Botulinum Toxins (BTX)
BTX therapy has been the focus of several lengthy reviews and prior educational programs and workshops at the AAN, so this summary addresses only the key aspects.[3, 9-11] The bacterium Clostridium botulinum makes seven different forms of BTX designated A through G. They block neurotransmission at the neuromuscular junction by acting as proteases that cleave critical proteins required for the docking and exocytosis of synaptic vesicles containing acetylcholine. Weakness occurs until the release apparatus is restored by replacing the cleaved proteins or until axons sprout new terminals. Only two types have been developed for clinical application. BTX-A is available as BotoxTM, DysportTM or XeominTM. BTX-B is available as MyoblocTM or NeuroblocTM.
For many dystonias, therapy with BTX is highly effective and the treatment of choice. Typical success rates are 80-90% for focal craniofacial and cervical dystonias, but lower for oromandibular and limb dystonias. Their use is supported by several double-blind and placebo-controlled trials, and extensive and long-term non-blinded experience. In most cases, benefits become evident 2-10 days after injections, they peak at 2-4 weeks, and they last for 10-14 weeks. Most patients return for re-injection at 3-4 months intervals. Intervals less than 3 months are discouraged because of a theoretical increased risk for developing immunological resistance, while intervals of 5-6 months or longer are discouraged because patients experience complete return of symptoms.
The most important factor determining success with BTX is proper selection of muscles for treatment and proper selection of doses for each muscle. The selection of muscles is based primarily on the clinical examination in concert with knowledge of the types of movements governed by each muscle. The use of ancillary EMG and/or stimulation to confirm targeting to appropriate muscles depends on the condition being treated and the preferences of the provider. EMG is valuable in some cases, such as focal hand dystonia where precise discrimination of multiple small muscles in close proximity in the forearm is challenging by clinical examination alone. On the other hand, EMG is rarely needed for blepharospasm and other facial dystonias, because these injections usually are made subcutaneously where the medication diffuses subcutaneously to the muscles. Many patients with cervical dystonia may not need EMG guidance, unless they have thick necks that make palpation of individual muscles difficult, complex patterns of movement where the involved muscles are unclear, or unreliable responses without EMG.
There are significant variations among providers in the number of injections per muscle, dilution factors, and doses applied. Targeting fewer injection sites minimizes pain from needle penetrations through the skin. At the same time, fewer sites requires delivery of larger volumes per site, thereby increasing local muscle discomfort and the risk of leakage from each site. Detailed guidelines are available for different forms of dystonia, anatomical charts for specific muscles involved, and doses for different formulations of BTX.
Doses and side effects vary according to the disorder treated. For cervical dystonia, the most common side effects include transient injection site pain, muscle weakness, dysphagia and dry mouth. For blepharospasm the most common side effects include transient pain, ecchymoses, ptosis, and dry or watery eyes. For spasmodic dysphonia, hoarseness or breathy voice is common shortly after injections but most often transient. For limb dystonia, the most common side effects are weakness and spread to nearby muscles.
Physical and Occupational Therapy
Many patients request various forms of physical (or occupational) therapy in lieu of other medical or surgical treatments. Although physical therapy rarely provides an adequate substitute for other therapies, it plays an important adjunctive role. Physical therapy can be very useful at the outset to mobilize joints and mitigate against contractures, and to provide safe exercise programs to maintain function. The physical therapist must have experience with dystonia and avoid interventions that cause pain or fatigue. An experienced therapist also may be able to design devices that take advantage of sensory tricks to suppress symptoms.
Voice Therapy for Laryngeal Dystonia
Voice therapy alone is not generally successful in patients with typical abductor or adductor spasmodic dysphonia, but it can be very effective in patients with muscular tension dysphonia. The exact relationship between muscular tension dysphonia and spasmodic dysphonia remains unclear, and the two conditions may co-exist. A trained speech pathologist or otolaryngologist usually can discriminate isolated muscle tension dysphonia from spasmodic dysphonia and determine whether voice therapy is likely to be successful.
Immobilization of a dystonic limb in solid casts or splinting devices, sometimes for periods of a month or more, has been advocated as treatment for dystonia.Unfortunately, the extent and duration of immobilization recommended for success are impractical for many patients. Additionally, therapeutic responses are inconsistent, and some patients may get worse. Immobilization therapy should not be recommended until further studies of its efficacy and safety are available.
H. A. Jinnah, MD PhD
Emory University School of Medicine
Atlanta, GA 30307