Multiple sclerosis

Multiple sclerosis (MS) is a chronic progressive disease associated with the degeneration of the myelin shealth surrounding neurons in the central nervous system (CNS) (Miller, 2001). Based on the rate of progression of the disease four clinical courses have been identified. These clinical patterns are not mutually exclusive and patients may experience changes in the pattern of their disease over time (Birnbaum, 2009). Relapsing-remitting is the most common clinical pattern affecting about 85% of people with MS (Murray, 2005). It is characterized by periods in which symptoms are exacerbated followed by periods where varying degrees of recovery are observed (Ibid.). Early in the course of the disease symptoms might resolve completely during the remission phase, however, as the disease progresses complete recovery is less common and deficits are permanent (Birnbaum,2009). About half of the individuals with remitting relapsing MS may start experiencing a progressive deterioration of their condition which may or may not be precipitated by occasional relapses (secondary progressive, Ibid.). About 20% of MS patients experience an almost continuous course of disease with some acute periods of symptom relapse (progressive relapsing) or without any clear-cut relapses or remissions (primary progressive) (Hannay et al., 2004). A smaller percentage of patients experience only infrequent relapses and may still be minimally impaired 15 years or more after diagnosis (benign MS) (Hannay et al., 2004). On the other hand, malignant MS may cause significant disability within a few years after disease onset, leading to dependency or death (Ibid.).

The estimated prevalence rate of MS in Europe for the past three decades is 83 per 100.000 with higher rates observed in northern countries (Pugliatti et al., 2006). It should be noted, however, that some heterogeneity in prevalence rates is observed between the countries as in the case of Scotland where prevalence rates were found to be higher than for the rest of the UK (Ibid.). This finding is consistent with the hypothesis that onset of the disease reflects a complex interaction between environmental factors and specific genetic susceptibility (Noseworthy et al., 2000; Rosati, 2001). The disease is between two and three times more common in women than in men, although the reason for this is unknown (Stauffer, 2006). It is considered to be the most common disabling neurological condition affecting young adults as the highest prevalence rates have been estimated for the age group 35 to 64 years (Pugliatti et al., 2006). The etiology of the disease is not known but immunological, genetic and viral factors are possible triggers (Hannay et al., 2004). At the

moment MS is incurable but disease progression can be delayed with one of several disease-modifying drugs (Goodin et al., 2002).

The lesions that MS causes in the white matter of the CNS are scattered in time and anatomically and may or may not lead to observable deficits (Hannay et al., 2004).

Consequently, the disease is characterised by considerable heterogeneity in clinical manifestations and rates of disease progression. Some common symptoms include problems with balance and mobility, visual impairments (i.e. optic neuritis), sensory disturbances (e.g. numbness, tingling), muscle spasms and spasticity, bowel and bladder dysfunction and fatigue (Hannay et al., 2004). Behavioural and mood disorders are also seen in people with MS such as affective instability, depression and bipolar disorder (ibid.).

Evidence suggests that cognitive deficits are particularly common in multiple sclerosis occurring approximately to 45% to 65% of patients at different stages of the disease (Benedict et al., 2006; Rao et al., 1991a). Impaired cognitive domains are usually information processing speed, mental flexibility, memory and attention (Calabrese, 2006).

The prevalence and impact of cognitive problems in MS used to be underestimated by researchers and clinicians who focused their attention on physical impairments (Fischer, 2001; Hoffman et al., 2007). This could be explained by a misconception that prevailed in the past according to which cognitive impairment occurs only in late stages of the disease (Fischer, 2001). Another explanation suggested by Fischer (2001) was that the brief assessments used to evaluate disability may not be sensitive to mild cognitive impairment.

The nature of cognitive impairment itself, which is usually limited to specific cognitive domains rather than global, may further hinder the detection of cognitive problems (Ibid.).

It has also been found that families and carers often disregard cognitive deficits attributing them to mood disturbances (Rao et al., 1991a). Over the past few decades, however, MS related cognitive impairment has been increasingly acknowledged and researched (Hoffmann et al., 2007). This interest is probably further stimulated by studies demonstrating the major impact that MS related cognitive impairment has on the patient’s quality of life, employment status, social function and mood (Amato, 1995; Cutajar et al., 2000; Rao et al.,1991b ). Reports from clinicians also suggest that the presence of cognitive impairment early in the course of the disease may be predictive of a more rapid progression of physical decline (Lynch et al., 2005).

Memory in particular is one of the most consistently impaired cognitive domains in MS, being evident in about 40% to 65% of patients (Calabrese, 2006; Chiaravalloti & DeLuca, 2008, Rao et al., 1993). It appears to be heterogeneous in nature with some patients

showing mild disturbances that are almost undetectable and others exhibiting striking performance deficits (Hannay et al., 2004). Deficits have been observed on working memory (Rao et al., 1993) and episodic memory (Rao et al., 1991a) but less often in semantic memory (Thornton& Raz, 1997) whereas implicit memory is usually preserved (Fischer, 2001). Verbal memory may be affected and people with MS often complain about word-finding problems (Fischer, 2001). Early research suggested that MS preferentially disrupts retrieval while sparing encoding and storage processes (Rao et al., 1989).

However, later studies have suggested that encoding problems may be the basis of memory deficits in MS (DeLuca et al., 1998; Thornton et al., 2002). At a functional level, memory problems in MS patients have been identified as presenting significant obstacles to maintaining meaningful employment and to successfully completing rehabilitation and vocational training (Beatty et al., 1995). Memory impaired MS patients take part in fewer social activities than their cognitively intact counterparts and require more assistance in performing complex household tasks (Rao, 1991). Another study (Benito-Leon, 2002) showed that memory impairment in MS patients was directly related to their health related quality of life.

There is some controversy in the literature over the factors that affect the course of cognitive impairment in MS. Rao et al. (1993), did not find any associations between memory performance and disease variables such as course, duration, physical disability and medication use. These findings were partly supported by studies showing that cognitive impairment does not correlate significantly with the duration of the disease and is only weakly associated with the extent of neurological and physical disability (Lynch et al., 2005; Thornton & Raz, 1997). The course of the disease, however, seems to have an effect on cognitive problems as clinical observations suggest that cognitive deficits fluctuate in accordance with disease activity (remissions/relapses) (Fischer, 2001). Other factors that potentially affect cognitive performance include emotional disturbances (Thornton & Raz, 1997) and fatigue (Bryant et al., 2004).