and has no cure. There’s no surgery and no medication designed specifically to treat it. If there was a silver lining, it’s that Bennett is a world expert on the disease, which afflicts only 15,000 people in the United States.
NMO occurs when the immune system mistakes a normal protein of the central nervous system (aquaporin-4) as being foreign. As a result, the immune system makes proteins called antibodies that attack astrocytes, support cells in the central nervous system, and recruit immune system cells that can harm healthy optic nerve, spinal cord, and the brain. NMO commonly presents with vision loss from inflammation of the optic nerve, optic neuritis, or paralysis from spinal cord inflammation, transverse myelitis. The symptoms and severity of NMO can vary from person to person; however, attacks often result in severe disability.
“In my case, it actually started with the hiccups of all things,’’ Newbrough said. “I had hiccups for about two weeks and I was getting very frustrated why they weren’t going away. My primary care doctor said ‘we don’t know why people get chronic hiccups.’ He gave me a muscle relaxer and sent me away.’’
Eight months after the hiccups episode, Newbrough’s vision went haywire. Before eventually seeing Bennett, a retina specialist checked to see if her retina had been torn and the specialist said the symptoms she was describing matched optic neuritis – inflammation that damages the optic nerve, a bundle of nerve fibers that transmits visual information from your eye to your brain. The retina doctor ordered an MRI and referred her to a neurologist in Colorado Springs
“You are supposed to be weaned off of steroids and starting to feel better. The theory is that if I did have optic neuritis, which is causing the optic nerve to swell, that the steroid would reduce that, but I was still getting worse,’’ Newbrough said.
At a follow-up checkup, Newbrough told the doctor she was nauseous, vomiting often, had a horrible headache and was bedridden. The neurologist wrapped her in blankets and rolled her in a wheelchair to a Colorado Springs hospital. She was treated symptomatically for her nausea and pain, and she received anti-viral medications in case she had meningitis. Her headache went away.
“I left the hospital, and I was still blind and I still didn’t feel well. I felt very weak and very tired, very ill but a little bit better. I was on morphine and that made my headache go away,’’ she said. “In hindsight, my entire myelin coating of my brain, along my spine, my optic nerve were being attacked by my own immune system as being foreign. I had so much pain, morphine didn’t help. I was bedridden at home but couldn’t lie down the pain was so severe. I had no idea why I felt it was getting worse and worse.”
Her husband, Nathan, and her mother and mother-in-law cared for her and her children, Eva and Sarah, then 7 and 10, when she couldn’t get out of a bed. Near Labor Day weekend in 2016, Newbrough and her husband met Bennett, a neurologist, neuro-ophthalmologist and an immunologist. Bennett is a Stanford-educated physician who is a foremost authority on the disease that often is mistaken for multiple sclerosis. Bennett has published multiple articles and won several awards for scientific discoveries aimed at helping people who have NMO, optic neuritis and MS.
He is also among a group of physicians who are funded by the Guthy-Jackson Charitable Foundation (GJCF) to conduct basic and clinical research desperately needed to better understand, treat and ultimately cure NMO.
Through GJCF, a bio-bank has been established so scientists can study blood and other bodily fluids donated by patients across the country. Because the GJCF has raised awareness about the condition, more people are being diagnosed sooner. As a result, patients are receiving acute and preventative treatments earlier.
In 2004, Dr. Vanda Lennon and a group at the Mayo Clinic discovered that patients who clinically met criteria for NMO had a serum antibody against the water channel protein aquaporin-4, called AQP4-IgG, Bennett said. That antibody does not appear in patients who have MS.
“We began to appreciate that this disease wasn’t a severe form of MS, but rather a unique inflammatory disorder of the central nervous system,’’ Bennett said. “Regardless of their initial presentation, whenever AQP4-IgG was found in a patient’s serum, they eventually behaved like NMO.’’
Besides optic neuritis and transverse myelitis, physicians subsequently discovered that NMO patients could present with a variety of problems such as protracted nausea and vomiting, hiccups, confusion, double vision, or narcolepsy due to lesions that develop in a variety of brain regions uniquely susceptible to damage from AQP4-IgG.
“AQP4-IgG testing has enabled physicians to garner a greater appreciation for the many ways in which this disease could present,’’ Bennett said.
Now, through the work of Bennett and many other physician scientists, it is well recognized that not only is the antibody AQP4 a diagnostic marker for the disease, it is also pathogenic, meaning it is the cause of the disease.
