Drugs Aging (2012) 29:941–947

DOI 10.1007/s40266-012-0034-z

THERAPY IN PRACTICE

The Pharmacological Management of Post-Stroke Muscle

Spasticity
Abdel Magid O. Bakheit

Published online: 9 November 2012

 Springer International Publishing Switzerland 2012

Abstract Muscle hypertonia following upper motor muscle spasticity. These factors should always be looked
neurone lesions (referred to here as ‘spasticity’) is a com- for as their adequate treatment is often sufficient to reduce
mon problem in patients with neurological disease, and its muscle tone without the need for specific antispasticity
management is one of the major challenges in clinical medication. Therefore, a careful evaluation of the patient’s
practice. Understanding the pathogenesis and clinical symptoms and their impact on function, and the setting of
course of spasticity is essential for the effective manage- clear and realistic therapy goals are important prerequisites
ment of this condition. The hypertonia initially results from to treatment. The best treatment outcomes are usually
increased excitability of the alpha motor neurones due to an achieved when pharmacological and non-pharmacological
imbalance between the excitatory and inhibitory influences treatment modalities are used in tandem. Different drugs
of the vestibulospinal and reticulospinal tracts. This is the are available for the management of spasticity, including
‘neural component’ of muscle hypertonia. However, usu- oral muscle relaxants, anticonvulsant drugs, intrathecal
ally within 3–4 weeks, changes in the structure and baclofen, cannabis extract, phenol and alcohol (for
mechanical properties of the paralysed muscles and the peripheral nerve blocks) and botulinum toxin injections.
effect of thixotropy also contribute to the hypertonia. The Similarly, there is a range of non-pharmacological methods
selection of the optimal treatment option is often influenced of treatment, e.g. regular muscle stretching, the use of
by whether the neural or the non-neural component is more splints and orthoses, electrical stimulation, etc. Although
pronounced. Muscle spasticity often interferes with motor these are not discussed here, this should not detract from
function or causes distressing symptoms, such as painful the importance of combining them with antispasticity drugs
muscle spasms. If untreated, spasticity may also lead to soft in order to maximize the clinical benefit of treatment.
tissue shortening (fixed contractures). However, spasticity
can also be beneficial to patients. For example, despite
severe leg muscle weakness, most hemiplegic patients are 1 Introduction
able to walk because the spasticity of the extensor muscles
braces the lower limb in a rigid pillar. Other reported Spasticity is common after stroke. In a recent prospective
benefits of spasticity include the maintenance of muscle study with a 16-week follow-up period, one in four patients
bulk and bone mineral density and possibly a reduced risk were found to have developed spasticity within the first
of lower limb deep vein thrombosis. Several factors, such 2 weeks of the cerebrovascular event [1]. The incidence of
as skin pressure sores, faecal impaction, urinary tract spasticity increases with time and by 12 months it is
infections and stones in the urinary bladder, can aggravate present in 39 % of stroke patients [2]. Interestingly,
patients who had spasticity in the first 2 weeks post-stroke
reported more muscle pain, were less independent with
regard to activities of daily living (as measured with the
A. M. O. Bakheit (&)
Barthel Index) and had a higher admission rate to nursing
Inpatient Neurological Rehabilitation Unit,
Moseley Hall Hospital, Birmingham B13 8JL, UK homes than those with normal muscle tone [1]. Post-stroke
e-mail: [email protected] spasticity is also associated with more severe morbidity
942 A. M. O. Bakheit

and higher costs of care. For example, in a recent study, function’ (see Sect. 6.1) or to improve the fit of a hand
Lundström et al. [3] found that the direct costs of care, i.e. splint or an ankle foot orthosis [7].
the costs of hospitalization, rehabilitation, primary health-
care and medication, and the costs of multi-disciplinary
services, for the first 12-months after stroke were four 4 Phenomena Associated with Spasticity
times higher for patients with spasticity than for those
without spasticity. Flexor and extensor muscle spasms, spastic dystonia and
associated upper and lower limb reactions frequently
coexist with established spasticity and often require
2 Definition of Spasticity treatment.

