Multiple Sclerosis: Classification

Stages and courses of multiple sclerosis (MS):

  • Clinically isolated syndrome (CLS) – initial stage of clinical presentation.
    • There is an initial symptom suggestive of multiple sclerosis. The diagnosis is not yet confirmed; however, a second episode occurs in 30% of patients with HIS within one year.
  • Relapsing-remitting (“RRMS”) form of progression.
    • Sudden onset of disease symptoms that temporarily subside.
    • Occurs in 85% of cases in the early stages.
  • Primary (chronic) progressive form of progression (PPMS).
    • Continuous course, no relapses.
    • The disease already begins with insidious symptoms.
    • No significant regression of symptoms.
    • Occurs in 15% of cases.
  • Secondary (chronic) progressive course (SPMS).
    • In this form, the disease begins relapsing, but later changes to a progressive course.
    • Gradual increase in clinical symptoms and neurological impairment.
    • The regression of symptoms after a relapse is increasingly incomplete.

In over 80% of cases, multiple sclerosis begins with a relapsing course. Often, the disease progresses over time to a secondary progressive course. Explanation of McDonald criteria 2010

Clinical presentation Additional parameters that must be present for a diagnosis of MS
1 ≥ 2 relapses; ≥ 2 objectively demonstrable lesions + evidence of a precedingrelapse event. None
2 ≥ 2 relapses; one objectively demonstrable lesion. Spatial dissemination, evidence by:

  • ≥ 1 T2 lesion in min. 2 of 4 MS-typical regions of the CNS,
  • Or waiting for another relapse caused by a lesion in a different location.
3 1 thrust; ≥ 2 objectively demonstrated lesions. Temporal dissemination, evidence by:

  • Simultaneous presence of asymptomatic gadolinium-uptaking and non-uptaking lesions.
  • Or new T2 and/or gadolinium-uptaking lesion(s) on follow-up MRI time-independent compared with baseline scan,
  • Or waiting for another episode
4 1 episode; one objectively demonstrated lesion (clinically isolated syndrome [CIS]) Spatial dissemination:

  • ≥ 1 T2 lesion in min 2 of 4 MS-typical regions of the CNS,
  • Or waiting for another relapse caused by a lesion in a different location, and

temporal dissemination:

  • Simultaneous presence of asymptomatic gadolinium-uptake and non-uptake lesions,
  • Or new T2 and/or gadolinium-uptake lesion(s) on follow-up MRI time-independently compared with baseline scan,
  • Or waiting for another episode
5 Gradual neurological progression (PPMS).
  • Continuous clinical progression over one year (retrospective/prospective).
  • Applicability of two of the following three items:
    • Evidence of spatial dissemination by ≥ 1 T2 lesion in min 2 of 4 MS-typical regions of the CNS,
    • Evidence of spatial dissemination by ≥ 2 T2 lesion in the spinal cord.
    • Or positive CSF findings (evidence of oligoclonal bands/increased IgG index).

Innovations in the McDonald criteria

  • If patients with clinically isolated syndrome (CIS) meet the criterion for spatial dissemination (scattering) and there is no other explanation for their symptoms, a diagnosis of MS is now also possible by detection of oligoclonal bands. That is, spatial dissemination in combination with a positive CSF analysis is sufficient as a diagnostic criterion for HIS.
    • Both symptomatic and asymptomatic lesions may now be used for spatial and temporal dissemination.
    • In addition to juxtacortical lesions, cortical lesions may now indicate spatial dissemination.
    • For the diagnosis of primary progressive MS, cortical and symptomatic lesions are now also allowed for the detection of dissemination.
  • With the diagnosis, physicians should use the history to determine the preliminary course of the disease based on the diagnosis, i.e., to indicate whether the disease is relapsing-remitting (“relapsing-remitting”, RRMS), primary (chronic) progressive (PPMS), or secondary (chronic) progressive (SPMS). Furthermore, it should be indicated whether there is an active disease with rapid disability progression (see below “Stages and courses of multiple sclerosis (MS)”).