An autoimmune disease (also called a disorder) develops when a person’s immune system, which normally defends his/her body from pathogens such as viruses and bacteria, harmful chemicals, and mutated cells (cancer), attacks healthy cells instead. For reasons not fully understood, the immune system mistakenly turns on the tissues it is supposed to protect.
According to the American Autoimmune Related Diseases Assn., autoimmune diseases affect up to 50 million Americans, 75 to 80 percent of whom are women. Perhaps the best-known autoimmune disorder is one that, honestly, until I saw the fall 2017 lecture schedule for the Georgetown University Mini-Medical School, I didn’t know was an autoimmune disorder. I’m talking about multiple sclerosis (MS).
Chances are that you, like I, personally know someone who has MS. Certainly, you’ve heard of celebrities who have or had MS, among them, actress Terri Garr, talk-show host Montel Williams, former presidential candidate Mitt Romney’s wife Ann, the late comedian Richard Pryor, and the late actress/mouseketeer Annette Funicello.
Thanks to fundraising efforts of the National Multiple Sclerosis Society, I’ve been aware of the disease since I was a child in the 1960s, but until last Tuesday, when I heard a talk by Dr. Carlo Tornatore, chairman of the neurology department at the Georgetown University Medical Center, I didn’t know much about its cause, only its symptoms.
I have since discovered that there are about 80 different types of autoimmune diseases, which affect such a wide range of body parts that scientists categorize them into two classes: the organ-specific variety (e.g., Graves’ disease, type 1 diabetes, and Addison’s disease) and the systemic or non-organ-specific variety (e.g., lupus, rheumatoid arthritis, and MS). Autoimmune diseases, the incidence of which is reportedly on the rise, are chronic diseases without cures—at least, not yet.
I also have discovered that the view that MS is an autoimmune disease is not unanimous among researchers who have studied this potentially debilitating neurological condition. But I am not going to attempt to explain conflicts among experts, just present what I learned. Consider the following a primer for the newcomer, which I definitely am.
Your immune system carries out its surveillance mostly with white blood cells called lymphocytes, which recognize foreign “antigens”—harmful invaders, such as toxins or bacteria—and either attack them directly or produce antibodies against them.
Lymphocytes protect your body from infection and cancer and significantly contribute to your inflammatory and allergic responses.
Very broadly speaking—I defer to immunologists for the details—lymphocytes are of two types: B lymphocytes, aka B cells, which secrete antibodies designed to attack antigens outside of healthy cells, and T lymphocytes, aka T cells, which destroy microbes hiding inside the cells, most notably viruses.
In multiple sclerosis, according to Dr. Tornatore, one specific type of T cell behaves abnormally, mounting an autoimmune attack against the myelin sheaths that cover healthy nerves in your central nervous system (CNS). Your CNS consists of your brain and spinal cord. MS does not affect your peripheral nervous system.
(Quick lesson: Nerves are made up of neurons, which are impulse-conducting cells that consist of a nucleated cell body with one or more dendrites and a single axon. See the illustration at left above. The axon, which is also called a nerve fiber, takes an electrical impulse away from the cell body, and the dendrites bring impulses from other nerve cells to the cell body. A single nerve can be as long as five feet.)
Myelin is a mostly fatty material that encloses and insulates the axons of myelinated nerves and facilitates the transmission of nerve impulses. When myelin is damaged—as it is, progressively, in multiple sclerosis—nerve pathways erode, and impulses do not transmit as quickly or as efficiently. Communication between the brain and the nerves goes awry. This erosion typically affects those neurological impulses related to muscular strength and coordination, speech, and vision. Another word for demyelination is myelopathy.
The term multiple sclerosis derives from the multifocal areas (multiple foci) of demyelination in the brain and spinal cord that the autoimmune disease causes and the hard (sclerotic) inflammatory lesions, called plaques, that develop at the site of damage. In time, this inflammation can cause the nerves themselves, not just their protective covering, to deteriorate or to be permanently damaged. It is also possible, however, for nerves to repair themselves.
Signs and symptoms of MS vary widely and depend on which nerves are affected and the amount of damage that has occurred. Some people with severe MS may lose the ability to walk, while others may experience long periods of remission without any new symptoms. Treatment, of course, is critical, as is the over-all health of the patient.
