Spasticity, botulinum toxin

MS patients usually have upper motor neuron spasticity. This type of spasticity cannot be treated with muscle relaxants such as carisoprodol. MS patients must be treated with agents specific for upper motor neuron spasticity (Table 26—8).48 MS spasticity is classified as focal or generalized. If the spasticity primarily involves only one muscle group, it is focal and may benefit from botulinum toxin administration.11 Systemic medications are used for generalized spasticity. No clear conclusion can be reached regarding the superiority in efficacy of one antispasticity agent over another medication selection is usually based on adverse effects (see Table 26-8).11,48... 

Focal spasticity Botulinum toxin Prevents release of acetylcholine in the neuromuscular junction Individualized... 

Botulinum toxin from Clostridium botulinum is the most potent poison known. The lethal dose in an adult is approx. 3x10 mg. The toxin blocks exo-cytosis of ACh in motor (and also parasympathetic) nerve endings. Death is caused by paralysis of respiratory muscles. Injected intramuscularly at minuscule dosage, botulinum toxin type A is used to treat blepharospasm, strabismus, achalasia of the lower esophageal sphincter, and spastic aphonia. 

Botulinum toxin is used clinically in the treatment of blepharospasm, writer s cramp, spasticities of various origins, and rigidity due to extrapyramidal disorders. It is also used to treat gustatory sweating and cosmetically to decrease facial wrinkles. Botulinum toxin A Botox, Oculinum) injected intramuscularly produces functional denervation that lasts about 3 months. Clinical benefit is seen within 1 to 3 days. Adverse effects range from diplopia and irritation with blepharospasm to muscle weakness with dystonias. 

The therapeutic use of botulinum toxin for ophthalmic purposes and for local muscle spasm was mentioned in Chapter 6. Local facial injections of botulinum toxin are widely used for the short-term treatment (1-3 months per treatment) of wrinkles associated with aging around the eyes and mouth. Local injection of botulinum toxin has also become a useful treatment for generalized spastic disorders (eg, cerebral palsy). Most clinical studies to date have involved administration in one or two limbs, and the benefits appear to persist for weeks to several months after a single treatment. Most studies have used type A botulinum toxin, but type is also available. 

Ronan S, Gold JT Nonoperative management of spasticity in children. Childs Nerv Syst 2007 23 943 [PMID 17646995] Verrotti A et al Pharmacotherapy of spasticity in children with cerebral palsy. Pediatr Neurol 2006 34 1. [PMID 16376270] Ward AB Spasticity treatment with botulinum toxins. J Neural Transm 2008 115 607. [PMID 18389166]... 

Berweck S, Heinen F. Use of botulinum toxin in pediatric spasticity (cerebral palsy). Mov Disord. 2004 (Suppl 8)19 S162-S167. 

More recently, there has been considerable interest in using botulinum toxin to reduce spasticity in specific muscles or muscle groups. This treatment has been used to treat spasticity resulting from various dis-... 

Botulinum toxin injection has been documented as a means to control severe spasticity in various clinical situations. This intervention, for example, can help remove spastic dominance in certain patients so that volitional motor function can be facilitated. For example, judicious administration of botulinum toxin can result in improved gait and other functional activities in selected patients with cerebral palsy, stroke, or traumatic brain injury.7,36,49,78 Even if voluntary motor function is not improved dramatically, reducing spasticity in severely affected muscles may produce other musculoskeletal benefits. For example, injection of botulinum toxin can reduce spasticity so that muscles can be stretched or casted more effectively, thus helping to prevent joint contractures and decreasing the need for surgical procedures such as heel-cord lengthening and adductor release.12,98... 

These injections can likewise enable patients to wear and use orthotic devices more effectively. Injection into the triceps surae musculature can improve the fit and function of an ankle-foot orthosis by preventing excessive plantar flexor spasticity from pistoning the foot out of the orthosis.49 Injections into severely spastic muscles can also increase patient comfort and ability to perform ADL and hygiene activities. Consider, for example, the patient with severe upper extremity flexor spasticity following a CVA. Local injection of botulinum toxin into the affected muscles may enable the patient to extend his or her elbow, wrist, and fingers, thereby allowing better hand cleansing, ability to dress, decreased pain, and so forth.7... 

Consequently, botulinum toxin represents a strategy for dealing with spasticity that is especially problematic in specific muscles or groups of muscles. Despite the rather ominous prospect of injecting a potentially lethal toxin into skeletal muscles, this intervention has a remarkably small incidence of severe adverse effects when administered at therapeutic doses.5,44 Botulinum toxin can therefore be used as part of a comprehensive rehabilitation program to provide optimal benefits in certain patients with severe spasticity. 

Most muscle relaxants are absorbed fairly easily from the gastrointestinal tract, and the oral route is the most frequent method of drug administration. In cases of severe spasms, certain drugs such as methocarbamol and orphenadrine can be injected intramuscularly or intravenously to permit a more rapid effect. Likewise, diazepam and dantrolene can be injected to treat spasticity if the situation warrants a faster onset. As discussed earlier, continuous intrathecal baclofen administration may be used in certain patients with severe spasticity, and local injection of botulinum toxin is a possible strategy for treating focal dystonias and spasticity. Metabolism of muscle relaxants is usually accomplished by hepatic microsomal enzymes and the metabolite or intact drug is excreted through the kidneys. 

