Effect of Volume and Concentration on the Diffusion of Botulinum Exotoxin A

Hsu, Te‐Shao; Dover, Jeffrey S.; Arndt, Kenneth A.

doi:10.1001/archderm.140.11.1351

Cited by 197 publications

(142 citation statements)

References 7 publications

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“…The toxin immediately diffuses to the surrounding tissues after injection, but the degree of diffusion may be affected by volume, injection site, and speed of injection in addition to the serotype and preparation of botulinum toxin. [6][7][8][24][25][26] Two previous studies noted better efficacy by increasing injection volume but few injection volumes were assessed. 20,26 While the aforementioned studies do offer promising insight into the most effective volume techniques, previous studies have noted limits on the effectiveness of high dilution volumes.…”

Section: Discussionmentioning

confidence: 99%

“…[6][7][8][24][25][26] Two previous studies noted better efficacy by increasing injection volume but few injection volumes were assessed. 20,26 While the aforementioned studies do offer promising insight into the most effective volume techniques, previous studies have noted limits on the effectiveness of high dilution volumes. A fourfold dilution of botulinum toxin A (100 U/ml) did not produce statistically significant differences in the degree of paralysis in children as judged by CMAP, static muscle range and the modified Ashworth scale.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Stone

Callahan

et al. 2011

Journal Orthopaedic Research

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Botulinum neurotoxin-A (BoNTA) is a potent neurotoxin used to alter muscle tone to manage spasticity and to provide tendon bioprotection; however, the appropriate dose and injection volume to administer is not defined. Male mice (n ¼ 120) received BoNTA injections into one gastrocnemius with either a constant volume (10 ml) with a variable dose (1, 3, 6 U/kg) or a constant dose (3 U/kg) in a variable volume (2.5, 5, 10, 20, 30 ml). Electromyographic (EMG) examination, muscle force generation (MFG), and wet muscle mass were measured in the ipsilateral and contralateral limbs at 1, 2, 4, or 12 weeks post-injection. MFG and EMG responses decreased to approximately 40% of contralateral after a 1 U/kg injection and 0% of contralateral by 3 and 6 U/kg injection at 1 week after injection. Neuromuscular blockade was greatest with a 10 ml injection volume. MFG, EMG examination, and wet muscle mass reached contralateral values 12 weeks after injection for all injection doses and volumes tested. Effective injection doses and volumes were identified for producing full and partial neuromuscular blockade in the mouse gastrocnemius. These findings have important clinical implications in the intramuscular administration of BoNTA to manage muscle tone. ß

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Stone

Callahan

et al. 2011

Journal Orthopaedic Research

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“…The phenomenon of BoNT diffusion has been considered in humans [12][13][14][15] and animals using both direct and indirect methods, 3,21,28 which included elec- trophysiological assessment of endplate activity, histological determination of glycogen depleted muscle, or of the acetylcholine esterase staining. 5,6,10,12,25 Here, N-CAM staining was used to assess the diffusion of the biological activity of three different BoNT/A formulations from the point of injection along the mouse hindlimb.…”

Section: Discussionmentioning

confidence: 99%

Assay of diffusion of different botulinum neurotoxin type a formulations injected in the mouse leg

2009

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Botulinum neurotoxin type-A (BoNT/A) is very effective in the therapy of a wide range of human syndromes characterized by hyperactivity of peripheral cholinergic nerve terminals. Little diffusion of this toxin from the site of injection is commonly observed, but even minor changes in this property would greatly affect the validity of the treatment. Different pharmacological formulations of BoNT/A are available, and they may have different diffusion characteristics due to protein complex size, product format, and pharmacological properties. Here we assessed the extent of diffusion of three commercial preparations of BoNT/A: Botox (Allergan), Dysport (Ipsen), and Xeomin (Merz Pharmaceuticals) using a novel and highly sensitive test based on neural cell adhesion molecule (N-CAM) expression in muscle. N-CAM is a membrane glycoprotein that accumulates on muscle fibers after denervation and is not expressed in untreated adult muscle. This allows fine monitoring of the functional diffusion of this toxin, and the sensitivity of this assay is emphasized by the use of the mouse model because of the small muscle dimensions. The results presented here indicate that there is no significant difference between Botox, Dysport, and Xeomin with respect to diffusion into adjacent muscles in the mouse leg.

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“…But a volume effect on the diffusion of BoNT is reported (an increase of BoNT efficacy is highlighted by an EMG test on animals when they receive an injection with a higher volume for the same dosage. On human patients, an increased surface action of BoNT is highlighted when a higher volume is injected for the same dosage [30,31]. The dose effect on migration is uncertain and remains highly controversial [7,13].…”

Section: Discussionmentioning

confidence: 99%

Intra Detrusor Botulinum Toxin and Lower Limbs Motor Deficit: About 2 Clinical Cases

Khenioui¹,

Berre²

2016

J Clin Case Rep

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Objective: To demonstrate how a single intra detrusor botulinum toxin injection could be responsible for lower limbs proximal motor deficit.Results: Two women-37 and 38 years old-presenting with secondary progressive multiple sclerosis, having received intra detrusor botulinum toxin injections (400 BOTOX® U and 750 DYSPORT® U) due to major neurogenic detrusor over activity with high-pressure and risks of uro-nephrologic complications despite an efficient-dose anticholinergic bi-therapy (DITROPAN®/CERIS®). Few days in post-injection they present heavy tiredness, instability of the pelvis, and a major reduction of the walking distance. Those symptoms last for several months. During the emergency neurology consultation set up in the event of a new relapse, an aggravation of the paraparesis at the proximal level is observed. This deficit accounts for the realization of a corticosteroids bolus, the effectiveness of which is questioned by the patient. A cerebral and medullary MRI is performed in order to certify the appearance of new lesions. The MRI doesn't objectify any new lesions or any pathological contrast enhancement.Discussion: Ramirez-Castaneda et al. describe three means of dissemination of the BoNT: migration by systemic or neuronal transport, propagation/spread and diffusion. Conclusion:The retrograde migration of the botulinum toxin via hypo-gastric nerves seems to prevail. It could be followed by axonal anterograde transport causing a deficit on the hip flexors via the L2 nerve root.

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Effect of Volume and Concentration on the Diffusion of Botulinum Exotoxin A

Cited by 197 publications

References 7 publications

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

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

Assay of diffusion of different botulinum neurotoxin type a formulations injected in the mouse leg

Intra Detrusor Botulinum Toxin and Lower Limbs Motor Deficit: About 2 Clinical Cases

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