‘Spasticity’ was defined by Lance [4] as ‘‘a motor disorder 4.1 Flexor and Extensor Spasms
characterised by a velocity-dependent increase in tonic
stretch reflexes (muscle tone) with exaggerated tendon Muscle spasms are sudden, brief, involuntary muscle
jerks, resulting from hyperexcitability of the stretch reflex, contractions due to the spontaneous firing of the alpha
as one component of the upper motor neurone syndrome’’. motor neurones. The limb may go into either flexion or
However, spasticity (according to this definition) is usually extension as a result of the spasm. They are sometimes
transient and rarely persists (in its pure form) for more than accompanied by urinary or faecal incontinence. Although
a few weeks after the onset of stroke. In reality, what is spasms usually occur at rest, they are sometimes triggered
observed in clinical practice is muscle hypertonia that by an attempt to move the affected limb or by sensory
results from a combination of ‘true’ spasticity, thixotropy stimuli, such as touch or loud noise. Each contraction lasts
and secondary changes in the visco-elastic and mechanical a few seconds but frequently many contractions occur in
properties of the paralysed muscles. quick succession and may last several minutes. The fre-
Thixotropy is the property of certain semisolid sub- quency and severity of muscle spasms are usually
stances, such as paint emulsions, to turn into liquid form increased by intercurrent infections and pressure sores.
under certain physical conditions. In muscle physiology, Muscle spasms are sometimes painful and they may also
thixotropy is used to mean the stiffness in a resting muscle interfere with sleep or motor function, such as placing the
that disappears when that muscle is stretched. Thixotropy spastic foot on the ground.
contributes to the stiffness of the paretic muscle and can
also inhibit voluntary movement [5]. It is important to take 4.2 Spastic Dystonia
into consideration the contribution of thixotropy and of the
changes in the structure and function of muscle because, The term ‘spastic dystonia’ is used to describe the
when severe, they often influence the choice and success of sustained muscle contractions that result in the typical
medical treatment. Recently, the term ‘reversible muscle postures seen in patients with upper motor neurone
hypertonia’ has been suggested as a more accurate alter- lesions. It causes the upper limb of a hemiplegic patient
native to ‘spasticity’ [6]. To prevent confusion, the term to be adducted, internally rotated and flexed at the elbow,
‘spasticity’ will be used throughout this paper to mean the wrist and fingers. By contrast, the lower limb is held in
clinically observed phenomenon of muscle hypertonia. extension with the foot in the equinus or equinovarus
position.

3 Clinical Symptoms of Spasticity 4.3 Associated Upper and Lower Limb Reactions

Patients may or may not report symptoms that are due to Associated reactions (ARs) or synkinesis are intermittent
spasticity. In some cases, pain in the spastic muscles and/or involuntary movements, often of the upper limb. Their
muscle spasms are the presenting symptoms, and occa- severity generally correlates with that of spasticity and
sionally patients seek medical advice because of the cos- they usually occur during a goal-directed volitional
metic appearance of the spastic limb. However, more often, movement of the unaffected limbs, especially when
patients are referred by their therapists for spasticity excessive effort is required to initiate or to maintain the
management because of the effect of the hypertonia on movement [8]. They can also be triggered by yawning,
motor function, e.g. interference with safe walking due to a sneezing, coughing or laughing. ARs are often mild and
spastic foot drop. In some cases, referral is made for do not require treatment. However, when severe, they
reduction of muscle tone in order to facilitate ‘passive usually impair motor function. For example, upper limb
Management of Post-Stroke Spasticity 943

