More MS news articles for August 2002

Spasticity in Multiple Sclerosis

http://www.epva.org/MSQR_Archive/Spring02_1.htm

MSQR - V21.  N1.   Spring  2002
Randall T. Schapiro, MD, Director, Fairview Multiple Sclerosis Center, Minneapolis, MN

Progress to Date

For patients with multiple sclerosis (MS), fatigue and muscle weakness can make it difficult just to get out of bed. The increased immobility and pain of spasticity can make performing daily tasks even harder.

Spasticity is a condition in which a muscle has increased tone and resists being stretched. Although the details of how muscles become spastic are still not completely understood, stretch reflexes are known to be involved. When a muscle is stretched (e.g., when the opposite muscle contracts), specialized receptors in the muscle tendons report the amount of stretch to the nervous system. In turn, the nervous system tells the stretched-out muscle to start contracting. In some neurologic disorders, including cerebral palsy and MS, stretch reflexes can become hypersensitive and initiate muscle contractions inappropriately. The affected muscles feel tight or stiff and are prone to painful spasms.

Normally, nerve signals from the brain and upper spinal cord help control the stretch reflexes, inhibiting them when necessary, to allow appropriate muscle contraction. In MS, lesions in the nervous system interrupt nerve signals, and it is thought that MS-related spasticity probably arises when the lesions block these inhibitory signals from the brain (Smyth & Peacock, 2000). Spasticity affects up to 60% of people with MS, and adds to existing problems with mobility and muscle weakness (Shakespeare, Boggild, & Young, 2001).

Current Research and Issues

A range of medications is available to treat spasticity. Many of these medications—baclofen and diazepam are examples––reduce spasticity by increasing muscle relaxation. These drugs often mimic the effects of a chemical called gamma-aminobutyric acid (GABA), which is normally found in the nervous system and is involved in inhibiting muscle contractions. While these medications can be effective, they often have unpleasant side effects, such as drowsiness or toxicity, that can limit their usefulness.

Tizanidine is also effective in treating spasticity. Tizanidine is a muscle relaxant, but in a different class from the GABA-related drugs. In a double blind, placebo-controlled trial of 187 patients, tizanidine effectively diminished spasticity with only minor side effects (The United Kingdom Tizanidine Trial Group, 1994). This drug has been approved for spasticity management in the US for 5 years and is an excellent addition to baclofen.

Recently, researchers have tried to identify additional oral medications that might be effective, but have less severe side effects. One of these is gabapentin, a drug originally developed to control seizures. In one small study of 22 patients with MS with spasticity, gabapentin treatment reduced spasticity without affecting the patients’ ability to concentrate or inducing fatigue (Cutter, Scott, Johnson, & Whiteneck, 2000).

When oral medications do not control spasticity sufficiently, there are other options for treatment. One alternative is to deliver medications by a different route. Instead of being given by mouth, one muscle relaxant, baclofen, has been used to successfully treat spasticity by being infused directly into the fluid-filled space around the spinal cord (e.g., Penn et al., 1989). This is accomplished by surgically implanting a small pump that continually infuses the medication in the right amounts. The pump can be refilled using a syringe, without additional surgery. This method can give significant relief from spasticity and, because the drug goes only into the spinal area, there are generally much fewer side effects. Since surgery is required and problems such as infection and dislocation of the pump or its tubing can occur, this method of drug delivery is generally undertaken only if oral medications fail.

When spasticity is severe and other methods of treatment have failed, other surgical treatment is available (Smyth & Peacock, 2000). The aim of this surgery is usually to interrupt the spinal reflex that is causing the spasticity. The nerves innervating the spastic muscle may be severed, the tendon or muscle may be cut, or spasticity may be reduced by lengthening a tendon. Surgery can be an effective way to treat spasticity, but because it is invasive and surgical changes are often irreversible, surgery should be chosen only after carefully considering the alternatives.

