The many symptoms (panel 1) associated with multiple
sclerosis (MS) cause functional impairment and
handicap. The symptom pattern depends on the location
of lesions in the CNS, although most inflammatory foci
do not cause symptoms. The most common symptoms
in relapsing-remitting MS are visual (46%) and sensory
disturbances (41%), whereas in primary progressive
forms of MS the most prevalent symptoms are gait
disorders (88%) and pareses (38%).1Other symptoms
such as bladder problems and cognitive disturbances
commonly develop later in the course of the disease and
can become the most noticeable. The consequences of
these functional deficits in activities of daily life are
variable. Many patients commonly view fatigue as
having the most adverse consequences in daily life,
followed by disturbances of balance, pareses, and
bladder disorders.2 MS has an early disease onset, a
progressive course, and very long duration with a
median survival time of about 40 years from diagnosis;
thus there is a high prevalence of disabilities with
consequences in personal as well as social domains.
15 years after diagnosis, around 50% of patients with MS
use walking aids and 29% need a wheelchair.3,4During
the first 10 years of disease, 50–80% become unable to
work.5Thus, the main burden of the disease manifests
during the 5th and 6th decades of a patient’s life, a time
when most people are particularly active socially as well
as in their careers. Socioeconomic consequences of MS
are substantial: the direct and indirect costs for one
person with MS per year are estimated at around ¤50 000
or US$62 000, and there is a strong correlation between
costs and increasing score on the expanded disability
status scale (EDSS).6Half of the direct costs are
attributable to care of 17% of patients—those with the
most severe disability of whom 6·5% live in nursing
For many patients with MS, quality of life can
deteriorate and they lose their independence and
become less able to participate in social activities.
Treatment of the symptoms of MS is essential and it
requires a multidisciplinary approach encompassing
drug therapy, psychological
Rehabilitation can be defined as an active process of
education and enablement, which is focused on the
appropriate management of disability and minimising
limitation of handicap, with the goal of achieving full
recovery. However, with a condition such as MS in
Lancet Neurol2005; 4: 643–52
Department of Neurology and
CH-7317, Valens, Switzerland
(JKesselring, S Beer)
Prof Jürg Kesselring, Department
of Neurology and
Rehabilitation Centre, CH-7317,
http://neurology.thelancet.com Vol 4 October 2005 643
Jürg Kesselring, Serafin Beer
Multiple sclerosis (MS) is associated with a variety of symptoms and functional deficits that result in a range of
progressive impairments and handicap. Symptoms that contribute to loss of independence and restrictions in social
activities lead to continuing decline in quality of life. Our aim is to give an updated overview on the management of
symptoms and rehabilitation measures in MS. Appropriate use of these treatment options might help to reduce
long-term consequences of MS in daily life. First, we review treatment of the main symptoms of MS: fatigue, bladder
and bowel disturbances, sexual dysfunction, cognitive and affective disorders, and spasticity. Even though these
symptomatic therapies have benefits, their use is limited by possible side-effects. Moreover, many common
disabling symptoms, such as weakness, are not amenable to drug treatment. However, neurorehabilitation has been
shown to ease the burden of these symptoms by improving self-performance and independence. Second, we discuss
comprehensive multidisciplinary rehabilitation and specific treatment options. Even though rehabilitation has no
direct influence on disease progression, studies to date have shown that this type of intervention improves personal
activities and ability to participate in social activities, thereby improving quality of life. Treatment should be adapted
depending on: the individual patient’s needs, demands of their surrounding environment, type and degree of
disability, and treatment goals. Improvement commonly persists for several months beyond the treatment period,
mostly as a result of reconditioning and adaptation and appropriate use of medical and social support at home. These
findings suggest that quality of life is determined by disability and handicap more than by functional deficits and
Symptomatic therapy and neurorehabilitation in
Panel 1: Symptoms associated with MS
Bladder and bowel dysfunction
Cognitive and emotional problems—eg, depression
Dizziness and vertigo
Speech and swallowing disorders
which full recovery is not possible, goals become focused
on achieving the best physical, mental, and social
potential of patients so that they can remain, or become,
integrated into a social environment that is appropriate
for them. The longer-term benefits from management of
symptoms and emotional status help to compensate for
functional deficits and enable patients to adapt to their
circumstances more readily.
