According to the traditional classification of MS, 90% present with a relapsing–remitting course
(RRMS), and if untreated, 50% of them will move on to a secondary progressive phase (SPMS)
fifteen years after the onset of disease7. Approximately 10% of multiple sclerosis patients present
with primary progressive multiple sclerosis (PPMS).
RRMS is characterized by clinical activity (neurological symptoms and signs), defined as fully or
partially recovering relapses, which may be suggested by, for example, blurred vision, paresthesia,
paresis, loss of bladder control, or walking disabilities. No or minimal disease progression is seen
between relapses (remission). The first relapse is termed clinically isolated syndrome (CIS). Some
patients may meet the formal definition of MS with a single clinical episode if their MRI reveals the
simultaneous presence of enhancing and non-enhancing lesions. Most patients with RRMS will
eventually enter a secondary progressive phase8, 9.
SPMS begins with a relapsing-remitting course, followed by gradual worsening with or without
occasional relapses. Phases with minor remission and disease plateaus are observed. The
transition from RRMS to SPMS usually occurs 10 to 20 years after disease onset.
PPMS is characterized by progressive disability. While relapses are rare, plateaus and temporary
minor improvements are occasionally seen. Progressive MS subtypes are diagnosed
retrospectively, based on patient history and clinical evaluation. A common clinical presentation of
PPMS is a spinal cord syndrome with progressive paraparesis, spasticity, and no clear sensory
level. Compared with RRMS, PPMS has a more even sex distribution and later onset, usually two
decades later in life. The course of PPMS tends to be more aggressive than that of RRMS4, 10, 11.
A recent update of the MS subtype classification has suggested a two-fold division of the disease
into relapsing and progressive forms, each of which has active and inactive stages;11 this
classification may be more appropriate when considering upcoming biological treatments being
efficient in progressive MS with inflammatory activity12, 13.