reactions in a hemiplegic subject may cause severe per- 6.1 Indications for Treatment
turbation of balance during walking.
The indications for treatment of spasticity are to improve
volitional goal-directed movements, to make carer-assisted
5 Assessment of Muscle Spasticity movements (passive function) easier, to relieve muscle
pain associated with spasticity, to correct abnormal pos-
Clinically, spasticity is confirmed by the presence of tures to facilitate seating or positioning in bed, to enable
resistance to rapid passive muscle stretching exerted by the the application of orthoses and to prevent fixed muscle
examiner. As spasticity is one of the features of the upper contractures [7, 15, 16].
motor neurone syndrome, muscle weakness (or, in mild
• Goal-directed movements: Spasticity of the antagonist
cases, muscle fatigability or loss of dexterity), increased
muscle may prevent the execution of voluntary move-
tendon reflexes, an extensor plantar response and clonus
ments by the paretic limb even when the weakness of
are also present. However, when the spasticity is very
the agonist muscle is relatively mild. Common exam-
severe, the tendon reflexes may be absent but they usually
ples are the patient’s inability to extend the elbow (to
reappear with successful reduction of muscle tone [9].
reach an object) because of spasticity of the elbow
Clinical, neurophysiological and biomechanical methods
flexors, or inability to dorsiflex the ankle (to clear the
are used for the confirmation of spasticity and the assess-
ground in the swing phase of the gait cycle) due to
ment of its severity.
spasticity of the tibialis anterior. In these situations,
The most frequently used clinical methods for the
successful treatment of spasticity usually improves
assessment of spasticity are the Modified Ashworth Scale
motor function.
[10], the Tardieu Scale [11] and measurement, with a
• Passive function: Recovery from severe upper motor
goniometer, of the joint range of motion on active and/or
neurone lesions is seldom complete and many patients
passive muscle stretching. The Modified Ashworth Scale is
never regain sufficient functional use of their affected
a hierarchical 6-point ordinal scale that scores the severity
limbs. Frequently these patients require assistance with
of spasticity from 0 (no increase in muscle tone) to 4 (the
personal care and other activities of daily living.
affected body part is rigid in flexion or extension) but
Spasticity often makes these carer-assisted (also called
subdivides the second grade into 1 and 1?. The Tardieu
passive functions) difficult. For example, access to the
Scale is also a 6-point scale based on the subjective
axilla for cleaning may require one carer to abduct the
assessment of the degree of the resistance felt by the
spastic upper limb and another to carry out the task.
examiner during passive limb displacement. The limb
Reduction of spasticity in such cases may reduce the
displacement is made at slow and fast velocities in order to
burden of care by allowing one person to perform the
distinguish whether the observed increase in muscle tone is
required assistance.
predominantly due to hyperexcitability of the stretch reflex
or due to secondary changes in the mechanical properties The selection of the treatment modality depends on
of the muscle. (Resistance to stretching, or ‘catch’, is felt whether the spasticity is focal or generalized, whether the
with high-velocity displacement when the hypertonia is neural or mechanical component is more severe, the cli-
mainly due to increased excitability of the stretch reflex.) nician’s expertise [e.g. ability to carry out peripheral nerve
Several neurophysiological tests and biomechanical blocks or botulinum toxin (BoNT) injections] and the
measurements of resistance to passive muscle stretching patient’s preference. The cost of treatment is also an
with an isokinetic dynamometer or other devices are important consideration (see Sect. 6.4).
available, but they are not suitable for routine clinical
practice. 6.2 Principles of Treatment

Empirical clinical observations suggest that urinary tract

6 Treatment of Spasticity infections, pressure sores, calculi in the urinary bladder,
faecal impaction or severe constipation, dehydration and
Spasticity may confer significant benefits for patients. It is excessive fatigue may aggravate spasticity, and their
necessary for the maintenance of trunk posture during sit- treatment is often sufficient to reduce muscle tone. It is
ting and standing, and it also enables weight bearing on the therefore essential to look for these factors and, if present,
paretic leg by bracing the weak limb in extension. Other to manage them appropriately before starting specific
benefits include maintenance of muscle mass [12], pro- antispasticity medication. Other important principles of
tection against excessive bone mineral loss [13] and pos- treatment (see Fig. 1) are to clearly define the treatment
sibly prevention of deep vein thrombosis [14]. objectives, which should be realistic and meaningful to the
944 A. M. O. Bakheit