According to Tornatore, MS symptoms fall into the following categories:
Motor symptoms: weakness, spasticity
Cerebellar symptoms: gait ataxia, tremors
Sensory symptoms: numbness, parethesias, pain
Bladder and bowel dysfunction
Cognition decline: memory, learning, attention, information processing
MS usually presents as a vision or sensation impairment, but fatigue, bladder urgency, muscular weakness, and impaired balance and coordination are also common early symptoms.
When the optic nerve is affected, blurred vision may result, as well as a partial or complete loss of vision, usually in one eye at a time, and sometimes with pain during eye movement. Impaired sensation usually manifests as tingling (“pins and needles”), pain, or numbness in different parts of your body, often on one side or the other of your trunk, but also in your extremities. The medical term for the tingling and “pins and needles” of MS is paresthesia.
When a person’s balance, mobility, and coordination are affected by MS, she may feel weak, unsteady, and clumsy. Affected speech is usually slurred.
MS symptoms usually present in people between the ages of 20 and 40, although the disease can occur at any age. Seventy-five percent of those affected are women.
MS is often said to be a disease of young white women, particularly those of Northern European ancestry, but half of the patients whom Dr. Tornatore sees at Georgetown’s Multiple Sclerosis Patient-Centered Specialty Practice are African-American.
The Georgetown neurologist introduced my class to one such patient, a 33-year-old woman who had been diagnosed with MS at age 31. She first experienced blurred vision, which went away on its own, and then suffered from paresthesia of her torso and arm and pain like an electric shock in her neck when she bent it forward.
“Gina,” like so many other MS patients, actually had other telltale symptoms before the symptoms that led to her diagnosis, but she ignored them because they abated: She recalled stumbling at age 29 for no reason. This is gait ataxia.
A psychiatric nurse practitioner, Gina said she could not afford to take time off from work to see a physician and only did so, a year later, when her vision became too poor for her to see. (She had blurred and double vision in both eyes.) At that time, her primary care physician took a wait-and-see approach and did not refer her to a neurologist. It was another year before she was finally diagnosed with MS.
Gina is African-American, but her father is of Irish and Polish descent.
Most people with MS have a relapsing-remitting disease course. They experience periods of new symptoms or relapses that develop over days or weeks and then usually improve partially or completely. It is, thus, common for primary-care physicians to dismiss early symptoms in young patients who are otherwise healthy.
There are three major clinical types of MS:
Relapsing-remitting (RRMS): affects approximately 85 to 90 percent of all patients; characterized by acute or subacute episodes of new or worsening old neurologic symptoms that increase in severity, plateau, and then partly or completely remit. Patients may have no detectable residual deficit or they accumulate significant permanent disability from attacks.
Secondary progressive (SPMS): a second stage to which most RRMS patients convert after 20 to 40 years; characterized by at least six months of progressive worsening without evidence of a relapse and diagnosed with confidence only retrospectively.
Primary progressive (PPMS): affects approximately 10 to 15 percent of all patients; characterized by progressive deterioration from the onset of symptoms for at least one year without a history of distinct relapses; more common in middle-aged men and typically involving the spinal cord more than the brain.
More than 95 percent of patients with clinically definite MS have an abnormal brain MRI. The imaging shows the presence of MS-distinctive lesions.
So what is causing the immune systems of young, healthy people—the majority of whom are women—to malfunction and attack the myelin covering of their nerves?
According to Dr. Tornatore, the cause of MS is multifactorial. It appears to involve the combination of an infectious agent, a genetic predisposition, and environmental factors.
Studies suggest that, if there is an infectious agent, it is viral. Viruses are well-known causes of demyelination and inflammation. No specific triggering virus for MS has been identified, however. Two of those that have been studied are Epstein-Barr virus and human herpes virus 6. Dr. Tornatore noted that canine distemper, which is a contagious and serious viral illness, is multiple sclerosis in dogs.
