Summary: Botulinum toxin, a muscle-nerve paralyzing bacterial toxin, is being used for controlled partial muscle paralysis in regulated doses to relax spastic muscles to improve function in Cerebral Palsy. However, the development of anti-toxin antibodies by the body, and regeneration of destroyed nerves within 2 to 4 months in most cases, limits its usefulness. Moreover, its sudden freedom from spasticity takes away the motivation for continued intensive OT/PT, and often results in the child going back to square one after a few months. In addition, the US FDA has cautioned that the higher doses used for CP spasticity in children have caused at least 16 fatal outcomes due to leakage of the toxin from the muscles into systemic circulation. Last updated February 12, 2008
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Botulinum is a bacterial toxin produced by a bacteria (Clostridium botulinum), that causes the most severe form of food poisoning. The disease is called Botulism, the potentially deadly food poisoning characterized by muscle paralysis.
In a normal muscle, the place where a nerve ends to give the command to the muscle is called the muscle end plate. There is a gap between the nerve ending and the muscle surface. From the stimulated nerve, a chemical called Acetyl choline is released that bridges the gap and stimulates the muscle to cause it to contract.
Botulinum is a toxin that destroys the muscle end-plates capability to respond to the chemical secreted from the nerve ending. It takes 2 to 4 months for the nerve to regenerate a new muscle end plate. Till that time, the affected muscle remains paralyzed. However, small doses of Botulinum toxin injections can have a paradoxical benefit for some stroke survivors and patients with spasticity due to CP. The toxin can reduce the leg muscle spasticity that hampers their ability to walk, run and do active work to a variable extent.
Phenol (Carbolic Acid) may be injected onto the nerve carrying the exaggerated nerve signals to produce a similar kind of controlled time-bound muscle paralysis of the hyper-spastic muscle. However, it is not recommended for more than one or two shots for fear of scar formation on the nerve, whereas, the newer Botulinum toxins may be re-used quite a number of times.
In a new report, German researchers detail further progress in using the experimental treatment to control abnormal muscle tone and activity in stroke patients. The study included two women and 10 men, average age 56. The scientists injected "Botulinum toxin A" directly into the patients' spastic muscles in the lower leg that control ankle movement. After four months, nine of the 12 had less muscle spasticity and were able to walk better and on average 34 percent faster than before, the Free University of Berlin researchers report. They saw a particularly prominent reduction in premature activity of the "plantar flexors," muscles that flex the foot. The other three treated patients failed to show improvement. "This study further supports the beneficial effects of Botulinum toxin on the treatment of lower limb extensor spasticity," the authors conclude in the American Heart Association journal Stroke.
All this must be taken with a pinch of salt. The toxin is a foreign substance, hence the body sooner or later develops antibodies to it that can destroy it as soon as it injected. One course of injection gives 2 to 4 months of benefit. But repeated injections fail to work after some time because of antibody development. Therefore, Botulinum toxin injection only gives a short term benefit, and is not likely to give permanent relief in cases of CP with spasticity, unless sophisticated chemical modifications to its structure take away its antibody-generating potential. Till that time, chair-bound spastics attending research institutions may hope for limited relief from complete wheel chair existence.
However, newer formulations of Botox ® claim to have the anti-toxin generating protein content of Botox, down from 12 parts to 4 parts, reducing its antigenicity so that many repeat injections may be possible.
Why Does The Cost Of Botox Treatment Vary So Much ($500-800 abroad, and more than $365 even in India)?
Giving botulinum toxin is not just like giving an aspirin tablet. It is an extremely dangerous drug, one teaspoonful of which can kill a small city. When used by trained hands in extremely small doses injected into spastic muscles, the doctor tries to induce a controlled partial flaccid paralysis that can just about overcome the spasticity, leaving the patient with (hopefully) a more supple body to give voluntary motor commands to. With growing interest and research, an experienced doctor can provide many months (at present, which may extend to years in future if we can overcome the problem of antibody development, which Botox® claims to have done to a large extent) of useful mobile life to the Spastic.
However, this regime is definitely not a one man show. It needs a pediatrician in overall in charge, who understands CP and its problems, a person trained in Electro-myography techniques (EMG) to assess muscle function with an instrument similar to one used to test the heart (ECG or EKG), the degree of spasticity and the number of muscles involved, as well as the degree of internal scissor like deformity that has already taken place, determine the dose, duration of therapy, and the possible outcome level. The team also includes long term follow up by a neurologist experienced in CP, Ear-Nose-Throat Specialist, and highly trained Pediatric Therapist, Special Educator, Occupational Therapist, Speech Therapist, etc. and motivated nursing staff well versed in the management of advanced CP cases.
In India, Botox is available at around $365 per vial, with a typical infant needing one vial. The other therapists and specialists are available at different institutions and clinics.
These multiple specialists do not come cheap. Now you get the picture .
Initially, we did give about a dozen children Botox or Phenol Nerve Block. The results were miraculous. On prolonged follow up, we found that all those children and their parents / guardians thereafter lost their motivation for continued intensive OT/PT. After a few months, when the effects of the injection began to wear off with regeneration of the nerve pathway, the opposing "normal" muscles were not ready to take on the spastic muscles. Final Result: Back to square one, with six valuable months lost for intensive OT/PT to give the child a permanent rehabilitation result.
American Academy of Orthopaedic Surgeons ; 1992 Annual Meeting - Scientific Program [Botulinum Toxin-A in the Management of Children with Cerebral Palsy]; Paper No. 30 ; Thursday, February 20, 1992 ; 1:46 PM ; & also Martindale's Extra Pharmacopoeia
Handouts supplied by M/s. Allergan, agents for Botox Type A, in India.
According to Aidan Cosgrove, MB, and H. Kerr Graham, MD, Belfast, Ireland, (29 January, 1997) spastic muscle groups in 33 children with cerebral palsy were injected with Botulinum toxin-A. There have been no systemic side effects and all but one patient had a reduction in tone. The reduction in tone occurred within three days and persisted for two to five months. There were significant improvements in the subjects' ambulatory status and in their gait analysis results. In some cases the functional gains persisted after the tone-reducing effects of the toxin had worn off. Injection of spastic muscles with Botulinum toxin-A reduces tone and may reduce the incidence of fixed contractures in this condition.
However, the NIH, USA cautions that though Botulinum toxin has shown great promise in relieving persistent spasticity due to stroke or cerebral palsy, its long term safety and efficacy are still under investigation, more so in children, where its long term effects are still to be established.
The drug is available as Botox in Australia, Canada, France, Germany, Sweden, UK and USA, and as another different yet functionally similar drug called Dysport, in France, UK and USA. However, Dysport manufacturers do not approve of their formulation for use in children / CP. Another brand is Myobloc, available in USA and some other countries. Generic Botulinum toxin is also being distributed by some Chinese firms at very low cost: we do not have data on its purity, safety and efficacy standards.
Botulinum toxin type A is available at a cost of about Indian Rs.15000/- per vial. A typical child with spastic calf muscles would need about 1 vial at a sitting, usually to correct equines deformity of foot or severe scissoring, to be repeated months later when he relapses. An inferior but cheap alternative is Phenol Nerve Block (about $17 per vial), which is still used in developing countries due to economic considerations. It gives temporary relief of spasticity but may cause paraesthesias and muscle damage if used repeatedly.
A few centres in India are using these injections now and then for CP but their long term benefits are open to discussion.
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