Future Research and Issues

Some additional treatments are in the process of being developed or evaluated. For example, in some recent studies, botulinum toxin has been directly injected into spastic muscles to allow them to relax (e.g., Hyman et al., 2000). Botulinum toxin is a neurotoxin that blocks the release of the chemical that tells muscles to contract. Many people know it as “Botox®,” and are familiar with its use to enhance appearance by preventing the contraction of the facial muscles that cause frown lines. Botulinum toxin works the same way in spasticity, allowing the muscles to relax by blocking nerve signals. In one study of 74 patients with MS and spasticity of the hip adductor muscles (which pull the legs together), botulinum toxin significantly reduced muscle tone at all of the doses used (slightly better effects were seen at higher doses). The researchers felt that the technique showed promise and that they had identified a safe and effective dose range for treatment, but believed that additional research should be done to identify the best use of botulinum toxin injections, especially when used in conjunction with other treatments.

More recently, researchers have reported that naturally occurring compounds called endocannabinoids, which resemble the active chemicals in marijuana, may be important in the body’s response to spasticity (Baker et al., 2001). In this study, the researchers showed that the levels of these chemicals rose in mice that had been induced to develop a form of spasticity similar to that seen in MS. The researchers thought the mice might be making larger amounts of endocannabinoids in an attempt to compensate for the spasticity. To test this, they injected the animals with additional endocannabinoids, and the spasticity was reduced. When the researchers did the opposite experiment, injecting drugs to block the animals’ own endocannabinoids, the spasticity worsened. The results of this study suggest a possible role for cannabinoids in future therapy.

One major impediment to understanding how best to treat spasticity is that there is no universally acceptable way to measure it. The usefulness of the best accepted method of measuring spasticity, the Ashworth Scale, has been called into question, and researchers often use altered versions of the Ashworth Scale in conjunction with other scales (for pain, disability, quality of life, etc.) in their studies (see Shakespeare et al., 2001). Since the results of each study are measured and reported differently, it is difficult to compare them. Therefore, an important step for future research in this field is the development of a reliable, objective method of measuring spasticity that will allow a comparison of treatments across studies.

Implications for Patient Care

Research into new treatments for spasticity is promising, and better treatments may be available before too long. For the moment, however, there is no conclusive evidence that newer treatments are better than older ones. Moreover, the lack of a good assessment instrument means that comparisons among agents to identify better treatments are difficult. Better clinical trial designs will hopefully lead to improved approaches for managing MS-related spasticity (Shakespeare et al., 2001).

References (*denotes suggested reading)

Baker, D., Pryce, G., Croxford, J. L., Brown, P., Pertwee, R. G., et al. (2001). Endocannabinoids control spasticity in a multiple sclerosis model. The FASEB Journal, 15, 300-302.

Cutter, N. C., Scott, D. D., Johnson, J. C., & Whiteneck, G. (2000). Gabapentin effect on spasticity in multiple sclerosis: A placebo-controlled, randomized trial. Archives of Physical Medicine and Rehabilitation, 81, 164-169.

Hyman, N., Barnes, N., Bhakta, B., Cozens, A., Bakheit, M., et al. (2000). Botulinum toxin (Dysport®) treatment of hip adductor spasticity in multiple sclerosis: A prospective randomized, double blind, placebo controlled, dose ranging study. Journal of Neurology, Neurosurgery, and Psychiatry, 68(6), 707-712.

Penn, R. D., Savoy, S., Corcos, D., Latash, M., Gottlieb, G., et al. (1989). Intrathecal baclofen for severe spinal spasticity. New England Journal of Medicine, 320, 1517-1521.

*Schapiro, Randall T. (1998). Symptom management in multiple sclerosis, 3rd edition. New York: Demos Publishing Company, 33-40

Shakespeare, D. T., Boggild, M., & Young, C. (2001). Anti-spasticity agents for multiple sclerosis (Cochrane Review). In The Cochrane Library, Issue 3, 2001. Oxford: Update Software.

Smyth, M. D., & Peacock, W. J. (2000). The surgical treatment of spasticity. Muscle and Nerve, 23, 153-163.

The United Kingdom Tizanidine Trial Group. (1994). A double-blind, placebo-controlled trial of tizanidine in the treatment of spasticity caused by multiple sclerosis. Neurology, 44 (Suppl. 9), S70-S78.
 

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