Multiple sclerosis (MS)

Multiple sclerosis (MS) is a common inflammatory demyelinating disorder of CNS white matter, the most common cause of neurological disability in young adults. Ultimately, it results from immune-mediated attack on the myelin–oligodendrocyte complex, although many features of pathogenesis remain unclear (Compston & Coles, 2002; Compston et al., 2006). Viral infections may be a sufficient but not necessary triggering or exacerbating factor (Larner, 1986; Kennedy & Steiner, 1994; Dalgleish, 1997). Natural history studies indicate that the disease may follow a variable course, permitting classification into a number of groups, which are helpful in defining cohorts for study: relapsing–remitting disease (RRMS), when acute exacerbations resolve over time with no permanent disability, is common at disease onset, but this may evolve into secondary progressive disease (SPMS) when disability accrues between or in the absence of acute exacerbations; rarely, disease is relentlessly progressive from the onset, the primary progressive pattern (PPMS). Benign variants are also recognized. Diagnostic criteria for MS encompass the clinical, neuroradiological, and laboratory findings (McDonald et al., 2001; Polman et al., 2005).

Although MS is most commonly recognized as a cause of physical disability, cognitive impairment is also common. This was described by Charcot, and a large literature has subsequently developed, most particularly in the last two decades (Rao, 1986; Langdon, 1997; Thornton & Raz, 1997; Wishart & Sharpe, 1997; Feinstein, 1999; Foong & Ron, 2000; Kesselring & Klement, 2001; Bobholz & Gleason, 2006; Calabrese, 2006; Fischer & Rao, 2007).