Physical training and fatigue, fitness, and

quality of life in Guillain–Barré

syndrome and CIDP
M.P.J. Garssen, MD; J.B.J. Bussmann, PhD; P.I.M. Schmitz, PhD; A. Zandbergen, MA; T.G. Welter, PhD;
I.S.J. Merkies, MD, PhD; H.J. Stam, MD, PhD; and P.A. van Doorn, MD, PhD

Abstract—Many patients with Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy
(CIDP) experience excessive fatigue, which may persist for years and reduce quality of life. The authors performed a
12-week study of bicycle exercise training in 20 patients with severe fatigue, 16 with relatively good recovery from GBS,
and 4 with stable CIDP. Training seemed well tolerated, and self-reported fatigue scores decreased 20% (p ⫽ 0.001).
Physical fitness, functional outcome, and quality of life were improved.
NEUROLOGY 2004;63:2393–2395

Despite relatively good neurologic recovery, the ma- tigue severity score (FSS) of at least 5.0 out of 7.0,1,5 neurologi-
cally stable (no changes in GBS disability score within 3
jority of patients with Guillain–Barré syndrome months before baseline), onset of GBS/CIDP ⬎6 months and
(GBS) or chronic inflammatory demyelinating poly- ⬍15 years ago, age of at least 18 years, and a GBS disability
neuropathy (CIDP) remain severely fatigued.1 Fa- score of ⱕ3 (able to walk 10 m).
tigue, different from the transient and mild fatigue Exclusion criteria were severe fatigue before GBS or CIDP,
concomitant conditions (e.g., malignancy, chronic infections, hypo-
healthy persons can experience, seems independent thyroidism, anemia, renal and liver disease, chronic pulmonary
of muscle strength and disability score and is one of and cardiovascular disease, chronic fatigue syndrome, diabetes) or
the most disabling symptoms.1 use of medication (⬍4 weeks before onset study) that might cause
Aerobic training decreases fatigue and improves or influence fatigue (e.g., benzodiazepines, antidepressants, and
immunotherapy), depression, hypertension, and ␤-blocking drugs.
physical fitness and quality of life in patients with Withdrawal criteria were inability to train for three consecu-
multiple sclerosis (MS).2 It is unknown whether tive sessions, persisting and disabling adverse events like severe
“neurologically recovered” GBS patients or stable muscle cramps, weakness, or increasing sensory deficits, and de-
velopment of new co-morbidity interfering with training
CIDP patients are able to perform a training pro- procedures.
gram. Training may not be tolerated because of the Patients registered in the database received a letter and FSS
initial complaints of severe fatigue or residual neuro- form, requesting participation. Patients who met the eligibility
logic deficits.3 However, some positive effects of low- criteria underwent a neurologic/physical examination (including
EKG); assessment scales were completed, and blood samples were
intensity training interventions on fatigue, fitness, drawn (to exclude other reasons for fatigue). Severely fatigued
and quality of life are reported.4 We determined the (mean FSS score of ⱖ5.0) and nondepressed (Hospital Anxiety and
feasibility and effect on fatigue severity of a struc- Depression Scale depression subscale score of ⱕ10) patients with
tured 12-week bicycle exercise training program. Ad- normal blood values were included and returned for a cardiorespi-
ratory fitness test, isokinetic muscle strength measurements, and
ditionally, we evaluated the effect on physical ambulatory activity measurement. Thereafter, patients started a
fitness, muscle strength, functional outcome, anxiety 12-week bicycle exercise training, with a short evaluation after 6
and depression, handicap, and quality of life. weeks. Afterward, all assessments and measurements performed
at baseline were repeated. Healthy subjects underwent all base-
line measurements but did not participate in the training
Patients and methods. Sixteen patients with relatively good intervention.
recovery from GBS and 4 patients with neurologically stable Primary outcome measures were the training feasibility and
CIDP, fulfilling the diagnostic criteria, participated in this pro- reduction of fatigue (improvement of at least 1 mean point on the
spective observational study. Two CIDP patients needed intermit- FSS).1,5 Secondary outcome measures were changes at the level of
tent IV immunoglobulins. Patients were recruited from the GBS/ cardiorespiratory fitness and isokinetic muscle strength, func-
CIDP databank at the Erasmus Medical Center Rotterdam or the tional outcome of daily physical activity (e.g., duration and distri-
Dutch GBS Patients’ Association. Ten sex- and age-matched (max- bution of standing, sitting, walking, cycling, and transitions from
imum 5-year difference) healthy subjects (not known to have any positions measured by the Rotterdam Activity Monitor [RAM]),6
disease or use of medication) were recruited from the patient Fatigue Impact Scale,7 and GBS disability score, Hospital Anxiety
community. The Ethics Committee of the Erasmus Medical Center and Depression Scale,8 Rotterdam Handicap Scale, and quality of
approved the study. life (Short Form-36 Health Questionnaire [SF-36]).
Inclusion criteria were severe fatigue, defined as a mean fa- Training consisted of three supervised training sessions, every

From the Departments of Neurology (Drs. Garssen and van Doorn), Rehabilitation (Drs. Bussmann and Stam, A. Zandbergen), and Statistics (Dr. Schmitz),
Erasmus Medical Center Rotterdam, and Department of Neurology (Dr. Merkies), Spaarne Hospital, Haarlem, the Netherlands.
Supported by the Dutch Organization for Scientific Research, (NWO, grant no. 940-38-009) and by the Erasmus Medical Center Rotterdam (Revolving Fund,
grant no. 1023).
Received May 21, 2004. Accepted in final form August 12, 2004.
Address correspondence and reprint requests to Dr. M.P.J. Garssen, Department of Neurology, Erasmus Medical Center Rotterdam, PO Box 1738, 3000 DR
Rotterdam, the Netherlands; e-mail: [email protected]

Copyright © 2004 by AAN Enterprises, Inc. 2393

Table 1 Baseline characteristics week, for 12 weeks. Each session consisted of 5 minutes of
warm-up (65% of maximum heart rate as measured by the cycle
Healthy ergometer test) and 30 minutes of cycling. The first weeks, train-
Patients, individuals, ing intensity increased from 70% to a maximum of 90% of maxi-
Characteristic n ⫽ 20 n ⫽ 10 mal heart rate. After the third week, the load of the home trainer
was weekly increased from 0 to 10 or 20 W, depending on the
GBS, n 16 — patient’s physical ability. Each training session was finished with
5 to 10 minutes of cool-down cycling. Exercise heart rates were
CIDP, n 4 —
monitored continuously.
Sex, F/M 14/6 6/4 Primary analysis was performed using the two-sample t-test
Median (range) age at start of 49 (22–66) 51 (23–64) with equal variances. Treatment effects were analyzed after 6 and
study, y 12 weeks, using the paired t-test, two-sample t-test with equal
variances, Wilcoxon signed-rank test, and two-sample Wilcoxon
Mean (range) duration since 4.1 (0.5–15) — rank sum (Mann–Whitney) test.
diagnosis, y
MRC sumscore distribution, n Results. Baseline characteristics are listed in table 1. Of
(score range: 0–60)
the 22 potential participants, 2 were noneligible: One pa-
52–57 2 — tient had cardiovascular diseases, and one patient was not
58–59 4 — able to adhere to all training sessions. Two included pa-
60 14 10 tients stopped training after 2 and 3 weeks: One patient’s
GBS disability distribution, n partner died, and the other developed cholecystitis.
(score range: 0–6) Side effects, occurring in five patients (25%), consisted
F⫽0 — 10 of muscle cramps, paresthesias, pain, and burning sensa-
F⫽1 15 — tions in legs. Side effects were experienced as mild and
F⫽2 5 — transient within 2 to 6 weeks and were no reason to inter-
FSS score, mean (range) 6.1 (5.8–6.4) 2.2 (1.6–2.8) rupt the training.
Training resulted in a 20% fatigue severity reduction
MRC sumscore distribution ranges from 0 (paralysis) to 60 (nor- (see table 2). Both GBS and CIDP patients showed compa-
mal strength), examined in six muscle pairs. GBS disability rable changes on the FSS.
score: F ⫽ 0 (healthy, no symptoms or signs), F ⫽ 1 (minor Changes in fatigue severity, impact of fatigue, anxiety,
symptoms or signs, capable of running), F ⫽ 2 (able to walk at
depression, handicap, and quality of life are listed in table
least 10 m across an open space without assistance, walking
2. Changes in physical fitness, muscle strength, and activ-
frame, or stick, but unable to run), F ⫽ 3 (able to walk 10 m
with walking frame, sticks, or support). FSS scores range from ity pattern are listed in table 3. Two patients improved in
FSS ⫽ 1 (no signs of fatigue) to FSS ⫽ 7 (most disabling fatigue). GBS disability score after training. Initially, both were
unable to run; after training, one was able to run, and the
GBS ⫽ Guillain-Barré syndrome; CIDP ⫽ chronic inflammatory other improved to score 0 (no symptoms).
demyelinating polyneuropathy; MRC ⫽ Medical Research Coun-
cil; FSS ⫽ Fatigue Severity Score.
Discussion. Despite our intensive training proto-
col, only five patients had mild and transient side

Table 2 Severity of fatigue, impact of fatigue, anxiety, depression, handicap, and quality of life scores

Exercise group Healthy individuals

Variable Baseline, n ⫽ 20 6 wk, n ⫽ 17 12 wk, n ⫽ 18 Baseline, n ⫽ 10

FSS 6.1 (0.65) 5.1 (1.35)* 4.8 (1.53)* 2.2 (0.88)‡

FIS
Cognitive, n ⫽ 10 1.37 (0.98) 1.05 (0.77) 0.81 (0.96)* 0.25 (0.34)‡
Physical, n ⫽ 10 2.18 (0.81) 1.39 (0.76)* 1.13 (0.89)* 0.23 (0.30)‡
Social, n ⫽ 20 1.35 (0.75) 0.97 (0.68)† 0.81 (0.81)* 0.21 (0.23)‡
HAD
Anxiety 1.89 (0.48) 1.71 (0.36) 1.59 (0.30)† 1.44 (0.32)‡
Depression 1.71 (0.37) 1.55 (0.44) 1.39 (0.28)* 1.26 (0.32)‡
RHS 3.56 3.78* 3.89* 4‡
SF-36
PCS 44.0 45.6 50.1† 58.4‡
MCS 51.6 52.7 55.9 55.7

Data are means (SD).

RHS data are centiles and were available in 17 patients.

* Significant change from baseline, p ⬍ 0.01.

† Significant change from baseline, p ⬍ 0.05.
‡ Significant difference compared with baseline values of exercise group, p ⬍ 0.01.

FSS ⫽ Fatigue Severity Score; FIS ⫽ Fatigue Impact Scale; HAD ⫽ Hospital Anxiety and Depression Scale; RHS ⫽ Rotterdam Handi-
cap Scale; SF-36 ⫽ Short Form-36 Health Questionnaire; PCS ⫽ Physical Component Summary; MCS ⫽ Mental Component Summary.
2394 NEUROLOGY 63 December (2 of 2) 2004
Table 3 Cardiorespiratory cycle ergometer test, maximum isokinetic muscle strength variables, and activity percentages

Exercise group Healthy individuals

Variable Baseline, n ⫽ 20 12 wk, n ⫽ 18 Baseline, n ⫽ 10

K4b2 physical condition

VO2 max, mL/kg/min 25 (8) 30 (10)* (⫹20%) 33 (7)†
POmax, W 133 (38) 172 (53)* (⫹29%) 190 (54)†
HRmax, beats/min 163 (17) 172 (12)* (⫹6%) 172 (15)
Isokinetic muscle strength
Elbow flexion, W 27.7 (13.2) 31.4 (14.9)* 34.5 (15.3)
Elbow extension, W 27.5 (14) 32.7 (16.7)* 33.9 (10.3)
Knee flexion, W 39.3 (17.6) 43.2 (19.7) 52.3 (16.3)†
Knee extension, W 74.4 (30.3) 84.8 (33.8)* 85.7 (22.4)
⌺ strength elbow 27.6 (13.3) 32 (15.6)* 34.2 (12.5)
⌺ strength knee 56.8 (23.4) 64 (25.4)* 69 (18.4)
RAM
Percentage activity 10.7 11.2 12.2

Values are means (SD).

* Significant change from baseline, p ⬍ 0.01.

† Significant difference compared with baseline values of exercise group, p ⬍ 0.05.

K4b2 ⫽ cardiorespiratory fitness test; VO2 max ⫽ peak oxygen uptake; POmax ⫽ maximal power output; HRmax ⫽ maximal heart rate;
⌺ strength ⫽ sum of all tested muscle groups; RAM ⫽ Rotterdam Activity Monitor, measuring percentages of activity during 24 h.

effects, and training seemed to be feasible. After tacts with fellow patients, besides promoting
training, we found a 20% reduction of self-reported exercise adherence, may have led to better psycho-
fatigue. Both severity as well as impact of fatigue logical performances.
showed corresponding improvements. VO2 max in- A randomized, controlled study of training inter-
creased 20%, consistent with effects of aerobic exer- vention in a larger number of patients is warranted.
cise training in healthy sedentary individuals (15%)
and in patients with MS (22%).2,9 Also, functional
outcome and quality of life improved. Most patients Acknowledgment
(80%) were motivated to continue with regular train- The authors thank the patients for their participation and M.
Scheerder and H. van Nieuwenhuizen for technical and adminis-
ing activities. trative assistance.
The patients reported that increased physical ac-
tivity in the past had often resulted in increased
neurologic complaints, resembling the initial phase References
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