Explaining multiple sclerosis

Diagnosing Multiple Sclerosis

Step 1: Identify cardinal clinical features

B. Mark Keegan, M.D., Neurology, Mayo Clinic: Multiple sclerosis is diagnosed usually by three or sometimes four steps. The first step is seeing if patients have the typical cardinal clinical features of multiple sclerosis. For instance, they may have symptoms of optic neuritis, which is highlighted typically by painful loss of vision in one eye, rarely both eyes simultaneously. And it usually comes on over a number of hours to days. It plateaus with some visual impairment, such as some eye blurriness, then stabilizes for a few weeks, and then improves either on its own or with the use of corticosteroids. Another cardinal clinical feature of multiple sclerosis is double vision, which means seeing two of the same image simultaneously. It's usually painless with multiple sclerosis, meaning no pain associated with it, and it must be binocular in nature. What that means is when somebody covers one eye or covers the other eye, the double vision goes away and it's replaced by normal single vision. Some patients have hemiparesis or hemisensory deficit as a cardinal feature of multiple sclerosis. Hemiparesis means weakness on one side of the body involving the face, arm and leg simultaneously. Hemisensory loss means numbness or reduced sensation, again, involving the face, arm, and leg. Just like optic neuritis, it usually comes on over a number of hours to days. It may plateau for a number of weeks and then improve again, either spontaneously or with steroid use. Other patients will experience progressive numbness with or without weakness from the feet, slowly up the knees, belly, chest or even up to the neck. Again, staying for a number of days or weeks, then slowly improving over time. This cardinal clinical feature is indicative of some inflammation within the spinal cord. Another common symptom is what's been termed Lhermitte symptom. Lhermitte symptom is an unusual sensation often described as a buzz or vibration on neck flexion, meaning putting the head forward. It's generally not painful and it's not typically just cracking of the neck -- which other people with or without MS commonly report -- but a vibratory or buzz-like sensation. This cardinal feature is also indicative of some inflammation within the spinal cord. Because MS can affect the spinal cord in some patients, they may have bowel and bladder disturbance, like urgency of bladder or bowel function, meaning rushing to get to the bathroom, sometimes associated with accidents of bowel or bladder called incontinence. Generally speaking, we don't think of cognitive concerns, memory concerns or just fatigue as necessarily being cardinal features highly indicative of multiple sclerosis. Because, although they occur very commonly with multiple sclerosis patients, they're also very nonspecific. That means they may occur in so many other medical conditions or with sleep impairment -- or other things, or even on their own entirely -- that they don't have diagnostic utility for patients in a diagnosis of multiple sclerosis, even though they are so common in MS itself.

Step 2: Neurological examinations

The second factor is neurological examination of the patient. This means checking their mental status, cranial nerve function -- meaning their vision, eye movements, speech quality -- as well as their motor strength -- meaning the strength of their muscles throughout their body -- as well as their reflexes and sensation. We also check their walking and balance as well as the sensory functions on a detailed neurological examination.

