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How is Primary Progressive Multiple Sclerosis Diagnosed?

Many Features of PPMS Make Diagnosis Challenging

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Updated July 03, 2008

Diagnosis of primary progressive multiple sclerosis (PPMS) has special challenges, as PPMS lacks both relapses and the striking MRI findings that are present in relapsing-remitting multiple sclerosis (RRMS).

Here’s the Bottom Line

Definite PPMS can be diagnosed when the following conditions are met:
  • At least one year of documented clinical progression
  • At least TWO of the following:
    • Positive brain MRI scan (nine T2 lesions or at least four T2 lesions with positive VEP)
    • Positive spinal MRI scan (two T2 lesions)
    • Positive lumbar puncture
  • No past relapses

Each one of these characteristics has some challenges and specific points, as covered below. Let’s take a look at what some of these things mean and what makes PPMS so hard to definitively diagnose…

Worsening of Symptoms for At Least One Year ("Dissemination in Time")

Most people with PPMS start with the symptom of gradually worsening difficulties with walking, referred to as “progressive spastic paraparesis.” However, other people have what is called “cerebellar syndrome,” which is characterized by severe ataxia and problems with balance. Regardless of which types of symptoms they are, it must be shown that the progression has been steady for over a year, with no relapses. Doctors use the Expanded Disability Status Scale (EDSS) to measure this.

MRI Findings

As many of us know, diagnosis of multiple sclerosis requires the dissemination (worsening) of symptoms and lesions in space and time. The “dissemination in time” is taken care of by the worsening of symptoms for at least one year (as discussed above). MRI scans are used to determine “dissemination of lesions in space,” with very specific criteria used to determine PPMS.

Using MRI scans to diagnose PPMS has its challenges, one being that the results of the MRI scan of the brains of people with PPMS may be more "subtle" than that of people with RRMS, with far fewer gadolinium-enhancing (active) lesions. However, the spinal cord MRI will usually show atrophy.

A Positive Lumbar Puncture

Also referred to as a spinal tap, there are some problems with using this test and it may be excluded in the future if MRI criteria continue to be validated. However, given the difficulties with MRI findings in some patients, lumbar punctures are still very helpful in confirming some diagnoses of MS (and ruling out other conditions). Two findings are important:
  • Presence of Oligoclonal Bands: This means that "bands" of certain proteins (immunoglobulins) show up when the spinal fluid is analyzed. Evidence for oligoclonal bands in the CSF can be seen in over 90% of people with MS, but can be found in other disorders, too.
  • Intrathecal IgG Antibody Production: This means that IgG is produced within the spinal fluid compartment. This does not usually happen – it is a hint that inflammatory cells (T cells and/or B cells) have entered the spinal fluid through the blood-brain barrier and begun producing IgG.

No Relapses in the Past

Think back, waaaay back. Eliminating the possibility that a person has had relapses is not as simple as looking at the symptoms that the person has experienced in the recent past or since they started worsening. Many times, people experienced symptoms in the past that were part of a relapse, but because they were vague, subtle or went away on their own, these people were never diagnosed as having MS. (In my case, I experienced tremor, the MS hug, vertigo and several other symptoms of MS for several years before ever being diagnosed with RRMS.) Doctors and patients have to look back for as many as 20 years trying to identify any sort of strange symptoms or transitory sensations that the person experienced in the past that actually could have been a relapse.

Additional Points:

Levels of Certainty? Because of the some of the challenges and obstacles to meeting all of the above criteria, three levels of “diagnostic certainty” have been established: definite, probable and possible PPMS. When the above criteria were applied to a set of people with PPMS, it turns out that 65% had “definite PPMS” and 35% had “probable PPMS.”

VEP: Visual evoked potentials is a test that involves wearing EEG (electroencephalographical) sensors on the scalp while watching a black-and-white checkered pattern on a screen. The EEG measures slowed responses to visual events, which indicates neurological dysfunction. VEPs have also been helpful in solidifying a diagnosis of PPMS, especially when other criteria are not met definitively.

PPMS Could Also Be(come) PRMS: Some people who start with a diagnosis of PPMS may experience relapses after diagnosis. Once that starts happening, the diagnosis of that person is changed to progressive-relapsing MS (PRMS). Everyone with PRMS starts out with the diagnosis of PPMS. This is the rarest form of MS, with only 5% of individuals with MS (and about a quarter of people who start out with PPMS) having this diagnosis.

Is It MS or Something Else? Many neurological diseases mimic MS, so much of the burden of diagnosing MS is eliminating the possibility that it could be something else. Other disorders that need to be ruled out include: Vitamin B12 deficiency, Lyme disease, spinal cord compression, neurosyphilis or motor neuron disease, just to name a few.

Sources:

Pohlman, CH, Reingold, SC, Edan, G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald criteria." Ann Neurol 2005; 58:840.

Ebers, George C. Natural history of primary progressive multiple sclerosis. Multiple Sclerosis. 2004; 10: S8-S15.

Thompson, Alan. Overview of primary progressive multiple sclerosis (PPMS): similarities and differences from other forms of MS, diagnostic criteria, pros and cons of progressive diagnosis. Multiple Sclerosis. 2004; 10: S2-S7.

Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol. 2007 Oct;6(10):903-12.

Coyle, Patricia K. and Haper, June. Living with Progressive Multiple Sclerosis: Overcoming the Challenges (2nd ed.). New York: Demos Publishing. 2008.

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