How is MS Diagnosed?
There is no single test that unequivocally detects MS. When faced with a patient whose symptoms, neurological exam results, and medical history suggest MS, physicians use a variety of tools to rule out other possible disorders and perform a series of laboratory tests which, if positive, confirm the diagnosis.
Imaging technologies such as MRI can help locate central nervous system lesions resulting from myelin loss. MRI is painless, noninvasive, and does not expose the body to radiation. It is often used in conjunction with the contrast agent gadolinium, which helps distinguish new plaques from old. However, since these lesions can also occur in several other neurological disorders, they are not absolute evidence of MS.
Several new MRI techniques may help quantify and characterize MS lesions that are too subtle to be detected using conventional MRI scans. While standard MRI provides an anatomical picture of lesions, magnetic resonance spectroscopy (MRS) yields information about the brain's biochemistry; specifically, it can measure the brain chemical N-acetyl aspartate. Decreased levels of this chemical can indicate nerve damage.
Magnetization transfer imaging (MTI) is able to detect white matter abnormalities before lesions can be seen on standard MRI scans by calculating the amount of "free" water in tissues. Demyelinated tissues and damaged nerves show increased levels of free" (versus "bound") water particles.
Diffusion-tensor magnetic resonance imaging (DT-MRI or DTI) measures the random motion of water molecules. Individual water molecules are constantly in motion, colliding with each other at extremely high speeds. This causes them to spread out, or diffuse. DT-MRI maps this diffusion to produce intricate, three-dimensional images indicating the size and location of demyelinated areas of the brain. Changes in this process can then be measured and correlated with disease progression.
Functional MRI (fMRI) uses radio waves and a strong magnetic field to measures the correlation between physical changes in the brain (such as blood flow) and mental functioning during the performance of cognitive tasks.
In addition to helping scientists and physicians better understand how MS develops-an important first step in devising new treatments-these approaches offer earlier diagnosis and enhance efforts to monitor disease progression and the effects of treatment.
Other tests that may be used to diagnosis MS include visual evoked potential (VEP) tests and studies of cerebrospinal fluid (the colorless liquid that circulates through the brain and spinal cord). VEP tests measure the speed of the brain's response to visual stimuli. VEP can sometimes detect lesions that the scanners miss and is particularly useful when abnormalities seen on MRI do not meet the specific criteria for MS. Auditory and sensory evoked potentials have also been used in the past, but are no longer believed to contribute significantly to the diagnosis of MS. Like imaging technologies, VEP is helpful but not conclusive because it cannot identify the cause of lesions.
Examination of cerebrospinal fluid can show cellular and chemical abnormalities often associated with MS. These abnormalities include increased numbers of white blood cells and higher-than-average amounts of protein, especially myelin basic protein and an antibody called immunoglobulin G. Physicians can use several different laboratory techniques to separate and graph the various proteins in MS patients' cerebrospinal fluid. This process often identifies the presence of a characteristic pattern called oligoclonal bands.
While it can still be difficult for the physician to differentiate between an MS attack and symptoms that can follow a viral infection or even an immunization, our growing understanding of disease mechanisms and the expanded use of MRI is enabling physicians to diagnose MS with far more confidence than ever before. Today, most patients who undergo a diagnostic evaluation for MS will be classified as either having MS or not having MS, although there are still cases where a person may have the clinical symptoms of MS but not meet all the criteria to confirm a diagnosis of MS. In these cases, a diagnosis of "possible MS" is used.
A number of other diseases may produce symptoms similar to those seen in MS. Other conditions with an intermittent course and MS-like lesions of the brain's white matter include polyarteritis, lupus erythematosus, syringomyelia, tropical spastic paraparesis, some cancers, and certain tumors that compress the brainstem or spinal cord. Progressive multifocal leukoencephalopathy can mimic the acute stage of an MS attack. Physicians will also need to rule out stroke, neurosyphilis, spinocerebellar ataxias, pernicious anemia, diabetes, Sjogren's disease, and vitamin B12 deficiency. Acute transverse myelitis may signal the first attack of MS, or it may indicate other problems such as infection with the Epstein-Barr or herpes simplex B viruses. Recent reports suggest that the neurological problems associated with Lyme disease may present a clinical picture much like MS.
Investigators are continuing their search for a definitive test for MS. Until one is developed, however, evidence of both multiple attacks and central nervous system lesions must be found before a diagnosis of MS is given.
