Secondary progression follows the RRMS in the majority of cases and it is likely that over 80% of RRMS patients will eventually enter a secondary progressive phase, with risk of progression increasing incrementally dependent on the length of time since diagnosis (see Chap. 3) [39–41]. Natural history studies regarding risk of progression have been hugely informative and rely upon the use of defining disability using specific scales (see below). The epidemiology of progressive MS gleaned from these studies will be further discussed in subsequent chapters.

Away from large-scale epidemiological studies, when faced with deterioration in an individual patient, it is useful to make a clinical diagnosis of disease stage in order to prognosticate, plan for long-term care and, importantly, decide on the suitability of disease-modifying therapy. Most physicians seeing patients with an initial diagnosis of RRMS would define secondary progression as period of sustained deterioration in neurological function without remission [2]. Once a given level of disability has been sustained for 6 months, the likelihood of reversibility (in treatment-naive patients) is likely to be negligible [42]. Deterioration may occur as a result of relapse activity and delineating relapse from progression at the point of onset of neurological worsening may be difficult. The speed of change in neurological function may give a clue to the onset of progression: if deterioration in neurological status is rapid, this suggests a relapse; whereas slow deterioration would generally be regarded as disease progression [43]. Another important observation on disease progression in MS is that for a given patient, progression of the disease appears to occur at a steady rate [44]. Furthermore, in patient populations, once progression has “set in,” further rates of progressive decline appear to happen in a uniform (and slowly progressive) way, and in a way that appears independent of previous clinical disease course [45–47]. Thus, the pattern of deterioration is highly indicative of progression and may delineate from relapse. However, the course of the disease may only become clear over time and may only become apparent after a period of retrospective analysis.

Progressive clinical deterioration can occur in a number of neurological domains (see Table 2.3), some of which will be discussed in more detail below. Usually, a fairly stereotyped clinical pattern emerges of an “upper motor neuron syndrome” causing impaired ambulation and spasticity, with variable degrees of superimposed ataxia and cognitive impairment. In addition, bladder and bowel dysfunction, fatigue, mood disturbance, and paroxysmal symptoms such as trigeminal neuralgia often occur. These will also be discussed further in Chap. 8 with a description of symptomatic therapies.

In order to determine whether a particular therapeutic agent is effective in preventing or slowing disease progression, outcome measures which will reflect disability are required. Several disability scales are in common usage. While many have their own individual benefits, several problems are linked to their use and some remain unvalidated. The short-term nature of many clinical trials may also make the use of disability scales difficult to interpret. A number of disability scales of relevance to MS will be discussed here. Further discussions on the use of disability scales in epidemiological studies will be provided in Chap. 3 and the results of treatment ­trials using disability scales in Chap. 9.