For the clinician confronted with a patient with multiple sclerosis (MS), it is of particular importance to determine signs of spasticity. This complex clinical syndrome consists of muscle hypertonia and exaggerated tendon reflexes (including clonus). MS plaques may inhibit supraspinal control of reflex activity and spinal programming and may thereby lead to impairment of functional movements of muscles of the extremities and of the trunk.

Clinically, spasticity is characterised by weakness, slowness in building up to maximal power of muscle activity and relaxing again, and clumsiness of voluntary movements. This usually results from inco-ordination of synergistic muscles or failure of inhibition of antagonists. Thereby, the range of functional voluntary movements may be reduced to a small number of stereotyped patterns. The heterogeneity of clinical manifestations and effects of function may be explained by the site and the chronicity of the lesion and the way the nervous system compensates for functional impairment.

Spasticity is largely responsible for the disability of affected individuals and it is often amenable to efficient treatment. Pathophysiologically, it may be defined as velocity-dependent increase of resistance of muscle to stretch and is thought to be due to central disinhibition of the reflex arcs 2. Alpha motor neurones which innervate the skeletal muscles are hyperexcitable in spasticity by reduction of inhibition and are therefore activated by inputs that normally would not provoke a response 2. Passive stretch as well as cutaneous stimulation may also trigger involuntary and usually self-limiting co-activation of agonists and antagonists called "spasms" which are often painful and may predispose to the development of pressure sores.

In clinical practice systematic positioning of paralysed limbs or inducing and maintaining stretch of the muscles by serial casting or by orthotic devices and rarely electrical stimulation of the dorsal columns of the spinal cord or of the cerebellar surface are used for reducing spasticity. In MS, the legs are usually more markedly affected by spasticity than the arms 3. Extensor spasticity of the legs, particularly of the quadriceps, might be considered advantageous for standing, walking and particularly transferring, as it may compensate for muscular weakness. The "clasp-knife" response, however, which is only known in extensor muscles may annihilate this apparent functional gain: progressive stretching of an extensor muscle initially leads to an increase of resistance but only until the muscle reaches a certain length. Then the tone collapses and the muscle becomes flaccid and may build up resistance again only after having shortened.

Spastic gait is not only characterized by hyperactivity of hip flexors and adductors and knee extensors but also by exaggerated plantarflexion, supination and inversion of the foot. Structural changes of spastic muscles and of connective tissues develop over periods of weeks to months, leading to changes in mechanical properties in leg extensors and arm flexors. Part of the clinical impression of a progressive course in MS may therefore be due to inadequate mangement of spasticity 3 which leads to such structural changes of muscles with subsequent functional impairment.

Prof Jürg Kesselring

Treatment

Treatment of spasticity should be considered only after careful assessement of the patient"s functional status in order to clearly identify treatment goals and to evaluate the potential risks and likely benefits of various therapeutic interventions 4. The management of spasticity always is a team approach and requires active co-operation of nurses, physiotherapists, physicians, occupational therapists, orthotists and wheelchair specialists and of course the disabled individual and their relatives 2.

Persons with MS should be advised to be as active as possible in all ways of life in accordance with individual strength and abilities. Longterm management is centred on the promotion of purposeful movements which are part of normal daily activities and should be integrated into a daily 24 hours scheme 5.

Clinical observations suggest that spasticity in MS may be triggered or aggravated by many conditions, noxious or potentially painful activity 6 - including urinary tract infections, faecal impaction, contractures, ingrowing toe nails, skin ulcerations and increased sensory stimuli from ill-fitting orthotic appliances, catheter bags or even tight clothing or footwear. They should routinely be looked for and, when present, appropriately managed.

Positioning

Correct positioning is most important for preventing limbs from becoming fixed in the position imposed by the pattern of spasticity. In order to prevent these complications with their late orthopaedic consequences, daily prone positioning must be made possible for every patient. Side-lying, sitting and standing all produce stretch on spastic muscles and facilitate their antagonists. In sitting, the body should be maintained in a balanced, symmetrical and stable posture and should be moved regularly in order to reduce inappropriate shear forces and to maintain as full as possible a range of movement of the joints.

