Primary progressive multiple sclerosis (MS) is primarily a neurodegenerative phenotype of MS. It is characterized by a predominant progressive disease course that largely determines the disability progression rather than the rare early superimposed relapses. Therefore, frustratingly, the immunomodulatory and immunosuppressive approaches have failed to have any meaningful impact on the disability progression in primary-progressive MS. Some benefit can still be obtained in select patients where notable number of superimposed relapses or significant ongoing subclinical magnetic resonance imaging activity may allow for immunomodulatory agents to work. Symptomatic treatment for MS should also not be overlooked in this population for impact on quality of life. Future work will likely focus more on the remyelinating and regenerative strategies to help this group of patients. Unfortunately, the lack of any warning symptoms hampers any future prevention trial in this population. However, inferring from previous studies in secondary progressive MS, a global effort to eliminate initiation of tobacco smoking in teenagers or young adults may also delay the onset of a progressive disease course in MS.
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