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Primary Progressive Multiple Sclerosis Explained

Posted on May 13, 2021
Medically reviewed by
Evelyn O. Berman, M.D.
Article written by
Brooke Dulka, Ph.D.

Primary progressive multiple sclerosis (PPMS) is a rare form of multiple sclerosis (MS). This disease is unique and has a different clinical course than other types of MS, such as the relapsing-remitting form. Primary progressive MS becomes gradually more disabling and affects 10 percent to 15 percent of people with MS. There are differences in the prognosis and treatment of PPMS compared to other forms of MS.

What Is Primary Progressive MS?

MS is an autoimmune disease in which the body’s immune system eats away at the protective covering of nerve cells. This protective covering is called myelin. It allows your nervous system to communicate with itself in order to plan and execute a variety of behaviors.

There are several types of MS. In particular, relapsing-remitting MS is characterized by distinct episodes of neurological symptoms, which are called relapses. These relapsing forms of MS are then followed by partial or even complete recovery, known as remission.

Primary progressive MS is characterized by steady MS disease progression from the time of onset, with no relapses and remissions early on. In brain scans, PPMS looks different from other forms of MS. The PPMS form of MS can be more challenging to treat than other forms of the disease.

Causes of Primary Progressive MS

What causes PPMS? Multiple sclerosis, in general, has a very complicated set of risk factors and underlying pathology that drive how the disease progresses. There is a genetic predisposition for MS, such as abnormalities in genes that code for human leukocyte antigen (HLA). This antigen is a protein responsible for regulating the immune system. Despite this fact, no specific genetic variations have been linked to the PPMS type of MS.

Environmental factors can also play a role in the development of MS. Low vitamin D is associated with an increased risk of developing MS. Vitamin D may also have some benefits for people already living with MS symptoms. Discuss taking any supplements with your doctor because taking too much vitamin D can be harmful. Smoking and obesity are also linked to MS, although less is known about the relationship of these risk factors to PPMS specifically.

How many types of MS are there? Read: Types of Multiple Sclerosis

The Epstein-Barr virus (EBV) has strong associations with MS. Epstein-Barr virus is also known as mononucleosis, or mono. In fact, the traces left behind by an EBV infection have been found in postmortem tissue collected from the central nervous system (CNS) and lymph nodes of a person who lived with PPMS. Scientists believe that EBV-transformed immune cells that repeatedly enter the brain and spinal cord, in connection with MS attacks, may be the cause of RRMS. In contrast, PPMS may be caused by the more long-term activity of EBV-transformed immune cells in the brain and spinal cord. The B cell is one type of important immune cell. Another important type of immune cell in PPMS (and MS in general) is T cells.

Signs and Symptoms of PPMS

In PPMS, the person’s neurological functions typically become steadily worse. Primary progressive MS is characterized by no symptom flare-ups (relapses) and no recovery (remission). The speed at which the disease progresses varies from person to person. Some of the signs and symptoms of PPMS include:

  • Motor difficulties (trouble standing or walking)
  • Pain (headaches, pain in the legs and feet, back pain, and muscle spasms)
  • Electric-shock sensations (Lhermitte sign)
  • Vision problems
  • Muscle weakness
  • Balance issues
  • Paralysis
  • Numbness and tingling
  • Dizziness
  • Shakiness
  • Difficulty thinking clearly
  • Mood changes (including depression)

Read more about the symptoms of PPMS here.

Diagnosis of PPMS

Diagnosis of MS is based on the McDonald criteria, which were last updated in 2017. These criteria rely on detecting active inflammatory “hot spots” in the CNS. These hot spots are identified by positron emission tomography (PET) imaging, magnetic resonance imaging (MRI), or spinal canal production of immunoglobulins (IgGs). Immunoglobulin proteins are also called oligoclonal bands. These bands are a measure of inflammation in the spinal fluid. Whether or not you have lesions also plays a major role in the diagnosis of MS. Lesions are damage to the brain or spinal cord. They are also sometimes called plaques because of the inflammation in the brain.

According to the McDonald criteria, in addition to one year of worsening disease without remission, two out of three of the following components are needed to diagnose MS:

  • More than one brain lesion (as seen on an MRI) recognized as MS
  • More than two spinal cord lesions (as seen on an MRI)
  • The presence of cerebrospinal fluid-specific oligoclonal bands

A doctor will come to a diagnosis such as PPMS after taking your medical history, doing a physical examination, ordering MRI scans (and potentially other types of imaging), and doing a spinal tap (also called lumbar puncture) to draw out fluid from the spinal canal. However, diagnosing MS can be difficult, especially when a person has MS-like symptoms but does not have any lesions.

