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In this chapter, we first review general concepts about multiple sclerosis (MS) and its treatment and general considerations to take into account when assessing and treating neuropsychiatric disorders in patients with MS. We then discuss specific neuropsychiatric disorders in MS.

Multiple Sclerosis: General concepts

MS is an immune-mediated demyelinating disease of the central nervous system (CNS).1 MS is the most common cause of non-traumatic neurological disability among young adults. Its prevalence is approximately 50–300 per 100,000 population, with an estimated 2.3 million MS patients living worldwide. MS patients typically present between 20 and 40 years of age, with a female-to-male ratio of approximately 2.3:1. MS patients present with a relapsing remitting course at the time of disease onset in 85–90% of individuals, and approximately half of these patients may evolve into a secondary progressive MS phenotype with gradual accumulation of neurologic disability over years. A minority of patients may present with a progressive course at disease onset and are classified as primary progressive MS.

MS has been traditionally considered to be mediated by toxicity of autoreactive T-lymphocytes against the myelin sheath, and demyelinated plaques in white matter (WM) are pathological hallmarks of the disease. However, accumulating evidence suggests key roles of other immune cells, such as B-lymphocytes and glial cells (microglia, astrocytes, dendritic cells) in the pathogenesis of MS. Further, in addition to WM demyelination, there has been an increasing recognition of gray matter (GM) pathology, axonal injury, oligodendrocyte apoptosis, and neuronal loss in MS.

The most common presenting symptoms of MS include visual impairment due to optic neuritis, diplopia due to brainstem involvement, sensory impairment and focal weakness due to involvement of long tracts, ataxia, fatigue, sleep problems, and bladder and bowel impairment. Additionally, a significant proportion of MS patients complain of neuropsychiatric symptoms including, depression, anxiety, and cognitive disturbances, among others.

TABLE 27-1MRI Findings in MS and Their Pathological/Clinical Correlation.

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