RESEARCH ON BOTULINUM TOXIN IN CP
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Cerebral palsy may cause spasticity of muscles, especially of thighs, arms, etc.. Botulinum toxin injections have been given in multiple injections into the belly of the spastic muscles to induce calculated partial paralysis of the spastic muscles to reduce spasticity and restore a more normal degree of function. A typical case may require one or two vials of the drug at a single sitting. Effects are see very fast and may last for 2 to 6 months or more. For prolonged benefit, it is mandatory to continue intensive OT/PT for long term, failing which the condition relapses to pre-treatment levels. Last updated January 21, 2007
Some published papers: 1993 up to 1999, on use of Botulinum Toxin in Cerebral Palsy
Lagueny et al, [writing in Neurophysiol Clin 1996; 26(4): 216-26] explained the mode of action of botulinum toxin in CP. They wrote that Botulinum toxin, the most potent of the neurotoxins, produces paralysis by blocking presynaptic release of the neurotransmitter (acetylcholine) at the neuromuscular junction, with reversible chemical denervation of the muscle fibre, thereby inducing partial paralysis and atrophy. Because chemical denervation is reversible, botulinum toxin has temporary effects, the muscle being progressively reinnervated by nerve sproutings. Type A botulinum toxin (Bix-A) is available under two dosage forms: Botox and Dysport. In regard to spasticity associated with cerebral palsy, Btx-A is a promising treatment requiring a multidisciplinary approach. Btx-A injections lead to effective reduction of muscle hyperactivity with minor side effects. They are painless, even though electromyographic guidance may be required for the injection of deep muscles. However, the production of antibodies to Btx-A may compromise the effect of long-term treatment.
Ed.: The authors clearly mention the efficacy, though of a temporary nature, of Botulinum toxin, in the management of spasticity associated with CP. The temporary nature of the relief is due both to the formation of toxin destroying antibodies as well as regenerartion of the destroyed muscle nervce fibres within 2 to 4 months. Some studies do have reports of longer relief, but they are anecdotal cases, and do not imply majority.
Koman et al, [writing in B J Pediatr Orthop 1993 Jul-Aug; 13(4):489-95] mention that they tried intramuscularly injected botulinum-A toxin (Botox) to produce neuromuscular blockade in 27 pediatric patients. Each patient had "dynamic deformities" unresponsive to other treatment, and operation was the only other realistic alternative. The dose of Botox was calculated on a unit/ body weight basis. In ambulatory patients, a physician's rating scale assessed clinical changes in gait. Reduction in spasticity became apparent in 12-72 h after injection; the effect of Botox after target threshold was reached lasted 3-6 months. No major side effects occurred.
Ed.: The authors think that Botox may prove a useful adjuvant in conservative management of the spasticity of cerebral palsy, and may allow delay of surgical intervention until the child is older and at less risk of possible complications, including the need for repeated surgical procedures.
Koman et al, [writing in J Pediatr Orthop 1994 May; 14(3): 299-303] in a subsequent work, carried out a trial to evaluate the efficacy of local intramuscular injections of botulinum-A toxin in the management of dynamic equinus deformity associated with cerebral palsy. They used a randomized (In such studies, a random number chart is used to determine which child gets what therapy.), double-blind placebo-controlled study (In such studies, there are two batches of drugs, one with actual botulinum toxin, and the other a matching form with inert substances like saline. Neither patient nor trial doctor is informed which ampoule contains which batch, so that patient and observer bias can be eliminated scientifically.) was undertaken. When evaluated using a Physician Rating Scale, 83% (five of six) of patients receiving toxin showed improvement, versus 33% (two of six) receiving placebo. There were no major complications.
Ed.: This is a more detailed abstract which suggests that the drug appears to be safe and effective in children, and merits further prospective study.
Denislic et al [writing in Neuropediatrics 1995 Oct; 26(5): 249-52] reported their findings on the use of botulinum toxin A treatment in 13 children with cerebral palsy. All patients except one exhibited dynamic deformities in one hand or foot and changes in muscle tone of corticospinal and extrapyramidal origin. The primary purpose of the treatment was to improve the impaired skilled movements, which resulted from dystonic limb posture and were the most disabling symptoms in the group studied. The study showed that the botulinum toxin treatment produced a significant improvement in functional disability in terms of amelioration of skilled hand movements and foot posture (p < 0.01). The injections took effect a few days after dystonic muscle infiltration, and the mean duration of improvement was 3.1 months (2.0-4.0 months). Side effects were negligible and transient; transitory muscle weakness was the most frequent.
The authors were of the opinion that Botulinum toxin A provides a safe and effective adjuvant treatment of dystonic skilled movements and gait disorders in children with cerebral palsy.
Ed.: Please note the rapid but low duration of benefit provided: 2.0 to 4.0 months.
Gooch et al [writing in Arch Phys Med Rehabil 1996 May; 77(5): 508-11] describe the use of botulinum toxin for spasticity or athetosis management in three children with cerebral palsy. Two of these children had severe spasticity or athetosis that was unresponsive to other forms of treatment. The injection of botulinum toxin decreased pain and improved ease of care in these two children. Another child with left hemiparetic cerebral palsy underwent injection of botulinum toxin into upper and lower limb muscles to improve function
Ed.: This is a limited experience study, but suggestive of the usefulness of the toxin.