Primary Progressive MS Treatment

There is no standard medical treatment for PPMS. There have been many failed medication trials for the treatment of PPMS. Nevertheless, several treatment options show some promise for slowing disease progression that distinguishes PPMS from other forms of MS.

Immunomodulatory Drugs

Ocrevus (ocrelizumab), a monoclonal antibody medication that reduces the number of B cells, is the first medication that has ever shown significant efficacy in slowing the disability progression of PPMS. This was shown in a phase 3 clinical trial in people living with PPMS. Another potential immunomodulatory medication that has shown some promise is biotin. Biotin is a vitamin that appears to be a remyelinating agent — it rebuilds the conductive sheath of myelin that MS destroys.

EBV-Specific T-Cell Therapy

Clinical improvements in people with PPMS have been seen in a phase 1 clinical trial of EBV-specific T-cell therapy. Although this very small phase 1 clinical trial showed that the medication was well-tolerated by participants and that improvement occurred, further research into this potential treatment option is necessary.

Prognosis and Outlook for PPMS

Compared with RRMS, people with PPMS have a poor prognosis. However, there is a lot of variation in the reported rates of progression among people who have the disease. In one large, long-term clinical study, the best predictors of outcome for PPMS were disease duration, scores on the expanded disability status scale (EDSS), and brain volume. All three of these predicted long-term outcomes in individuals with PPMS. However, a better understanding of PPMS is critical in the health care community. More knowledge and awareness of this elusive disease will lead to an earlier diagnosis and more effective treatment options.

Read more about PPMS prognosis and life expectancy here.

Talk With Others Who Understand

MyMSTeam is the social network for people with multiple sclerosis and their loved ones. On MyMSTeam, more than 167,000 members come together to ask questions, give advice, and share their stories with others who understand life with multiple sclerosis.

Are you living with primary progressive multiple sclerosis? Share your experience in the comments below, or start a conversation by posting on MyMSTeam.

References
  1. Primary-Progressive Multiple Sclerosis — The Lancet Neurology
  2. What Is MS? — National Multiple Sclerosis Society
  3. Diagnosis of Multiple Sclerosis: 2017 Revisions of the McDonald Criteria — The Lancet Neurology
  4. Primary Progressive MS (PPMS) — National MS Society
  5. Patterns of Disease Activity in Multiple Sclerosis: Clinical and Magnetic Resonance Imaging Study — British Medical Journal
  6. Primary Progressive Multiple Sclerosis: Putting Together the Puzzle — Frontiers in Neurology
  7. Burden of Risk Variants Correlates With Phenotype of Multiple Sclerosis — Multiple Sclerosis
  8. Vitamin D and MS: Is There Any Connection? — Mayo Clinic
  9. Multiple Sclerosis & Smoking — Cleveland Clinic
  10. Obesity — Multiple Sclerosis Trust
  11. Epstein-Barr Virus in the Central Nervous System and Cervical Lymph Node of a Patient With Primary Progressive Multiple Sclerosis — Journal of Neuropathology & Experimental Neurology
  12. Epstein-Barr Virus and Multiple Sclerosis — Frontiers in Immunology
  13. Primary Progressive Multiple Sclerosis — Johns Hopkins Medicine
  14. Diagnosing PPMS — National Multiple Sclerosis Society
  15. Primary Progressive Multiple Sclerosis (PPMS) — Cleveland Clinic
  16. Ocrelizumab: A New Milestone in Multiple Sclerosis Therapy — Therapeutic Advances in Neurological Disorders
  17. High Doses of Biotin in Chronic Progressive Multiple Sclerosis: A Pilot Study — Multiple Sclerosis and Related Disorders
  18. Epstein-Barr Virus–Specific T Cell Therapy for Progressive Multiple Sclerosis — JCI Insight
  19. Long-Term Clinical Outcome of Primary Progressive MS: Predictive Value of Clinical and MRI Data — Neurology
All updates must be accompanied by text or a picture.
Evelyn O. Berman, M.D. is a neurology and pediatric specialist and treats disorders of the brain in children. Review provided by VeriMed Healthcare Network. Learn more about her here.
Brooke Dulka, Ph.D. is a freelance science writer and editor. She received her doctoral training in biological psychology at the University of Tennessee. Learn more about her here.

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