The Challenges of a Multiple Sclerosis Diagnosis
For someone with multiple sclerosis (MS), the earliest signs can be subtle. One day, your hand feels weak. You find you’re having trouble carrying your grocery bag. The problem lasts a couple of weeks and then disappears. Months later, numbness spreads through your leg but then eventually fades, too. Then you develop blurred vision in one eye, as even more alarming symptoms set in.
Affecting the central nervous system, including the brain, spinal cord and optic nerves, multiple sclerosis has been historically tricky to diagnose. Neurologist Misbah Azeem, MD, pointed to research (Opens in a new window) indicating that roughly 1 in 5 cases of MS had been misdiagnosed. Part of this has to do with the variety of symptoms which can affect different parts of the body. “MS is a snowflake disease,” said Dr. Azeem. “No two patients are alike because their lesions happen in different parts of the central nervous system. So careful diagnosis is crucial, because there are a lot of mimics out there.”
Multiple sclerosis is a disease that impacts the immune system, turning the body’s defense system against itself. During periods of inflammation, immune cells can cross the blood-brain barrier, the protective boundary surrounding the brain and spinal cord, and cause areas of damage known as lesions.
The location of those lesions determines what a patient experiences. A lesion involving an optic nerve may cause vision problems, while one in the spinal cord may affect sensation, strength or bladder function. A lesion elsewhere in the brain might interfere with balance or coordination.
According to Dr. Azeem, it’s this variation that makes a patient’s medical history so important. In order to arrive at a correct multiple sclerosis diagnosis, a neurologist may need to look not only at what is happening today but also at unexplained neurological problems that occurred months or even years earlier. “If your doctor has a better idea of your history, you're already halfway toward a diagnosis,” said Dr. Azeem.
Recognizing the Patterns of MS
Multiple sclerosis often first appears between ages 15 and 45, although the disease can begin earlier or later. Many patients initially have relapsing-remitting MS, in which symptoms appear during a period of inflammation, improve and then return later during another attack.
Typical attacks often involve a specific part of the nervous system. A person might develop weakness or numbness primarily on one side of the body, suddenly have blurred vision in one eye or experience new trouble walking or coordinating movements. Changes can also involve speech or bowel and bladder control. Unlike a stroke, where symptoms often reach their worst point within seconds, an MS attack generally develops over hours or longer.
According to Dr. Azeem, multiple sclerosis symptoms can resemble numerous other conditions. Doctors have to distinguish these from other common complaints. Fatigue, brain fog and tingling, for example, can occur in MS but are not enough by themselves to establish the diagnosis.
Fatigue can be particularly severe in people with MS, but Dr. Azeem cautions against assuming that unexplained tiredness automatically points toward the disease. Depression, nerve compression and many other conditions can produce similar symptoms.
For someone who has experienced repeated MS symptoms, early evaluation can be worthwhile. A primary care doctor may refer the person to a neurologist, who can take a detailed history and perform a neurological examination before deciding whether additional testing makes sense.
Looking for Evidence in Time and Space
Neurologists use a set of standards known as the McDonald Diagnostic Criteria (Opens in a new window) to help determine whether someone has multiple sclerosis. These criteria are continuously updated as researchers learn more about the disease.
At the center of the diagnosis are two ideas: evidence that disease activity has occurred at different times and evidence that it has affected different parts of the central nervous system. Doctors call these concepts “dissemination in time” and “dissemination in space.”
A patient who had arm weakness two years ago and who later develops optic neuritis, or inflammation of the optic nerve, may already provide evidence of two attacks at different times. An MRI could then show lesions in different MS-associated areas, adding evidence that the disease has occurred in different locations.
“We need three elements: a good history, a physical exam, and we have to get imaging,” said Dr. Azeem.
Magnetic resonance imaging (MRI) is one of the most important tools because MS lesions tend to occur in recognizable locations and develop certain shapes. Doctors commonly look for lesions around fluid-filled spaces in the brain—near the outer portions of the brain, in the brainstem, spinal cord and optic nerves.
One newer feature of modern imaging is called the central vein sign. MS inflammation often develops around a small vein, and certain MRI techniques can reveal a vein passing through the center of a lesion. Another feature, known as a paramagnetic rim lesion, can show a distinctive rim around an area of inflammation.
When MRI findings and the patient’s history do not provide enough evidence, a spinal tap may be the next step. Doctors can examine cerebrospinal fluid for signs of inflammation. Newer biomarkers may provide additional information as researchers continue refining the diagnostic process.
MS Lookalikes
Part of the challenge of a multiple sclerosis diagnosis is that abnormalities on an MRI are not automatically MS lesions. High blood pressure, diabetes, high cholesterol, smoking and migraines can all contribute to small spots in the brain that may resemble MS, particularly in older adults.
Other diseases can mimic MS as well. According to Dr. Azeem, sarcoidosis, certain infections, lymphoma, stroke and other inflammatory neurological disorders may sometimes produce overlapping findings.
“I cannot tell you how many times I see patients above the age of 50 who come in with a previous multiple sclerosis diagnosis, and I go through their imaging and tell them, ‘This is not MS,’” said Dr. Azeem.
The consequences of getting the diagnosis wrong can be significant. Many MS treatments work by altering or suppressing the immune system. Some of the more powerful treatments can increase susceptibility to infections, including pneumonia and urinary tract infections.
“It's very important that you have a thorough process and just don't go on a hunch, because MS medications are potent,” said Dr. Azeem. “We accrue as much objective data as we possibly can. We then combine the history, examination, imaging and laboratory findings to make the best possible diagnosis.”
Earlier Diagnosis, Better Treatment
Improved diagnosis methods are helping doctors recognize MS sooner. In some people, an MRI performed for an unrelated reason may reveal lesions that look like MS before neurological symptoms occur. Other patients may experience only one clear neurological attack but already have imaging findings suggesting a high risk of developing further disease.
Doctors no longer wait for multiple obvious attacks before considering treatment. Additional testing and individual risk factors can help determine whether earlier treatment is appropriate.
“The treatment for MS is phenomenal now,” said Dr. Azeem. “We're very good at addressing acute attacks.”
However, challenges still remain, particularly with progressive MS. Some patients gradually accumulate disability even when they are no longer experiencing obvious inflammatory attacks. Treatments for this slower progression remain less effective, and finding better options is a major focus of MS research.
For patients worried that unexplained fatigue, tingling or other symptoms might mean MS, Dr. Azeem’s message is not to make assumptions. These symptoms have many possible causes, and neurologists now have increasingly sophisticated ways to distinguish MS from impostors.