Botulinum toxin type A has long and well established itself in the treatment of various clinical conditions when it is necessary to correct local muscle hyperactivity.
However, scientists and practitioners continue to actively discuss the possibility of drug diffusion after injection and the likelihood of side effects from the procedure.
IPSEN specialists shared with readers of estet-portal.com the results of clinical studies conducted on the basis of neurological departments at the University of Newcastle (Britain), Mestre Hospital (Italy), Diagnostic Clinic Wiesbaden (Germany).
How can diffusion occur with botulinum toxin injection
In most preparations, botulinum toxin type A (BoNT-A) is in combination with stabilizing proteins. Upon injection, the BoNT-A complex enters the slightly alkaline muscle microenvironment (pH approximately 7.4) and the stabilizing proteins are released (dissociated) in less than a minute, releasing the neurotoxin core.
Its molecules tend to reach SV2 receptors and be absorbed by nerve endings.
Diffusion – it is the passive movement of BNT-A away from the injection site. As the neurotoxin binds to receptors at the neuromuscular junction, any excess that has not bound diffuses further in search of new receptors.
Complications after botulinum toxin injections: treatment and prevention
This passive movement continues until all neurotoxin molecules are bound. This determines the size of the post-injection denervation field, which can be affected, for example, by the concentration of BoHT-A at the injection site – more BoNT-A molecules will diffuse further.
Different BNT-A preparations diffuse in the same way. If all muscle receptors are saturated, the additional dose will not enhance the clinical effect, but is more likely to diffuse further into adjacent muscles, thereby causing side effects.
In practice, the balance between the effect and side effects of BoNT-A is extremely important and requires ongoing clinical evaluation.
When, for example, we inject into the muscles of the neck in the treatment of muscular dystonia, our goal is to relax the muscles involved in the dystonic process without relaxing the muscles involved in swallowing. Therefore, it is very important to adapt the dose of BoNT-A in relation to the target receptors in order to improve the effects of the treatment.
How to choose the dosage of the drug for injections of botulinum toxin
Experts at IPSEN note that dosage is the main variable as the effect of the toxin depends on the dose administered. Larger muscles need a higher dose and vice versa.
While clinical guidelines developed around dosing protocols are useful even for the less experienced clinician performing the procedure, clinical judgment should still be used in selecting the correct dose.
The response to the same dose of botulinum toxin varies greatly from patient to patient, and even within the same patient after a series of injections.
Therefore, it would be reasonable to start with medium doses, according to the guidelines for a particular muscle, and then adjust the appropriate dose, depending on the clinical response.
In clinical practice, when the reaction to BoNT-A injection is negligible, a higher dose is usually used. This approach does not necessarily improve the clinical effect, but, more importantly, it may cause excessive diffusion of the drug into adjacent muscles, which can lead to side effects.
How to achieve the desired effect using botulinum toxin injections
Clinical common sense should be used at all times when performing procedures using botulinum toxin preparations.
• Injection Volume: A larger infusion volume will cause more spread of the toxin and therefore more diffusion. When injecting into relatively large muscles, it makes sense to inject a large volume, as it is likely to spread more efficiently throughout the muscle without the need for multiple injections.
Conversely, in smaller muscles, such as the facial or small muscles of the arm or foot, injections of large volumes can not only cause pain, but also lead to undesirable spread to adjacent muscles.
• Number of injection points: for the patient, of course, fewer injections are preferable. Despite this, it is clear that large muscles will require several injections (up to 4 per muscle) in order for the toxin to diffuse adequately and relax the whole, not part of the muscle.
• Precise localization of the muscle: In standard clinical practice, a thorough knowledge of muscle anatomy is essential for correct injection.
Experience with injection dose is the best way to "focus" the effect of the injection for the benefit of the patient.
What parameters should be taken into account to optimize the results
Procedures using BNT-A preparations require the clinician to have a complete understanding of the preparation and a good knowledge of anatomy and physiology. They are needed to deliver the optimal dose and volume to the desired muscle.
• Optimal dose and volume. The dose of BNT-A is selected in accordance with the indication and the desired effect (the degree of reduction in muscle tone and preservation of functionality). The volume must also be adapted to the indication, type of injection (subcutaneous or intramuscular) and muscle mass. Preferring a larger volume (less concentrated solution) is not justified and may result in effects beyond the desired muscle.
• Number of injections. The number of injections per muscle depends on the indication, the skill of the practitioner and the patient. Generally, the more precise the injection into the muscle, the fewer injections are required.
• Helper methods. In neurological practice, when a doctor chooses complex injection protocols and hard-to-reach muscles, it is recommended to use ultrasound, EMG, and electrical stimulation. These techniques allow for more precise, targeted injections into non-palpable muscles, which greatly improves response and reduces the incidence of side effects.
Thus, the success of the use of BNT-A is still largely determined by the knowledge of drugs and clinical experience. Correctly selected dose and precise targeted administration optimize the binding of neurotoxin to receptors and are important factors for achieving a good clinical result. At the same time, dilution volumes and the number of injections are less important.
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