Diagnosing Primary Progressive Multiple Sclerosis

Many Features of PPMS Make Diagnosis Challenging

Close-up view of spinal injection
Sisu/RooM/Getty Images

Diagnosis of primary progressive multiple sclerosis (PPMS) has special challenges, as people with PPMS have a slow gradual loss of function over months to years. This is in contrast to relapsing-remitting MS, in which a person may recover neurological function after a relapse.

Diagnosis of Primary Progressive MS

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:
    • A brain lesion that is typical of MS
    • Two or more MS lesions in the spinal cord
    • Positive lumbar puncture -- meaning there is evidence of either oligoclonal bands or an elevated IgG antibody level (these are proteins that indicate inflammation is occurring in the body)
  • Worsening of Symptoms for At Least One Year 

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, to diagnose PPMS. Doctors use the Expanded Disability Status Scale (EDSS) to measure this.

MRI Findings in PPMS

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.” 

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 in PPMS

Also referred to as a spinal tap, lumbar punctures can be very helpful in making or confirming the diagnosis of PPMS 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 percent 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 -- a sign that there is immune activity going on. 

VEP to Help Confirm the Diagnosis of PPMS

Visual evoked potential is a test that involves wearing EEG (electroencephalogram) 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.

Progressive-Relapsing MS

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 percent of individuals with MS affected. 

Ruling out Other Health Conditions

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:

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

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

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

National MS Society. Diagnosing PPMS. Accessed February 2nd 2016.

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

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.

Continue Reading