This paper provides an overview of management
options for each group of symptoms that accompany MS
and examines clinical-trial evidence that supports the
efficacy of neurorehabilitation. In 2004, a group of
experts in MS from Germany, Switzerland, and Austria
published a comprehensive review and consensus
statement on symptomatic treatment and rehabilitation
in MS;8it consists of existing evidence based literature
and neurologists’ therapeutic experience who have dealt
with these problems over a long time.
Fatigue is the single symptom that patients identify as
interfering most with their daily activities. The causes
are multifactorial. A poor sleep pattern, resulting from
pain, nocturia, and spasticity, is commonly the cause.
Another equally important factor might be the
immunological processes of MS. Several of the cytokines
involved in the pathogenesis of MS are known to induce
sleep, especially interleukin, which affects the
hypothalamic axis and results in reduced cerebral
Motor disturbances associated with
spasticity are also likely to contribute to the fatigue
syndrome. In patients with MS, the reciprocal inhibitory
mechanisms are disturbed, which results in a reduced
rate of motor-unit firing. Electrophysiological studies
have suggested that an impaired drive of motor impulses
to the primary motor cortex can decay the maximal
muscle force.10In addition to these pathophysiological
mechanisms, treatments for MS, such as beta
interferons, antispastic drugs, and antidepressive
agents, have also been reported to cause fatigue.
New evidence suggests that fatigue might be linked to
disturbances in regulation of body temperature.11There
seems to be an association between dysregulation of
body temperature and
endothelins that accompany ischaemia.12The role of
endothelins as mediators in temperature regulation and
fatigue is currently being investigated in our clinic.
Treatment of fatigue requires a multidisciplinary
approach; appropriate strategies include graded exercise
programmes, behaviour modification therapy, or
medication. In a comparative, double-blind randomised
study, 93 patients were assigned amantadine (100 mg
twice daily), pemoline (18·75–37·5 mg), or placebo for
6 weeks.13 The group assigned amantadine had a
significant improvement in fatigue compared with the
placebo group. There was no difference in fatigue
between the pemoline and placebo groups. In clinical
high concentrations of
practice, however, the effect of amantadine is less
impressive, and a recent meta-analysis criticised trials
for not investigating the relevance and effect on quality
of life.14A randomised, double-blind cross-over trial with
36 patients with MS by Tomassini and co-workers,15
showed significant improvement in fatigue (rated by the
fatigue severity scale) during 3 months of treatment
with acetyl L-carnitine compared with amantadine; the
researchers concluded that acetyl L-carnitine was
superior and better tolerated than amantadine.15In a
non-randomised, single-blind phase II study with a
titration design in 72 patients with MS who had fatigue
(measured by MS fatigue scale) fatigue improved with
daily modafinil treatment (200 mg) for 9 weeks.16Even
though treatment with modafil was tolerated well, long-
term safety and efficacy remain unclear. An alternative
therapy to modafil could be methylphenidate—another
drug with central stimulating effects—which has also
been of benefit in patients with other diseases causing
fatigue (HIV, cancer).17,18Aminopyridines (3-4-diamino-
pyridine, 4-aminopyridine) work by blocking potassium
channels and thus improving central conduction in
demyelinated fibres; this mechanism has been shown to
lead to an improvement of fatigue and other
symptoms.19In a randomised, double-blind, placebo-
controlled, cross-over trial, 54 patients with MS were
treated with 4-aminopyridine (32 mg daily over
6 months);20 although there was no significant
improvement in fatigue among the whole study group,
patients with serum concentrations of 4-aminopyridine
above 30 ng/L showed significant improvement. The
treatment was tolerated well in this study, however,
serious side-effects of aminopyridines have been
reported, making safety an important issue for future
trials.21Nutritional supplements such as creatine (in
combination with magnesium)
conditioning training and improve physical endurance;22