Various adaptable and adjustable seating systems are commercially available which allow to accomodate the large range of different spastic patterns and deformities. The lack of support for the trunk and pelvis in conventional wheelchair upholstery leads to poor positioning of the trunk and torso, leading to a "hammock" effect. Improper positioning in wheelchairs may become painful and may be disadvantageous in relation to reaching activities of the upper extremities. For most patients, pull-away desk arms, leg elevators and pneumatic tires are recommended.

Tetraplegic patients may benefit the most from powered wheelchairs, but good cognitive functions and visuo-spatial orientation are absolute prerequisites.

Drug treatment

A number of drugs are available which effectively reduce increased muscle tone and painful muscle spasms in a variety of clinical disorders, including MS. Before introducing drug treatment for reducing spasticity, it should be considered, however, that a relatively rigid or spastic limb may be useful for walking or transferring for an individual with muscle weakness, and that inappropriate alleviation of spasticity in such circumstances can lead to a functional reduction in mobility and independence.

Since like all clinical manifestations of MS spasticity tends to change over time it is important to re-evaluate antispastic treatment at intervals. Major failings in most reported clinical trials of such drugs are that the pattern of spasticity is inadequately described, the objectives of treatment are not specified, and only short-term rather than medium- or long-term outcomes are assessed 7. As a rule, the use of only one substance at a time is recommended, although combinations of drugs with different mechanisms of action may eventually be tried. Because relief of muscle spasms and muscle hypertonia may be achieved only at the cost of reduced muscle power, and because all antispastic drugs may induce side effects, doses should be kept to a minimum, especially in mobile patients 4.

Tizanidine is an imidazoline derivative closely related to clonidine and acts by stimulation of alpha-2 adrenergic receptors in the spinal cord. It reduces presynaptic release of excitatory amino acids such as glutamate 14 and this may partly explain its inhibitory effect on polysynaptic pathways. In controlled trials the effective dose of tizanidine for reducing spasticty ranged from 12 - 36 mg, on average 18 mg. All basic symptoms associated with spasticity, e.g. increased muscle tone, muscle spasms and clonus improved to a similar extent (60 - 80% responders). A useful improvement of the clinical applicability of tizanidine is the introduction of "constant-release" forms of 6 mg and 12 mg tablets. The most frequent side effects are tiredness, drowsiness and dry mouth.

Baclofen is an agonist of GABA-B receptors, acting mainly at the terminals of primary afferent fibres in the spinal cord. Here it functions both presynaptically to reduce release of excitatory amino acids and - at higher concentrations - postsynaptically to antagonize their actions. It reduces monosynaptic stretch reflexes more effectively than polysynaptic reflexes and interneurones. Baclofen as oral medication is given in doses starting at 10 mg and stepwise increased until the desired benefit is achieved or side-effects (such as drowsiness, fatigue and muscle weakness) become unacceptable. On avarage, 40 - 80 mg/day are given in 3 doses. Abrupt discontinuation may result in withdrawal symptoms such as hallucinations and seizures.

In very severe spasticity as it may occur in longstanding MS, baclofen may be given intrathecally via a subcutaneously placed infusion pump. This may be indicated for facilitating nursing and for alleviating painful muscle spasms and automatic movements of the legs. The effect of intrathecal baclofen is tested by a bolus injection of 30 - 50 mg via a lumbar puncture. If a clear effect lasts for more than 4 hours, continuous drug application can be achieved by the subcutaneous implantation of an electronically programmed electronic drug delivery system (e.g. Medtronic® 10). The intrathecal daily dosage is small (0.1 - 0.4 mg/day) but the antispastic effect, especially on muscle tone, is powerful 11. With this application form, systemic effects of baclofen seldom occur. The main complications are technical and include pump malfunction, catheter-related problems (kinking, breaking, displacement), local inflammation and spinal meningitis. Continuous intrathecal application of baclofen is a safe and effective adjunct to physical therapy in severe spasticity and particularly so in longstanding MS.

