4.2 Spasticity

4.2.1  Definition of Spasticity

Define spasticity

  1. Spasticity is a common symptom encountered post acquired brain injury and is an element of the upper motor neuron syndrome.
     
  2. Spasticity is defined as a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon reflexes, resulting from excitability of the stretch reflex.
     
  3. Common features include increased muscle tone, exaggerated tendon reflexes and clonus.

Spasticity is a common symptom encountered post acquired brain injury and is part of the upper motor neuron syndrome 10. Spasticity has been formally defined as “a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon reflexes, resulting from excitability of the stretch reflex” 11.  Common features of spasticity included increased muscle tone, exaggerated tendon jerks, and clonus.

4.2.2  Treatment of Spasticity

When is treatment of spasticity indicated?

  1. Spasticity may require intervention when it interferes with functional abilities such as mobility, positioning or hygiene, or when it is the cause of deformity or pain.
     
  2. Factors that must be taken into consideration when proposing treatment of spasticity include chronicity of the problem, the severity, the pattern of distribution (focal versus diffuse) and even the locus of injury12.

Some studies have found that spasticity of cerebral origin versus spinal cord injury respond differently to the same medications13. Typically, the clinical approach to spasticity is to first employ treatments that tend to be less interventional and costly. Management of spasticity is not unique to brain injury survivors, since it is often associated with other conditions affecting the central nervous system such as spinal cord injury and multiple sclerosis.  However, interventional strategies may differ between diagnoses based on the location of the spasticity (e.g. paraplegia in SCI versus hemiplegia in ABI) and other co-existing morbidities (e.g. cognitive impairment in ABI).  Ultimately, multiple strategies may need to be administered concurrently.

4.2.3  Treatment Approach to Spasticity Post ABI

Describe a treatment approach to the treatment of spasticity.

1.    Remove those factors which may increase spasticity.

2.    Oral antispastic medications.

3.    Botulinum toxin for focal spasticity, where oral antispastic medications are ineffective.

4.    Intrathecal baclofen should be used as a last resort for severe spasticity.

4.2.3.1  Oral Antispasticity Drugs Post ABI 

When should oral antispastic drugs be used in the ABI patient, what drugs are available and what are some of the concerns with using these medications?

  1. Oral agents are often used to manage spasticity particularly when a systemic agent to treat upper and lower extremity spasticity is required14.
     
  2. Although anti-spasticity agents may be used with other medical conditions such as spinal cord injury or multiple sclerosis14, the effectiveness should not be presumed to be similar for brain injury survivors. 
     
  3. Multiple medications have been evaluated to treat spasticity of both cerebral and spinal cord origin. The more common medications include GABA agonists such as baclofen, benzodiazepines, dantrolene sodium which affects ion flux, and agents that affect alpha-2 adrenoreceptors such as tizanidine and clonidine. 
     
  4. One particular limitation is the associated cognitive and behavioral changes associated with brain injury.

What evidence is there for oral anti-spasticity drugs in ABI?

  1. There is level 1 evidence that oral tizanidine improves lower and upper extremity spasticity when compared to placebo.
     
  2. There is level 4 evidence that oral baclofen improves lower extremity spasticity but not upper extremity spasticity.

Oral Tizanidine

Meythaler et al. 15 completed a randomized, double blinded placebo controlled cross over trial of tizanidine in the management of spasticity in acquired brain injury. This study evaluated both stroke (53%) and traumatic brain injury (47%) survivors.  For both lower and upper extremity, there was a significant decrease in spasticity scores compared to treatment with placebo.  However, upper and lower extremity spasm and reflex scores did not improve compared to placebo.  A common adverse effect was increased somnolence (41%) compared to placebo (0%). Oral tizanidine was found to be effective for improving upper and lower extremity spasticity.

Oral Baclofen

Meythaler et al. 16completed a retrospective study evaluating the use of oral  baclofen to manage spasticity in brain injury survivors. Pre and post testing of spasticity using the Ashworth scale revealed a significant decrease in lower extremity spasticity scores; however, results were not significant for upper extremity spasticity scores or frequency of spasms. A noted common adverse effect of the oral baclofen was the onset of considerable sleepiness in 6 (17%) patients.Although only one study was found, it appears as though oral baclofen does improve lower extremity spasticity.

