Cerebral Magnetic Resonance Imaging in active Crohn*s Disease patients with fatigue

Inflammatory bowel diseases (IBD), Crohn*s disease (CD) and ulcerative colitis
(UC), are chronic inflammatory diseases characterized by inflammation of (a
part of) the gastrointestinal tract with a relapsing and remitting course. IBD
patients with active disease as well as in remission, frequently complain of
fatigue. This often has consequences for patients* work and social lives and
the importance of fatigue in chronic disease has been increasingly recognized.
A hospital-based and population-based study showed prevalence rates of fatigue
in Dutch IBD patients in remission of 41% and 12,5% respectively, resulting in
a lowered Health Related Quality of Life (HRQoL).(1,2) Furthermore,
Romberg-Camps et al. (2) showed that CD patients suffered significantly more
from fatigue and scored lower on the quality of life questionnaires compared
to UC patients.

Despite the high prevalence of fatigue, it remains poorly understood. From
studies with patients with the chronic fatigue syndrome (CFS), it has been
shown that there is an association between elevated levels of choline (a marker
of cell membrane turnover) and fatigue.(3,4)

Reumatoïd arthritis (RA) is a chronic inflammatory autoimmune disease. Apart
from joint complaints, patients frequently complain of neuropsychiatric
symptoms (mood disorders, sleep disturbances) and fatigue.(5,6) In 2009,
(protocolnumber #p232/99) researchers from the LUMC departments of
Rheumatology, Radiology and Neurology have demonstrated an association between
inflammation in reumatoïd arthritis (RA) patients and metabolic changes in the
brain, using Magnetic Resonance Spectroscopy (1H-MRS).(7) Elevated levels of
choline were present in patients with active RA. Furthermore, the ratios of
choline to creatine were positively correlated with the erythrocyte
sedimentation rate (ESR) and with the disease activity in RA patients (DAS28).
The clinical consequences, like nonspecific symptoms such as fatigue and the
pathophysiological processes of elevated choline levels are still unknown and
therefore, further research is necessary.

The aim of this pilot study is to assess whether the cerebral metabolic changes
in RA patients, are also present in CD patients with active disease and
fatigue. The influence of chronic inflammation on cerebral metabolism in CD
patients will be determined by 1H-MRS on a 3T MRI. 1H-MRS results of CD
patients will be compared to the 1H-MRS results of a group of healthy controls.
Furthermore, cerebral changes will be examined by MRI and these changes will be
related to clinical symptoms (e.g. fatigue), disease activity and
neuropsychological examination.
If such changes can be detected, it would pave the way for a more comprehensive
study into the nature of the observed changes, and it would provide essential
ammunition for a full grant application.


2. OBJECTIVE
1) To investigate the influence of chronic inflammation on the cerebral
metabolism in CD patients

2) To detect cerebral structural changes in CD patients

3) To correlate the MRI changes to clinical characteristics, disease activity
and neuropsychological investigation.

The study is initiated by the department of Gastroenterology & Hepatology, the
department of Radiology, the department of Neurology and Neuropsychology the
department of Rheumatology of the Leiden University Medical Center, Leiden, the
Netherlands.

The study is a single center pilot case-control study

The patient has to sypply a blood and feces sample, lie still in the MRI
scanner for 1 hour and undergo neuropsychological investigation.