even though the use of these supplements might be
useful during intensive training, no clinical trials have
investigated the benefit during rehabilitation of patients
Bladder symptoms are particularly incapacitating in
daily life. Spinal-cord disease in MS is thought to be the
main cause of pelvic-organ dysfunction. Impairment of
bladder function is commonly characterised by urgency,
which is the consequence of detrusor hyper-reflexia. The
symptom of urgency is in many cases coupled with
urinary frequency resulting from reduced bladder
capacity. A few patients also have difficulty in initiating
micturition or are unable to achieve complete bladder
emptying. These bladder symptoms make many patients
reluctant to engage in social activities. Urgency can be
made worse by motor disabilities that prevent the patient
from reaching the toilet quickly. Apart from drug
therapy, pelvic-floor training can help to improve
http://neurology.thelancet.com Vol 4 October 2005
bladder symptoms. In a controlled study of 80 patients
with MS, pelvic floor training with combined instruction
for home programmes led to significant improvements
in incontinence, urgency, and frequency.23Incomplete
bladder voiding can be treated with an external bladder
stimulator (Queen Square stimulator), leading to a
substantial reduction in resting urinary volume.24,25
Detrusor hyperactivity can be effectively treated with
physiotherapy to train the pelvic-floor muscles26or
bladder-training protocols, which aim to re-establish a
normal urinary frequency and increase bladder capacity
through behavioural modification.27
agents, especially tolterodine, are effective at decreasing
micturition and urge incontinence.28However, these
pharmacological treatments commonly have typical
anticholinergic side-effects (dry mouth and thirst),
which in turn can exacerbate bladder problems.
Management of bladder dysfunction can also be
achieved in some cases by simpler methods, such as
effective management of fluid intake and a reduction in
the intake of diuretic agents such as caffeine. These
approaches can be used alongside the methods
described above. Alternatively,
therapy (anal or vaginal) has been used to stimulate the
pudendal nerves and inhibits the hyper-reflexia. Some
patients with detrusor-sphincter dys-synergy need clean
intermittent self-catheterisation, and others need
permanent catheterisation; in these cases suprapubic
catheters carry a lower risk of infection and
complications than intraurethral catheters.29A new way
of treating hyper-reflexia is injection of botulinum A
toxin into the detrusor muscle. In a study of 31 patients
who had spinal-cord injury with severe hyper-reflexia
and who needed intermittent self-catheterisation, an
injection of botulinum toxin (300 units) was highly
effective in restoring continence and had no side-
effects.30,31The effects of a single dose of botulinum toxin
lasted for 9 months.
Urinary-tract infections can occur as a result of urine
retention or catheter use. Management of these
infections is an important part of MS therapy, and
patients should be monitored closely. Urinary tract
infections can be managed with antibiotics such as
ciprofloxacin, sulfamethoxazole, and nitrofurantoin,32
and phenazopyridine can be used for symptom relief.33
prophylactically to prevent infections,34although this use
is still controversial.35In some patients, infection of the
upper urinary tract results in severe illness and
permanent damage to the kidneys. Patients with
symptoms consistent with such infections and those not
responding to treatment should be carefully monitored.
can also be used
Many patients with MS experience sexual dysfunction.36
In a comparative study, sexual dysfunction was found in
73% of patients with MS compared with 39% of those
with other chronic diseases and 13% of healthy
The main complaints for women are
anorgasmia or hyporgasmia,
lubrication, and reduced libido. In men, the main
complaints are impotence or erectile dysfunction,
ejaculatory dysfunction, orgasmic dysfunction, and
reduced libido.37These symptoms can have an important
effect on self-esteem and relationships. Even though
some of these complaints can be attributed to the
psychological factors related to having a chronic
disabling disease, others are a result of the dysfunction
of neural pathways that are important for sexual activity.
