Fatigue in patients with primary Sjögren*s syndrome

Fatigue is one of the most pronounced and disabling symptoms for patients with
primary Sjögren*s syndrome (pSS) (Segal et al. 2008). The mechanisms underlying
fatigue remain poorly understood. In MS patients, we have shown that fatigue
(measured with questionnaires in which participants are asked to rate the
impact of fatigue) strongly correlate with force decline during a fatiguing
motor task and depressed feelings (Steens et al. 2012a), and lower activity in
motor areas in the brain (primary motor cortex, secondary motor areas) (Steens
et al. 2012b, METc 2008-003). Recent studies have suggested an important role
of the immune system in fatigue (Morris et al. 2015, Dantzer et al. 2014). We
aim to investigate the underlying mechanisms of fatigue in pSS patients
according to the model of our previous MS study. In addition, we aim to extend
from the previous studies by assessing whether fatigue correlates with the
serum levels of proinflammatory cytokines in pSS patients.

The findings in pSS patients will help to understand fatigue in Sjögren*s
syndrome and may also be relevant for our understanding of fatigue across
different patient groups. In order to facilitate this, we aim to compare the
findings of the proposed study to previous results from the experiments with MS
patients and additionally, patients with mild traumatic brain injury (in whom
similar studies have been performed).

References:
> Dantzer, R., Heijnen, C.J., Kavelaars, A., Laye, S. &Capuron, L. 2014. The
neuroimmune basis of fatigue. Trends Neurosci37, 39-46.
> Morris, G., Berk, M., Walder, K. &Maes, M. 2015. Central pathways causing
fatigue in neuro-inflammatory and autoimmune illnesses. BMC Med 13,
28-014-0259-2.
> Segal, B., Thomas, W., Rogers, T., Leon, J.M., Hughes, P., Patel, D., Patel,
K., Novitzke, J., Rohrer, M., Gopalakrishnan, R., Myers, S., Nazmul-Hossain,
A., Emamian, E., Huang, A., Rhodus, N. & Moser, K. 2008. Prevalence, severity,
and predictors of fatigue in subjects with primary Sjogren's syndrome.
Arthritis Rheum 59, 1780-1787.
> Steens, A., de Vries, A., Hemmen, J., Heersema, T., Heerings, M., Maurits, N.
& Zijdewind, I. 2012a. Fatigue perceived by multiple sclerosis patients is
associated with muscle fatigue.NeurorehabilNeuralRepair26, 48-57.
> Steens, A., Heersema, D.J., Maurits, N.M., Renken, R.J. & Zijdewind, I.
2012b. Mechanisms underlying muscle fatigue differ between multiple sclerosis
patients and controls: a combined electrophysiological and neuroimaging
study.Neuroimage59, 3110-3118.

> Can fatigue in pSS patients be explained by force decline during a fatiguing
task, muscle activation, mood, and the serum levels of proinflammatory
cytokines?
> What is the contribution of central factors (muscle activation) and
peripheral factors to force decline during a fatiguing motor task?
> What changes in cortical (brain) activation occur during a fatiguing motor
task in pSS patients?

The present study is an experimental study investigating muscle force, muscle
activation, and changes in cortical (brain) activation. During the study,
subjects are asked to fill out six questionnaires (3 questionnaires about
fatigue, 1 questionnaire about mood, and 2 disease specific questionnaires).
The study is similar to the previous studies performed in patients with
multiple sclerosis (Steens et al. 2012a, Steens et al. 2012b, METc 2008-003).

The study comprises two sessions lasting approximately two hours. The first
session takes place at the department of neuroscience. Subjects perform 3 motor
tasks during which they have to produce force with their index fingers (FDI
muscle). The ulnar nerve is activated using electrical stimulation to determine
the muscle activation. The second session takes place at the neuroimaging
center to repeat the motor tasks in the MR-scanner. Changes in cortical
activation during the tasks are measured using a 3T MR-scanner. Muscle force is
measured using MR-compatible force transducers, and muscle activation is
measured by stimulating the ulnar nerve with MR-compatible surface electrodes.

For the serum levels of proinflammatory cytokines, data from a cohort study
will be used and no additional material needs to be collected from pSS
patients.

No risk. Short painful sensation during electrical stimulation of the ulnar
nerve. During the MR session subjects have to lay still for one hour in the
scanner. The total time investment is 2* 2 hours.