can also be given intrathecally (usually in patients with

Establish whether the clinical problem spastic paraplegia). Other drugs used for spasticity are some
is mainly due to spasticity
anticonvulsants and cannabinoids.
The use of the different oral muscle relaxants varies
from one country to another. For example, baclofen, tiza-
Treat the factors that aggravate or
nidine, dantrolene and diazepam are all approved for use in
precipitate spasticity
spasticity in the UK and are freely prescribed. By contrast,
If symptoms persist: in France, baclofen is used as the first-line oral antispas-
ticity drug and tizanidine is recommended only if baclofen
is ineffective, is contraindicated or has resulted in signifi-
Define the treatment goals cant adverse effects [16].
The different oral antispasticity drugs have different
modes of action and may be used in combination with each
other. Baclofen, a gamma aminobutyric acid (GABA)
Exclude fixed muscle
shortening (contractures) agonist, inhibits muscle tone by acting on the fusiform
system in the spinal cord [17]. By contrast, tizanidine is a
central a2 receptor agonist that suppresses the activity of
Choose appropriate treatment modality the excitatory descending cortico-spinal pathways [18]. On
and carry out treatment the other hand, dantrolene acts directly on muscle. It
interferes with the release of calcium from the endoplasmic
reticulum, which inhibits the excitation-contraction cou-
Combine with non-pharmacological pling [19]. Diazepam potentiates GABA effects in the
interventions as necessary spinal cord and also inhibits the excitatory influence of the
descending pathways.
Oral muscle relaxants reduce tone in the spastic and
Monitor the effect of treatment on non-spastic muscles, and this may result in generalized
muscle tone and motor function weakness and loss of function. For example, loss of tone in
the trunk muscles may prevent the patient from maintain-
Fig. 1 Algorithm for management of spasticity ing a sitting posture. In addition, pharmacological tolerance
to some of these drugs frequently develops after a few
patient, and to exclude fixed muscle shortening (contrac- months of continuous use, and so the dose often needs to be
ture), as this complication does not respond to antispas- progressively increased to maintain the same clinical effect
ticity drugs and may require surgical treatment [7]. [20]. Antispasticity drugs also have systemic adverse
Assessment by an experienced clinician is usually suffi- effects (see Table 1). Therefore, they should be used
cient to confirm the presence of muscle contractures, but sparingly in patients with localized spasticity.
sometimes the diagnosis may need to be confirmed with Oral muscle relaxants have interactions with many
examination under sedation or using diagnostic nerve drugs. In stroke patients, the important interactions are
blocks with a long-acting local anaesthetic. (Spasticity, but usually with antihypertensive agents, sedatives and dopa-
not contracture, is abolished by anaesthesia or peripheral minergic drugs. Baclofen and tizanidine can enhance the
nerve blocks.) hypotensive effect of ACE inhibitors, calcium channel
blockers, b-blockers and diuretics. They also increase the
6.3 Treatment Options effect of sedatives and hypnotics and the neuropsychiatric
adverse effects of dopaminergic drugs [21].
A number of treatment modalities may be used, either
individually or in combination, for the management of 6.3.2 Intrathecal Baclofen
muscle spasticity. These include oral muscle relaxants,
some anticonvulsants, BoNT injections, cannabinoids and Direct administration of baclofen into the spinal cord via an
peripheral nerve blocks with phenol or alcohol. intrathecal catheter connected to a programmable infusion
pump implanted into the abdominal or chest wall is very
6.3.1 Oral Muscle Relaxants effective in the treatment of severe lower limb spasticity.
Although a beneficial effect of intrathecal baclofen has
The most commonly prescribed oral antispasticity drugs are been reported in spastic hemiplegia associated with stroke,
baclofen, tizanidine, dantrolene and diazepam. Baclofen this treatment is usually used for severe spastic paraplegia.
Management of Post-Stroke Spasticity 945

