The Pharmacological Management of Spasticity

By Saulino, Michael; Jacobs, Beth W

Spasticity is formally defined as a velocity-dependent increase in resistance to passive range of motion. It is a hallmark of neurological diseases that affect the central nervous system, including conditions that are congenital (e.g., cerebral palsy), acquired (traumatic brain injury), static (stroke), and progressive (multiple sclerosis). Spasticity results in involuntary contractions of synergistic muscles in the extremities, which are clinically manifested as flexor or extensor spasms (Mayer & Esquenazi, 2003; Meythaler, 2001).

Spasticity can be both beneficial and deleterious. Therefore, clinicians who care for such patients must consider all aspects of a patient’s spasticity before embarking on a treatment plan. Spasticity beneficially contributes to assistance with mobility, maintenance of posture, vascular circulation, preservation of muscle mass and bone mineral density, prevention of venous thrombosis, and reflexive bowel and bladder function. Conversely, spasticity can interfere with positioning, mobility, comfort, and hygiene. Impaired dexterity can be observed in individuals with both spasticity and some voluntary muscle movement. Ambulatory patients can benefit from formal gait analysis to precisely assess the impact of hypertonitity on locomotion. Spasticity has also been linked to increased metabolic demands in patients who are not adequately nourished (Saulino, Kancherla, & Phillips, 2004). Spontaneous spasms can interfere with sleep or duration of wheelchair use. Spasms can also lead to skin breakdown because of shearing effects or to impaired healing of surgical wounds due to tension along suture lines (Satkunam, 2003).

The relationship of spasticity to pain is complex. Spasticity can limit the range of motion around a joint and result in musculoskeletal pain. Reduction of spasticity may reduce the pain associated with biomechanical problems. However, central nervous system disease can also produce neuropathic pain. Modulation of spasticity may not be effective in reducing neuropathic pain (Ward & Kadies, 2002).

Because the effects of spasticity can be complex, the goal of treatment may not be its complete elimination but rather titration to maximize the risk-benefit ratio. Traditionally, this syndrome is managed in a sequential fashion. However, most practitioners currently apply a more synergistic approach to reducing spasticity. Regardless of the approach, any anti-spasticity regimen must be tailored to the patient.

Nonpharmacological Treatment

The two mainstays of nonpharmacological spasticity management are the removal of noxious stimuli that can drive hypertonicity and the application of physical modalities. Comorbidities of neurological dis ease can act as noxious stimuli that trigger increased spasticity. Examples include urinary tract infections, bladder distention, urolithiasis, bowel impaction, decubitus ulcers, and osteomyelitis. Such problems should be treated before beginning pharmacological treatment for spasticity. As patients become more aware of their reactions to such triggers, they can help the healthcare professional with the ongoing management of their spasticity.

Physical measures can also modulate spasticity. Stretching of the involved muscles is often helpful. Continuous or static stretching is preferred to short-duration or ballistic stretching (Gracies, 2001a). Longduration stretching techniques can be applied manually or by means of adaptive equipment such as casts or splints. Application of heat and cold has been reported to reduce spasticity. Cryotherapy has the more extensive history; methods for oyotherapy include cooling sprays, cold packs, and cooling garments. Other potential modalities for moderating spasticity include ultrasound and short-wave diathermy, microwave irradiation, and transcutaneous electrical nerve stimulation (TENS; Grades, 2001b).

Surgical interventions are the most invasive nonpharmacological interventions for spasticity management. Muscle-tendon lengthening can decrease spasticity by altering the tension-to-length relationship of contracting muscle. Techniques for destroying nerves, such as neurectomy, rhizotomy, and myelotomy, can also be used to control hypertonicity, but these are typically reserved for the most recalcitrant cases (Smyth & Peacock, 2000).

Pharmacological Approaches

Three medications have spasticity reduction as their primary indication: baclofen (Lioresal), dantrolene (Dantrium), and tizanidine (Zanaflex). These drugs represent the mainstays of pharmaceutical treatment for hypertonicity. Table 1 summarizes their important features. The decision process for pharmacological intervention should integrate several factors. The course of neurological dysfunction can influence the choice of modality. A progressive disease such as multiple sclerosis might be better managed using an intervention that can escalate as the disease advances, such as an intrathecal baclofen pump. The areas of the body affected by the neurological disease can dictate treatment. For example, a focal intervention such as a botulinum toxin injection might benefit a stroke patient with focal hypertonicity but would not be appropriate for a patient with global hypertonicity resulting from a traumatic spinal cord injury. Concurrent medical problems should also be considered in the decision process. For patients with known liver dysfunction, medications that are known to affect hepatic function should be avoided. Similarly, for a patient who is chronically colonized by microbial agents, the use of implanted devices must be approached with caution, given the possibility that infectious agents could directly infect the device. For example, infection of an implanted intrathecal pump can lead to meningitis. Such problems are becoming more common (Teddy, Jamous, Gardner, Wang, & Silver, 1992).