Step 3: Looking at investigations consistent with MS

The third step is looking at investigations consistent with multiple sclerosis. Typically, the main important diagnostic test is MRI scans of the brain, cervical and thoracic spinal cord. Because multiple sclerosis affects the central nervous system white matter, that means the brain, cervical and thoracic spine -- all may be involved with multiple sclerosis. An MRI is important to identify typical MS lesions there. Typical MS lesions are commonly ovoid in appearance. They appear coming off the ventricles, meaning they're periventricular. They may occur within the brain stem or right up against the cortical rim, meaning juxtacortically. Commonly, acute MS lesions may be seen to leak gadolinium dye, the dye that is administered in the patient's vein during the procedure. The gadolinium enhancement -- or brightness -- shows that there's active inflammation going on at the time of that MRI scan. Other tests sometimes are recommended as well. Occasionally, a lumbar puncture -- also known as a spinal tap, or cerebral spinal fluid assessment -- is recommended. Most patients with multiple sclerosis, but not all, have abnormalities on spinal tap testing. Specifically, they present with elevations in immunoglobulins or antibodies, known as unique cerebral spinal fluid oligoclonal bands, or they may have elevations in immunoglobulin G index or antibody index. Other cerebrospinal fluid assessments aren't specific for multiple sclerosis. But we do check the white blood cell count, the protein count, and other values to make sure these aren't consistent with other neurological diseases that are more likely than multiple sclerosis. We also check blood tests on patients with multiple sclerosis. There isn't a single blood test that's diagnostic of multiple sclerosis, but we may do blood tests occasionally in patients to rule out other conditions that might mimic multiple sclerosis. Generally speaking, if something is very typical and characteristic of multiple sclerosis and they're very unlikely to see other diagnoses, there may be no further blood tests required. However, if it's unusual or atypical, the number of blood tests to rule out other conditions may be more important and more extensive. We also check some blood tests because some patients qualify for medications aimed at multiple sclerosis and they need to be done as screening evaluations as well.

Clinical courses for MS: Relapsing remitting MS and progressive MS

Now I'm going to talk about the various clinical courses of multiple sclerosis. By far the most common form of multiple sclerosis, occurring in about 85% of patients, is relapsing remitting multiple sclerosis. A relapse is the new onset of neurological symptoms or signs characteristic of multiple sclerosis, and generally speaking, they must last at least 24 hours, but generally they last even longer than that -- many days or weeks. The remission is improvement in those symptoms. Sometimes those symptoms don't get 100% back to baseline, but they should reliably improve at least a little bit. Sometimes patients are treated for relapses with corticosteroids, either intravenously -- meaning by vein -- or by mouth at very high doses for brief courses, usually between three to five days. The other clinical courses of multiple sclerosis are called progressive forms of multiple sclerosis. Patients with secondary progressive multiple sclerosis are those patients that have had at least one definite attack or relapse of multiple sclerosis in the past. And as I noted before, that should have improved at least to some degree, even if it doesn't get entirely back to baseline. But what heralds progressive forms of multiple sclerosis, typically occurring many years after attack or relapse-related disease, is slow but steady decline in neurological function with or without occasional relapses, and with or without new MRI lesions developing from multiple sclerosis. Primary progressive multiple sclerosis is distinguished from secondary progressive multiple sclerosis in that those patients with primary progressive MS have never been found to have had a clinical relapse ever in their history, as best as the physician and the patient and their family members can identify. Both progressive forms of MS, however, are heralded by slow but steady decline, typically in walking or gait function, over many months to years. Again, usually without any attack related disease. This is in contrast to relapsing remitting multiple sclerosis where, in between the relapses, it appears that the patient is entirely stable over time without any progressive impairment that comes in.

Treatment options for progressive MS patients

Now I want to talk to you about treatment options for patients with progressive forms of multiple sclerosis. In patients with primary progressive multiple sclerosis, or in patients with secondary progressive multiple sclerosis without any ongoing attacks or without any ongoing new MRI lesions, there doesn't seem to be any medication currently available that will reliably stop progressive multiple sclerosis, slow it down or even improve that progression. This is very unfortunate for our patients and, of course, very disappointing for patients and physicians. But so far, that seems to be the best information gained from investigational experience with these immunomodulatory medications. But that doesn't mean we can't help patients with progressive forms of multiple sclerosis. The best way to help these patients, though, is through gait assistance, walking assistance, sometimes with gait aids, sometimes with recommendations from our physical medicine and rehabilitation colleagues for spasticity. Spasticity is severe tightness of the legs and arm due to brain and spinal cord disease. Generally speaking, for spasticity, they recommend a routine daily or twice daily stretching program, as well as the occasional use of antispasticity medications like baclofen or tizanidine. And sometimes, as I mentioned before, patients with multiple sclerosis have bowel and bladder dysfunction. The bladder evaluation can be done by our urology colleagues or bladder specialists.

These are some of the important features involving diagnosis, evaluation and treatment of multiple sclerosis.