Table 1 Effective daily dose range, maximum dose and adverse effects of the main oral muscle relaxants
Drug Effective dose range; maximum daily dose Most frequently reported adverse effects

Baclofen 15–60 mg; maximum 100 mg Confusion, hallucinations, seizures, fatigue, gastrointestinal symptoms
Tizanidine 6–24 mg; maximum 36 mg Hypotension, bradycardia, hallucinations, confusion, fatigue
Dantrolene 75–150 mg; maximum 400 mg Liver dysfunction, dizziness, generalized weakness, gastrointestinal symptoms
Diazepam 15–60 mg; maximum 60 mg Sedation, amnesia, mental confusion, depression, dependence

6.3.3 Anticonvulsants of most limb muscles. However, the motor endplates in

some muscles, e.g. the hamstrings, are concentrated along
Some antiepileptic drugs, such as pregabalin and gaba- the long axis of the muscle [31]. In these cases, targeting
pentin, are used off-label in the management of spasticity, the motor endplate by injections into multiple sites results
especially when associated muscle pain is a prominent in better reduction of muscle tone [32]. The optimal dose of
feature. Their mode of action is not fully understood, BoNT depends on the muscle size, the severity of spas-
although a number of mechanisms have been postulated ticity, the desired degree of reduction of muscle tone and
(e.g. see Rose and Kam [22]). These drugs have been the BoNT product used. Guidelines on the recommended
shown in open-label [23] and small, randomized, placebo- dose for most muscles have been published [7, 15].
controlled trials [24–26] to reduce muscle spasticity when Three commercial brands of BoNT-A are currently
used alone or as an adjunct to muscle relaxants. The available in the UK. These are Dysport (Ipsen Pharma,
reported effective dose of pregabalin is 300 mg twice daily, Boulogne-Billancourt, France), Botox (Allergan Inc.,
while that of gabapentin varies from 400 to 800 mg three Irvine, CA, USA) and Xeomin (Merz Pharmaceuticals
times daily. At these doses, the beneficial effect of pre- GmbH, Frankfurt, Germany). Unit-for-unit, Dysport is
gabalin and gabapentin is modest and the incidence of not equivalent to the other two products and it is advisable
treatment adverse events is high. Consequently, these drugs that once treatment is started with one product it is con-
have a minor role in the management of spasticity but may tinued with that product to avoid inadvertent dose errors.
be valuable when pain is also present. There is disagreement between clinicians regarding the
dose equivalence of Dysport and Botox. For example, in
6.3.4 Botulinum Toxin an open-label study, Durif [33] reported that 5.3–6 units of
Dysport are equivalent to one unit of Botox. However,
The introduction of botulinum neurotoxin type A (BoNT- other authors using a double-blind study design reported a
A) and type B (BoNT-B) more than a decade ago has 3:1 ratio [34]. Botox and Xeomin were shown to have
revolutionized the management of localized (focal and the same potency unit-for-unit [35]. BoNT-B is less effi-
multi-focal) post-stroke muscle spasticity. The advantage cacious than BoNT-A. It has a shorter duration and less
of BoNT treatment is that the reduction in muscle tone is magnitude of benefit [36].
largely limited to the injected muscles and has no detri- The adverse effects of BoNT-A are usually mild and
mental effect on distant muscle groups. The efficacy and transient, lasting only a few days. They include flu-like
safety of this treatment has been demonstrated in large, symptoms, a skin rash, fatigue, dizziness and dry mouth.
randomized, controlled trials [27–30] and protocols and Serious adverse effects, such as severe generalized muscle
guidelines for its use have been developed [7, 14]. weakness, are very rare. However, a few cases of gen-
BoNT reduces muscle tone by interfering with the eralized botulism-like syndrome have been reported [37].
release of acetyl choline at the motor endplate and thus Treatment failure after a good initial clinical response to
blocks neurotransmission. The treatment is given by BoNT-A may occur after repeated treatment cycles. This may
intramuscular injections, and the beneficial effect lasts on be due to immunological resistance resulting from the for-
average 3–4 months. Most patients require 3 treatment mation of BoNT antibodies [38]. However, secondary treat-
cycles per year. The injection procedure is simple. Accu- ment failure is more often due to an insufficient BoNT dose,
rate placement of the injections into the motor endplate inaccurate placement of the injection, the development of
zone using electrical stimulation, electromyography or contractures or progression of the underlying disease [39].
ultrasound improves clinical outcomes and may be neces-
sary for the treatment of deep seated muscles or upper limb 6.3.5 Cannabinoids
muscles that have residual muscle strength [7]. However,
the use of anatomical landmarks is often sufficient for The cannabis resin contains two main cannabinoids: 9-tetra
injecting large muscles and muscles in non-functional hydrocannabinol and cannabidiol. The evidence for the
limbs. A single injection site is sufficient for the treatment antispasticity effect of cannabinoids is inconclusive,
946 A. M. O. Bakheit