The association of sexual disturbances with disability,
neurological impairment, and bladder dysfunction is
evidence for dysfunction of these neural pathways; MRI
data suggest an association with pontine pathology.38
Another cause of sexual dysfunction might be the use of
drugs (eg, intrathecal baclofen) which can affect erectile
function.39Management for these symptoms, is again,
multifactorial in nature because the problem can be
organic, psychological, or related to relationship
problems. The primary approach is to refer patients for
psychological counselling; this approach for couples can
improve sexual satisfaction.40Drug treatment is mainly
limited to erectile dysfunction, which can be treated with
oral sildenafinil.24,41Intracavernous self-injections of
vasoactive drugs are another treatment option,42
however, this approach can be difficult for patients with
advanced disability. Other treatments occasionally used
are vacuum devices and implants.
Chronic constipation is a substantial source of distress
for patients with chronic neurological diseases including
MS. Non-specific measures to control constipation
include: body fitness programmes, dietary intervention
in the form of fibre, avoidance of chocolate, and
adequate intake of fluids. However, increased fluid
intake can in turn complicate co-existing bladder
problems. Pharmacological interventions are in the
form of laxative-type agents.43,44
Cognitive deficit and affective disturbances
40–65% of patients with MS have some degree of
cognitive deficit.45These deficits can occur early in the
course of the disease and can have long-term effects on
patients and their families. Unemployment, social
isolation, and the need for personal assistance at home
are more likely in patients with cognitive impairment
(figure 1),46and these patients also have a high risk of
developing depression. Many patients with cognitive
deficits, particularly early in the course of MS, have to
give up work with subsequent loss of income. This loss
is an important part of the indirect costs of MS; loss of
earnings for both patient and carer and costs of informal
care account for up to 60% of the financial cost of MS.47,48
Memory is the most commonly affected function; long-
http://neurology.thelancet.com Vol 4 October 2005645
term memory is more impaired than the short-term
memory. Attention is also compromised as shown by
diminished alertness, a reduction of mental processing
speed, and impaired visuospacial perception.
Cognitive deficits must be recognised as early as
possible, enabling rehabilitation strategies to be
employed to limit effects on the patient’s life. These
strategies are focused primarily on non-pharmacological
measures, such as cognitive rehabilitation, occupational
therapy, and psychotherapy. Pharmacological measures
focus mainly on the control of comorbid symptoms,
such as fatigue and depression. Because of the
difficulties of undertaking clinical trials to assess the
effect of treatment on cognitive deficits, there are
currently few effective pharmacological agents approved
as symptomatic therapy for cognitive dysfunction in
Cognitive training can
improvement of attention and therefore a reduction in
attention-associated problems in comparison with non-
specific training;51these effects were measurable even
several weeks after the end of treatment. Lincoln and
examined the influence of detailed
neuropsychological testing with cognitive intervention
(which consisted, however, only of instruction in self-
training rather than of peforming therapy by
neuropsychological testing alone. At 4 months and
8 months after neuropsychological testing, there were
lead to substantial
no significant differences between the groups. The
group assigned neuropsychological testing without
cognitive intervention reported a reduction of quality of
life after 8 months.
intervention should be avoided.
In addition to loss of cognitive function, the lifetime
frequency of affective disorders (25–50%) is three
times higher among patients with MS than in the
general population.53,54An estimated 73% of patients
with MS have difficulty in controlling their emotions
(for example, irritability, anger, and crying).55
Emotional instability occurs in 10% of patients and
impairs social interaction. Uncontrollable crying is
more common than uncontrollable laughing;56such
symptoms might be related to lesions in the anterior
part of the limbic system, which are common in MS.
