Diagnosing Primary Progressive Multiple Sclerosis

A less common type of MS that may take longer to diagnose

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.

The differences between these two types of MS has somewhat to do with the unique biology behind them.

Research suggests relapsing-remitting MS is an inflammatory process (the immune system attacking nerve fibers) whereas primary progressive MS is a more degenerative process, where nerve fibers slowly deteriorate. Why one person develops PPMS as opposed to relapsing-remitting MS is unclear, but experts believe genes may play a role, although the scientific evidence to back this up is still scant.

an asian chinese male nurse getting ready to perform MRI scan for a male patient in the MRI room
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Diagnosis of Primary Progressive MS

Definite PPMS can be diagnosed when the following conditions are met:

  • A person has at least one year of documented clinical progression (meaning a worsening of his or her MS symptoms).
  • At least two of the following:
    A brain MRI lesion that is typical of MS
  • Two or more MS lesions in the spinal cord
  • A 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)

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.

MRI in Diagnosing PPMS

The 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.” 

That said, using MRI scans to diagnose PPMS has its challenges. One major challenge is 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 of people with PPMS will classically show atrophy. Since the spinal cord is greatly affected in PPMS, people tend to have problems with walking, as well as bladder and bowel dysfunction. 

Lumbar Puncture in Diagnosing PPMS

Also referred to as a spinal tap, lumbar punctures can be very helpful in making the diagnosis of PPMS and ruling out other conditions.

Two findings are important in confirming a diagnosis of PPMS:

  • 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—this is a sign that there is an immune system response.

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

It's important to note that 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).

However, everyone with PRMS starts out with the diagnosis of PPMS. Progressive-relapsing MS is the rarest form of MS, with only 5 percent of individuals with MS affected. It should be noted that a previous categorization of PMS (progressive relapsing) was abandoned in this more contemporary classification.

A Word From Verywell

In the end, many neurological diseases mimic MS, so much of the burden of diagnosing any type of 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.

This is why it's important to see a doctor for a proper diagnosis if you are experiencing neurological symptoms. While the diagnosis process may be tedious, remain patient and proactive in your health care.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  3. Abdelhak A, Hottenrott T, Mayer C. CSF profile in primary progressive multiple sclerosis: Re-exploring the basicsPLoS One. 2017;12(8):e0182647. doi:10.1371/journal.pone.0182647

  4. Chirapapaisan N, Laotaweerungsawat S, Chuenkongkaew W. Diagnostic value of visual evoked potentials for clinical diagnosis of multiple sclerosisDocumenta Ophthalmologica. 2014;130(1):25-30. doi:10.1007/s10633-014-9466-6

  5. Gaitán MI, Correale J. Multiple Sclerosis Misdiagnosis: A Persistent Problem to SolveFrontiers in Neurology. 2019;10. doi:10.3389/fneur.2019.00466

  6. Coyle PK, Halper J. Living With Progressive Multiple Sclerosis: Overcoming the Challenges. Demos Medical Publishing.

Additional Reading
  • Cree BA. Genetics of primary progressive multiple sclerosis. Handb Clin Neurol. 2014;122:211-30.

  • National MS Society. Diagnosing PPMS.

By Julie Stachowiak, PhD
Julie Stachowiak, PhD, is the author of the Multiple Sclerosis Manifesto, the winner of the 2009 ForeWord Book of the Year Award, Health Category.