Botulinum Toxin in Therapy

Introduction[edit | edit source]

Botulinum toxin (BT) is a neurotoxin class of medication and is used both in the aesthetic and therapeutic spheres of medicine. Within therapeutics, it is used in both management and treatment of a variety of conditions.[1]

BT is produced from the bacteria Clostridium botulinum which is a spore-forming, gram-positive, anaerobic bacterium. While botulinum neurotoxins are grouped into seven serotypes (A-G) they are prepared in four types for practical use. [1] Type A is used in therapeutic interventions.[2]

Mechanism of action[edit | edit source]

BT acts on the presynaptic membrane by inhibiting the release of acetylcholine, the principal neurotransmitter at the neuromuscular junction. this causes paralysis of the muscle.

  • Weakness is observed in striated muscle due to the inhibition of transmission at the alpha motor neurons.[3]
  • Reflex overactivity is also decreased with inhibition at the gamma neurons in muscle spindles.[3]
  • BT has also been documented in the inhibition of acetylcholine release in all parasympathetic and cholinergic postganglionic sympathetic neurons, thus being of use in the treatment of overactive smooth muscle and glands.[3]

Peak paralysis occurs four to seven days after administration with a return to function occurring eight to twelve months after administration.[3]

Neurons affected by BT do not degenerate, but also will never recover function. The activity of the muscle is thus restored by the sprouting of nerve terminals, giving rise to new synaptic contacts.[3]

The development of neutralizing antibodies is observed in 5-15% of patients, this according to a 1997 article. New formulations of BT have recently shown less antibody formation. In addition, work into using botulinum toxin type B with those who have developed antibody formation to type A is also been undertaken.[3]

Conditions Treated[edit | edit source]

Conditions commonly treated include those of dystonia and spasticity.[6]

Examples of dystonia include: [6]

  • Cervical dystonia
  • Facial dystonia
  • Writer's cramp
  • Oromandibular dystonia
  • Arm dystonia

In addition:

  • Strabismus, migraines and even pain resulting from a neurogenic origin may also be treated with BT.
  • Intraglandular botulinum neurotoxin (BoNT) injections are used to treat hypersalivation (drooling) in neurological diseases. eg Parkinson's disease.[7]
  • Diabetic neuropathy is listed as a condition in which BT may be used.[1]

Treatment algorithms in BT administration in Spasticity and Dystonia[edit | edit source]

Treatment algorithms are determined by various factors including:[6]

  1. Target muscle dosing
  2. Total BT doses
  3. Injection intervals
  4. The type of BT drugs (with different BT drugs possessing different physical and chemical properties)
  5. Drug potency labeling
  6. BT application (this considers the volume of BT injected together with those substances which are used to dilute BT - most often NaCl/H20)
  7. Drug stability
  8. Guidance techniques. This includes palpation, EMG and ultrasound.

The principle in BT administration is to "hit the right muscle with the right dose"[6]and is described as a dosage scheme.

The right muscle is selected based on pathological positioning and movements by the patients as well as the presence of pain. It is important in this regard to distinguish pathological movement from compensatory muscle activity and protective postures[6]

The right dose is dependent on:[6]

  • Target muscle mass
  • Therapeutic window (Sensitivity of a target muscle to receive BT without functional impairment)
  • Paresis risk of adjacent muscles

While there are prescriptive amounts when considering these variables, whether to administer on the higher or lower spectrum of these recommendations further depends on:

  • Pathological muscle activity
  • The usefulness of pathological muscle activity.

In considering dosing algorithms it is important to note that dosing for spasticity is different to that for dystonia. Thus treatment goals for BT administration should be different for each. In an article written to provide clearer guidelines and consensus to dosage administration, Dressler et al (2021) noted the presence of paresis in spasticity, often not involved in dystonia. This leads to less functional improvement following BT administration.[6]

Physiotherapy Management[edit | edit source]

Physiotherapy treatment will be personalised for each patient. Goals will include maintaining and increasing range of motion, increasing strength, selectivity and function, and reducing spasticity[8]. Treatment can include passive and active stretching, strengthening exercises, functional mobility and/or gait training, and in addition some patients may require splinting or bracing [9].

For stroke patients with upper limb spasticity, constraint-induced movement therapy can be used with BT to assist with motor recovery[10].

Outcome Measures[edit | edit source]

The appropriate outcome measure should be selected depending on the patient's presentation and goals.

For example, for children with Cerebral Palsy this can include[9]:

Resources[edit | edit source]

References[edit | edit source]

  1. 1.0 1.1 1.2 Padda IS, Tadi P. Botulinum toxin. InStatPearls [Internet] 2021 Nov 25. StatPearls Publishing.
  2. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. New England Journal of Medicine. 1991 Apr 25;324(17):1186-94.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Nigam PK, Nigam A. Botulinum toxin. Indian journal of dermatology. 2010 Jan;55(1):8.
  4. Medinaz. Botulinum Toxin: Mechanism of Action. Available from: [last accessed 22/6/2023]
  5. Amerra Medical. US WorldMeds - Mechanism of Action. Available from: [last accessed 6/6/2009]
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Dressler D, Altavista MC, Altenmueller E, Bhidayasiri R, Bohlega S, Chana P, Chung TM, Colosimo C, Fheodoroff K, Garcia-Ruiz PJ, Jeon B. Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity. Journal of Neural Transmission. 2021 Mar;128:321-35. Page 3
  7. Corrêa LB, Basso MB, Sousa-Pinto B, Leal SC. Oral health effects of botulinum toxin treatment for drooling: a systematic review. Medicina Oral, Patologia Oral y Cirugia Bucal. 2021 Mar;26(2):e172.Available: (accessed 9.10.2023)
  8. Farag SM, Mohammed MO, EL-Sobky TA, ElKadery NA, ElZohiery AK. Botulinum Toxin A Injection in Treatment of Upper Limb Spasticity in Children with Cerebral Palsy: A Systematic Review of Randomized Controlled Trials. JBJS Reviews 8(3):p e0119, March 2020
  9. 9.0 9.1 Fonseca PR Jr, Calhes Franco de Moura R, Galli M, Santos Oliveira C. Effect of physiotherapeutic intervention on the gait after the application of botulinum toxin in children with cerebral palsy: systematic review. Eur J Phys Rehabil Med. 2018 Oct;54(5):757-765.
  10. Nasb M, Shah SZA, Chen H, Youssef AS, Li Z, Dayoub L, Noufal A, Allam AES, Hassanien M, El Oumri AA, Chang KV, Wu WT, Rekatsina M, Galluccio F, AlKhrabsheh A, Salti A, Varrassi G. Constraint-Induced Movement Therapy Combined With Botulinum Toxin for Post-stroke Spasticity: A Systematic Review and Meta-Analysis. Cureus. 2021 Sep 1;13(9):e17645