The psychological problems of MS commonly cause
more distress than the physical effects. Some, studies
have shown that there is a positive association between
depression and physical disability.57
subsyndromes of affective disability respond well to
antidepressants, detection and treatment offer the
opportunity of substantially reducing one important part
of morbidity associated with MS.58
Some patients with depressive symptoms can benefit
from professional psychological or psychiatric therapy
supported with drug treatment;59group therapy can
improve motivation, social interaction, and participation
of patients in daily life.
Pain in MS can be the result of demyelination in one of
the pain-conducting pathways. The most common form
is trigeminal neuralgia, in which the block is in the root
entry zone of the trigeminal nerve.60Other nerve regions
are affected as a result of similar processes. The
increased pain perception is a result of abnormal
impulse transmission caused by demyelination and is
best treated with antiepileptic drugs.61Other sources of
pain are indirectly related to the disease. Wheelchair use
(figure 2) can cause secondary forms of pain resulting
from contractures, flexor spasm, or indirectly via
guidelines by WHO for treatment of cancer pain,62the
general principle of pain management in MS is to
progress in a stepwise manner.
According to published
Difficulties arising from spasticity include limitations in
the range of movement and malpositioning of the joints,
commonly accompanied by pain, and limitations of
normal pursuit of movements. Individual factors and
type and distribution of spasticity must be taken into
account in decisions on therapeutic options. Spasticity
can initially be managed with exercise (figure 3),
changes in daily activities, physiotherapy, occupational
http://neurology.thelancet.com Vol 4 October 2005
Figure 1: Training activities of daily life—climbing stairs
therapy, or a combination of these methods. If these
approaches are unsuccessful,
successful, spasticity can be managed with orally
administered drugs; there is good evidence to support
use of agents such as baclofen or tizanidine.63,64Some
patients with severe spasticity who are unable to walk
and do not respond to oral medication benefit from
intrathecal baclofen. Botulinum toxin is also effective in
the management of spasticity.65,66
management of spasticity
accompanied by physiotherapy. In tetraspasticity, an oral
antispastic is used first (baclofen, tizanidine, dantrolene,
diazepam). The disadvantage of these medications is a
general lowering of muscle tone also in muscle groups
with an already reduced tone (eg, trunk muscles).
Furthermore, other possible side-effects, such as fatigue
and vertigo, reduce physical fitness and cooperation. In
severe paraspasticity, if a trial intrathecal injection is
successful, implantation of an intrathecal baclofen
pump can be a good alternative; advantages of this
treatment are the very low dose needed, the absence of
systemic side-effects, optimum dosing, and limitation of
the effect on the legs.67Regional spasticity (especially
adduction spasticity of the legs) can be improved by
botulinum-toxin injections.68In some patients, standing
and walking are only possible because of the spastic
increase in muscle tones; this feature must be taken into
account in decisions on treatment of spastic syndromes,
because reduction of spasticity, by drugs can lead to
or only partially
should always be
striking deterioration in mobility. Furthermore, in every
syndrome of spasticity provoking triggers should be
sought and treated if found (eg, urinary tract infections
and pain from other causes).44
Of all the symptoms of MS, ataxia and tremor are least
susceptible to drug treatement. Benzodiazepines
(eg, clonazepam), the tuberculostatic drug isoniazid, or
ondansetron can relieve symptoms in single cases; the
use of such therapies is limited, however, because of
Evidence-based research on the effectiveness of
neurorehabilitation69is compromised by difficulties in
trial design. There are no specific guidelines on the
duration of treatment or its intensity. Controlled studies
are rare owing to the justifiable reluctance, on ethical
grounds, to withhold therapy judged to be the best.
Moreover, masking of treatment blinding is never
possible, although masking of observers might be
Measurement of effectiveness
Assessment of the effectiveness of rehabilitation is
particularly difficult in MS. First, the activity and the
course of the disease are difficult to measure reliably.
