Multiple Sclerosis (MS)


Primary progressive multiple sclerosis (PPMS) is one of the disease courses in multiple sclerosis (MS), as defined by the International Advisory Committee on Clinical Trials of MS.1 It is characterized by worsening neurologic function from symptom onset without early relapse or remission.

The disease is further classified as either active or nonactive and with progression or without progression. In active PPMS, there may be an occasional relapse and/or evidence of new magnetic resonance imaging (MRI) activity over a specified period of time. In PPMS with progression, there is evidence of an increase in disability over time, with or without relapse or new MRI activity.2

Primary progressive MS affects 10% to 15% of patients diagnosed with MS.3 The disease course affects men and women equally.4

Primary Progressive MS Causes

Multiple sclerosis is characterized by an immune attack on oligodendrocytes which form the myelin sheath in the central nervous system. The exact cause of the disease is not known, but it is likely multifactorial. It is widely accepted that MS is immune-mediated, but research has shown that it can be triggered by environmental risk factors in people who may have a genetic predisposition.5

Unlike relapsing-remitting MS (RRMS) and secondary-progressive MS, which are characterized by symptomatic episodes caused by inflammation, the worsening of symptoms in PPMS is caused by nerve damage or loss.4 This impairs the nerve signals and leads to the symptoms of PPMS.

Risk factors for MS include Epstein-Barr Virus infections, smoking, HLA-DR2 haplotype, geographic location, and vitamin D deficiency.5

Primary Progressive MS Symptoms

The symptoms of PPMS can be mild, moderate, or severe, and no two patients are affected in the same way.6

Symptoms usually start around age 35 to 39 and include pain, Lhermitte’s sign, vision impairment, muscle weakness, spasticity, paralysis, fatigue, numbness, dizziness, balance and coordination issues, cognitive issues, depression, incontinence, and sexual dysfunction.4,6 

Symptoms steadily worsen over time with no relapses and remissions, but the rate of progression can vary from person to person.

Primary Progressive MS Diagnosis

The diagnosis of PPMS begins with a detailed medical history and neurological examination. It may also include optical coherence tomography and visual evoked potentials.6

For a patient to be diagnosed with PPMS, they must have 1 year of worsening neurological function without remission plus at least 2 of the following symptoms: an MS lesion in the brain, 2 or more lesions of a similar type in the spinal cord, and oligoclonal bands or an elevated IgG index in the cerebrospinal fluid.7 

Because meeting these criteria can take several years, the diagnosis of PPMS is usually delayed and can take 2 to 3 years longer than that of RRMS.2 

Primary Progressive MS Treatment

Treatment approaches for PPMS include modifying the course of the disease, managing its symptoms, rehabilitation, and lifestyle changes.8

Most disease-modifying therapies available for MS work by reducing inflammation in the brain and spinal cord and, therefore, are not effective in PPMS, which is characterized by nerve degeneration. The US Food and Drug Administration approved 1 disease-modifying treatment, ocrelizumab (Ocrevus®), for patients diagnosed with PPMS, as well as other forms of MS.9

There are also ongoing clinical trials testing other potential new treatments that may be effective in people with PPMS. These include the Bruton’s tyrosine kinase inhibitor tolebrutinib (SAR442168), selective tyrosine kinase inhibitor masitinib dimethyl fumarate, idebenone, hydroxychloroquine, the allogeneic T-cell immunotherapy ATA188, and the proteasome inhibitor ixazomib (Ninlaro®).

Treatments aimed at managing the symptoms of PPMS and improving patients’ quality of life include medications to treat muscle spasms, medications to treat bladder dysfunction and erectile dysfunction, and antidepressants.4 

Rehabilitation strategies include physiotherapy to improve strength, balance, and posture, as well as to reduce pain and fatigue. Physiotherapy can also improve bladder dysfunction through pelvic floor exercises. Occupational therapy can be used to teach patients energy conservation techniques and adaptations to maintain independence. Speech and language therapy can be used to improve speech and swallowing issues. Rehabilitation strategies also include vocational rehabilitation to help patients maintain their current employment or find new employment, and cognitive rehabilitation to help them function despite the cognitive changes they are experiencing.10

Diet, exercise, and healthy behaviors can also help manage the symptoms of PPMS. These include adopting healthy eating habits, engaging in physical activity, ceasing smoking, reducing alcohol consumption, and spending as much time outdoors as possible.11

Primary Progressive MS Prognosis

There are no tests available that can predict the rate of disability progression in PPMS, and the progression rate varies from patient to patient. Research has shown that, in general, the life expectancy of someone with MS is 7 to 14 years shorter than that of the general population.12 However, PPMS is not a terminal condition and patients can live well into old age with proper treatment and symptom management.

References

  1. Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278-286. doi:10.1212/WNL.0000000000000560
  2. Primary progressive MS (PPMS). National Multiple Sclerosis Society. Accessed June 10, 2021.
  3. Holland NJ, Schneider DM, Rapp R, Kalb RC. Meeting the needs of people with primary progressive multiple sclerosis, their families, and the health-care community. Int J MS Care. 2011;13(2):65-74. doi:10.7224/1537-2073-13.2.65
  4. Primary-progressive multiple sclerosis (PPMS). Cedars Sinai. Accessed June 10, 2021.
  5. Waubant E, Lucas R, Mowry E, et al. Environmental and genetic risk factors for MS: an integrated review. Ann Clin Transl Neurol. 2019;6(9):1905-1922. doi: 10.1002/acn3.50862
  6. Primary progressive multiple sclerosis. Johns Hopkins Medicine. Accessed June 10, 2021.
  7. Thompson AJ, Montalban X, Barkhof F, et al. Diagnostic criteria for primary progressive multiple sclerosis: a position paper. Ann Neurol. 2000;47(6):831-835.
  8. Treating PPMS. National Multiple Sclerosis Society. Accessed June 10, 2021.
  9. FDA approves new drug to treat multiple sclerosis. US Food and Drug Administration. March 29, 2017. Accessed June 10, 2021.
  10. Khan F, Amatya B, Turner-Stokes L. Symptomatic therapy and rehabilitation in primary progressive multiple sclerosis. Neurol Res Int. 2011;2011:740505. doi:10.1155/2011/740505
  11. Diet, exercise & healthy behaviors. National Multiple Sclerosis Society. Accessed June 10, 2021.
  12. Scalfari A, Knappertz V, Cutter G, Goodin DS, Ashton R, Ebers GC. Mortality in patients with multiple sclerosis. Neurology. 2013;81(2):184-192. doi:10.1212/WNL.0b013e31829a3388

Reviewed by Kyle Habet, MD, on 7/1/2021

Reviewed by Kyle Habet, MD, on 7/1/2021.