Dantrolene has a peripheral target of action and exerts its antispastic effect within the muscle itself. It suppresses the release of calcium from the sarcoplasmic reticulum which in turn inhibits the excitation, contraction and coupling process and thereby leads to reduced muscle strength. Because of this different site of action it may be used in combination with one of the above mentioned antispastics of first choice. Side-effects include drowsiness, weakness and fatigue and can be minimized by starting dose at 25 mg and slowly increasing to a maximum of 400 mg over several weeks. Hepatotoxicity, depending on dosage and duration of treatment often limits the use of Dantrolene.

Benzodiazepines reduce muscle tone by three different mechanisms: suppression of sensory impulses from muscle and skin receptors, potentiation of GABA action postsynaptically and inhibition of excitatory descending pathways 6. In spite of their excellent antispastic effect, benzodiazepines have only limited usefulness as single agents to treat spasticity of MS patients because of their serious side effects, such as drowsiness, tolerance and dependency. Other antispastic drugs which are available, such as memantine, glycine, cannabinoids (for review see 1, 4, 6) are only rarely used in clinical routine of MS management.

Injections and surgical procedures

Transient blockade of peripheral nerves or nerve roots with phenol has been tried for relief of spasticity of various origin including MS. Most of these techniques (review e.g. 1, 6), however, have not gained wide acceptance because of the difficulty to find the appropriate injection site (e.g. "motor points"), the necessity to repeat the injection at intervals and because of the serious side-effects (loss of motor function, dysaesthesias, damage to local structures etc).

Treatment with Botulinum toxin A is usually a safe procedure and has an established role in various movement disorders. Its usefulness in the treatment of spasticity due to MS, however, is only recently being investigated 12. In contrast to chemical neurolysis, botulinum toxin does not cause sensory loss or dysaesthesias. The optimal site of injection is the muscle innervation zone but accurate placement into the motor points is usually not necessary when large muscles are injected as the toxin diffuses freely in muscles. In non-ambulatory patients with longstanding MS, local injection of botulinum toxin into severely spastic hip adductors may make peroneal hygiene, urethral catherization, sitting and positioning in bed much easier and reduce muscle tone and spasm frequency. This benefit can be expected to last an average of three months. In patients with incomplete bladder voiding due to hypertonia of the sphincter externus muscle, botulinum toxin injection into the latter through a special EMG needle may lead to significant improvement of bladder function. Although several methods of neurosurgical alleviation of spasticity by interrupting the reflex arc exist, none of them has gained wide acceptance in the treatment of MS because of untoward sequelae and complications 1, 6.

References:

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2. Lance JW Symposium synopsis In: Feldman RG, Young RR, Koella WP (eds.): Spasticity: disordered motor control. Yearbook Publishers, Chicago, Illinois 1980, 485 - 495


3. Kesselring J Multiple Sclerosis Cambridge University Press 1997


4. Bakheit AMO Management of muscle spasticity Critical Reviews in Physical Medicine and Rehabilitation 1996; 8(3): 235 - 252


5. Mertin J, Paeth B Physiotherapy and multiple sclerosis - application of the Bobath concept MS management 1994; 1: 10 - 13


6. Dietz V, Young RR The syndrome of spastic paresis In: Brandt T, Dichgans J (eds.): Neurological disorders: Course and Treatment. Academic Press 1996, chapter 74, pp. 861 - 871


7. Mostert S, Kesselring J Effects of a short term exercise training program on aerobic fitness, fatigue, health perception and activity level of subjects with multiple sclerosis. Multiple Sclerosis (in press)


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10. Ochs G, Struppler A, Meyerson BA et al Intrathecal baclofen for long-term treatment of spasticity: a multi-centre study J Neurol Neurosurg Psychiat 1989; 52: 933 - 939


11. Coffey JR, Cahill D, Steers W et al Intrathecal baclofen for intractable spasticity of spinal origin: results of a long-term multicenter study Journal of Neurosurgery 1993; 78: 226 - 232


12. Ward A Management of spasticity - botulinum toxin In: Hawkins CP, Wolinsky JS: Principles of Treatment in Multiple Sclerosis Butterworth - Heinemannn, Oxford 2000, pp. 201 - 227