What is Botulinum Toxin A (BtA)? And how does it work?
Botulinum toxin A (BtA) is a chemical that interacts with the nervous system to reversibly block muscle contraction. Nerves send messages along their lengths (neurons) using electrical impulses called action potentials. When these impulses reach the end of a neuron (pre-synaptic terminal), chemicals such as acetylcholine may be released outside of the terminal into the synaptic cleft. Another neuron (Post-synaptic neuron) has receptors that get excited by the chemicals released by its neighboring neuron and begin to create action potentials itself. These impulses will then flow down the newly excited neuron towards another synapse which innervates a muscle and causes that muscle to contract. Botulinum toxin A interferes with the pre-synaptic terminals that release acetylcholine thereby blocking muscle activity downstream. This is referred to as chemical denervation or neuromuscular blockade. The figure below displays how BtA functions.
Injections of BtA diffuse between 2 and 3cm around the injection site of a targeted muscle. The chemical does not interfere with peripheral nerves, thus perception should not be affected by treatment.
There are two commercially produced brands of BtA. Botox has been approved for use globally whereas Dysport has not been approved in the United States of America. Unfortunately the two types are not identical and thus when comparing dosage recommendations of Botox to that of Dysport or vice versa, the units, given as “U,” are not interchangeable. In fact, Dysport has 1/3 to 1/5 the potency of Botox.
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Are BtA treatments safe for children? Are there any side effects?
There have been many documented treatments of CP using BtA, a majority of which claim the therapy to be safe. No articles have been published in which BtA treatment caused the direct death of a patient, however mild side effects have been reported. The type and location of adverse events attributed to BtA injection may depend on where the injections took place. Examples include: crying and discomfort during injection, soreness at the injection site, generalized or localized transient weakness of muscles, transient unwillingness to walk, headaches, fatigue, unsteadiness, decreased grip strength, urinary incontinence, somnolence, fever, skin irritation, flu-like symptoms, irritability, transient autonomic nervous system dysfunction (non-conscious body regulation), falling, leg cramps, muscle atrophy.
To put these effects into perspective we may look at BtA administration to stem drooling problems. The side effects associated with BtA are less frequent and severe as those associated with another drug, scopolamine, which is issued for the same purpose. This is a clear advantage as both treatments have been shown (with limited evidence) to improve drooling an equal amount.
To manage pain during the injection process, doctors may choose from several options guided by their personal inclinations and patient preferences. These options include the use of general anesthesia, oral narcoleptics, topical thermal techniques, topical anesthetics, or no analgesics. In general, when clinicians are using electromyographic (EMG) guidance to make accurate injections into muscle bodies, young patients will be sedated unless exceptionally cooperative.
The dose administered to children may also affect whether patients suffer from side effects or not. Doses are measured by Units per kilogram bodyweight (U/kg BW). The estimated lethal dose in humans based on primate testing is 39U Botox/kg BW, however since the early 1990s doses have been increased steadily so it is normal to see injection sessions where children receive over 20U Botox/kg BW. This increase in dosage may be due to more muscles being targeted during treatments per session than were done historically. Dosage increases may be correlated to increased incidences of side effects. Adverse effects were reported 5 times more frequently in children receiving total doses of Dysport over 1000U compared to children receiving under 250U total according to one study.
Finally, medical histories must be investigated before BtA can be considered. Fixed contractures, allergies to the materials, excessive spasticity, neuromuscular diseases, or the use of other drugs already affecting the neuromuscular system have all been documented as being reasons for abstaining from BtA treatments.
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Why use BtA treatment? And does it work?
Botulinum toxin A injections have been administered for a plethora of reasons associated with CP. These include reducing drooling (sialorrhea), improving equinus foot deformity, substituting for casts, and improving range of motion, walking velocity and energy expenditure, joint range of movement, muscle tone, gross and fine motor skills, and reducing post-operative pain. The effectiveness of these interventions, especially when compared to the effects of other types of treatment varies depending on what is being monitored. This variability requires specific goals of treatment to be identified and thus no blanket statement such as “BtA treatment is effective” can be offered. Several treatment goals are discussed in the “In-Depth Review” section on BtA. Please refer there for more information.
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Is BtA treatment costly? And who administers the treatment?
Before considering the treatment procedures and the medical doctors who have to administer BtA injections, it should be noted that a vial containing 100U of BtA can be as expensive as US $250 (price taken from a 1998 paper). Injections are administered by trained clinicians. Procedures may include local or general anesthetics, electromyography, and assistants and thus increase the costs of treatment.
A study assessing the economics and efficacy of treatment of calf spasticity with BtA compared to casting found BtA treatment to be more expensive by an additional 20-25% (Houltram et al. 2001). The authors conclude that BtA treatment is cost-effective and safe and is thus worthy of consideration.
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Are any additional resources available offering information on BtA treatments for CP?
The Cochrane Collaboration, a respected systematic review service, has provided two reviews focusing on either upper or lower limb treatment with BtA. Abstracts can be accessed and full versions can be purchased at www.thecochranelibrary.com . The reviews include:
Wasiak, J., Hoare, B., and M. Wallen. Botulinum toxin A as an adjunct to treatment in the management of the upper limb in children with spastic cerebral palsy (Review). The Cochrane Library (2005) Issue 4.
Ade-Hall, R.A. and A.P. Moore. Botulinum toxin type A in the treatment of lower limb spasticity in cerebral palsy (Review). The Cochrane Library (2005) Issue 4.