Baclofen is a classic medication for spasticity management. It exerts its clinical effects by interacting with neurons that use gamma aminobutyric acid (GABA) as a neurotransmitter. It acts both pre- and postsynaptically to inhibit spinal reflexes. Baclofen is rapidly and completely absorbed following enterai administration. It has a mean half-life of 3.5 hours. Baclofen is metabolized by the liver and eliminated by renal excretion. Because baclofen readily crosses the blood-brain barrier, sedation, fatigue, dizziness, lowering of the seizure threshold, and cognitive dysfunction are common adverse effects. The typical starting dose is 5-10 mg two or three times per day, and the dosage can be increased by 5-10 mg per week. Although 80 mg per day is a commonly accepted maximum, dosing up to 200 mg per day has been used safely and effectively. A badofen withdrawal syndrome can occur with rapid cessation of usage. Withdrawal symptoms include a rebound increase in spasticity, fever, altered mental status, seizures, malignant hyperthermia, and, very rarely, death. Badofen withdrawal is typically treated by gradual reinstitution of oral baclof en. In the case of serious withdrawal, intravenous benzodiazepines can be used. Baclofen overdose syndrome can also occur. It is characterized by sedation, depressed arousal, and respiratory suppression and is treated by temporarily stopping or tapering off baclofen. Intravenous physostigmine, flumazenil, or both may be used in severe cases. Repeated dosing may be needed, because these agents have a shorter half-life than baclofen.

Dantrolene is unique among the oral agents in that its site of action is the peripheral muscle rather than the central neurotransmitter systems. This medication inhibits the release of calcium from the sarcoplasmic reticulum during muscle contraction. The usual starting dose is 25 mg twice per day, and it can be increased by 25-50 mg per day per week. The commonly accepted maximum dosage is 400 mg per day, although use of as much as 800 mg per day has been reported. The halflife of oral dantrolene is 15 hours. Liver abnormalities can be seen with this agent; thus, liver enzymes must be monitored periodically. Abnormal liver enzymes are observed in approximately 2% of patients, with fatal hepatic failure seen in 0.3% of cases. Hepatotoxicity can usually be reversed by ceasing treatment. Laboratory monitoring of liver enzymes (i.e., AST, ALT) is recommended at the initiation of treatment and periodically thereafter. Other reported adverse effects of dantrolene include weakness, nausea, diarrhea, and paresthesias. Dantrolene is the initial medication of choice for spasticity of cerebral origin, because it acts at the level of the peripheral muscle with minimal untoward central effects.

The newest drug for spasticity modulation is tizanidine. This agent is chemically similar to the antihypertension medication clonidine. It acts through agonist effects on the alpha-2 adrenergic system at both the spinal and supraspinal levels to reduce spasm. Peak plasma levels occur 1 hour after oral administration, with a half-life of 2.5 hours. The typical starting dose is 1-4 mg as a single dose at bedtime. The typical maximum daily dosage is 36 mg. This drug is extensively metabolized by the liver to inactive compounds and is then excreted by the kidneys. As with dantrolene, liver function should be monitored during treatment, although no cases of hepatic failure have been reported with tizanidine. Common adverse effects of this agent include sedation, di\zziness, hypotension, nausea, and dry mouth. Some studies have suggested that tizanidine has pain relief properties in addition to its antispasticiry effects (Elovic, 2001).

Several other agents, while not carrying primary indications for spasticity reduction, are occasionally used in appropriate patients. These agents include gabapentin (Neurontin), tiagabine (Gabitril), diazepam (Valium), and clonidine (Catapres). Gabapentin exerts its therapeutic effects by binding to a calcium channel receptor that resides on neurons. Tiagabine and diazepam similarly exert their effects through interactions on the GABA neurotransmitter systems (Francisco, Kothari, & HuIs, 2001). Clonidine, a well-known antihypertension medication, is an agonist to the alpha2 adrenergic system. Its effects are similar to those of tizanidine. The centrally acting muscle relaxants, such as cyclobenzaprine (Flexeri), carisoprodol (Soma), methocarbamol (Robaxin), metaxalone (Skelaxin), and chlorzoxazone (Parafon Forte), are more commonly used to treat painful musculoskeletal conditions rather than spasticity. Their mechanisms of action are poorly understood. All of these medications are considered second-line agents and are valuable treatment options (Kita & Goodkin, 2000).

Alternative techniques for administering oral medications can be quite useful in the appropriate patient setting. Both diazepam and dantrolene have intravenous formulations that can be effectively substituted while a patient is temporarily unable to use oral medication (e.g., during a hospitalization or prolonged procedure). Intravenous diazepam can also be useful in managing baclofen withdrawal. Clonidine is available as a transdermal patch that is applied every 3 days. The long duration of action and continuous administration also can be useful for patients with limited personal assistance or limited hand function. Both baclofen and clonidine can be delivered directly to the nervous system via implanted intrathecal pump. Intrathecal baclofen therapy is indicated for patients with severe spasticity who have not responded to conservative procedures or cannot tolerate other spasticity interventions or who require the precise dosing administration that the pump system affords (Ivanhoe, Tilton, & Francisco, 2001; Remy- Neris, Tiffreau, Bouillard, & Bussel, 2003).