although patients with multiple sclerosis reported fewer Table 2 Focal and multi-focal treatment of post-stroke spasticity
muscle spasms and less pain, and an improvement in their Spastic Effect on function Best treatment option
sleep quality and their general wellbeing [40]. Cannabi- muscles
noids are best administered as a nasal spray. Their main
Shoulder Difficult access to axilla BoNT into pectoralis
adverse effects are neuropsychiatric and cardiovascular,
adductors for cleaning; difficult to major ± subscapularis
and include cognitive impairment, paranoid delusions, don upper body
panic attacks, tachycardia and postural hypotension. The garments
effectiveness of cannabinoids has not been systematically Elbow Difficult to reach objects; BoNT into biceps brachii
studied in post-stroke spasticity and, at present, they are flexors difficult to don upper and brachioradialis
only licensed for use in multiple sclerosis. body garments
Wrist Difficult to apply hand BoNT into flexor carpi
flexors splint ulnaris and flexor carpi
6.3.6 Peripheral Nerve Blocks radialis
Finger Difficult access to palm BoNT into flexor
Destruction of peripheral nerves with alcohol or phenol flexors of hand for cleaning; digitorum sublimis and
(chemical neurolysis) is effective in reducing muscle difficult to access finger flexor digitorum
hypertonia for several months and usually has no signifi- nails for cutting; profundus
difficult to apply hand
cant effect on muscle strength. The procedure is relatively splint
easy to do and is cost-effective. However, destruction of Hip Difficult access to Obturator nerve block
mixed sensory-motor nerves leads to skin sensory loss and adductors perineal area for
may cause painful dysaesthesia. In the distal upper limb cleaning,
muscles, it may also cause loss of manual dexterity. catheterization, etc.
A useful strategy is to use BoNT as first-line treatment for Hamstrings Knee flexion interfering BoNT into medial and
with gait lateral hamstrings
upper limb spasticity and peripheral nerve blocks for lower
Ankle Equinus or equinovarus BoNT into
limb muscles, especially when treatment of the hip
plantar foot deformity causing gastrocnemius ± tibialis
adductors is required. A major disadvantage of chemical flexors/ tripping and falls posterior
neurolysis is that after repeating the procedure a few times, invertors
it is often difficult to localize the nerve, presumably BoNT botulinum neurotoxin
because of fibrosis of the adjacent tissue [41].
stroke spasticity and peripheral nerve blocks are also a
6.4 Selection of the Most Suitable Treatment Option
valuable treatment modality, especially for proximal lower
limb muscles and when the cost of medication is a major
The management of spasticity should be individualized and
consideration.
based on the treatment objectives, the patient’s preference,
and the available resources and expertise. The cost of Acknowledgments The author has served on advisory boards and
treatment is also an important consideration. has received research grants and sponsorship from Ipsen Pharma,
In most stroke patients, spasticity that causes functional Allergan and Merz. No sources of funding were used to prepare this
limitations is localized to one or two muscle groups. These article.
muscles could be targeted for treatment with BoNT or
peripheral nerve blocks. Usually there is no need for sys-
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