Behavioural problems in MS patients: the relation with executive functioning and psychological factors

Multiple sclerosis (MS) is a progressive inflammatory and degenerative disease
of the human central nervous system that leads to demyelisation and neuronal
and axonal loss. Four disease courses have been identified: relapsing remitting
MS (defined by exacerbations with partial or complete recovery), secondary
progressive MS (a frequently transition from relapsing remitting, characterized
by a progressive course, without exacerbations), primary progressive MS
(characterized by a progressive deterioration from disease onset) and
progressive relapsing MS (a progressive deterioration form disease onset with
some acute periods of symptom relapse; there might or might not be recovery
from these acute periods). For many years it was thought that MS mainly leads
to physical disabilities. More recent studies indicate that, besides the
physical consequences, cognitive deficits occur and impair 43% to 72% of the MS
patients. There is an overall consensus of which kind of cognitive impairments
are seen in MS, which are deficits in speed of information processing, memory,
executive functioning and spatial perception. Furthermore, over the past years
emotional changes in MS patients are better recognized. Physical disabilities
and cognitive impairment are considered as predictors of a reduced quality of
life in MS patients and the association with depressive symptoms has been
extensively studied. Half of the MS patients is diagnosed with a depressive
disorder somewhere during the course of their lifetime. This could be
considered as an emotional reaction or an adjustment response to the
progressive illness. Also more neuropsychiatric symptoms, such as anxiety,
bipolar disorder, euphoria, pseudobulbar affect and psychosis, occur more often
in the MS population than in the general population. Several underlying
disease-related and neurobiological factors are postulated for these
neuropsychiatric symptoms, including immunological and inflammatory changes,
interferon-beta treatment or structural brain abnormalities.
In addition to the emotional changes and cognitive deficits, in clinical
practice we regularly observe subtle behavioural problems. In particular
behavioural problems that could result from executive dysfunction, i.e. signs
of rigidity, increased disinhibition and apathy. Studies addressing executive
functioning in MS patients described deficits in planning and organisation
skills, fluency and shifting. Studies in MS patients examining behavioural
problems in the executive field, such as self-initiating behaviour,
flexibility, self-inhibition, apathy and self-monitoring, are scarce.

The aim of the present study is to examine whether MS patients report a
significant higher amount of behavioural problems compared to the normal
population and another patient group diagnosed with a non CNS-involved chronic
disease (patients with rheumatoid arthritis). Furthermore we want to study
whether proxies also report the same behavioural problems or whether they
report different types and amount of problems.
We are interested what the underlying mechanisms are of the reported
behavioural problems. The following mechanisms will be taken into account:
- Executive functioning. We hypothesize that a decrease in executive
functioning may lead to an increase of behavioural problems. This may differ
for the different types of disease courses and disease duration.
- Depression. Depression is important to take into account when studying
executive and behavioural problems in MS patients. Data of several studies
suggest that clinically significant depression may lead to impaired cognitive
functioning, and more specifically executive dysfunction. Furthermore,
depressed patients tend to overreport their executive dysfunction. It is
therefore the question whether self-reported behavioural problems represent
executive dysfunction or rather depression.
- Acceptance. When studying depression and the relationship with executive
dysfunction and behavioural problems, it is also important to consider the role
of acceptance. It has been previously found that the relationship between
executive functioning and stress, depression and anxiety is mediated and
moderated by coping strategies and the level of illness acceptance. Illness
acceptance and the way that patients perceive and think about their disease are
also important mediators between disease and patient* well-being and account
for much of the individual differences regarding physical and psychological
health status. On the other hand, executive dysfunction can possibly lead to a
more rigid way of thinking, resulting in maladaptive coping responses and
changes in illness cognition and illness acceptance. We would like to
investigate whether there is an association between the amount of self-reported
depressive symptoms, illness acceptance, executive dysfunction and
self-reported behavioural problems.
- Fatigue. we are interested in the relationship between fatigue and
behavioural changes. Fatigue is apart from physical and cognitive symptoms one
of the most common symptoms of MS, with negative impacts extending from general
functioning to quality of life. Furthermore, people with MS may be at the
lowest end of the physical activity participation spectrum when compared to
people without MS, and people with other chronic diseases. One could argue that
the physical inactivity e.g. apathy, is an expression of fatigue, rather than
executive disfunction. On the other hand, loss of planning ability and loss of
initiative (e.g. executive disfunction) may in itself lead to apathy. To regain
more insight in this underlying mechanism, fatigue will be considered as a
secondary parameter in this study.
- Disease characteristics: The neurological impairment, the disability, and the
dependence of the patients are measured by an Expanded Disability Status Scale
(EDSS). The EDSS score will be used to quantify disability in multiple
sclerosis and to investigate whether there is a correlation between a higher
level of neurological disability, depression and the amount of behavioral
changes. Furthermore, disease type and disease duration will be taken into
account.

The study is a cross-sectional design.

All adverse events reported spontaneously by the subject or observed by the
investiga¬tor or her staff will be recorded. Examples of adverse events are
some psychological distress during completion of the neuropsychological tasks,
due to time constraints for example. Any psychological discomfort will be
minimalized by creating breaks when the participant requires one. Furthermore,
the subject is free to stop with the neuropsychological tests at any time.
Prior to completing the neuropsychological tests, the subject will be informed
by a flyer and the administrator of the neuropsychological test regarding what
a neuropsychological test entails, so subjects can prepare themselves. Another
adverse event is a high score on the HADS, indicating a possible depression or
anxiety disorder. Above a total cut-off score of 15 points on the HADS,
subjects will be informed and invited for a follow up session at the medical
psychology department to investigate the need for further psychological
treatment. If a subject wishes so, options for psychological treatment will be
explained. If a test subject does not want to be approached after a high score
on the HADS, this subject cannot participate in the study.