Therapists can therefore play a vital role in facilitating the substitution of normal physiologic motor control for the previously used spastic tone. This idea seems especially true when one of the parenteral antispasticity techniques is used, such as intrathecal baclofen or botulinum toxin injections. For example, patients who receive intrathecal baclofen through programmable pump systems often require a period of intensive rehabilitation to enable the benefits from decreased spasticity and increased voluntary motor function to occur. Therapists must therefore be ready to use aggressive rehabilitation techniques to help patients adapt to the relatively rapid and dramatic decrease in muscle tone that is often associated with antispasticity drug therapy. 

Barnes M. Botulinum toxin—mechanisms of action and clinical use in spasticity. J Rehabil Med. 2003 41 (suppl) 56-59. 

Bottos M, Benedetti MG, Salucci P, et al. Botulinum toxin with and without casting in ambulant children with spastic diplegia a clinical and functional assessment. Dev Med Child Neurol. 2003 45 758-762. 

Fock J, Galea MP, Stillman BC, et al. Functional outcome following Botulinum toxin A injection to reduce spastic equinus in adults with traumatic brain injury Brain lnj. 2004 18 57-63. 

Frasson E, Priori A, Ruzzante B, et al. Nerve stimulation boosts botulinum toxin action in spasticity. Mov Disord. 2005 20 624-629. 

Fried GW, Fried KM. Spinal cord injury and use of botulinum toxin in reducing spasticity. Phys Med Rehabil Clin NAm. 2003 14 901-910. 

Gordon MF, Brashear A, Elovic E, et al. Repeated dosing of botulinum toxin type A for upper limb spasticity following stroke. Neurology. 2004 63 1971-1973. 

Grades JM. Physiological effects of botulinum toxin in spasticity Mov Disord. 2004 19(suppl 8) S120-S128. 

Sarioglu B, Serdaroglu G, Tutuncuoglu S, Ozer EA. The use of botulinum toxin type A treatment in children with spasticity. Pediatr Neurol. 2003 29 299-301. 

Verplancke D, Snape S, Salisbury CF, et al. A randomized controlled trial of botulinum toxin on lower limb spasticity following acute acquired severe brain injury. Clin Rehabil. 2005 19 117-125. 

Wasiak J, Hoare B, Wallen M. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy. Cochrane Database Syst Rev. 2004 CD003469. 

Botulinum toxin A complexed with haemagglutinin is currently employed medicinally to counter involuntary facial muscle spasms, e.g. around the eye. Very small (nanogram) amounts are injected locally and result in the destruction of the acetylcholine release mechanism at the neuromuscular junction. Since new nerve junctions will gradually be formed over two months or so, the result is not permanent, and the treatment will need to be repeated. It has also been found useful in easing muscle spasticity in children with cerebral palsy. 

Botulinum toxin is the treatment of choice for focal dystonias such as torticollis and writer s cramp and for hemifacial spasm, and may complement the management of spasticity. 

Spasticity, if moderate to severe, may impede rehabilitation after stroke. Botulinum toxin has been shown in small studies to reduce tone and improve range of movement but robust evidence for improvement in function is lacking (van Kuijk et al. 2002). 

Recently, the extreme potency of botulinum toxin has led to multiple medical uses of this substance, including the treatment of cervical torticollis, strabismus, and other musculoskeletal disorders, as well as in cosmetic plastic surgery as Botox for the elimination of facial lines or wrinkles (Lemonick, 2002). The irreversible action of botulinum toxin on nerve transmission when used in minute amounts leads to prolonged therapeutic effects of greater than 3 months in duration. An iatrogenic form is also reported secondary to adverse effects of local injection of the toxin in cosmetic procedures or in patients with spasticity (Ihgnoli, 2002). 

Botulinum toxin is used in the treatment of excessive muscle contraction disorders (dystonias), such as strabismus, blepharospasm, focal dystonias, and spasticity. One of its uses is in the removal of facial wrinkles by paralysing mimic muscles. It can reduce sweat production by blocking cholinergic innervation of eccrine sweat glands. 

The use of botulinum toxin has been increasing in cosmetic dermatology, muscle rigidity/spasticity syndromes, hyperhidrosis, some types of chronic pain syndromes, and headaches. It has the unfortunate distinction of being the most potent toxin that exists and is a weapon of mass destruction. 

Several agents, many of limited efficacy, have been used to treat spasticity involving the a-motor neuron with the objective of increasing functional capacity and reheving discomfort. Agents that act in the CNS at either higher centers or the spinal cord to block spasms are baclofen, the benzodiazepines, and tizandine. Botulinum toxin and dantrolene act peripherally. 

Uses The uses of botulinum toxin in Parkinson s disease [54" ], anal fissure [55" ], women with chronic pain [56" ], spasticity after stroke in adults [57", 58 ], and urological conditions [59 have been reviewed. The pharmacology and formulations of botuhnum toxins and data from clinical trials, demonstrating their efficacy in dystonia, spasticity, tics, tremor, dysphonia, and autonomic disorders, have been reviewed [60 ]. 

Placebo-controDed stndies In a double-bUnd, randomized, placebo-controlled comparison of an injection of botulinum toxin type A into spastic upper Umb muscles... 

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