Over 25 Years of Pediatric Botulinum Toxin Treatments: What Have We Learned from Injection Techniques, Doses, Dilutions, and Recovery of Repeated Injections?

Abstract

<jats:p>Botulinum toxin type A (BTXA) has been used for over 25 years in the management of pediatric lower and upper limb hypertonia, with the first reports in 1993. The most common indication is the injection of the triceps surae muscle for the correction of spastic equinus gait in children with cerebral palsy. The upper limb injection goals include improvements in function, better positioning of the arm, and facilitating the ease of care. Neurotoxin type A is the most widely used serotype in the pediatric population. After being injected into muscle, the release of acetylcholine at cholinergic nerve endings is blocked, and a temporary denervation and atrophy ensues. Targeting the correct muscle close to the neuromuscular junctions is considered essential and localization techniques have developed over time. However, each technique has its own limitations. The role of BTXA is flexible, but limited by the temporary mode of action as a focal spasticity treatment and the restrictions on the total dose deliverable per visit. As a mode of treatment, repeated BTXA injections are needed. This literature reviewed BTXA injection techniques, doses and dilutions, the recovery of muscles and the impact of repeated injections, with a focus on the pediatric population. Suggestions for future studies are also discussed.</jats:p>

Quantification and Monitoring of the Effect of Botulinum Toxin A on Paretic Calf Muscles of Children With Cerebral Palsy With MRI: A Preliminary Study

“…Based on animal and human data and clinical experience, BTX diffusion is likely to occur up to a distance of 4.5-5 cm from the injection site (to some extent, even into adjacent muscles). This depends on the dosage and volume injected (31) and on the muscle fiber structure and presence of spasticity (23). The hyperintense region's extent in our study in CP patients with muscle contractures was smaller than this maximum distance.…”

“…The method may be applied in future studies with other BTX treatment protocols to quantify BTX-induced effects on muscle tissue and to investigate the spatial BTX distribution. A spatially limited extent of the BTX-induced effect, i.e., if the spread of BTX does not fully cover the zone of the motor end plates in the muscle (31), may help to explain a limited treatment effect on the gait and on the clinical scores of CP patients. Based on the MRI results, a revision of the applied treatment protocol regarding dose, dilution, or injections sites may be considered.…”

“…The recommended total dose was reduced in the last years after serious side effects, especially in severely affected CP patients (2,15). As discussed in a recent review (31), in relatively large muscles like leg muscles, it may be beneficial to use higher doses or higher dilutions (if a dose increase is not beneficial) and divide the dose over multiple injection sites.…”

Botulinum toxin injection for Cockayne syndrome with muscle spasticity over bilateral lower limbs: A case report

“…BoNT-A can block acetylcholine release at cholinergic nerve endings of skeletal muscle. It results in temporary chemical denervation and reversible paralysis of striated muscles for a period of two to six months[ 14 , 15 ]. BoNT-A has proven effective in patients with spasticity in many upper motor neuron diseases[ 5 ].…”

Botulinum Toxin: From Poison to Possible Treatment for Spasticity in Spinal Cord Injury

“…If after 3 months from the previous injection, there is a better functional situation than the one before the injection, it shows that BoNT has been effective, and, therefore, we can continue with this treatment. It has been shown that over the years, the effectiveness of repeated toxin injections is not usually lost; the main studies have been done in dystonia, but it has also been evidenced in spasticity, even in SCI [ 46 , 49 , 74 ].…”