In recent years, awareness of cognitive dysfunction in MS patients has increased, although abnormalities have been variably reported in 0% to 90% of cases (104,105). A follow-up study of 45 patients with MS, initially studied early in their disease course, found that only 20 of 37 initially cognitively normal individuals remained so after 10 years (106). Clearly, severe dementia is unusual in MS, but more subtle abnormalities of cognitive function are common. These are often unnoticed by patients, families, or physicians, but they may be detected on more formal neuropsychiatric evaluation. The most frequently encountered difficulties are with memory, attention-concentration, and conceptual reasoning-problem solving (104-109). Although cognitive impairments are variable, they typically follow patterns usually associated with subcortical lesions. Several recent studies have provided evidence of impaired driving in patients with MS and cognitive dysfunction (110-112). Aphasia, apraxia, neglect, and other cognitive features of cortical pathology are uncommon, although several cases with language impairment as the sole or major feature of an acute exacerbation have been reported. Zarei et al. (113) have recently reported six patients who presented with progressive dementia marked by prominent amnesia but also featuring classical cortical features such as dysphasia, dyslexia, and dysgraphia, in the absence of any other neurological signs. All patients had mood disturbances and three had a long history of severe depression. Eventually prominent neurologic signs with marked disability occurred in all. The authors proposed the concept of a "cortical" variant of MS, which appears consistent with recent pathologic and MRI observations suggesting that cortical involvement is more widespread than previously believed. Thus far, correlation of cognitive status with either duration or severity of illness has been poor. Dementia did not correlate with the number of distribution of lesions on MRI scans in one study (114), but a more recent study did find such a correlation (115). More focal cognitive abnormalities, such as aphasia (116-118) and neglect (119), have been reported, but they are very unusual.
Earlier literature described euphoria as a feature of MS (120). However, depression is now recognized much more commonly, with 50% or more of patients experiencing this affective disturbance in some form during the course of the illness (121-123). Although this is usually relatively mild, major depression can occur (123). Suicide may be a major cause of mortality, accounting for 15% of adult deaths in one series (124). Recently, Feinstein (125) identified warning signs that include living alone, having a family history of mental illness, and reporting social isolation. Patients with a prior history of major depression, anxiety disorder, or alcohol abuse are also particularly vulnerable. The so-called euphoria is actually the inability to inhibit emotional expression, resulting in "inappropriate" laughing and crying. This occurs with subcortical forebrain lesions (126). Other instances of apparent euphoria seem to be associated with evidence of significant cognitive decline. Euphoria is rarely, if ever, seen as an early sign in patients with mild symptoms (41).
On rare occasions, other psychotic states, mimicking schizophrenia or other delusional syndromes, may occur in MS. Limited data suggest that the patient with these symptoms may have more disease in the temporal lobe periventricular area (127,128). Also, one must always consider the possibility of iatrogenic symptomatology in patients being treated with a variety of the medications used in MS.
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