• In most clinical contexts, progression to SPMS is diagnosed retrospectively due to a gradual worsening of symptoms following a disease relapse course, which may or may not be inclusive of short periods of acute exacerbations.1 However, a study by Lorscheider et al. has proposed an objective definition to describe the onset of secondary progressive disease as the following:2
    • An increase in EDSS by 1.5 points if the last EDSS before conversion to SPMS was 0, an increase by 1 point if the EDSS was between 1 and 5.5, or an increase by 0.5 points if the EDSS was above 5.5 
    • A minimum EDSS score at the time of progression of 4
    • A minimum pyramidal FS score at the time of progression of 2
    • Confirmation of disability progression at two or more consecutive visits separated in time by the minimum of 3 months 
  • The transition phase from RRMS to SPMS is gradual and variable, thus there are no clear clinical, imaging, immunological or pathological criteria to determine transition1,3
    • The early indicators for SPMS disease are typically subtle and less evident, and so these might not be caught in regular neurological examinations. Hence, a period of diagnostic uncertainty exists4

Hourglass with tick icon for prompt diagnosis and early management

Prompt diagnosis and early management may help patients4,5

  • Progression to SPMS is identified by a combination of clinical evaluation of disability progression and imaging, and often requires repeated assessments6
  • Methods include clinical interview and examination, EDSS and other screening tools, assessment of cognitive function, relapse monitoring, and MRI7,8
    • Engaging in clinical interviews and examinations allows clinicians to realistically assess the patient’s transition from RRMS to SPMS7
    • An integrated multidisciplinary healthcare approach is therefore vital at the progressive stage of the disease to identify information needs and tailor support interventions7

Papers and magnifying glass icon for tests and tools to identify progression

Several common tests and tools exist to help identify disease progression associated with cognitive and physical symptoms of SPMS:8

  • Cognitive assessments include the PASAT and the BICAMS tests, however the SDMT and BVMT-R tests, which form part of the BICAMS assessment, can also be administered individually8,9
    • The SDMT is a widely used measure of information processing speed that involves symbol-digit matching by the participant; it has been shown to be a significant predictor of several patient-related outcomes in MS including driving, employment, and instrumental daily activities10,11
  • Physical tests include the T25-FW, 9-HPT, EDSS, and MRI assessments8
  • It is important to identify ‘hidden symptoms’ (i.e. mood and/or cognition) that may signal a change in disease course by asking patients about everyday activities, mobility or their interactions with friends or family3
  • As the symptom profile of progression to SPMS differs for each patient, discussions should be tailored to the individual patient3
  • Monitoring cognitive function for evidence of progression is recommended, but is currently not routine12,13
    • The prevalence and severity of cognitive impairment appears greatest in SPMS, and information processing and memory are the most commonly affected cognitive domains13

9-HPT, 9-Hole Peg Test; BICAMS, Brief International Cognitive Assessment for MS; BVMT-R, Brief Visuospatial Memory Test-Revised; EDSS, Expanded Disability Status Scale; MRI, magnetic resonance imaging; MS, multiple sclerosis; PASAT, Paced Auditory Serial Addition Test; RRMS, relapsing-remitting multiple sclerosis; SDMT, Symbol Digit Modalities Test; SPMS, secondary progressive multiple sclerosis; T25-FW, Timed 25-Foot Walk.


  1. Lublin FD, et al. Neurology. 2014;83(3):278–286.
  2. Lorscheider J, et al. Brain. 2016;139(Pt 9):2395–2405.
  3. Oh J, Alikhani K, et al. Neurodegener Dis Manag. 2019;9(6):301–317.
  4. Katz Sand I, et al. Mult Scler. 2014;20(12):1654–1657.
  5. Giovannoni G, et al. Mult Scler Rel Disord. 2016:9:S5–S8.
  6. Davies F, et al. Int J MS Care 2016;18(5):257–264.
  7. Bogosian A, et al. BMJ Open. 2019;9(3):e026421.
  8. Tur C, Moccia M, et al. Nat Rev Neurol. 2018;14(2):75–93.
  9. Sumoski JF, et al. Neurology. 2018;90(6):278–288.
  10. Strober L, et al. Mult Scler. 2019 Nov; 25(13): 1781–1790.
  11. Pham L, et al. NPJ Digit Med. 2021 Feb 24;4(1):36.
  12. Hobart J, et al. Mult Scler. 2019;25(13):1809–1818.
  13. Kalb R, et al. Mult Scler. 2018;24(13):1665–1680.
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UK | December 2021 | 145907

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