Cosgrove et al, [writing in Dev Med Child Neurol 1994 May; 36(5): 386-96] evaluated the role of intramuscular botulinum toxin A in the treatment of 26 children with cerebral palsy and dynamic contracture of lower-limb muscles interfering with positioning or walking. Spastic target muscles were identified by clinical examination and, in ambulant children, by gait analysis. Between 50 and 320 units of botulinum toxin were injected into each muscle group to a total dose of 100 to 400 units per child. The effects of injection were monitored by repeated clinical examination and gait analysis. There were no clinically detectable systemic side-effects, and all but one patient had a reduction in tone, which occurred within three days and persisted for two to four months. There were significant improvements in ambulatory status and in sagittal-plane kinematics. In some cases these gains persisted after the tone-reducing effects of the toxin had worn off.
Ed.: This study gives a more specific guideline on the dose of Botulinum toxin required. This study also repeats the caution that the effects of the toxin, which appear fast, last for two to four months only.
García Ruiz PJ
García Ruiz et al, [writing in Neurologia 1996 Jan; 11(1):34-6] evaluated the safety and efficacy of Botulinum- A toxin BTX) in patients with equinus deformity associated with cerebral palsy (CP). They prescribed BTX to six patients (all of whom had previously participated in a multicenter, randomized, double blind study of the same drug); treatment continued for at least 15 months. Four children showed striking improvement, being converted from toe-toe to consistent or occasional heel-toe gait. No side effects were observed.
Ed.: This study reinforces the efficacy and safety of the toxin in CP.
Corry et al, [writing in Dev Med Child Neurol 1997 Mar; 39(3): 185-93] carried out a randomised, double-blind (saline as placebo) study on the effects of intramuscular injection of botulinum toxin type A (BtA) into the upper in 14 patients with cerebral palsy. Their mean age was 9 years. Range of movement and function were assessed before injection and at 2 and 12 weeks after injection. BtA injection significantly increased maximum active elbow and thumb extension and significantly reduced tone at wrist and elbow. The hand grasp-and-release score improved, representing a modest functional change, but fine motor function, assessed by the ability to pick up coins, did not improve and in some cases deteriorated temporarily. The most notable subjective change was the cosmetic benefit of reduced involuntary elbow flexion. The tone-reducing effect of BtA was clinically detectable in comparison with the placebo and patients and parents perceived the change as beneficial.
Ed.: This small study shows the areas where the toxin is useful and where it is of limited efficacy. Hence, it should be used in carefully selected patients, rather than indiscriminately.
Calderon Gonzalez R
Calderon Gonzalez etal, [writing in Pediatr Neurol 1994 Jun; 10(4):284-8] studied the efficacy of local injection of botulinum toxin A in selected skeletal muscles to relieve muscle hypertonia and muscle contracture, and increase range of motion in 15 children (mean age: 6 years, 8 months) with cerebral in an open ABA (baseline-treatment-posttreatment phase) type of study. The first 6 months were the baseline phase, the day of injection the treatment phase, and the next 6 months the posttreatment phase. The patients acted as their own controls. All had limb deformities associated with non-fixed joint contractures that had not responded to physical therapy.
Clinical assessment of passive and active muscle tone was performed using a modified Ashworth scale. The range of motion to passive movement was measured with a manual goniometer. Botulinum toxin was injected directly into the muscle at several sites. The postinjection scores of muscle hypertonia were significantly lower (P < .01) and the range-of-motion values demonstrated a significant increase (P < .001). Functional improvement was measured by decreased scissoring on standing in all 6 children with adductor muscles injected; all 6 children with knee flexor muscles injected were able to straighten the knees. The 3 children with injected gastrocnemius muscles were able to achieve heel-strike while bare-footed.
Ed.: This fairly detailed controlled study shows the usefulness of the drug in improving muscle function in CP.
Wall at al, [writing in Br J Plast Surg 1993 Dec; 46(8): 703-6] reviewed some of the work done with botulinum toxin in CP. They commented that the modality was simple, safe and effective over the period reported (229 days). The benefit was sustained beyond the period of muscle paresis and ongoing long-term follow-up would document the need for, and timing of, reinjection.
Ed.: This is a review article in a polular medical journal, for the academically minded to follow up in a local medical library.
Denislic et al, [writing in Ann N Y Acad Sci 1994 Mar; 710(): 76-87] reviewed botulinum toxin treatment of 97 patients: 36 had blepharospasm, 41 had torticollis, and 20 had diverse movement disorders. Patients with blepharospasm and torticollis improved markedly after botulinum toxin injections. The most common side effect in BS patients was ptosis (44.4%); in TC patients, it was dysphagia (29.3%). The mean duration of the improvement in both groups was 3.4 months. Very promising results were obtained also in the heterogeneous group including patients with other focal dystonias and cerebral palsy.
On the basis of these results, the authors concluded that BTA injections must now be considered the mainstay of therapy for focal dystonias and other involuntary movement disorders.
Ed.: Though this study shows improvement in spastic conditions in a number of diverse disorders, it is better to keep reminding ourselves that CP is a permanent damage, and not a temporary condition. Botulinum toxin provides temporary relief only.
These abstracts are modified and simplified versions of Medline data, for non-commercial use only. They are only meant to familiarize sufferers and caretakers to bring them up to date on what is being tried out for their benefit.
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