“Back in 2009, our group was the first to show that this antibody could reproduce disease,’’ he said. “And we cloned the first antibodies from patients with the disease to have an experimental resource to directly test that the antibodies were pathogenic and could cause the full spectrum of nervous system damage that NMO patients present with,’’ Bennett said.
“If you deliver it to animals, you can reproduce the features of the disease,’’ Bennett said. “I got into NMO research because of my prior laboratory work on MS and optic neuritis, as well as my clinical interest in neuro-immunology and neuro-ophthalmology.’’
Bennett’s expedient diagnosis and understanding of the disease helped to ease Newbrough’s anxiety.
“Dr. Bennett took time with me, and he showed me the initial MRI scan and he said ‘look, here are your two optic nerves. Your right one is crystal clear and your left one is white and fuzzy.’ He said, ‘Can you see the difference between those two?’’’
When he pointed out the distinct difference and explained NMO, Newbrough said, “I was very distressed. And I just remember feeling helpless, like there is nothing that can get rid of it.’’
She was admitted to UCHealth University of Colorado Hospital on the Anschutz Medical Campus over the 2016 Labor Day weekend, only a few days after she saw Bennett for the first time. She received further tests and a therapy called plasmapheresis (PLEX), a process similar to dialysis that filters the blood to remove potential harmful antibodies and inflammatory mediators.
Bennett also sent blood to the Mayo Clinic to test specifically for NMO antibody. A few days later, the test came back positive. Bennett also ordered a full body scan, which showed lesions (transverse myelitis) on her spine and in the brain stem – the cause of her hiccups months earlier, numbness and nerve pain.
While hospitalized, Dr. Bennett brought neurology residents to see Newbrough, explaining that she had a rare disease, one they would rarely see again – maybe only once or twice in their careers.
During her hospitalization, a hepatologist also told Newbrough that her liver was inflamed because her immune system was attacking the organ. Due to autoimmune hepatitis, her liver was on the verge of failure. Indeed, NMO is frequently associated with other autoimmune disorders.
In some patients, PLEX treatment can help to restore lost vision, but Newbrough is still blind in her left eye.
Newbrough was placed on a drug called Rituximab, and within about 30 days, the tingling in her toes and fingers subsided, her hair started to grow and she generally began to feel better.
“Rituximab has kept me stable and in remission,’’ she said, noting that it has been nearly three years. “My balance is still a problem, and my depth perception is not there, but I’m feeling better.’’ Rituximab is a drug that works by depleting B lymphocytes, essentially turning off a part of the immune system that is not working properly in autoimmune diseases. Rituximab is a medicine for lymphoma that also has been found to work for rheumatoid arthritis and for some patients who have NMO.
The search for future therapies and biomarkers are off to a strong start thanks to the forward thinking of the GJCF, who assembled a nationwide network of physicians to contribute to a biorepository of NMO patient samples.
“When you have a rare disease it is hard for any one researcher to rely on his own supply of patient material,’’ Bennett said. “You need to have a resource to get a hold of enough samples to test hypotheses.’’
Thanks in part to the efforts of the GJCF, physicians, and industry leaders, four clinical trials have been recently conducted to test medications for the treatment of NMO. Preliminary results of clinical trials have been published, and the FDA recently approved the anti-complement medication eculizumab for the prevention of NMO attacks. Two additional medications, inebilizumab and satralizumab, are under FDA review. “This is an exciting time for NMO therapy. We are moving from a time when there is no proven therapy to one where we have three therapies, perhaps by the end of this year,’’ Bennett said.
For Newbrough, that’s exciting news. She sees Bennett every six months and she has been stable. Her best defense against illness is washing her hands, eating well and taking care of herself. Like MS, attacks can occur randomly. In between, she lives a normal life.
“Similar to patients who have cancer, this is something that could take me with my next attack,’’ she said. “This is something that changes you on every level of being; I can’t even put it into words. I always appreciated what I have and I have always been grateful but now I’m on a different level. I can’t explain it.’’
Over the years, Newbrough has become a student of her disease. She attends Guthy-Jackson conferences and has met many other people who have NMO. She has met people in New York and Baltimore who have to travel many hours to find an expert on NMO. She is grateful that one of the world’s experts on NMO is only a short drive up Interstate 25. She keeps up on the latest medical breakthroughs.
Her husband, Nathan, and her girls have been by her side every step of the way. She has been able to continue working from home and she is there for her daughters’ activities.
The family is together and all in all, Newbrough is doing well.