An Overview of Multiple Sclerosis: Diagnosis and Management Strategies

Kathleen Costello, RN, MS, CRNP, MSCN; Colleen J. Harris, RN, MN, NP, MSCN

Disclosures

Topics in Advanced Practice Nursing eJournal. 2006;6(1) 

In This Article

Diagnosis

The diagnosis of MS can be challenging and frustrating. It is a clinical diagnosis, as there is no single test to make a definitive diagnosis. Thus, the clinician must piece together the history, neurologic exam, diagnostic tests, and the exclusion of potential MS mimics before a definitive diagnosis can be made. In general, to make a diagnosis of MS, an individual must have 2 episodes of neurologic symptoms referable to the CNS that are separated in space and time and that are not attributable to any other cause.

History taking is the most important factor in arriving at a diagnosis of MS. Family background and past medical history can be significant and, often, earlier health events can be linked to a relapsing-remitting presentation. The patient needs to be encouraged to report all past events no matter how they view their importance. Obtaining and reviewing past medical records for reliable evidence of previous neurologic symptoms or findings that may have been forgotten by the patient and family are also important.

It is imperative that the clinician arrive at an accurate temporal profile of the illness and clearly identify the date of onset of symptoms, the rate of progression or diminution of the intensity of symptoms, the presence of other associated symptoms such as fatigue, and the duration of remission from a symptom.

Focused questions should be asked about the presence of other symptoms such as an electrical sensation in the arm, back, and into the legs with the forward flexing of the neck (Lhermitte's symptom) or the appearance of optic symptoms with the exposure to heat (Uhthoff phenomenon), which a patient may not associate with the current presenting problem.[11]

Magnetic resonance imaging (MRI) has emerged over the past 10 years as an important diagnostic tool. While it cannot be used exclusively to make a diagnosis of MS, it can help differentiate MS from other diseases. The MRI uses the water content of normal and abnormal tissues and the different relaxation properties of that water to produce images.[12]

In an MRI, water protons aligned in the magnetic field move with the application of a radio frequency pulse signal. When the pulse is withdrawn, the water protons return to their original alignment, in a process known as relaxation. The energy released by the movement of the protons is captured mathematically by computer and translated into a visual image. The signal can be captured at different times, and different techniques can be applied to obtain the images we see. In MS the images of interest are T1, T1 with contrast (gadolinium [Gd]), T2, and fluid attenuated inversion recovery (FLAIR). (See Figure 1.)

Magnetic resonance imaging in MS.
Fig 1A: Courtesy of J. Alex Becker and Keith Johnson, Whole Brain Atlas, available at www.med.harvard.edu/AANLIB, and Figs 1B, 1C, 1D: Courtesy of Hillel Panitch, MD.

Magnetic resonance imaging in MS.
Fig 1A: Courtesy of J. Alex Becker and Keith Johnson, Whole Brain Atlas, available at www.med.harvard.edu/AANLIB, and Figs 1B, 1C, 1D: Courtesy of Hillel Panitch, MD.

Magnetic resonance imaging in MS.
Fig 1A: Courtesy of J. Alex Becker and Keith Johnson, Whole Brain Atlas, available at www.med.harvard.edu/AANLIB, and Figs 1B, 1C, 1D: Courtesy of Hillel Panitch, MD.

Magnetic resonance imaging in MS.
Fig 1A: Courtesy of J. Alex Becker and Keith Johnson, Whole Brain Atlas, available at www.med.harvard.edu/AANLIB, and Figs 1B, 1C, 1D: Courtesy of Hillel Panitch, MD.

On T1 images of the CNS, the cerebrospinal fluid (CSF) appears dark gray or black, the white matter light gray, and the gray matter a darker gray. Some MS lesions may appear as dark gray or black on T1. These indicate increased water content and axonal disruption.[13] On T1 with contrast, the blood vessels appear bright, and any areas of blood brain barrier disruption will appear bright. (Gd is normally prohibited from entry into the CNS tissue by an intact blood brain barrier.)