Meythaler JM, Guin-Renfro S, Johnson A, Brunner RM. Prospective assessment of trizanidine for spasticity due to acquired brain injury. Archives of Physical Medicine and Rehabilitation 2001;82:1155-1163

  • 17TBI and stroke subjects between 16 and 75 diagnosed with severe chronic spastic hypertonia in one or both lower extremities for at least 6 months were given either 4 mg of tizanidine or a placebo.
  • Tizanidine was gradually increased to 36 mg over the next 6 weeks. 
  • Following a one week tapering off period, those on placebo began taking tizanidine and those on tizanidine began taking placebo.
  • The average lower extremity Ashworth score significantly decreased from 2.3 ± 1.4 to 1.7 ± 1.1 (p<0.0001), spasms scores decreased rom 1.0 ± 0.9 to 0.5 ± 0.8 (p=0.0464). reflex scores decreased from 2.2 ± 1.0 to 2.0 ± 1.1 (p=0.0883), and motor tone improved significantly (p=0.0006).
  • Upper extremity Ashworth scores also decreased significantly from 1.9 ± 1.1 to 1.5 ± 0.9 (p<0.0001); however no significantly changes in the upper extremity spasm and reflex scores were noted.
  • Although changes in the Ashworth scores were noted while on placebo these changes were not as great as the changes seen while on tizanidine.
  • Motor tone of both the upper (p=.007) and lower extremities (p=.0006) was significantly improved (a significant reduction was noted) while on the tizanidine resulting in an increase in motor strength (p=.0089).

 

4.3.2.2  Botulinum Toxin Injections for Spasticity Post ABI 

How does botulinum toxin work in the treatment of spasticity?  When should it be used?

  1. Botulinum toxin type A (BTX-A) acts at pre-synaptic terminals to block acetylcholine release into the neuromuscular junction.  
     
  2. When selectively injected into a specific muscle, BTX-A is thought to cause local muscle paralysis thereby alleviating hypertonia due to excessive neural activity 17.
     
  3. BTX-A is a relatively new treatment strategy for the management of spasticity in ABI.
     
  4. It has been suggested that BTX-A may be useful in the treatment of localized spasticity if oral treatments such as benzodiazepines, baclofen, dantrolene sodium or tizanidine cause significant adverse effects 14.

What is the evidence for the use of botulinum toxin to treat spasticity in ABI  patients?

  1. There is level 4 evidence that botulinum toxin A injections may be effective in the management of localized spasticity following ABI.

Three single group intervention studies (2 conducted within the adult population and 1 with a pediatric population), specifically looked at the use of BTX-A for the management of spasticity following ABI. 

Yablon et al.18 reported that BTX-A injections into the upper extremities improved range of motion, and spasticity as measured by the modified Ashworth scale (MAS) in 21 ABI patients. 

Fock et al.19 reported that BTX-A injections into the lower extremities improved measures of walking performance including walking speed, stride length, cadence, dorsiflexion on contact with the ground and passive dorsiflexion; however, there were no significant improvements in overall spasticity as measured by MAS scores. 

In a study conducted in a pediatric cohort, van Rhijn et al.20 reported that BTX-A was effective in improving MAS scores up to 5 months post-treatment with concomitant improvements in range of motion. Overall the findings suggest botulinum toxin type A injections may be effective in the management of localized spasticity following ABI.

4.2.3.3  Intrathecal Baclofen for Spasticity Post ABI 

What is the rationale behind use of Intrathecal Baclofen?  What are the pros and cons of using it to treat spasticity post ABI?

  1. A limitation of oral baclofen is the inability to achieve sufficient concentrations in the cerebrospinal fluid in order to modify spasticity without first causing significant sedation14.
     
  2. Intrathecal baclofen refers to direct administration of baclofen into the intrathecal space and cerebrospinal fluid at the lumbar level.  For therapeutic treatment, a subcutaneously placed pump is required to provide continuous administration of the medication into the intrathecal space. 
     
  3. This treatment procedure is more invasive and is associated with complications including infection, pump failure and tube complications such as kinking or disconnection14.

What is the evidence for the use of Intrathecal Baclofen in the treatment of spasticity post ABI?

  1. There is level 1 evidence, based on a single RCT, that bolus intrathecal baclofen injections produce short-term (up to 6 hours) reductions in upper and lower extremity spasticity.
     
  2. There is level 4 evidence prolonged intrathecal baclofen results in longer-term (3 months and one year) reductions in spasticity in both the upper and lower extremities following an ABI.
     
  3. There is level 4 evidence, based on one study, that intrathecal baclofen results in short-term improvements in walking performance, particularly gait velocity, stride length and step width.

Ten studies which investigated the efficacy of intrathecal baclofen for the management of upper and lower extremity spasticity following ABI were looked at in detail 21;21-30.