More interesting, I believe, are results from epidemiological studies that examined disease incidence in different world populations. The global distribution of the disease clearly shows that you have a higher risk of developing MS if you live in the northern latitudes, far removed from the Equator. In fact, in the United States alone, your risk is higher in the North, above Georgia on the East Coast, than it is in the South.
Epidemiologists have discovered that people who migrate from a low-incidence MS area to a high-incidence MS area before the age of 15 have a high risk of developing multiple sclerosis. Similarly, migrants from a high-incidence MS area who travel to a low-incidence area before age 15 have a smaller risk of developing MS than if they had remained in their home environment. After the age of 15, migration has no effect on a person’s risk of developing MS.
Such conclusions suggest that exposure to an as-yet-unidentified environmental agent before puberty predisposes a person to developing MS later.
Could it be sunlight? Vitamin D definitely plays an important role in the disease. MS patients have low vitamin D levels and bone demineralization early in the course of the disease. According to Tornatore, vitamin D also inhibits the proliferation of the T cells that cause MS.
Certainly, people who live closer to the Equator have a greater amount and intensity of sun exposure year-round than do those in northern climes and are naturally producing higher levels of vitamin D.
The relationship between MS and vitamin D is unclear; nonetheless, Dr. Tornatore advises all of his MS patients to take vitamin D supplements, as well as B-12, biotin, and omega-3 fatty acids. Vitamin D, he said, reduces relapses of symptoms.
(Studies also have shown that smoking, another conceivable environmental factor, increases a person’s risk of developing MS, and that smoking cessation among MS patients slows the disease’s progression. But smoking would not explain geographic distribution.)
While MS is not hereditary, studies establish that having a first-degree relative, such as a parent or sibling, with MS increases your risk of developing the disease. In the case of identical twins, the concordance rate is 30 percent; among fraternal twins, it’s 5 percent, which is still significant. According to Dr. Tornatore, 200 genes associated with MS have been identified, all of them having to do with the immune system.
What about the sex link with autoimmune disorders? Surely the fact that most people with MS are women, and that puberty serves as a dividing line in worldwide-distribution studies, suggests a sex hormonal factor. Research is on-going in this regard. According to Dr. Tornatore, pregnancy–which is a dramatic hormonal event–provides symptomatic relief for mothers-to-be with MS.
The bottom-line theory on MS causation to date is this: MS develops because a person is born with a genetic predisposition to react to an environmental agent that, upon exposure, triggers an immune-mediated response.
Once, the only treatment available to MS patients was steroids. Today, an assortment of so-called immunomodulatory agents exists to slow down the immune system in patients with relapsing-remitting MS, including injectable interferons, infusions of monoclonal antibodies, and oral immune-suppressing drugs. Regular exercise, a sufficient amount of sleep, good nutrition, and other well-known elements of healthy living are also beneficial.
The “next frontier,” said Dr. Tornetore, is shutting down the immune system completely, either with medications to promote the formation of new myelin from resident stem cells in the brain or with transplants of stem cells into the nervous system that will, in turn, repair injured nerves.
Nerves can heal themselves. There is some evidence, according to Dr. Tornetore, that the nerves of MS patients with “brain reserve” heal better.
I am familiar with, and have written about, the concept of cognitive reserve in the progression of Alzheimer’s disease and other dementias. This theory posits that early enriching cognitive experiences and educational attainment, especially in childhood, attenuates the effect of dementia on a person’s cognition in later life. I believe in this theory because I’ve seen evidence of its benefits in my well-educated and well-read 93-year-old mother, a retired psychiatrist and lifelong learner who has cognitive impairment.
“Brain reserve” is similar, but appears to have more to do with maximal lifetime brain volume, which can be estimated with head size and is determined almost entirely by genetics. Dr. Tornatore did not cite any studies supporting a prescription of intellectual enrichment as a therapeutic intervention to minimize or prevent MS-related cognitive decline. The hope is there, but not the evidence.
I spoke with Dr. Tornatore after his talk and asked him if he thought MS would be cured in his lifetime. One hundred and fifty years of research have been invested in this disease. Will there ever be a curative breakthrough?
He said, yes, and then quantified his lifetime as another 35 years.
Even without knowing the cause of MS, people are living longer and better with the disease than ever before, thanks to increased understanding and advances in treatment.