The differences within and between individuals
complicate prediction of outcome even in patients with
the same form of disease (primary relapsing remitting,
secondary chronic progressive,
progressive). Triggering factors for progression and
http://neurology.thelancet.com Vol 4 October 2005647
Figure 2: Transfer from wheelchair to bed using skidding board
Figure 3: Training of force, endurance, and full range of movements
relapses are not well understood. Basic pathological
processes (inflammation, demyelination, and axonal
damage) are heterogeneous and can be discriminated
only with great difficulty
neuroradiology.70Furthermore, the symptom pattern
can fluctuate as a result of various factors that may make
assessment of functional capacity difficult because
different functional CNS systems are affected. The
consequences in terms of the kind and amount of
disability, handicap, and quality of life vary.71MRI is not
helpful in assessment of functional capacity because
there is no close relation between conventional MRI
findings and degree of disability.70To achieve a
homogeneous cohort of patients, which satisfies
scientific criteria for assessment of effectiveness of a
medical intervention, is therefore very difficult. Perhaps
this difficulty explains why only a few studies on the
efficacy of rehabilitation in MS have been done.
Assessment of outcome by appropriate methods is not
only of scientific interest, it also enables comparison of
efficacy of different treatment modalities and allows
adaptations and development of new approaches.
Assessment systems should be related to impairment,
disability and handicap, quality of life, goal achievement,
coping skills, self efficacy, and they should be clinically
useful, scientifically sound (reliable, valid, and
responsive), and acceptable (appropriate to sample).69
Panel 2 shows the range of possible measures that can
be used to assess outcomes in rehabilitation trials. Based
on our experience with patients at our centre, disability,
handicap, and quality of life are the most important of
these measures, but a general consensus on how to
measure them is lacking.
rehabilitation clinics, but there is a general consensus on
personnel and infrastructure requirements and essential
components of a rehabilitation programme.71,72Owing to
the broad range of symptoms and disabilities in MS, a
programmes vary widely among
comprehensive assessment of functional disturbances
and of personal needs is essential for an individualised,
therapeutic interventions are only one part of the
rehabilitation programme. Comprehensive information
and instruction of patients and relatives and other non-
specific factors are equally important.
The timing and mode of rehabilitation treatment in
MS patients should be set individually, with account
taken of the degree and extent of disability, and
personal and environmental factors. The need for
rehabilitation should be assessed early in patients at
risk of losing important functions, activities, or
independence. Preservation of functions is much
easier and more reliable than restoration of functions
that have been lost for some time. Patients with
complex functional deficits and disabilities should be
admitted to the hospital for multidisciplinary
rehabilitation treatment because outpatient treatment
can be too difficult for logistic reasons. Even though,
the best evidence for efficacy of rehabilitation came
from studies with patients with chronic progressive
MS, there is growing evidence that patients with
relapsing-remitting MS can benefit from rehabilitation
measures after an acute relapse with incomplete
Realistic goals must be laid down in collaboration with
patients and carers before the rehabilitation process
starts. Features that limit comprehensive rehabilitation
treatment include severe, cognitive disturbances, which
affect cooperation and learning capabilities, and severe
concomitant diseases, which limit training capacity.