Meythaler et al. 23confirmed the effectiveness of intrathecal baclofen for decreasing upper and lower extremity spasiticity in a randomized, double blinded, placebo controlled cross-over trial.  In subsequent studies, the same investigators went on to demonstrate the effectiveness of intrathecal baclofen for decreasing upper extremity spasticity for up to 3 months 22;23and 1 year 30duration.  However, all of these studies used a single group intervention design which lacked a placebo control group during the phase when the subcutaneously placed pump was used to provide continuous administration of the medication into the intrathecal space. 

Investigations carried out by other research groups have reported similar findings regarding the efficacy of intrathecal baclofen for the management of spasticity post-ABI 24;25;27-29.  However, these studies still lacked a control group thereby limiting the conclusions of their findings. 

For the 154 participants in the ten studies identified by this review, it appears that intrathecal baclofen is an effective treatment for spasticity, however some adverse effects such as urinary hesitancy were reported. Only two of the nine studies examined the long-term effectiveness of the treatment.  One study also evaluated the functional consequences by assessing walking performance following a bolus injection of intrathecal baclofen 26. Future studies should be conducted using prospective controlled trials or RCTs that include control or placebo groups to further establish the efficacy of intrathecal baclofen for the management of spasticity. Overall, the results from these 10 studies suggest: 1) bolus injections of intrathecal baclofen produce short-term reductions in upper and lower extremity spasticity post ABI; 2) prolonged Intrathecal baclofen reduces upper and lower extremity spasticity post ABI; 3) intrathecal baclofen may cause short-term improvements in walking performance. 

Table 1: Effects of Intrathecal Baclofen in Modifying Spasticity

Author/Year

N size

Intervention

Results

Meythaler et al.,

(1996) 23

 

N=11

placebo vs bolus injection of intrathecal baclofen intrathecal baclofen (50 ug) or placebo (normal saline)

+ significant reduction in scores on the spasm scale, Ashworth scale and the deep tendon reflex scale.

+ maximum reduction for all measures occurred 4 hours post-treatment. 

Horn et al., (2005)26

 

N=28.

single 50-µg intrathecal baclofen bolus injection was administered to subjects. 

+ improvements in gait velocity stride length and step width

+ reductions in Ashworth scores at 2, 4 and 6 hours post-injection

Dario et al., (2002)27

N=14

continuous intrathecal baclofen infusions was administered to patients.

+ decrease in Ashworth score in both lower and upper extremities

+ reduction in Spasm Frequency Scalescores

 

Becker et al., (1997)25

 

N=18

patients received continuous intrathecal baclofen infusion.

+ spasticity was reduced

+ Mean Ashworth and Spasm Frequency Reduction score was reduced

Reduction in spasticity lead to a reduction in pain.

Meythaler et al., (1997)22

 

N=12

patients were fitted with an infusion pump for continuous intrathecal baclofen delivery for 3 months.

+ spasm frequency and reflex scores significantly decreased after 3 months of treatment

Meythaler et al., (1999) 30

 

N=17

patients were surgically fitted with a programmable infusion pump for continuous administration of baclofen

+ intrathecal baclofen treatment resulted in a decrease of Ashworth, spasm, and reflex scores in both upper and lower extremities
 

 

Meythaler et al.,

(1999)21

 

N=6

 

patients were surgically fitted with a programmable infusion pump into the lower abdominal wall for continuous administration

+ a significant reduction in Ashworth scores, affected lower limb reflex score ,normal side  of the lower extremities.

+ reductions in Ashworth scores on affected side of the upper extremities

Stokic et al., (2005)24

 

N=30

patients received a single 50-µg intrathecal baclofen bolus injection. 

+ Ashworth score on the more involved side decreased

+ H/M ratio decreased bilaterally

+ F-wave persistence decreased on the more involved side with no change in F/M ratio.

Francisco et al., (2005)29

 

N=14

patients were surgically fitted with an infusion pump for continuous intrathecal baclofen delivery. 

 

head injuries were sustained within the past year

+ reductions from baseline to follow up in upper and lower extremity MAS scores. 

- DRS scores

Francois et al., (2001)28

 

N=4

intrathecal baclofen infusion was started within 1 month following injury onset.

+ reductions in spasticity, and lower limb Ashworth scores at 6 months post-treatment were reported in three of the four cases. 

(+) Indicates statistically significant differences between treatment groups; (-)  Indicates non-statistically significant differences between treatment groups.