1. Defining the Clinical Course of Multiple Sclerosis

2. 1996 Multiple Sclerosis Clinical Subtypes Subtype Description Relapsing-remitting MSFull recovery from relapses or residual deficit after incomplete recovery Secondary progressive MSProgressive accumulation of disability after initial relapsing course, with/without occasional relapses and minor remissions Primary progressive MSProgressive accumulation of disability from onset, with/without temporary plateaus, minor remissions, and improvements Progressive relapsing MSProgressive accumulation of disability from onset but clear acute clinical attacks with/without full recovery Lublin FD, et al. Neurology. 1996; 46: 907-911.

3. 2013 MS Phenotype Modifications Definitions Disease activity – Relapses; acute/subacute episodes of new/increasing neurological dysfunction, followed by full/partial recovery – New contrast-enhancing T1 hyperintense or new/ enlarging T2 hyperintense lesions Disease progression – Increasing, objectively documented neurologic dysfunction/ disability without recovery (fluctuations and periods of stability may occur) – Imaging not yet established/standardized Lublin FD, et al. Neurology. 2014;83:278–286.

4. 2013 MS Phenotype Modifications Worsening Disease/Disease Progression Worsening disease: Relapsing forms of MS – Documented increase in neurologic dysfunction/disability as a result of relapses or progressive disease Disease progression: Progressive forms of MS – Reserved for worsening disease in those solely in a progressive phase of disease Confirmed worsening/progression – Increase of neurologic dysfunction confirmed throughout a specified time interval – “Sustained progression” should no long be used, as neurologic dysfunction may still improve, even if progression is confirmed Lublin FD, et al. Neurology. 2014;83:278–286

5. 2013 Multiple Sclerosis Clinical Subtypes Subtype Modifications Clinically isolated syndrome Not active Active (transitioning to MS) Relapsing-remitting MS Not active Active Primary progressive MS Active and with progression Active but without progression Not active but with progression Not active and without progression Secondary progressive MS Active and with progression Active but without progression Not active but with progression Not active and without progression Lublin FD, et al. Neurology. 2014;83:278–286.