Several randomised controlled trials have added
evidence of efficacy of rehabilitation measures. Although
some studies suggest that some cortical reorganisation
in patients with MS can occur,75this mechanism of
recovery probably plays only a minor part in MS
rehabilitation. The main effect results from improved
Furthermore, information and instruction to patients
and carers and the use of medical and social resources
can improve the patient’s ability to cope with disease and
disability, thereby improving quality of life of patients
and their relatives. The specific effect of treatment
modalities on functions only partly explains the
observed long-term benefit; adaptation, improved
coping strategies and better use of personal and social
resources are also important contributing factors.76
In an open, non-controlled study after short duration of
inpatient rehabilitation (15 days) in 79 patients, there
was a significant improvement in disability and
handicap.77This positive effect persisted for 3 months,
particularly in patients with relapsing-remitting disease,
but also in progressive forms. These findings were
confirmed in a randomised, controlled study by the
http://neurology.thelancet.com Vol 4 October 2005
Panel 2:Criteria for selection of outcome variables in
Disability and handicap
Quality of life
Scientific soundness (reliable, valid and responsive)
Acceptability (appropriateness to sample)
same research group;7832 patients with MS, who
followed an inpatient multidisciplinary rehabilitation
programme for 3 weeks, were compared with another
group of 34 patients who were on a waiting list and
started rehabilitation later. All patients were examined at
the beginning of treatment and after 6 weeks; patients in
the control group had slight deterioration in disability
and handicap, but those in the treatment group showed
a significant improvement. There were no significant
changes in either group in function as measured by
EDSS.79In a longitudinal study on the duration of the
benefit of multidisciplinary inpatient rehabilitation, after
3 weeks of treatment in 67 patients with chronic
progressive disease there was a significant improvement
in disability in the inpatient group compared with the
outpatient treatment group.80This benefit was apparent
3 months after treatment but not after 12 months. In
another prospective, non-controlled longitudinal study,
50 patients with chronic progressive MS were examined
every 3 months after a multidisciplinary inpatient
rehabilitation treatment of 23 days; disability, handicap,
and quality of life improved significantly over 6 months
and even over 9 months.76These benefits occurred
despite progressive deterioration in function (measured
by EDSS),79reflecting further progression of the disease
In our own study,81a group of 90 men and 196 women
with MS were treated for a mean of 28 days (range
11–92 days). These patients showed a significant
increase in score on the extended Barthel index (EBI,
0–64) of 0·85 points per week in patients with moderate
disabilities (EBI, 30–39). Patients with low disability
(EBI, 60–64) had a small gain (0·18 per week), possibly
owing to a ceiling effect.81
The effect of multidisciplinary inpatient rehabilitation
on measures of disability and quality of life in the long
term was investigated in a randomised controlled study
with patients on the waiting list as controls;78this study
included 66 patients with progressive MS who
participated in a short period of inpatient rehabilitation
(mean 20 days). At the end of the treatment period there
were significant improvements in scores of handicap
(London handicap scale) and disability scores (functional
independence measure, FIM) compared with patients in
the control group. The improvements in disability and
handicap were maintained
Improvements in emotional well-being lasted for
7 months and those in health-related quality of life for
10 months. These sustained benefits were achieved
despite worsening neurological status.
The influence of outpatient
rehabilitation of patients with MS was studied82in a
prospective, longitudinal, randomised study; and it
showed a significant reduction in the frequency of
symptoms, particularly fatigue compared with a control
group. These patients had undergone an outpatient
therapy programme (physiotherapy,
for 6 months.76
therapy, individual counselling) 1 day per week over
1 year. A more recent randomised, controlled trial83
examined the effect of a short multidisciplinary
treatment in patients with chronic progressive MS:
58 patients randomly
multidisciplinary outpatient rehabilitation (6 weeks)
were compared with a control group of 53 patients
taking exercise at home. After 6 weeks and 12 weeks,
there was a significant improvement in disability (FIM)
in the treatment group, while impairment remained
unchanged. 32 patients in the treatment group improved
by more than 2 FIM steps compared with only four
patients in the control group.