Invasive Pharmacological Treatment Options

The two major invasive interventions for managing spasticity are administration of intravenous and intrathecal medication (discussed above) and chemodenervation. Before using invasive treatment, clinicians should consider the same issues as for oral medications. These treatments can be used in combination with oral agents.

Chemodenervation is the injection of a chemical into a neural structure to decrease excitability within the target. It is an excellent technique for areas of focal spasticity, such as a clenched-fist deformity; the technique may not be as beneficial for global or multifocal hypertonicity. Neural areas that are amenable to chemodenervation include peripheral muscle, motor points, or peripheral nerves. Electrodiagnostic techniques should be used to locate the appropriate neural target for denervation (Childers, 2003). Temporary effects can be obtained by using anesthetic agents such as lidocaine or procaine; relatively permanent effects are obtained by using ethanol or phenol to denature the proteins of the neural structures. The main adverse effects of these agents are dysesthesia of the selected nerve and excessive focal weakness.

Another agent used for denervation is botulinum toxin. Currently, two toxins are commercially available: type A (Botox) and type B (Myobloc). The toxins exert their effect by inhibiting the release of acetylcholine into the neuromuscular junction. Cost is a major concern in the use of botulinum toxin. A typical treatment can cost hundreds of dollars, and repetition may be necessary, because the effect is often temporary.

Summary

The spectrum of antispasticity therapies is fairly broad. Familiarity with the various therapies will enable a nurse involved in the care of neurological patients to deliver the effective treatment and minimize adverse events. Referral to specialty care centers may be appropriate for selected patients who require more complex interventions for spasticity control.

References

Childers, M. K. (2003). The importance of electromyographic guidance and electrical stimulation for injection of botulinum toxin. Physical Medicine and Rehabilitation Clinics of North America, 14, 781-792.

Elovic, E. (2001). Principles of pharmaceutical management of spastic hypertonia. Physical Medicine and Rehabilitation Clinics of North America, 12, 793-816, vii.

Francisco, G. E., Kothari, S., & HuIs, C. (2001). GABA agonists and gabapentin for spastic hypertonia. Physical Medicine and Rehabilitation Clinics of North America 12, 845-888, viii.

Gracies, J. M. (200Ia). Pathophysiology of impairment in patients with spasticity and use of stretch as a treatment in spastic hypertonia. Physical Medicine and Rehabilitation Clinics of North America 12, 747-768, vi.

Gracies, J. M. (200Ib). Physical modalities other than stretch in spastic hypertonia. Physical Medicine and Rehabilitation Clinics of North America 12, 769-792, vi.

Ivanhoe, C. B., Tilton, A. H., & Francisco, G. E. (2001). Intrathecal baclofen therapy for spastic hypertonia. Physical Medicine and Rehabilitation Clinics of North America, 12, 923-929, ix.

Kita, M., & Goodkin, D. E. (2000). Drugs used to treat spasticity. Drugs, 59, 487-495.

Mayer, N. H., & Esquenazi A (2003). Muscle overactivity and movement dysfunction in the upper motor neuron syndrome. Physical Medicine and Rehabilitation Clinics of North America, 14, 855-883, vii-viii.

Meythaler, J. M. (2001). Concept of spastic hypertonia. Physical Medicine and Rehabilitation Clinics of North America, 12, 725-732, v.

Remy-Neris, O. M. P., Tiffreau, V. M., Bouillard, S. M., & Bussel, B. M. (2003). Intrathecal baclofen in subjects with spastic hemiplegia: Assessment of the anti-spastic affected during gait. Archives of Physical Medicine and Rehabilitation, 84, 643-650.

Satkunam, L. E. (2003). Rehabilitation medicine: 3. management of adult spasticity. Canadian Medical Association Journal, 169, 1173- 1179.

Saulino, M., Kancherla, V., & Phillips, E. (2004). Effects of intrathecal baclofen on glycemie management in diabetic quadriplegic patient: A case report. Archives of Physical Medicine Rehabilitation 85, e50.

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

Teddy, P., Jamous, A., Gardner, B., Wang, D., & Silver, J. (1992). Complications of intrathecal baclofen delivery. British Journal of Neurosurgery, 6, 115-118.

Ward, A. B., & Kadies, M. (2002). The management of pain in spasticity. Disability and Rehabilitation, 20, 443-453.

Questions or comments about this article may be directed to Michael Saulino, MD PhD, at docsaulino@msn.com. He is a staff physiatrist at MossRehab, Elkins Park, PA, and assistant professor in the department of rehabilitation medicine at Thomas Jefferson University, Philadelphia, PA.

Beth W. Jacobs, RN CRRN CCM, is clinical coordinator of spinal cord injury care at MossRehab, Elkins Park, PA.

Copyright 2006 American Association of Neuroscience Nurses 0047- 2606/06/3806/ 0456$5.00

Copyright American Association of Neurosurgical Nurses Dec 2006

(c) 2006 Journal of Neuroscience Nursing. Provided by ProQuest Information and Learning. All rights Reserved.