In an active MS lesion the blood brain barrier is disrupted, allowing immune system cells into the brain. At this time, the contrast medium may also enter the brain, causing the active lesion to appear bright. Acute lesions can remain enhanced for approximately 2-8 weeks.[12]

T2 images can show MS lesions of any age; new inflammatory lesions, or old, more chronic lesions. On T2 the white matter appears dark gray and the gray matter light gray. The CSF is bright white as are the MS lesions. FLAIR is used to suppress the signal from the CSF so the MS lesions are more easily seen. This is useful for seeing supratentorial lesions, particularly in the periventricular white matter.

Over the past several decades, criteria for the diagnosis of MS have been published and used to increase the reliability of diagnosing MS. The current criteria, published in 2005, are known as the revised McDonald criteria.[14] The criteria require 2 episodes of neurologic symptoms, referable to the CNS, separated in space and time, but allow the use of MRI to establish a second episode in lieu of a second clinical episode. See Table 2 .

On the basis of revised McDonald criteria, an individual may present with a first onset of neurologic symptoms and have an MRI suggestive of MS. All other possible causes for the symptoms may have been excluded. However, using these clinical criteria a diagnosis of MS would not be made, because there has been just 1 episode of symptoms and therefore no separation in time. In the absence of another clinical event, MRI can be utilized to establish separation in time.

According to the revised criteria, a second MRI, compared with a reference MRI obtained at least 30 days after the onset of symptoms, which demonstrates an additional T2 lesion compatible with MS, is sufficient to make the diagnosis. Alternatively, dissemination in time can be established by the detection of a Gd-enhancing lesion at least 3 months after the initial clinical event. The revised criteria also address diagnosis of primary progressive MS by requiring progression of neurologic symptoms for a period of 1 year plus at least 2 of the following:

  1. Positive brain MRI (9 T2 lesions or ≥ 4 T2 lesions with positive visual evoked potential)

  2. Positive spinal cord MRI (2 focal T2 lesions)

  3. Positive CSF (elevated IgG index or positive oligoclonal bands in the CSF, but not the serum)

Thus, MRI, although not able to make the diagnosis in isolation of clinical activity, has emerged over the past 2 decades as the most important of the diagnostic tests utilized in MS diagnosis. Over this period of time, MRI endpoints have become important considerations in all clinical trials of disease-modifying therapies.

Unfortunately, the MRI does not always correlate with clinical symptoms. Discrete areas such as the optic nerve, brainstem, and spinal cord are more likely to correlate to specific symptoms, but lesions in the deep white matter of the cerebral hemispheres are not correlated as easily. Some individuals may have many lesions and very few symptoms. The converse can also be true with very few lesions and multiple symptoms. The McDonald criteria define the types of lesions suggestive of multiple sclerosis, and that can help to establish dissemination in space, necessary for diagnosing MS. (See Figure 2.)

McDonald MRI criteria.
MRI images courtesy of Aaron Miller, MD.

Three out of 4 of the following must be present to be considered a lesion compatible with MS:

  1. Nine T2 hyperintense lesions (if no Gd) or 1 Gd-enhancing lesion present

  2. One or more juxtacortical lesions

  3. One or more infratentorial lesions

  4. Three or more periventricular lesions

A spinal cord lesion can substitute for any other cerebral lesion.

Other diagnostic testing may also be used to help the clinician establish the MS diagnosis. These include CSF analysis, evoked potentials, and the exclusion of other potential causes. When utilizing CSF analysis, elevated IgG index and/or oligoclonal IgG bands in the CSF, but not in the serum, are both suggestive of a demyelinating process such as MS.[14] A number of additional analyses should be performed to rule out other potential causes of symptoms, including basic cell count, protein, and analysis for chronic infections.[11]

Evoked potential testing (also known as evoked response) may also be used in an effort to establish dissemination in space by identifying additional areas of the CNS that have been affected. Visual, auditory, and somatosensory stimuli can be used to evaluate response time. In MS, the wave form is preserved but is delayed.

Serum analysis should also include testing for other inflammatory or infectious illnesses that could provoke the presenting symptoms (see Table 3 ).

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