Highlights
- •Rehabilitation outcomes in MS were related to coagulation inhibitors plasma levels.
- •Decreased TFPI levels were associated with improved functional recovery.
- •Higher PS baseline levels were associated with favorable rehabilitation outcomes.
Abstract
Background
Increasing evidence for contribution of hemostasis components in multiple sclerosis
(MS) has been reported. Hemostasis protein inhibitors display key regulatory roles,
extending to regulation of innate immune response and inflammation, and promotion
of blood–brain barrier integrity. Whereas the effects on hemostasis of exercise and
rehabilitation strategies have been extensively investigated, relationships between
MS rehabilitation strategies and hemostasis have not been previously reported.
Objectives
To investigate in MS patients the association between outcomes of rehabilitative exercise
and plasma levels of selected hemostasis inhibitors.
Methods
Sixty-one severely disabled progressive-MS (P-MS) patients were randomized in the
RAGTIME trial to receive 12 walking session of robot-assisted gait training (RAGT)
or conventional overground therapy (CT). Outcome parameters were: timed 25-foot walk
test (T25FWT) speed, 6-minute walking test (6MWT), Berg Balance Scale (BBS), and MS
impact scale-29 (MSIS-29). Plasma levels of coagulation inhibitors protein S (PS),
soluble thrombomodulin (sTM), and tissue factor pathway inhibitor (TFPI) were assayed
by multiplex assay and ELISA at 4-time points: baseline (T0), intermediate (T1), end
of rehabilitation (T2), 3-month follow-up (T3). Descriptive analysis, trend analysis,
Spearman's rank and Pearson's correlations, and multiple regression models were used.
Results
Rehabilitative exercises moderately modified plasma protein concentrations. A significant
trend to increase was observed for PS (p=0.015) and TFPI (p=0.047) in the whole population, and for PS (p=0.011) in the CT group. Correlation between TFPI and sTM levels was detectable at
all time points in the whole P-MS patients and in RAGT group. The correlation between
TFPI and PS, present at T0, was lost during the rehabilitation, and recovered at T3
in the whole population and CT group. During rehabilitation, positive variations of
TFPI were inversely related with changes in 6MWT in the whole population (r=-0.309, p=0.021), and in the RAGT group (r=-0.51, p=0.004). In all P-MS, PS T0 levels were associated (r=0.379, p=0.004) with increased gait speed, which in the RAGT group was associated both with
PS T0 (r=0.378, p=0.040), and sTM T0 (r=0.453, p=0.012). Accordingly, in the regression model including age, sex and EDSS and the
stepwise enter of PS T0, higher PS T0 levels predicted increased gait speed in all
P-MS (F=3.4, p=0.016) The regression model in the RAGT group indicated that higher PS and sTM T0
levels were both predictors of increased gait speed (F=5.7, p=0.001).
Conclusions
Plasma levels of coagulation inhibitors were related to variations of outcome measurements
after high-intensity walking rehabilitation programs. Patients with decreased TFPI
levels from T0 to T2 displayed the most significant functional recovery following
rehabilitation, and particularly after RAGT. Higher baseline total PS levels were
associated with favorable outcomes of rehabilitation therapies in MS. These novel
findings, which suggest that plasma levels of hemostasis inhibitors might have implication
for rehabilitative therapy options in MS, warrant further investigation.
Keywords
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Article info
Publication history
Published online: June 19, 2020
Accepted:
June 18,
2020
Received in revised form:
June 13,
2020
Received:
April 26,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
