Primary Progressive Multiple Sclerosis (PPMS) Disease Course:

Primary-progressive multiple sclerosis (PPMS) is a course or some consider it a form of the disease that is characterized from onset of the disease as a progressively worsening condition. This is in contrast to relapsing-remitting multiple sclerosis (RRMS) which is characterized by episodes of symptoms, brought on by inflammation, followed by periods of limited or no symptoms. Secondary Progressive MS (SPMS) is similar to primary progressive MS however, SPMS is characterized as the patient first experiencing relapsing-remitting MS often for many years.  The disease cours then presents fewer relapses and moves towards a more steady progression and accrual of disability quite similar to PPMS.

The progressive worsening of symptoms is thought to be caused by nerve damage or loss of neurons rather than the inflammation.

In PPMS symptoms generally, do not remit. About ten to fifteen percent (10%-15%) of people with MS are diagnosed with Primary-progressive multiple sclerosis, although the diagnosis usually needs to be made after a person has been living for a period of time with progressive, accrued disability but not acute attacks.

The term “primary” as from the first sign of symptoms this disease course is progressive gradually getting in time rather than appearing as exacerbations (relapses or attacks) as is characterized by relapsing-remitting MS.

Early symptoms of PPMS are often subtle issues in ambulation (walking) that continue to develop, often at a slow pace, over time.

Presenting symptoms can and do vary from patient to patient and progression of symptoms also can vary from patient to patient along a line of time.  Many PPMS patients experience long periods of time where the disease appears to be stable with no changes while others continue to accrue disability.

Primary-progressive MS most often is diagnosed in people who are older with average onset in their forties or fifties which is older than the mean average in relapsing-remitting MS.  This is not to say that PPMS cannot occur earlier or later in life as cases do exist diagnosed both earlier in life and later in life.

Symptoms in PPMS can present themselves quite similar to the relapsing-remitting disease course with patients experiencing the same or similar symptoms.

Unlike the relapsing-remitting disease course, statistical distribution of PPMS is near equal among women and men.  Relapsing-remitting multiple sclerosis has a significantly higher statistical distribution among women than men.

Progressive relapsing MS:

Some people who have progressive MS from the start also experience relapses on top of the clear progression. This is sometimes described as progressive relapsing MS as exacerbations (attacks) similar to relapsing-remitting MS accompany disease progression.

Diagnosing Primary Progressive Multiple Sclerosis (PPMS)

Diagnosing any form of multiple sclerosis for many patients may take a long time due to variance of the disease courses, symptoms that may mimic other diseases and more.

Primary progressive MS patients are most often diagnosed in their in their forties and fifties which also is when symptoms from other existing conditions are more likely to present themselves.  An example would be arthritis or diabetes.  Other existing diseases can complicate the diagnosis of PPMS.  In the relapsing-remitting course of the disease, Magnetic Resonance Imaging (MRI) clearly displays plaques (lesions or scars) in the Central Nervous System which is considered a signature of the RRMS disease course.  In PPMS diagnosis can be considerably more difficult up to and including MRI evidence, brain atrophy (shrinkage) and other characteristics of this course of the disease.

Diagnosis of all forms of MS begins with a detailed medical history and neurological examination.

Because MS can have similar symptoms of other nervous system disorders, diagnostic tests help rule out other causes and confirm a diagnosis. These tests may include a magnetic resonance imaging (MRI) scan of the brain and spinal cord. The patient’s medical team may order a lumbar puncture, also known as a spinal tap, and cerebrospinal fluid analysis, as well as nerve function tests. Blood tests may be performed to rule out other conditions that have similar symptoms.

The only definitive way to diagnose PPMS apart from other forms of multiple sclerosis is by observation.

In order to confirm a diagnosis of PPMS, the patient must:

  • Have a year of consistent progression of the condition, including worsening neurologic function
    AND meet two of the following criteria:
  • A type of lesion in the brain that is recognized by experts in as being typical of multiple sclerosis
  • Two or more lesions of a similar type in the spinal cord
  • Evidence in the spinal fluid of oligoclonal bands or an elevated IgG index, both of which are indicative of immune system activity in the central nervous system

Meeting these criteria can sometimes take a fairly long time, particularly if the person has only recently begun to experience neurologic symptoms. Several studies have suggested that the PPMS may take two to three years longer to diagnose than relapsing-remitting MS.

Monitoring of Primary Progressive Multiple Sclerosis (PPMS):

Disease activity and progression should be evaluated at least yearly by your healthcare provider and any significant progression or new symptoms warrant a visit to your provider.

Just as is the case with relapsing-remitting MS or secondary progressive MS it is important to document any progression of primary progressive MS.  Documenting the course of the disease daily can help your care team understand the progression of the disease and try to best manage its progression towards the patients quality of life.

Treatment of Primary Progressive MS: 

Until recently (March of 2017) there were no approved medications available for PPMS, however several do exist in off-label usage.

The United States Food and Drug Administration (FDA) recently approved a medication called Ocrevus (Ocrelizumab) for both relapsing-remitting and primary progressive multiple sclerosis patients.  Expectations are that Ocrevus will soon become available in other nations around the world.

Off-label medications that have displayed positive impacts for PPMS patients include:

  • Rituximab
  • Cladribine
  • Methotrexate
  • Mitoxantrone

The experimental oral therapy MN-166 (ibudilast) has been designated by the U.S. Food and Drug Administration as a “Fast Track Product” in terms of its development as a possible treatment of progressive MS, including primary progressive and secondary progressive MS. Investigators are currently conducting a phase II clinical trial of ibudilast in 250 people with progressive forms of MS, principally funded by the National Institutes of Neurological Diseases and Stroke (NINDS), with additional support by MediciNova and the US National MS Society.

Many patients who endure life with PPMS take high dose Biotin as some clinical trials have shown improvements in the disease course in small scale studies.

As with any chronic care condition, it is important that you discuss all your options with your health care provider before beginning any medications, supplements or alterations in lifestyle.

Research:

People who have received a diagnosis of PPMS are often frustrated by the relatively small number of clinical trials in PPMS compared to the large number in RRMS. MS clinicians and researchers share this frustration and are actively looking for ways to increase the number of trials of treatments for PPMS, addressing several obstacles:

  • The disease modifying medications currently used to treat relapsing forms of MS primarily target inflammation in the central nervous system (CNS). Because inflammation plays a much smaller role in PPMS than in relapsing forms of MS, these medications do not seem to be as effective in PPMS — which means that new treatment targets need to be identified.
  • In PPMS, there is a lack of easily-identifiable outcomes to measure in clinical trials. In the trials for the approved disease-modifying therapies, investigators looked at outcomes such as number of relapses and number of new lesions (also called plaques) seen on magnetic resonance imaging (MRI) to determine if people who received the treatment had lower numbers than those who received a placebo (non-active substance). The outcome measurements do not adequately quantify disease progression in the PPMS group.
  • Disease progression in PPMS can be quite slow, making the ability to identify an effect on progression difficult in a two- or three-year trial.

Researchers are working to understand why some people experience aggressive worsening of MS and others experience a milder course, and to identify other ways to measure the changes that occur in PPMS so that they can more easily test potential treatments.

Read More About Progressive MS Research at The US National MS Society – Click Here

Summary:

While presently there is no cure for any forms of multiple sclerosis a tremendous amount of research is taking place towards progressive courses of multiple sclerosis academically and seeking effective treatments.  As with all forms of multiple sclerosis moving towards a more healthy lifestyle can help towards quality of life including examination of diet, exercise, and overall wellness regimens.  Having a skilled care provision team that is multi-discipline and multiple sclerosis aware can vastly improve quality of life outcomes in all forms of multiple sclerosis.

Patients and families should have a Neurologist, physical and occupational therapist, dietician and mental wellness professionals preferably all skilled in the management of multiple sclerosis.  It is best to be proactive and establish a quality care team from onset of diagnosis of any form of MS.

Most nations where significant numbers of citizens endure life with multiple sclerosis have patient associations available to help navigate life with the disease.  We encourage you to speak to your health care provider and contact patient associations available to you.

Finally, just recently there is some consensus occurring that characterizing multiple sclerosis as “Forms” of the disease is not only confusing patients but actually working against moving towards more progress against the disease and understanding of it.  Multiple Sclerosis is one disease and while its trajectory is different from patient to patient there is much to be said towards this new way of looking at MS towards both academic and medications research.  There exists more common aspects of multiple sclerosis regardless of which “form” is characterized than not.

Some patients have rapid progression of the disease while others live the majority of their lifetime and accrue little disability.  What is clear is that the disease in most of the patient population is either a relapsing characterization or a progressive one and left to it’s own, without treatment, relapsing will in time become more progressive and may well do so even with disease modifying treatments.  Effective treatments for relapsing-remitting multiple sclerosis have only existed for a little over 10 years when the RRMS medication Tysabri (Natalizumab) came to market in 2006.

Since Tysabri’s introduction, many new therapies have become available that in clinical trials and real-world usage are displaying reduced disease activity in RRMS patients in MRI imaging. Thus the train of thought is that movement towards secondary progressive MS may be staved off.  However, transition to secondary progressive MS for relapsing remitting patients is often in a 10-20 year time frame.

Whether or not the therapies slow disease progress and symptom accrual, at this point in time towards multiple sclerosis research this proposed alteration in describing multiple sclerosis is something patients and families need seriously consider.  In doing so it is important to put aside mentally differentiation of your disease course towards communicating with others and instead consider how such changes can impact research and clinical care.  Due to current characterization, clinical trials for example, may exclude “progressive” (SPMS/PPMS/PRMS) patients and thus research knowledge is not obtained.  It has been shown that inflammation, brain atrophy and other disease characteristics do appear across the full spectrum of multiple sclerosis.  It is one disease with differing characteristics per patient.  Whether an individual has aggressive MS, relapsing MS or progressive MS research towards all aspects of the disease .vs. “types of MS” is in question among many research professionals.  As a patient, caregiver or family living with MS please take some time to consider this.  It is one disease, not four with two clear courses, relapses and progressive.