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.
Clinical
data alone may be sufficient for a diagnosis of MS if an individual has
suffered separate episodes of neurologic symptoms characteristic of MS.
Since some people seek medical attention after only one attack, other
testing may hasten and ease the diagnosis. The most commonly used
diagnostic tools are neuroimaging, analysis of cerebrospinal fluid and evoked potentials. Magnetic resonance imaging of the brain and spine shows areas of demyelination (lesions or plaques). Gadolinium can be administered intravenously
as a contrast to highlight active plaques and, by elimination,
demonstrate the existence of historical lesions not associated with
symptoms at the moment of the evaluation.
Testing of cerebrospinal fluid obtained from a lumbar puncture can provide evidence of chronic inflammation of the central nervous system. The cerebrospinal fluid is tested for oligoclonal bands, which are an inflammation marker found in 75–85% of people with MS.
Being
all previous tests non specific for MS, only biopsies or post-mortem
examinations can yield a diagnosis of MS beyond doubt. Recently, a test
over serum autoantibodies has been proposed to make a safer diagnosis
and to stablish a difference between the different types of multiple
sclerosis.
The nervous system of a person with MS often responds less actively to stimulation of the optic nerve and sensory nerves due to demyelination of such pathways. These brain responses can be examined using visual and sensory evoked potentials.
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