At first I thought it had to be stress. The patient was in her early forties, and she had been coming to my clinic for several years, complaining of weakness, stiffness when walking, numbness in her hands, occasional falls, and headaches. I ran tests the first year, including an extensive check for diabetes, anemia, and internal-organ dysfunction. All were normal. I ordered nerve-conduction studies to see whether her numbness might be from carpal tunnel syndrome, which is caused by pressure on the median nerve in the wrist. They were normal. I did an echocardiogram. It was normal. I discovered that her job would be eliminated in a downsizing, and I suspected that played a major role in her complaints.
Then one Friday night, she noticed the vision in her left eye had become a bit hazy, so she came to the clinic that evening. The doctor on duty found no abnormality in either eye but thought she might have a detached retina, a true emergency and one of the few things that could get the on-call ophthalmologist to come see a patient late on a Friday night. Her retinas seemed fine, though, so he decided to see if she might have an inflamed optic nerve or a problem in her brain and ordered an MRI of her head and eye for the coming week.
The patient called me five days later to say her vision was improving and to get the results of the MRI, which had not clarified what happened. Her orbit, or eye socket, was normal. Her brain showed several small, nondescript areas that signal alterations in the white matter, the pathways along which neural impulses travel. The radiologist's report said these areas were "nonspecific and can be attributed to senescent changes." I was a little irked that the radiologist had not looked at the patient's age, which was 43. Why would a 43-year-old have "senescent changes," a throwaway term applied to the nonspecific findings that show up in our brains as we get older?
But the report did set off a question in the back of my head: Could she be in the early stages of multiple sclerosis? Optic neuritis, an inflammation of the optic nerve, could cause the visual problem. About half of all patients with optic neuritis go on to develop multiple sclerosis.
"Your MRI was pretty much normal," I hedged. "But I want you to see a neurologist for a consultation."
She pressed me to say why, so I explained that I was concerned about the possibility of MS. Like so many other illnesses, multiple sclerosis is a disease whose cause is unknown. The body's immune system attacks and destroys myelin, which is a major component of white matter. In MS, immune cells attack myelin in scattered areas, affecting the optic nerve and nerves in the brain and spinal cord. Symptoms result from delays or blockages in electrical impulses traveling down affected nerves, and problems with vision are often the first to appear. Other signs can be the loss of bladder or bowel control, difficulty walking, and heat intolerance, as well as almost any symptom of neurological dysfunction.
What leads the immune system to start attacking parts of the body itself no one knows for sure, but some evidence suggests that the response may be due to as-yet-unidentified environmental factors combined with a genetic tendency toward the disease. Multiple sclerosis occurs more frequently in the northern latitudes of Europe and the northern reaches of North America than it does closer to the equator. People born in these northern realms who move south before the age of 15 acquire the lower risk of those who were born and stayed in the south. Conversely, those born in the southern areas of Europe and North America who move to northern climes acquire the higher risk of those who were born and live in the north. Recent studies suggest that lack of sun exposure and vitamin D deficiency may play a role.
Another clue comes from genetics. It turns out that when one identical twin develops multiple sclerosis, the other has a 25 to 30 percent risk of getting it as well. For nonidentical twins and other immediate family members, the risk is 2 to 5 percent. For the population as a whole, the risk is far, far less—a tenth of a percent. Women are twice as likely as men to get it. Something genetic appears to be at work, but there must be more to the picture. One hypothesis concerns exposure to a virus or a bacterium that carries a protein similar to a protein in myelin. When a person with a genetic predisposition is exposed to this hypothetical virus, her immune system gets confused. It not only fights off the virus but also begins to view the body's own myelin tissue as a foreign invader. A couple of suspect pathogens are a herpesvirus and a form of the bacterium Chlamydia.
My patient saw the neurologist several weeks later. He told her she might have multiple sclerosis, but because she had no symptoms then—her vision had cleared—there was nothing to treat. At that time, in the early 1990s, even with the possibility of illness looming in her future, there was no medication to slow the progression of the disease. The neurologist offered to do a spinal tap because an examination of the fluid surrounding the spinal cord can help make a definitive diagnosis. She declined. She accepted the fact that she might have a serious illness brewing, but watchful waiting was the only treatment option.
Seven years went by. She found a new job. Her health seemed stable, although she usually felt tired and was unable to exercise because her muscles felt weak.
Then one day she developed double vision. This can be due to the effect of multiple sclerosis on the nerve cells controlling eye movement. I sent her for another MRI, which showed much more extensive involvement of the white matter in a pattern typical of multiple sclerosis. Although the condition cannot be diagnosed based only on an MRI, a suggestive scan along with a history consistent with MS, abnormalities in the neurological exam, and the elimination of other diseases can be conclusive. There was no way to predict the course of her illness. Some patients have only occasional attacks and can go years without symptoms. Others have disabling symptoms that recur frequently.
She was started on a corticosteroid drug, which would curb the immune response, in hopes of suppressing the attack on her own nerve cells. At the time this patient first started experiencing symptoms, treatment for multiple sclerosis was not very effective. The only reliable medications were steroids, which reduce inflammation during an attack. Since then other agents have become available that can influence the course of the disease. These include interferon beta-1a, interferon beta-1b, and glatiramer acetate. By altering the body's immune response to myelin, these drugs help prevent damage to the central nervous system, thereby reducing the frequency and severity of the attacks.
Over the following year, her disease progressed rapidly, and she became confined to a wheelchair because of intractable dizziness. Her vision declined in both eyes. In an attempt to slow the progress of her illness, she was given glatiramer acetate. But the drug works best if started early in the disease, and the treatment came too late to benefit this patient. She continued her rapid decline and died of pneumonia eight years after she first developed vision problems that Friday night. Her disease had proven to be unusually severe. Most patients with multiple sclerosis have a close to normal life span.
Why did she get multiple sclerosis? Was she a victim of having lived in Northern California, and could she have avoided this illness by moving south decades earlier? There is no way she could have known sooner in life what fate had in store for her. And there is no way to know whether moving south would have made a difference.
Her daughter from out of town called me several weeks after her mother died to thank me for my care. After we talked for a few minutes, she asked if she was at increased risk for the disease. I said her risk might be slightly higher than the average, but it was still very small, and she shouldn't worry. Then I asked her where she lived.
"San Diego," she said.
"I hear it's nice down there," I responded. "You're lucky to live in such a beautiful town."
Richard Fleming is a general internist in Vallejo, California. The cases described in Vital Signs are true stories, but the authors have changed some details about the patients to protect their privacy.