Spasticity Associated with Cerebral Palsy in Children

Abstract

Botulinum A toxin produces selective and reversible chemodenervation that can be employed to balance muscle forces across joints in children with cerebral palsy (CP). Currently, there are two commercially available botulinum A toxin formulations (BOTOX) and Dysport). The amount of botulinum A toxin required depends upon the number of muscles that are targeted, and the size of the patient. In order to achieve adequate chemodenervation with botulinum A toxin, the following conditions must be met: (i) a sufficient number of units of toxin must be injected in order to neutralize neuromuscular junction (NMJ) activity; (ii) an appropriate drug volume is required in order to optimize the delivery of the toxin to the NMJs; and (iii) localization of the injecting needle through the fascia of the target muscle is necessary. Localization of the injection may be facilitated by active electromyography, ultrasonography, palpation of the muscle belly, and/or use of anatomic landmarks. Botulinum A toxin injections are indicated for use in pediatric patients with CP to: (i) improve motor function by balancing muscle forces across joints; (ii) improve health-related quality of life by decreasing spasticity and/or decreasing caregiver burden; (iii) decrease pain from spasticity; (iv) enhance self-esteem by diminishing inappropriate motor responses; and (v) provide a presurgical diagnostic tool. Following intramuscular injections of botulinum A toxin, short-term benefits of reduced spasticity are observed in approximately 70-82% of children. The intermediate term (1-2 years) efficacy rate is approximately 50%. The most common deformity treated with toxin injections in pediatric patients with CP is equinus foot deformity. However, efficacy of toxin injections for the management of crouched gait, pelvic flexion contracture, cervical spasticity, seating difficulties, and upper extremity deformity also has been documented. In addition, toxin injections have been shown to manage painful muscle spasticity associated with surgery or application of casts and painful cervical spasticity with or without dystonia. Toxin injections can also be used as a diagnostic tool to determine the appropriateness of other interventions by observing the muscle response to the injection in order to gain additional information for the development of a treatment plan. Botulinum A toxin, when used in appropriate doses, is well tolerated.

Dose‐ and volume dependent‐response to intramuscular injection of botulinum neurotoxin‐A optimizes muscle force decrement in mice

“…[2][3][4][5][6] Although many clinicians administer BoNTA injections, little consensus exists regarding the appropriate injection dose and volume. 2,7,8 Clinical preparations for BoNTA intramuscular injection are most commonly in concentrations of 50 and 100 U/ml with an injection volume of 2-4 ml, but may be as concentrated as 500 U/ml and injected in volumes of up to 8 ml. 2,7,9 Furthermore, the dose administered to reach clinical goals in muscle tone is highly variable.…”

“…2,7,9 Furthermore, the dose administered to reach clinical goals in muscle tone is highly variable. [7][8][9] Endocytotic uptake of BoNTA by the distal neuron results in a conformational change in the light chain with subsequent proteolytic cleavage of the vesicle docking protein, SNAP-25. 1,10 Cleavage of SNAP-25 prevents vesicular release of acetylcholine into the synaptic cleft of the neuromuscular junction causing muscle paralysis.…”

“…[14][15][16][17] Muscle recover occurs within 3-6 months in humans which enables BoNTA to be a valuable tool in reversibly altering muscle tone. 8,18 Literature to date offers little information on a systematic approach to the effects of dose and volume on the neuromuscular physiology following intramuscular administration of the toxin. [6][7][8][9] Detailed evaluation of BoNTA injections and neuromuscular physiology with an animal model would provide valuable insight into dosing techniques for the clinical administration of BoNTA.…”

“…8,18 Literature to date offers little information on a systematic approach to the effects of dose and volume on the neuromuscular physiology following intramuscular administration of the toxin. [6][7][8][9] Detailed evaluation of BoNTA injections and neuromuscular physiology with an animal model would provide valuable insight into dosing techniques for the clinical administration of BoNTA. A murine model was used to test the hypothesis that the degree of muscle inhibition can be optimized by delivering the appropriate dose and volume to the targeted muscle through alteration of the independent variables, BoNTA dose and injection volume, as assessed by outcome measures of electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass.…”

Botulinum Toxin Use as an Adjunctive Modality in a Patient with Multiple Flexor Tendon Ruptures

“…This may be especially evident in children, noncompliant patients, and patients with muscle spasms. Most literature concerning the use of botulinum toxin in the management of muscle spasms has been associated with cerebral palsy and hemifacial spasm [2][3][4]7]. However, there appears to be a patient subset in which adjunctive modalities, such as botulinum toxin, are beneficial for the treatment of their upper extremity condition [1,5,6].…”