Multiple Sclerosis,
Background:
Autonomic dysfunction is frequently
observed in patients with multiple sclerosis (MS) but the evolution over
time and the relationship to clinical characteristics are not yet established.
Objectives:
We investigated the correlation of
disease activity and progression of disability with composite scores of
cardiovascular autonomic dysfunction and serum levels of catecholamines
in a cross-sectional study of patients with clinically active and clinically
stable MS. In a longitudinal study of clinically active MS patients, we
performed cardiovascular reflex tests for up to 2 years.
Methods:
Twenty-six patients with clinically
active relapsing – remitting MS, age 33.0±7.3 years, and nine patients
with clinically stable MS, age 41.3±10.9 were studied. Twenty-four
healthy volunteers served as controls. Standard autonomic tests were repeated
at 3, 6, 12, 18 and 24 months in 18 of the 26 active patients participating
in a placebo-controlled trial with interferon--1a. Parasympathetic dysfunction
was assessed by heart rate response to the Valsalva manoeuvre, deep breathing
and active change of posture, while sympathetic dysfunction was analysed
by blood pressure response to active change of posture and to sustained
handgrip, and by measuring levels of norepinephrine and epinephrine in
serum obtained in the supine position.
Results:
In the cross-sectional study, the
number of patients with at least one abnormal sympathetic test was higher
in the `active' patient group (39%) than in healthy controls (8%, P<0.02)
or `stable' patients (0%, P<0.04), while no difference was seen in the
parasympathetic score. Median catecholamine levels were significantly lower
in `active' MS patients than in those with stable disease (norepinephrine,
204 ng/l (interquartile range 158 – 310 ng/l) vs 363 ng/l (269 – 507 ng/l),
P<0.02 and epinephrine, 23 ng/l (16 – 28 ng/l) vs 32 ng/l (24 – 107
ng/l), P<0.04). In the subgroup of patients studied longitudinally,
parasympathetic but not sympathetic dysfunction increased slightly during
the follow-up period, with a significant correlation to the increase in
clinical disability (r=0.7, P<0.002). No difference was seen for any
of the autonomic scores between patients treated with interferon- (n=12)
and those receiving placebo (n=6). During acute exacerbations, only parasympathetic
dysfunction tended to increase in parallel with a deterioration in the
EDSS.
Conclusions:
Parasympathetic dysfunction was closely
related to the progression of disability in patients with MS. In contrast,
sympathetic dysfunction was associated to the clinical activity of MS.
This is in line with previous observations suggesting that the autonomic
nervous system may be intimately linked with the disordered immune regulation
in MS.
© 2001 ingenta
October 2001, vol. 7, no. 5,
pp. 327-334(8)
Flachenecker P. [1] *; Reiners K.
[1]; Krauser M. [1]; Wolf A. [1]; Toyka K.V. [1]
[1] Department of Neurology, Julius-Maximilians-Universität
Würzburg, Germany [*] Correspondence: P Flachenecker, Department of
Neurology, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Str.
11, 97080 Würzburg, Germany
Abstract: