Acta Myologica • 2019; XXXVIII: p.

215-232
OPEN ACCESS © Gaetano Conte Academy - Mediterranean Society of Myology

Exercise therapy for muscle and lower motor

neuron diseases
Aisha Munawar Sheikh, John Vissing
Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark

Muscle and lower motor neuron diseases share a common de- that contractions in the pathological muscle would accel-
nominator of perturbed muscle function, most often related to erate the disease process. This notion was supported by
wasting and weakness of muscles. This leads to a number of experiments in the mdx mouse model of Duchenne muscu-
challenges, such as restricted mobility and respiratory difficul-
ties. Currently there is no cure for these diseases. The purpose
lar dystrophy that showed signs of damage after exercise.
of this review is to present research that examines the effects of However, the types of exercise used were highly unphysi-
exercise in muscle and lower motor neuron diseases. Evidence ological as they involved eccentric exercise and electrical
indicates that moderate intensity aerobic- and strength exercise stimulation of muscle (2, 3) types of exercise that would
is advantageous for patients with muscle diseases, without caus- also induce muscle damage in a healthy individual.
ing harmful exercise-induced muscle damage. On the contrary, Exercise is physical activity that is planned, structured,
motor neuron diseases show a rather blunted response from ex-
and repetitive for the purpose of conditioning any part of
ercise training. High-intensity training is a modality that seems
safe and a promising exercise method, which may circumvent the body. The general population is encouraged to exercise
neural fatigue and provide effect to patients with motor neuron because of its great health benefits, and it’s importance as
disease. Although we have come far in changing the view on a means of physical rehabilitation is also widely acknowl-
exercise therapy in neuromuscular diseases to a positive one, edged (4). Lack of exercise, regardless of condition, leads
much knowledge is still needed on what dose of time, intensity to a variety of changes in the body. The heart’s ability to
and duration should be implemented for different disease and pump blood efficiently, aerobic capacity, and muscles’ ca-
how we should provide exercise therapy to very weak, non-am-
pacity to process oxygen declines, which ultimately leads
bulatory and wheelchair bound patients.
to decreased endurance, muscle weakness, and fatigue (4),
as well as numerous lifestyle-related diseases. Patients
Key words: muscle disease, motor neuron disease, exercise
with muscle and lower motor neuron diseases are more
prone to developing disorders associated with a sedentary
lifestyle, such as obesity and metabolic syndrome due to
restricted mobility  (5-7). Currently there are no specific
Background guidelines about the type or intensity of exercise recom-
mended to these patients. One of the challenges health care
Muscle and lower motor neuron diseases encompass professionals often face is the question of how much, and
a large number of conditions with a common denomina- what type of exercise should patients engage in. None-
tor of muscle weakness and wasting in most cases, which theless, the body of evidence favoring exercise training
may lead to a number of challenges, such as fatigue, re- in patients with muscle and lower motor neuron diseases
stricted mobility, and respiratory difficulties that impact a has increased substantially in the last two decades, and the
person’s quality of life (1). Currently, treatment options purpose of this review is to present the current evidence for
for these diseases are scarce, and patients rely on support- physical conditioning in these disease groups.
ive disease management that may contribute to enhance
quality of life by improving physical function and possi-
bly stabilizing or slowing down disease progression.
Methods
For a long time, physical exercise was considered del- A literature search on PubMed, using key words
eterious for patients with muscle diseases, the notion being “Limb girdle muscular dystrophy”, “Becker muscular

Address for correspondence: Aisha Munawar Sheikh, Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet,
University of Copenhagen, Juliane Maries Vej 28, 2100 Copenhagen, Denmark. E-mail: aisha.munawar.sheikh@regionh.dk

215
Aisha Munawar Sheikh and John Vissing

dystrophy”, “facioscapulohumeral muscular dystrophy”, from the high resistance training group due to training-in-
“myotonic muscular dystrophy”, “McArdle disease”, duced CK elevation. Resistance training could potentially
“Pompe disease”, “mitochondrial myopathy”, “spinal be a beneficial part of a functional rehabilitation program,
and bulbar muscular atrophy”, “spinal muscular atrophy” but should be carefully monitored for muscle damage.
combined with key words “exercise”, “training”, “physi-
cal activity”, “resistance training”, “resistance exercise”, Assisted exercise
“strength training”, “strength exercise”, “aerobic train- Sczesny-Kaiser et al. (11) performed a treadmill ex-
ing”, “aerobic exercise”, “endurance training”, “endur- ercise study using hybrid assistive limb (HAL®) in three
ance exercise”, was performed from January 2018 to July LGMD patients; LGMD2A, LGMD2I, and a LGMD of
2019. Article selection was based on 1) studies assessing unknown subtype. HAL® is a powered exoskeleton and
the effects of exercise on humans with these diseases, is used during exercise to enhance physical capabilities
2) articles that included a well described diagnosis of a in people with disabilities. Physical endurance improved
muscle or motor neuron disease, and 3) articles that pro- and no adverse events were reported. Despite a small sam-
vided a well-described exercise intervention. We includ- ple size, the results are interesting, and the technology al-
ed randomized controlled trials (RCT), cohorts, and case lows health care professionals to train very weak patients.
reports. Articles were excluded if they did not include an Anti-gravity training improved functional ability in weak
exercise intervention, lacked intervention description, or patients with LGMD2I  (12), and enhanced lower limb
were animal studies. In addition, articles exclusively fo- strength and walking distance (13). Both studies were safe
cusing on training of respiratory muscles were also ex- and well tolerated and plasma CK levels did not indicate
cluded. Using these inclusion and exclusion criteria’s, any exercise-induced muscle damage. Bodyweight-sup-
fifty articles were chosen to form the basis for this review. ported training allows patients to work at a certain per-
centage of bodyweight due to off-lifting of weight by
slings or air pressure making it possible for weak patients
Experience with exercise training to exercise. However, it is costly and cannot be performed
in individuals with muscle and in patients’ habitual environment.
lower motor neuron diseases
Other exercise modalities
Effect of electrical stimulation therapy and exer-
Muscular dystrophies
cise therapy in patients with LGMD was investigated by
Kılınç et al.  (14). In the electrical stimulation therapy
Limb girdle muscular dystrophy group, stimulation was applied bilaterally on the deltoid
Aerobic exercise and quadriceps muscles using high voltage-pulsed galvan-
More than 32 different kinds of Limb girdle muscular ic stimulation with a pulse frequency of 50Hz for optimal
dystrophies (LGMD) are known, and exercise has only contractions. Duty cycle was set at 5 seconds on and 10
been studied in a few of the disorders. Aerobic exercise seconds off, during 10 minutes of stimulation of each mus-
has been studied in smaller cohorts of LGMD2I and LG- cle. The exercise therapy group consisted of bilateral pro-
MD2L. Patients with LGMD2L completed a 10-week gressive resistance exercise of the deltoid and quadriceps
moderate aerobic training program (8). The six patients muscles. The electrical stimulation therapy group gained
completing the training experienced improvements in fit- muscle strength and physical function improved. The ex-
ness, functional capacity, and lower limb strength. No ad- ercise therapy group had similar improvements. This study
verse events were reported. Moderate endurance training provides important information on the role of electrical
also improved aerobic capacity in 9 patients with LGM- stimulation therapy and exercise therapy for health care
D2I (9), and patients expressed feeling an improvement professionals working in rehabilitation clinics.
in physical function. There was no significant increase in Intervention specifications for LGMDs are presented
training-induced creatine kinase (CK) levels. Moderate in Table 1.
aerobic training seems to provide patients with LGMD
Becker muscular dystrophy
better physical function and appears safe, but longer-term
studies are needed. Aerobic exercise
Moderate cycle training improves aerobic capacity
Strength exercise and strength in patients with Becker muscular dystrophy
Low- and high-intensity resistance training in patients (BMD) after three months of exercise, and these im-
with LGMD2A and LGMD2I was found to be generally provements are maintained after additional 9 months of
well tolerated (10). Two LGMD2A patients were excluded training, without any rise in CK level (15). Enhancement

216
 Exercise therapy for muscle and lower motor neuron diseases

in muscle strength and physical function after treadmill found that bodyweight-supported training improved low-
training were also reported in a case study (16). Interest- er limb strength and walking distance (13). In both stud-
ingly, an elevation in CK level was observed, indicating ies, exercise was well tolerated and CK levels did not in-
that rehabilitative intervention should be carefully mon- dicate any exercise-induced muscle damage. Intervention
itored to avoid harmful exercise-induced side effects de- specifications for BMD are presented in Table 2.
spite functional improvement.
Facioscapulohumeral muscular dystrophy
Strength exercise
In patients with BMD, low- and high-intensity resis- Aerobic exercise
tance training was generally well tolerated and patients Moderate aerobic exercise improved self-reported
showed an increase in endurance and arm strength (10), changes in activities of daily living (ADL) in a cohort of
without signs of muscle damage. 8 patients with facioscapulohumeral muscular dystrophy
(FSHD) (17). Similar improvements were discovered in
Assisted exercise a randomized, double-blind, placebo-controlled parallel
Anti-gravity training resulted in improved physical study where the investigators found improvements in
function and functional ability  (12), and another study fitness, self-assessed physical capacity, and health  (18).

Table 1. A representation of exercise interventions done in LGMD 2A, LGMD 2L, and LGMD 2I. Number in parenthesis
represents the article reference.
Exercise Duration Frequency Intensity Improved outcome
mode/N
Cycling 10 weeks 3 days/week 70% of VO2max VO2max, lower limb
N=6 30 min/session strength, 6MWT, 5 x STS,
6SST.
(8)
Cycling 12 weeks 50 sessions in 65% of VO2max VO2max, workload,
N=9 total self-reported physical
30 min/session endurance, lower limb
(9) muscle strength, and
walking distance.
Strength: Low intensity Bicep strength and
LOIT Knee extension, Elbow flexion endurance, wrist
N=6 6 months 3 days/week 40% of 1RM, increase with 5% every flexion, extension, and
Twice at home other week endurance
and once at lab 3 sets x 12-15 reps
HIT
N=3 3 months 3 days/week at High intensity:
lab Knee extension, Elbow flexion
Control group Wrist flexion & extension
N=6 Ankle plantar flexion
70-85% of 1RM 3 x 8-12 reps for 1
(10) month
80-90% of 1RM 3 x 6-10 reps for 2
months
85-92% 3 x 8-4 reps for 3 months
Treadmill 8 weeks 3 days/week Velocity of treadmill was set 10MWT, 6MWT, and TUG
training using Maximum of 30 individually
HAL® F/U at 6 minutes/session
N=3 weeks post Up to 50% body weight support
intervention
(11)

u
217
Aisha Munawar Sheikh and John Vissing

Exercise Duration Frequency Intensity Improved outcome

mode/N
Anti-gravity: 10 weeks of 3 days/week 70-80% of maximum heart rate 6MWT and dynamic
control period 40 min/session (HRmax) balance
N=3 Run/walk, jogging, and high knee lift

(12) 10 weeks of 12 reps of squats and lunges

training 15-20 reps of calf raise
Bodyweight 10-week 3 days/week 70-80% of HRmax Closed kinetic chain leg
supported: control period 40 min/session strength and training
Closed-kinetic-chain strength distance
N=3 10 weeks of exercises: squats, calf raises, and
training lunges
(13)
Aerobic:
Walk/run, jogging
in place, or high knee-lift
Electrical 8 weeks 3 days/week Shoulder abduction Strength, VAS, climb 8
stimulation Knee extension steps, 10MWT, dressing
N = 11 with t-shirt, endurance
25% 1RM, 2 sets x10 reps (number of reps per
Strength 30% 1RM, 3 sets x 10 reps minute), and modified
N = 13 35% 1RM, 3 sets x 10 reps Lawton ADL.
50% 1RM, 3 sets x 10 reps

(14) Monophasic wave type. Surface

electrodes. Pulse frequency 50Hz,
voltage output 0-500 V, pulse
duration 200 μs, duty cycle 5:10, 10
minutes of stimulation

Voet et al examined the effects of moderate aerobic exer- by van der Kooi et al in a randomized, double-blind, pla-
cise therapy and cognitive behavioral therapy on fatigue, cebo-controlled trial (21). Training group consisted of 34
strength, and exercise tolerance. One group underwent patients and a non-training control group consisted of 31
cycling and one group underwent cognitive behavioral patients. At week 26 during the intervention, albuterol was
therapy comprising of 6 modules directed towards insuffi- added. Some improvements in strength were observed in
cient coping with the disease. After a 12-week follow-up, the training group and any training-induced muscle fatigue
the majority of patients continued their level of activity that occurred lasted less than an hour, and patients were
and the beneficial effects remained (19). This study pro- able to carry out their habitual ADL. Of the 34 trained pa-
vides valuable information about the impact of physical tients, 19 patients complained of neck and shoulder pain
activity on fatigue. Fatigue can have a detrimental effect after the intervention. Plasma CK levels were not reported.
on quality of life, and it is substantial to apply appropri- The authors determined the training to be generally well
ate management. Safety and efficacy of a 6-month home- tolerated and found no enhancing effects of albuterol. The
based exercise program was assessed in a multicenter number of patients reporting pain in neck and shoulder is
randomized controlled trial (20). The results showed an great and the tolerability to strength training should be ex-
improvement in aerobic capacity, strength, and functional plored further.
capacity. Exercise did not elevate CK levels in any of the
presented studies. Health care professionals are encour- Other exercise modalities
aged to promote regular exercise compatible with FSHD Andersen et al.  (22) investigated the effects of super-
patients’ daily professional and social life. vised high-intensity training (HIT) in an RCT. Fitness im-
proved and CK measurements did not indicate any muscle
Strength exercise damage during and post training. The majority of patients
Strength training in patients with FSHD was examined preferred HIT over moderate-intensity training. High-inten-

218
 Exercise therapy for muscle and lower motor neuron diseases

Table 2. A representation of exercise interventions done in BMD. Number in parenthesis represents the article refer-
ence.
Exercise Duration Frequency Intensity Improved outcome
mode/N
Cycling 12 weeks 50 sessions in 65% of VO2max VO2max, workload, hip
N = 11 12 months total abduction, and ankle
F/U 30 min/ plantar flexion and
Control group session dorsiflexion
N=7

(15)
Treadmill 4 weeks 3 days/week 65-80% HRmax Lower limb strength,
N=1 20 min/ TUG, 10MWT, and
session 6MWT
(16)
Strength: Low intensity: Bicep strength and
Knee extension, Elbow flexion endurance, wrist
LOIT 6 months LOIT 40% of 1RM, increase with 5% every other flexion, extension, and
N=2 3 days/week week endurance
Twice at 3 sets x 12-15 reps
HIT 3 months home and
N=1 once at lab High intensity:
Knee extension, Elbow flexion
Control group HIT Wrist flexion & extension
N=6 3 days/week Ankle plantar flexion
at lab 70-85% of 1RM 3 sets x 8-12 reps, month
(10) 1
80-90% of 1RM 3 sets x 6-10 reps, month
2
85-92% 3 sets x 8-4 reps, month 3
Anti-gravity: 10 weeks 3 days/week 70-80% of maximum heart rate (HRmax) 6MWT and dynamic
of control 40 min/ Run/walk, jogging, and high knee lift balance
N=5 period session
12 reps of squats and lunges
(12) 10 weeks 15-20 reps of calf raise
of training
intervention
Bodyweight 10 weeks 3 days/week 70-80% of HRmax Closed kinetic chain leg
supported: control 40 min/ Closed-kinetic-chain strength exercises: strength and training
period session squats, calf raises, and lunges distance
N=5
10 weeks Aerobic:
(13) of training Walk/run, jogging
intervention in place, or high knee-lift

sity training may be a good option for patients struggling Intervention specifications for FSHD are presented in
with fatigue. Neuromuscular electrical stimulation (NMES) Table 3.
is passive muscular training that can easily be adapted in the
clinic and may be advantageous for very weak patients. Col- Myotonic muscular dystrophy
son et al. (23) studied the safety and efficacy of NMES and Aerobic exercise
found that the treatment was safe and well tolerated. Patients Ørngreen et al.  (24) studied the effects of aerobic
reported a reduction in pain, fatigue, and an increase in func- training. Twelve of the 17 patients completed the study,
tional capacity and strength. In addition, patients expressed five patients discontinued due to low compliance, and
feeling a positive effect on ADL. There was no significant nine adhered adequately to the training protocol. Most
CK level elevation during the intervention. patients reported beneficial changes in ADL and fitness

219
Aisha Munawar Sheikh and John Vissing

improved after the training. Plasma CK levels did not in- were also observed in the strength and aerobic group and
crease, but one patient reported a worsening of fatigue. no adverse events were reported. Fatigue can limit every-
day activities and adherence to exercise in these patients,
Strength exercise and a reduction in treatment time, could possibly improve
The effect of strength training was first reported in patient compliance.
1993, where modest strength improvements were ob- Patients with myotonic muscular dystrophy (DM) of-
served after 12 weeks of exercise (25). Tollbäck et al. (26) ten face challenges with impaired hand function. Aldehag
also found improvements in strength after training for 12 et al. (30) investigated the effects of hand training with a
weeks. Two patients dropped out for personal reasons and silicone-based resistance putty in a randomized controlled
one dropped out due to severe back pain. No other adverse crossover pilot study. Patients improved hand strength
events were reported by the authors in the two studies. A and self-perception of occupational performance. Despite
study reported in 1995 (27) and another in 1999 (28) that a large dropout due to personal reasons, lack of motiva-
strength training was safe and well tolerated, but no ap- tion, and fatigue, the study addresses an important issue
parent improvements were observed, neither any adverse that hand impairment can have on ADL.
events nor deterioration was reported. The absence of any Recently, Okkersen et al assessed the effects of cog-
prominent changes differs from previous studies (25, 26). nitive behavioral therapy with optional graded exercise
One explanation could be that the patients exercised at therapy in patients with severe fatigue in a single-blind,
home, which may influence the validity of their report- large randomized trial (31). Cognitive behavioral therapy
ing and compliance or the effect of exercise was assessed increased patients’ capacity for activity and participation,
with unfitting outcome measures. compared with standard care alone.
Intervention specifications for DM are presented in
Other exercise modalities Table 4.
Cudia et al investigated the effects of functional elec-
trical stimulation induced cycling (29) and compared the Glycogen storage disease
intervention with strength and aerobic training. Muscle
strength and walking distance improved. Improvements McArdle disease

Table 3. A representation of exercise interventions done in FSHD. Number in parenthesis represents the article reference.
Exercise Duration Frequency Intensity Improved outcome
mode/N
Cycling 12 weeks 5 days/week 65% VO2max VO2max, workload,
N=8 35 min/session and ADL

Control group
N=7

(17)
Cycling + 12 weeks 3 days/week 70% VO2max 6MWT, workload,
post exercise fitness, and SF-36
protein- 12 months F/U 15 min/session week 1
carbohydrate 20 min/session week 2
supplement
N = 18 30 min/session from week 3

Cycling +
placebo
supplement
N = 13

Control group
N = 10

(18)

u
220
 Exercise therapy for muscle and lower motor neuron diseases

Exercise Duration Frequency Intensity Improved outcome

mode/N
Cycling 16 weeks 3 days/week (2 days at home and 1 50-65% HRmax Fatigue
N = 20 day supervised)
12-14 RPE (Borg
38 min/session, including a 5 min Scale)
Cognitive- warm up 30 min exercise 3 min cool
behavioral down
therapy
N = 13 Cognitive-behavioral therapy
comprised of 6 modules:
Usual care Dysfunctional cognitions regarding
N = 24 fatigue, activity, pain, or other
symptoms; fatigue catastrophizing
(19) (a cognitive process that involves
negative outcome expectations
from fatigue); dysregulation of sleep
or activity; poor social support;
and negative social interactions.
Both aerobic exercise therapy and
cognitive behavioral therapy were
found to be superior to usual care in
reducing fatigue
Cycling 24 weeks 3 days/week 2 sessions at VO2max, 6MWT, and
N=8 35 min/session 60% max aerobic fatigue severity
power scale
Control group 1 session interval
N=8 training 40% and
80% max aerobic
(20) power
Strength 52 weeks 3 days/week 10 RM, 2 sets x 1RM, and dynamic
N = 34 5-10 reps Dynamic elbow flexor
and isometric strength
Control strength:
N = 31 Elbow flexion
and ankle dorsal
(21) flexion
HIT: 8 weeks 21 min/session, including an 8-min Each minute VO2max and
Cycling supervised warm-up and two sets of of HIT was workload
N=6 5-min HIT with 3-min break at very low performed at three
8 weeks with intensity. different work
UC unsupervised intensities: 30 s of
N=7 for all. 3 days/week easy pedaling (low
intensity), 20 s of
Control group hard work (middle
N=7 high intensity),
and
(22) 10 s of all-out,
maximal intensity
NMES 5 months 5 days/week Rise time 1.5s; Pain, fatigue,
N=9 20 min/session steady tetanic shoulder flexion
stimulation strength, knee
(23) time: 6s; fall time extension strength,
1.5s and 6MWT

221
Aisha Munawar Sheikh and John Vissing

Aerobic exercise oxidative and work capacity in patients with McArdle

Haller et al. (32) found that patients generally benefit- disease.
ted from moderate aerobic training. However, one patient A case study reported the effects of a 6-week strength
had elevated CK levels the first two weeks of intervention, training program. The results from the low weight and
which stabilized thereafter, and another patient had elevat- high repetition training program lowered the patient’s dis-
ed CK levels during week 8, possibly due to unusual phys- ease severity class  (35). The training closely resembles
ical exertion at home, according to author reporting. Aside aerobic training intensity, which could explain the bene-
from the two patients, CK levels remained stable, indicat- fits obtained from the training. Intervention specifications
ing that exercise did not provoke muscle injury. Porcelli for McArdle disease are presented in Table 5.
et al. (33) found that home-based aerobic training also in-
creased fitness in patients with McArdle disease. However, Pompe disease
patients did not feel any benefits from the exercise nor did Combined aerobic and strength exercise
the intervention increase their habitual ADL. Muscle strength and functional capacity was shown
Maté-Munoz et al.  (34) examined the acute and to increase with moderate aerobic and strength exer-
chronic responses to exercise in patients with McArdle cise training in patients with late-onset Pompe disease
disease. The acute response consisted of two tests (see receiving enzyme replacement therapy  (36). Despite
Table  5). Ten patients underwent an 8-month long su- small sample size, the results are encouraging. Van den
pervised moderate aerobic exercise program to test the Berg et al evaluated the safety and efficacy of moderate
chronic exercise response. Most patients chose walking endurance, strength, and core stability training (37). Af-
as preferred exercise mode. Both the acute and chron- ter 12-weeks, core stability, muscle strength in hip and
ic group showed an increase in fitness and ventilatory shoulder, and functional capacity improved. The first
threshold. No adverse events or discomfort were reported week of training, two patients had elevated plasma CK
and CK levels remained stable post exercise. levels, experienced muscle pain, and fatigue. During the
From the presented studies, it appears that regular ex- second week, CK levels dropped to their normal range,
ercise may lead to physiological adaptations that increase and fatigue and pain diminished greatly. Both patients

Table 4. A representation of exercise interventions done in DM. Number in parenthesis represents the article reference.
Exercise mode/N Duration Frequency Intensity Improved
outcome
Cycling 12 weeks 5 days/week 65% of VO2max Self-reported
N=9 35 min/session improvements in
ADL, VO2max, and
(24) workload
Strength 12 weeks 3 days/week Knee extension: 30-40% of max, 3 sets x Increase in strength
N = 27 4-8 reps

Control group Elbow flexion 10-20% of max, 3 sets x 4-8

N =14 reps

(25) Hand grip: 100%, 3 sets x 4 reps

Strength 12 weeks 3 days/week Knee extension 1RM
N=6 60-80% of 1RM, 3 x 10 reps

(26)
Strength 24 weeks 3 days/week Knee extension and flexion, hip extension Neither positive or
N = 33 30 min/session and abduction negative effects of
the training
(27) 60-80% of 1RM

Week 1-8: 60% of 1RM, 3 sets x 25 reps

Week 9-16: 70% of 1RM, 3 sets x 15 reps

Week 17-24: 80% of 1RM, 3 sets x 10 reps

u
222
 Exercise therapy for muscle and lower motor neuron diseases

Exercise mode/N Duration Frequency Intensity Improved

outcome
Strength 24 weeks 3 days/week Knee extension and flexion, hip extension Neither positive or
N = 33 and abduction negative effects of
the training
(28) 60-80% of 1RM

Week 1-8: 60% of 1RM, 3 sets x 25 reps

Week 9-16: 70% of 1RM, 3 sets x 15 reps

Week 17-24: 80% of 1RM, 3 sets x 10 reps

Functional 3 weeks Functional Functional electrical stimulation: MRC, 6MWT and
electrical electrical Frequency of 30 Hz (pulse width, 200 10MWT
stimulation stimulation: µseconds)
induced cycling 30 minutes
N=4 5 days/week Strength training:
Knee extension, knee flexion, ankle
Strength and 6 weeks Strength: dorsiflexion, ankle plantarflexion
cycling 5 days/week 2 sets x 10 reps at 60% of 1RM (week 1-3)
N=4 30 min/session 2 sets x 5 reps at 80% of 1RM (week 4-6)
Cycling:
(29) 5days/week Cycling:
30 min/session 60% of HRmax
Hand-training 12 weeks of Minimum of 27 Week 1-4: 1 set x 10 reps Handgrip, pinch,
training sessions Week 5-8: 2 sets x 10 reps and wrist strength
Cross-over study 12 weeks of 60 min/session Week 9-12: 3 sets x 10 reps
N = 9 Group A wash out
N = 4 Group B 12 weeks of Isolated finger movement:
control 1 set x 3 reps, 2 sets x 3 reps, 3 sets x 3
(30) reps

Wrist extension/flexion
Finger extension/flexion
Isolated finger extension/flexion
Thumb extension/flexion
Finger adduction/abduction
Stretching wrist in flexion/flexion

continued the training. This study indicates that a com- ease progression long term, and if nutrition and exercise
bination of aerobic, resistance and core stability training therapy can minimize muscle deterioration at symptom
can be performed safely in patients with Pompe disease. onset should be further explored.
However, when combining different modes of exercise, Moderate intensity exercise appears to have an ad-
it can be challenging to determine which exercise im- juvant effect on patients with Pompe disease and regular
proved which outcome. exercise is recommended.
In 2007, a published paper evaluated whether the
adherence to nutrition and exercise therapy could slow Other exercise modalities
the deterioration of muscle function (38). Of the 34 pa- Side alternating vibration training (SAVT) is me-
tients included, 22 were fully compliant with nutrition chanical oscillation applied while standing on a vibrating
and exercise therapy. Patients demonstrated a slowing of platform. The oscillation is characterized by amplitude
their deterioration in muscle function and some showed and frequency which determine the intensity of the work
improvement in their Walton score. Whether continued performed. One patient with Pompe underwent SAVT,
compliance with nutrition and exercise therapy slows dis- and after 15 weeks of SAVT the patient showed an im-

223
Aisha Munawar Sheikh and John Vissing

Table 5. A representation of exercise interventions done in McArdle disease. Number in parenthesis represents the
article reference.
Exercise mode/N Duration Frequency Intensity Improved
outcome
Cycling 14 weeks Week 1-7: 60-70% HRmax Oxidative and
N=8 4 days/week work capacity
30 min/session
(32)
Week 8-14:
4 days/week
40 min/session
Electromagnetically 12 weeks 4 days/week 65-70% of HRmax Aerobic
braked cycling 60-90 min/session capacity and
N=7 work load

(33)
Acute: Acute: 1 day 1. Workload increased with 10 Watt/ Aerobic
Cycling 1 day min until exhaustion, starting at 10 capacity,
(strictly monitored) Watt peak power
N = 46 2. A 12-minute constant-load test at output, and
the power output reaching ventilatory ventilatory
Control group threshold on a cycle threshold
N = 46
The two tests were separated by
Chronic: Chronic: 5 days/week a 10-minute active rest period
Walking or cycling 8 months 60 min/session (freewheel pedaling)
N=9
75 g sucrose beverage prior to test
(34) 60% of HRmax

Complex carbs 1 hour before exercise

and simple carbs during exercise
Strength 6 weeks 2 days/week 65-70% of 1RM Patient
N=1 Up to 60 min/session 10-minute warm-up consisting of 5 changed to a
minutes of light-intensity dynamic lower disease
(35) exercise (on a cycle ergometer or severity class
rowing ergometer), followed by 5
minutes of mobilization exercisesand
body weight exercises (eg,
shoulder shrugs and rotations, arm
elevations, changing squat stance,
walkinglunges, push-ups on the wall).

Benchpress with free weights,

multipower squat, shoulder press,
armcurls and elbow extensions
with dumbbells, lateral pulldown,
abdominal crunches, and low back
extensions.

2-3 sets x 10-15 reps

provement in functional capacity and strength (39). The The level of safety of SAVT is questionable and should be
patient reported muscle soreness, stiffness, and aches in the subject for further exploration.
legs, twitching while at rest, cramping, and fatigue. De- Intervention specifications for Pompe disease are
spite the discomfort, her level of activity did not change. presented in Table 6.

224
 Exercise therapy for muscle and lower motor neuron diseases

Mitochondrial myopathy found it challenging to exercise for 30 minutes due to fa-

tigue or not feeling well recovered in between training
Aerobic exercise
sessions. Patients did not experience any change in their
The aspect of training patients with mitochondri-
daily physical activity, and one patient felt daily phys-
al disease is somewhat different from other myopathies
ical activity worsened post intervention. Fatigue level
in that patients experience a metabolic bottleneck in the
increased in seven patients and only one patient experi-
mitochondrial respiratory chain function. Taivassalo et al
enced improvement. A few patients did feel an increase
found that aerobic capacity increased with moderate in-
in endurance, strength, and the distance they were able to
tensity exercise on a treadmill. Fatigue and tolerance to
walk, while others didn’t experience physical improve-
daily activities also improved, and lactate concentration
ments or reported a worsening in endurance, strength,
decreased (40). In 6 of the 10 participating patients, CK
and walking distance. No CK level elevation occurred in
levels rose slightly, but not to a level indicating significant
seven of the 8 patients, one patient was asked to exercise
muscle damage. These findings are in agreement with a
with a lower frequency.
study examining the effects of moderate intensity cycling
exercise (41). Similar findings were reported by Sicilia-
Other exercise modalities
no et al.  (42)  (43) showing a decreased lactate concen-
High-intensity training improved fitness and work-
tration, improved SF-36, and improved muscle oxidative
load in 8 patients after 8 weeks of training  (51). One
metabolism with aerobic training. Jeppesen et al.  (44)
patient was excluded due to lack of compliance and one
demonstrated that moderate aerobic training was safe and
patient did not wish to continue for personal reasons. No
improved aerobic capacity. No training-induced increas-
rise in CK levels occurred after 8 and 16 weeks of train-
es in plasma CK levels were observed. Trenell et al also
ing. Self-rated muscle fatigue, muscle pain, and activity
found beneficial effects from moderate aerobic training
level remained the same throughout the training period.
including improvement in functional abilities (45). Jeppe-
Patients expressed an interest in HIT. High-intensity
sen et al. (46) investigated the effects of short- and long-
training seems to be a beneficial alternative in compari-
term moderate home-based endurance exercise. Exercise
son to moderate aerobic training, likely because neuronal
increased oxidative capacity and peak work load. These
fatigue due to short duration of exercise is avoided.
improvements were sustained after 12 months of exer-
Bulbar involvement in patients with SBMA can
cise. No training-induced CK elevation was observed and
cause dysphagia and swallowing difficulties. Effects of
patients reported feeling a physical improvement. The ef-
head lift exercises in swallowing showed an improvement
fects of moderate intensity cycling and moderate intensi-
in functional scores for oral dysphagia, indicating that
ty arm strength exercise revealed an increase in functional
head lifting exercise may factor into improving swallow-
capacity and muscle strength (47). The training effect was
ing  (52). Any clinical relevance should be integrated in
also reflected as improvements in symptoms. To counter-
the clinic with caution, considering the small sample size
act limitations in the oxygen transport pathway, exercise
of the study.
seems to be a promising therapeutic avenue for persons
Shrader et al. examined the effects of functional exer-
affected by mitochondrial myopathy (48).
cise (53). The authors concluded that functional exercise
is well tolerated, however, they did not find any functional
Other exercise modalities
changes and a modest increase in CK levels was observed.
The effects of SAVT was considered safe and pa-
High-intensity training is recommended in patients
tients showed some increase in muscle power (49). The
with SBMA because it has the best efficacy and is pre-
presented studies indicate that moderate intensity aerobic
ferred by patients. Intervention specifications for SBMA
exercise is safe and can improve physical capabilities in
are presented in Table 8.
patients with mitochondrial myopathy.
Intervention specifications for mitochondrial myopa- Spinal muscular atrophy
thies are presented in Table 7.
Aerobic exercise
Motor neuron diseases Effects of arm cycling in patients with SMA type II
showed no adverse events during or after exercise. There
was an increase in their cycling distances and durations,
Spinal and bulbar muscular atrophy (SBMA, Kennedy
but no improvements were observed in Hammersmith
disease)
Functional Motor Scale (HFMS) (54).
Aerobic exercise Effects of home-based cycling was investigated by
Moderate aerobic training was examined by Preisler Madsen et al in 8 ambulatory patients with SMA type
et al. (50). By week 5 of the intervention three patients III (55). One patient discontinued the intervention due to

225
Aisha Munawar Sheikh and John Vissing

Table 6. A representation of exercise interventions done in Pompe disease. Number in parenthesis represents the
article reference.
Exercise Duration Frequesncy Intensity Improved outcome
mode/N
Cycling and 20 weeks 3 days/week Week 1-3: Strength increased
Strength 10-15 min/session Cycling at level 1-2 and 6MWT
N=5 (week 1-3)
30 min/session (week Strength: ¼ squat, leg curl, knee
(36) 4-20) raise, push-ups against a wall, back
extensions, as well as sit ups, ¼
overhead press, elbow extensions and
elbow curl

50% of 1RM, 2 sets x 10 reps

Week 4-20:
Cycling at level 2-4

50% of 1RM, 3 sets x 10 reps

Cycling, 12 weeks 3 days/week 60% of VO2max Climb 4 steps,
strength, and muscle, strength in
core stability 70% of 4RM shoulder abductors
N = 23 and hip flexors,
One session consisted of: 6MWT, rise from
(37) 5 minutes warm up supine to standing,
15 minutes cycling workload, VO2max,
Shoulder extension, flexion and ventilatory threshold,
abduction, elbow flexion, knee extension and core stability
and flexion, hip flexion, abduction and
adduction: 3 sets x 15-20 reps
15 minutes cycling
3 x 30 seconds: Abdominal bridge, side
bridge, back bridge
High-protein 2y-10y Daily Not exceed RPE of 11–12 Slowing of
and low- deterioration in
carbohydrate 45 min/session on muscle function
nutrition and treadmill
exercise 10-15 min/session
therapy upper body
ergometer
Treadmill and
upper body
ergometer
N = 34 (22
complied
with nutrition
and exercise
therapy

(38)
SAVT 15 weeks One cycle: Vibration frequency 5 Hz, progressing to Improved strength
N=1 60 seconds 20 Hz by week 11, and continuing at 20 and 6MWT
(39) vibration-on Hz to week 15
60 seconds
vibration-off Starting with two cycles initially,
progressing to four cycles by week 11
and continuing with four cycles to week
15.

226
 Exercise therapy for muscle and lower motor neuron diseases

Table 7. A representation of exercise interventions done in Mitochondrial myopathy. Number in parenthesis represents
the reference.
Exercise mode/N Duration Frequency Intensity Improved
outcome
Treadmill 8 weeks 3-4 days/week 60-80% HRmax Aerobic
N = 10 20-30 min/session capacity, lactate
Not exceed 15 RPE concentrations
(40) decreased,
fatigue
decreased, and
tolerance to
daily activities
Cycling 14 weeks Week 1-7: 70-80% HRmax SF-36 and
N=8 49 sessions 3 days/week aerobic peak
30 min/session capacity
(41)
Week 8-14
4 days/week
40 min/session
Cycling 10 weeks Week 1-5: Max 70% HRmax Partially
N=7 30 min/session reverting
60-70 revolution (paddling)/min oxidative stress
Control group Week 6-10:
N = 12 45 min/session Max 70% of predicted normal
maximum power output
(42)
Cycling 10 weeks Week 1-5: Max 70% HRmax Lactate
N = 12 Every other day concentration
30 min/session 60–70 revolution (paddling)/ and
Control group N = 4 min muscle
Week 6-10: oxidative
(43) Every other day 60-70% of predicted normal metabolism
45 min/session maximum power output
Cycling 12 weeks 50 sessions in total 65-75% HRmax Oxidative
N = 20 30 min/session capacity,
VO2max, and
Control group workload
N = 13

(44)
Cycling 12 weeks 3 days/week 70-80% HRmax Mitochondrial
N = 10 30 min/session function
and functional
Control group ability
N = 10

(45)
Cycling Initial: 12 weeks 5 days/week 70% of VO2max Oxidative
N=4 Deconditioning: capacity and
3-12 months 3 days/week workload
(46) Second training
phase: 12 30 min/session
months

u
227
Aisha Munawar Sheikh and John Vissing

Exercise mode/N Duration Frequency Intensity Improved

outcome
Cycling and strength 12 weeks 3 days/week 70% of peak work load Oxygen uptake,
N = 10 60 min/session work output,
Shoulder press, chest press, endurance,
Control group bicep curl shuttle walking
N = 10 test, muscle
50% of 1RM strength, NHP,
(47) 1 set x 10-15 reps (first two and clinical
weeks) symptoms
From week 3: 2 or 3 sets x
10-15 reps (according to
tolerance)
SAVT 12 weeks 3 days/week 5-20 Hz (steady increase within Some increase
N=7 2 weeks) in muscle force
Week 1:
(49) 5 Hz 1 min on, 1 min off, 1 min
on
Week 2:
10 Hz 2 min on, 1 min off, 1
min on
Week 3:
15 Hz 2 min on, 1 min off, 1
min on
Week 4:
20 Hz 2 min on, 1 min off, 1
min on
Week 5–12:
20 Hz 2 min on, 1 min off, 2
min on

severe fatigue and one patient due to difficulty using the it is uncertain whether combined strength and aerobic ex-
cycle independently. Among the remaining patients, the ercise is beneficial or harmful in people with SMA (58).
authors found that the exercise was safe. However, pa- Further research is needed to understand the rather blunt-
tients reported either no change or an increase in fatigue, ed response from exercise. High-intensity training could
and no improvements in physical function. be a better exercise modality in SMA patients, as it has
been shown to be in SBMA. Intervention specifications
Strength exercise for SMA are presented in Table 9.
Submaximal resistance training is found to be well
tolerated with some strength improvements with no
study-related adverse events occurred (56).
Conclusions
There is considerable amount of evidence indicating
Combined aerobic and strength that moderate intensity aerobic- and strength exercise is
Moderate intensity cycling and strengthening exer- advantageous for patients with muscle diseases, with-
cise was well tolerated among all patients participating out causing harmful muscle damage. Exercise should be
in a single blind randomized controlled clinical (57). The planned carefully and be well monitored, and should be
authors reported a large number of falls among the pa- performed within the patients’ limitations. Extreme fa-
tients, potentially related to fatigue following training. tigue and muscle pain, during or after exercise is indic-
Reporting of muscle soreness and low back pain was also ative of negative response to exercise, and intensity and
documented. The most notable change was an increase in frequency should be reconsidered.
oxidative capacity. No harmful impact was observed on In contrast, motor neuron diseases show different
motor function, strength, and fatigue. outcomes from exercise. Exercise has a rather blunted re-
In a recent Cochrane review the authors conclude that sponse in these patients. One possible explanation could

228
 Exercise therapy for muscle and lower motor neuron diseases

Table 8. A representation of exercise interventions done in SMBA. Number in parenthesis represents the article refer-
ence.
Exercise Duration Frequency Intensity Improved out-
mode/N come
Cycling 12 weeks Week 1-2: 65-70% VO2max Workload and
N=8 2 days/week citrate synthase

(50) Week 3-4:

3 days/week

Week 5-12:
5 days/week

30 min/session
Cycling 8 weeks of 3 days/week 2×5-min exercise periods with 1-min VO2max, workload,
N=8 HIT and 8 cyclic blocks of intermittent maximal and 6MWT
weeks of intensity
(51) self-training
Head lift 6 weeks 6 times a day for 6 Component 1: 1 min isometric, 1 min Functional scores
(Shaker weeks rest x 3 for oral dysphagia
exercise) Component 2: 30 seconds of isokinetic
N=6

(52)
Functional 12 weeks Week 1+2: Trunk sit back, STS, standing squat No functional
exercise 2 days/week with theraband row, standing lunge changes
N = 24 with theraband, forward reach, double
Week 3 - 12: limb heel raise, and wall pushup
Stretching 3 days/week
N = 26 Week 1+2:
Weeks 4-6: 1 set x max reps at 50-70%% of 1RM
(53) 3 days/week
Week 3 - 12:
Week 7-12: 1 set x max reps at 50-70%% of 1RM
3 days/week
Weeks 4-6:
2 sets x max reps at 50-70%% of 1RM

Week 7-12:
3 sets x max reps at 50-70%% of 1RM

be that they reach a level of fatigue quicker due to larger groups vs. whole-body. Future research should direct the
motor units that need to fire more frequently, which may focus on determining duration, frequency, and intensity
cause a neural fatigue, which these patients experience in order to create an exercise guideline that clinicians and
after long-lasting exercise. In these patients, high-inten- patients can use.
sity training seems safe and may be a promising exercise One of the challenges in studying exercise in mus-
method which allows the patient to train effectively. cle and lower motor neuron diseases is that the diseases
The presented studies include ambulatory patients. are rare and heterogeneous and one type of exercise may
In recent years, a few studies have explored the effects not work for everyone. Furthermore, it can be difficult
of exercise using assisted devices. The effects of exercise to recruit a sufficient number of subjects for RCTs and
using assistive devices should be further explored in very examine the long- term effects of exercise, because of the
weak and non-ambulatory and wheelchair bound patients. rareness of the diseases. Lastly, quality of life and social
In addition, it is imperative to set a goal for the exer- aspects of exercise, as well as motivation and compliance
cise in order to obtain clinical relevance, and also deter- needs more emphasis in trials on exercise therapy in mus-
mine the appropriateness of training in isolated muscle cle and motor neuron diseases.

229
Aisha Munawar Sheikh and John Vissing

Table 9. A representation of exercise interventions done in SMA. Number in parenthesis represents the article reference.
Exercise Duration Frequency Intensity Improved out-
mode/N come
Arm cycle 12 weeks 3 days/week 60% HRmax Cycling distances
N=5 30 min/session and durations

(54)
Cycling 12 weeks 2-4 days/week (gradual 65-70% of VO2max Aerobic capacity
N=6 increase)
30 min/session 60-75% max HR
Control group
N=9

(55)
Home based 12 weeks 3 days per week 2 sets x 15 reps Some improvement
strength 45-60 min/session in upper limb
training All participants exercised the strength
N=9 Shoulder flexion, shoulder
extension, elbow flexion, and elbow
(56) extension. Additionally, ambulatory
participants exercised lower
extremity muscles including the hip
flexion, hip extension, and knee
extension
Home based 1 month Cycling Exercise regimen was structured Exercise ability
cycling and lead in 5 days/week based on participant performance increased slowly
strengthening period 30 min/session on the exercise and VO2max
N=9 6 months - tolerance test and strength
intervention Strengthening: assessments
Control group 12 month - 3 days/week
N=7 all exercised

(57)

Conflict of interest 6. Aitkens S, Kilmer DD, Wright NC, et al. Metabolic syndrome in
neuromuscular disease. Arch Phys Med Rehabil 2005;86:1030-6.
The Authors declare to have no conflict of interest.
7. Kilmer DD, Zhao HH. Obesity, physical activity, and the metabolic
syndrome in adult neuromuscular disease. Phys Med Rehabil Clin
References N Am 2005;16:1053–62, xi.

1. Jacques MF, Stockley RC, Onambele-Pearson GL, et al. Quality of 8. Vissing CR, Preisler N, Husu E, et al. Aerobic training in patients
life in adults with muscular dystrophy. Health Qual Life Outcomes with anoctamin 5 myopathy and hyperckemia. Muscle Nerve
2019;17:121. 2014;50:119-23.

2. Sacco P, Jones DA, Dick JR, et al Contractile properties and sus- 9. Sveen M-L, Jeppesen TD, Hauerslev S, et al. Endurance training:
ceptibility to exercise-induced damage of normal and mdx mouse an effective and safe treatment for patients with LGMD2I. Neurol-
tibialis anterior muscle. Clin Sci Lond Engl 1979. 1992;82:227-36. ogy 2007;68:59-61.

3. Carter GT, Abresch RT, Fowler WM. Adaptations to exercise train- 10. Sveen M-L, Andersen SP, Ingelsrud LH, et al. Resistance training
ing and contraction-induced muscle injury in animal models of mus- in patients with limb-girdle and becker muscular dystrophies. Mus-
cular dystrophy. Am J Phys Med Rehabil 2002;81(Suppl):S151-61. cle Nerve 2013;47:163-9.
4. Exercise | definition of exercise by Medical dictionary [Internet]. [cited 11. Sczesny-Kaiser M, Kowalewski R, Schildhauer TA, et al. Treadmill
2019 Jul 29] (https://medical-dictionary.thefreedictionary.com/exercise). training with HAL exoskeleton-A novel approach for symptomatic
5. McCrory MA, Kim HR, Wright NC, et al. Energy expenditure, therapy in patients with Limb-Girdle muscular dystrophy-prelimi-
physical activity, and body composition of ambulatory adults with nary study. Front Neurosci 2017;11:449.
hereditary neuromuscular disease. Am J Clin Nutr 1998;67:1162-9. 12. Berthelsen MP, Husu E, Christensen SB, et al. Anti-gravity training

230
 Exercise therapy for muscle and lower motor neuron diseases

improves walking capacity and postural balance in patients with 28. Lindeman E, Spaans F, Reulen J, et al. Progressive resistance train-
muscular dystrophy. Neuromuscul Disord NMD 2014;24:492-8. ing in neuromuscular patients. Effects on force and surface EMG.
13. Jensen BR, Berthelsen MP, Husu E, et al. Body weight-supported J Electromyogr Kinesiol Off J Int Soc Electrophysiol Kinesiol
training in Becker and limb girdle 2I muscular dystrophy. Muscle 1999;9:379-84.
Nerve 2016;54:239-43. 29. Cudia P, Weis L, Baba A, et al. Effects of functional electrical stim-
14. Kilinç M, Yildirim SA, Tan E. The effects of electrical stimula- ulation lower extremity training in myotonic dystrophy type 1: a
pilot controlled study. Am J Phys Med Rehabil 2016;95:809-17.
tion and exercise therapy in patients with limb girdle muscular
dystrophy. A controlled clinical trial. Neurosci Riyadh Saudi Arab 30. Aldehag A, Jonsson H, Lindblad J, et al. Effects of hand-training in
2015;20:259-66. persons with myotonic dystrophy type 1 – A randomised controlled
cross-over pilot study. Disabil Rehabil 2013;35:1798-807.
15. Sveen ML, Jeppesen TD, Hauerslev S, et al. Endurance training
improves fitness and strength in patients with Becker muscular dys- 31. Okkersen K, Jimenez-Moreno C, Wenninger S, et al. Cognitive be-
trophy. Brain J Neurol 2008;131(Pt 11):2824-31. havioural therapy with optional graded exercise therapy in patients
with severe fatigue with myotonic dystrophy type 1: a multicentre,
16. Tramonti C, Rossi B, Chisari C. Extensive functional evaluations
single-blind, randomised trial. Lancet Neurol 2018;17:671-80.
to monitor aerobic training in Becker muscular dystrophy: a case
report. Eur J Transl Myol 2016;26:5873. 32. Haller RG, Wyrick P, Taivassalo T, et al. Aerobic conditioning: an
effective therapy in McArdle’s disease. Ann Neurol 2006;59:922-8.
17. Olsen DB, Ørngreen MC, Vissing J. Aerobic training improves
exercise performance in facioscapulohumeral muscular dystrophy. 33. Porcelli S, Marzorati M, Morandi L, et al. Home-based aerobic
Neurology 2005;64:1064-6. exercise training improves skeletal muscle oxidative metabolism
in patients with metabolic myopathies. J Appl Physiol (1985)
18. Andersen G, Prahm KP, Dahlqvist JR, et al. Aerobic training and
2016;121:699-708.
postexercise protein in facioscapulohumeral muscular dystrophy:
RCT study. Neurology 2015;85:396-403. 34. Maté-Muñoz JL, Moran M, Pérez M, et al. Favorable responses
to acute and chronic exercise in McArdle patients. Clin J Sport
19. Voet N, Bleijenberg G, Hendriks J, et al. Both aerobic exercise and
Med2007;17:297-303.
cognitive-behavioral therapy reduce chronic fatigue in FSHD: an
35. García-Benítez S, Fleck SJ, Naclerio F, et al. Resistance (weight
RCT. Neurology 2014;83:1914-22.
lifting) training in an adolescent with McArdle disease. J Child
20. Bankolé L-C, Millet GY, Temesi J, et al. Safety and efficacy of a
Neurol 2013;28:805-8.
6-month home-based exercise program in patients with facioscapu-
36. Terzis G, Dimopoulos F, Papadimas GK, et al. Effect of aerobic
lohumeral muscular dystrophy: a randomized controlled trial. Med-
and resistance exercise training on late-onset Pompe disease pa-
icine (Baltimore) 2016;95:e4497.
tients receiving enzyme replacement therapy. Mol Genet Metab
21. van der Kooi EL, Vogels OJM, van Asseldonk RJGP, et al. Strength 2011;104:279-83.
training and albuterol in facioscapulohumeral muscular dystrophy.
37. van den Berg LE, Favejee MM, Wens SCA, et al. Safety and effi-
Neurology 2004;63:702-8.
cacy of exercise training in adults with Pompe disease: evalution of
22. Andersen G, Heje K, Buch AE, et al. High-intensity interval train- endurance, muscle strength and core stability before and after a 12
ing in facioscapulohumeral muscular dystrophy type 1: a rand- week training program. Orphanet J Rare Dis 2015;10:87.
omized clinical trial. J Neurol 2017;2641099-106.
38. Slonim AE, Bulone L, Goldberg T, et al. Modification of the natural
23. Colson SS, Benchortane M, Tanant V, et al. Neuromuscular elec- history of adult-onset acid maltase deficiency by nutrition and exer-
trical stimulation training: a safe and effective treatment for faci- cise therapy. Muscle Nerve 2007;35:70-7.
oscapulohumeral muscular dystrophy patients. Arch Phys Med
39. Khan A, Ramage B, Robu I, et al. Side-alternating vibration train-
Rehabil 2010;91:697-702.
ing improves muscle performance in a patient with late-onset
24. Orngreen MC, Olsen DB, Vissing J. Aerobic training in patients Pompe disease. Case Rep Med 2009;2009:741087. https://doi.
with myotonic dystrophy type 1. Ann Neurol 2005;57:754-7. org/10.1155/2009/741087
25. Aitkens SG, McCrory MA, Kilmer DD, et al. Moderate resistance 40. Taivassalo T, De Stefano N, Argov Z, et al. Effects of aerobic
exercise program: its effect in slowly progressive neuromuscular training in patients with mitochondrial myopathies. Neurology
disease. Arch Phys Med Rehabil 1993;74:711-5. 1998;50:1055-60.
26. Tollbäck A, Eriksson S, Wredenberg A, et al. Effects of high resist- 41. Taivassalo T, Gardner JL, Taylor RW, et al. Endurance training and
ance training in patients with myotonic dystrophy. Scand J Rehabil detraining in mitochondrial myopathies due to single large-scale
Med 1999;31:9-16. mtDNA deletions. Brain J Neurol 2006;129:3391-401.
27. Lindeman E, Leffers P, Spaans F, et al. Strength training in patients with 42. Siciliano G, Simoncini C, Lo Gerfo A, et al. Effects of aerobic
myotonic dystrophy and hereditary motor and sensory neuropathy: a training on exercise-related oxidative stress in mitochondrial myo-
randomized clinical trial. Arch Phys Med Rehabil 1995;76:612-20. pathies. Neuromuscul Disord 2012;22(Suppl 3):S172-7.

231
Aisha Munawar Sheikh and John Vissing

43. Siciliano G, Manca ML, Renna M, et al. Effects of aerobic training 57. Montes J, Garber CE, Kramer SS, et al. Single-blind, randomized,
on lactate and catecholaminergic exercise responses in mitochon- controlled clinical trial of exercise in ambulatory spinal mus-
drial myopathies. Neuromuscul Disord 2000;10:40-5. cular atrophy: why are the results negative? J Neuromuscul Dis
44. Jeppesen TD, Schwartz M, Olsen DB, et al. Aerobic training is safe 2015;2:463-70.
and improves exercise capacity in patients with mitochondrial myo- 58. Bartels B, Montes J, van der Pol WL, et al. Physical exercise train-
pathy. Brain J Neurol 2006;129:3402-12. ing for type 3 spinal muscular atrophy. Cochrane Database Syst
45. Trenell MI, Sue CM, Kemp GJ, et al. Aerobic exercise and mus- Rev 2019;3:CD012120.
cle metabolism in patients with mitochondrial myopathy. Muscle
Nerve 2006;33:524-31.
46. Jeppesen TD, Dunø M, Schwartz M, et al. Short- and long-term
Abbreviations
effects of endurance training in patients with mitochondrial myopa- ADL = Activities of Daily Living
thy. Eur J Neurol 2009;16:1336-9. BMD = Becker muscular dystrophy
47. Cejudo P, Bautista J, Montemayor T, et al. Exercise training in mi- CK = Creatine Kinase
tochondrial myopathy: a randomized controlled trial. Muscle Nerve DM = Myotonic muscular dystrophy
2005;32:342-50. DMD = Duchenne muscular dystrophy
48. Porcelli S, Grassi B, Poole DC, et al. Exercise intolerance in pa- F/U = Follow-up
tients with mitochondrial myopathies: perfusive and diffusive limi- FSHD = Facioscapulohumeral muscular dystrophy
tations in the O2 pathway. Curr Opin Physiol 2019;10:202-9. HFMS = Hammersmith Functional Motor Scale
49. Newell C, Ramage B, Robu I, et al. Side alternating vibration HIT = High Intensity Training
training in patients with mitochondrial disease: a pilot study. Arch HR = Heart rate
Physiother 2017;7:10. LGMD = Limb-girdle muscular dystrophy
50. Preisler N, Andersen G, Thøgersen F, et al. Effect of aerobic train-
LOIT = Low Intensity Training
ing in patients with spinal and bulbar muscular atrophy (Kennedy Min = Minutes
disease). Neurology 2009;72:317-23. MRC = Medical Research Council
NHP = Nottingham Health Profile
51. Heje K, Andersen G, Buch A, et al. High-intensity training in patients
NMES = Neuromuscular Electrical Stimulation
with spinal and bulbar muscular atrophy. J Neurol2019;266:1693-7.
RCT = Randomized Controlled Trial
52. Mano T, Katsuno M, Banno H, et al. Head lift exercise improves
Reps = Repetitions
swallowing dysfunction in spinal and bulbar muscular atrophy. Eur
RPE = Rate of Perceived Exertion
Neurol 2015;74:251-8.
SAVT = Side Alternating Vibration Training
53. Shrader JA, Kats I, Kokkinis A, et al. A randomized controlled trial SBMA = Spinal and Bulbar Muscular Atrophy
of exercise in spinal and bulbar muscular atrophy. Ann Clin Transl SF-36 = 36 Item Short Form Survey
Neurol 2015;2:739-47.
SMA = Spinal Muscle Atrophy
54. Bora G, Subaşı-Yıldız Ş, Yeşbek-Kaymaz A, et al. Effects of arm SST = Stair Step Test
cycling exercise in spinal muscular atrophy type 2 patients: a pilot STS = Sit-to-Stand
study. J Child Neurol 2018; 33:209-15. TUG = Timed Up and Go
55. Madsen KL, Hansen RS, Preisler N, et al. Training improves oxida- UC = Usual Care
tive capacity, but not function, in spinal muscular atrophy type 3. VAS = Visual Analog Scale
Muscle Nerve 2015;52:240-4. VO2max = Maximum volume oxygen consumption
56. Lewelt A, Krosschell KJ, Stoddard GJ, et al. Resistance strength 6MWT = Six-Minute Walk Test
training exercise in children with spinal muscular atrophy. Muscle 1RM = One-repetition maximum
Nerve 2015;52:559-67. 10MWT = 10 Meter Walk Test

How to cite this article: Sheikh AM, Vissing J. Exercise therapy for muscle and lower motor neuron diseases. Acta Myol
2019;38:215-32.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC
4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative
works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated,
and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

232