**5. Neuropsychiatric aspects of MS**

lesions visible in this way does not correlate with clinical disability as it is not known whether

The only areas described as hypodensities ("black holes") are areas where a loss of axons, thus the definitive loss of tissue, has occurred. The typical brain damage in the white matter in MS patients is clearly associated with a loss of axons [23]. Loss of axons is also a natural sign of

Recent neuropsychological studies especially use functional magnetic resonance imaging (fMRI) to assess the plasticity of functional cognitive deficits in patients with MS. The method consists of recording the activation of brain areas during the presentation of various simple neuropsychological tests. Compensatory mechanisms of cognitive functions already in the early stages of chronic MS are described. The results of fMRI scans in a group of MS patients with mild cognitive impairment and a healthy control group were compared. The functional activation areas of the brain were completely distinct during the presentation of the verbal naming test in each group (in MS patients in the frontal part of the right cortex and in the left Brodmann's area, and in the right cingulate gyrus in the healthy group). The functional reorganizations of motor functions are also described in fMRI assessments of MS patients, when compared to healthy subjects. MS patients with mild cognitive deficits assessed by neuropsychological tests were presented with auditory memory tests during an fMRI and were found to display heightened activity in different areas. Patients with greater neuropsycholog‐ ical deficits were found to exhibit lower activation of brain areas during the fMRI assessment, which probably supports the theory of adaptive mechanisms resulting from neural disorga‐ nization or inhibition associated with MS [24]. It is therefore also possible to explain the unproven relationship between the extent of morphological findings of gliosis and plaques in the white matter, and the severity and location of neuropsychological deficits in terms of this plasticity of neuropsychological functions. The range of specific cognitive deficits, such as memory disorders, reduced processing speed, and attention disorders, can be better explained by the cortical gray matter lesions (lesions and atrophy) than subcortical white matter lesions [25]. It has been shown that neocortical atrophy is associated with impaired verbal memory, visual episodic and working memory, verbal fluency, attention/concentration, and processing speed [26]. It is also possible that the neocortical atrophy is further responsible for slight personality changes, such as euphoria, that are seen in MS patients [27]. The left frontal atrophy occurs in patients with impaired verbal/auditory memory, while the right frontal atrophy is associated with impaired visual episodic and working memories. The medial temporal cortex atrophy is associated with a decrease in processing speed and impaired episodic and verbal memories. The most important within the subcortical gray mater are atrophy, structural changes, and an altered metabolism of the thalamus, which are associated with the impairment of many cognitive domains [28]. Generally, it can be concluded that the cognitive impairment observed in MS patients is caused by inflammatory lesions and a widespread loss of gray matter. Although it is not possible to define the neuropsychological profile of MS patients as strictly "cortical" or "subcortical", it seems that it is the disruption of the cortical gray matter which determines the degree and nature of cognitive dysfunction. Instead of the term sub‐

the lesion is currently in the stage of reparation or destruction.

218 Trending Topics in Multiple Sclerosis

brain aging, and its verification is only possible postmortem.

Cognitive and affective disorders in MS have largely been ignored for many years, yet they occur in 5% of the patients early in the disease, while in its advanced stages, this can be up to 70% of cases. MS is associated with a variety of behavioral changes. These may be associated with emotional disorders and cognitive distortions and may often overlap. The prevalence of depression is at least 50%; it is often manifested in parallel with the MS attack, and suicidal tendencies may occur. The causes of depression are probably neuropathological changes associated with the limbic system, neuroendocrinological, and psychoneuroimmunological changes, responses to life change, or a side effect of MS therapy (especially corticosteroids). The prevalence of bipolar disorders in MS is approximately 15%, and the prevalence of anxiety disorders in MS is about 36%. The occurrence of bipolar disorder and psychosis in MS is twice as common as in the general population, and the so‐called pseudobulbar affectation (invol‐ untary emotional expression disorder) affects one in ten patients. It is likely that the interrup‐ tion of frontolimbic and temporolimbic connections plays a role in the pathogenesis of euphoria. Euphoric patients tend to have higher EDSS and a significantly more impaired cognition, including anosognosia. The incidence of euphoria is lower (approximately 2%) than is described in the older literature, thanks to an earlier diagnosis and treatment of MS. Symptoms of depression do not correlate with neurological findings or with disease severity, as measured by the sum of symptoms of physical disability and cognitive dysfunction [30]. However, depression positively correlates with subjective experience of stress, memory deficits, and with age in elderly patients over 65 years of age, in patients with the chronic progressive form and in patients with a predominance of spinal distortion. The neuropsycho‐ logical assessment should therefore, in addition to cognitive domains, also include assessments of emotional alterations, especially depression and anxiety scales (e.g., methods HAD– Hospital Anxiety and Depression Scale, BDI‐II) and their development over time [31].

Other changes in patients with MS, particularly changes in values and attitudes, progress together with the psychosocial adjustment and are mostly associated with the subjective perception of a physical handicap, but do not correlate with the duration of MS or other demographic indicators. Specific quality of life with MS questionnaires is used to measure the quality of life in these patients, such as the MSQOL‐54 [32], which measures 12 subscales: physical function, role limitations—physical, role limitations—emotional, pain, emotional well‐being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function.

The Multi‐domain battery Multiple Sclerosis Quality of Life Inventory (MSQLI) contains 10 scales, both generic and specific to MS [33]; some scales also have a shortened version: Health Status Questionnaire (SF‐36), Modified Fatigue Impact Scale (MFIS), MOS Pain Effects Scale (PES), Sexual Satisfaction Scale (SSS), Bladder Control Scale (BLCS), Bowel Control Scale (BWCS), Impact of Visual Impairment Scale (IVIS), Perceived Deficits Questionnaire (PDQ), Mental Health Inventory (MHI), and MOS Modified Social Support Survey (MSSS). The scales can also be presented individually.