Specific treatment modalities
In a randomised, controlled trial, the effect of inpatient
physical therapy (two 45 min sessions per day for
3 weeks) in 27 ambulatory patients with MS was
examined in comparison with a control group of
23 patients instructed on self training at home.84
Significant improvements in disability and quality of
life were apparent after 3 weeks and 9 weeks, but after
12 weeks there was no significant difference. Both
groups remained unchanged in terms of functional
level (EDSS). In an earlier controlled study no
significant improvement had been shown after
inpatient physical therapy of 2 weeks duration (one
39 min session per day).85In another controlled, cross-
over trial, 40 patients were treated in randomised order
over 8 weeks as outpatients in a specialised
rehabilitation clinic, by a physical therapist at home, or
not at all.86There was a significant improvement in
mobility and disability during the active treatment
periods compared with phases without therapy. In
addition the frequency of falls was lower. Despite the
lower costs for treatment at home, there was no
significant difference between outpatient and home
treatment. The effect was of short duration and was no
longer detectable after 8 weeks.
The efficacy of aerobic training (three sessions per
week for 15 weeks) was studied in a randomised
controlled trial of 54 patients; aerobic capacity and
isometric strength were significantly better during the
observation period than in a control group.87In addition,
there was transient improvement in psychological
features (anxiety and depression) and fatigue. The role of
aerobic training during multimodal rehabilitation
programmes has also been analysed in a randomised
controlled study;88with individually adapted ergometer
training at the aerobic threshold (30 min per day for
4 weeks), the functional capacity, aerobic capacity, and
level of activity could be increased. Scores of vitality and
social interaction also improved, and fatigue was slightly
but not significantly reduced. Furthermore there was a
trend of reduced fatigue. Another important finding was
that the physical stress of this study had no negative
effect on the clinical course.
http://neurology.thelancet.com Vol 4 October 2005649
For occupational therapy (ergotherapy) in MS, only a
few open, non-controlled studies have been published.
In a meta-analysis, a positive effect of ergotherapy (tone
modulating measures and specific training of manual
and practical functions) on muscle function, range of
movement, and activities of daily living was shown.89
Because aphasia is rare in MS, specific speech therapy
is rarely necessary. In patients with dysarthrophonia,
however, speech training and exercises in respiration
can help increase the capacity to articulate. Furthermore,
as for patients after strokes, training in swallowing with
triggering of reflexes, training of the swallowing process,
compensatory measures and appropriate consistency of
food and liquids can help to improve the process of
swallowing and reduce the risk of aspiration.90,91In more
severe dysphagia, percutaneous endoscopic gastrostomy
should be discussed.
In the most severely disabled dependent patients, in
addition to problems with swallowing and insufficient
respiratory functions, reduced coughing can lead to
pulmonary infections. Respiratory training can help to
improve respiratory functions and cough reflex.92
Despite newer immunomodulating therapies, there is a
continuing demand for treatments that address the
negative effects of MS symptoms on daily life.
Symptomatic treatment and rehabilitation are effective
in this respect. There is, however, much scope for
further research on more effective and more tolerable
drug treatments and the accurate nature and extent of
rehabilitation techniques in MS. The main priorities are
to define which treatment modalities are most effective
and to identify the optimum duration and frequency of
such interventions.69However, the philosophies behind
rehabilitation and evidence-based medicine often
conflict with one another. The main issue is that
reductionism used in clinical trials can be insensitive to
the individually tailored aims of rehabilitation
medicine. The correct balance between these two aims
must be found for elucidation of how to integrate new
scientific advances into clinical practice. Despite
these difficulties, multidisciplinary inpatient neuro-
rehabilitation regimens do offer benefits to patients
with MS in terms of improvements in disability,
handicap, and well-being. The improvements achieved
persist for several months after the treatment period
even though the procedures have no direct influence on
underlying disease activity or progression; clinical
features that are perceived as disease progression can
simply be the result of inadequate management of the
Both authors collaborated closely for ten years in leading the
Neurorehabilitation Centre in Valens and contributed equally in writing
Conflicts of interest
JK has been or is a member of independent advisory boards for several
trials with new immunomodulating drugs for the treatment of MS
(trials sponsored by Schering AG/Berlex, Serono, Biogen, Wyeth).
SB has no conflicts of interest.
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