Botulinum Toxin in Therapy

Original Editor - Chloe Waller Lauren Heydenrych

Top Contributors - Lauren Heydenrych, Chloe Waller, Rucha Gadgil and Lucinda hampton  

Introduction

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.

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. Type A is used in therapeutic interventions.

Mechanism of action

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.
• Reflex overactivity is also decreased with inhibition at the gamma neurons in muscle spindles.
• 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.

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

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.

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.

Conditions Treated

Conditions commonly treated include those of dystonia and spasticity.

Examples of dystonia include:

• 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.
• Diabetic neuropathy is listed as a condition in which BT may be used.

Treatment algorithms in BT administration in Spasticity and Dystonia

Treatment algorithms are determined by various factors including:

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"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

The right dose is dependent on:

• 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.

Physiotherapy Management

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. 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 .

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

Outcome Measures

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:

• Gross Motor Function Measure
• Five-Times Sit-and-Stand Test
• Goal Attainment Scale (GAS)
• Pediatric Evaluation of Disability Inventory (PEDI)
• Modified Ashworth Scale
• Goniometry
• Canadian Occupational Performance Measure (COPM)
• Edinburgh Visual Gait Score
• Quality of life questionnaire for children with cerebral palsy (CP QOL-Child)
• One-Minute Fast Walk Test

Resources

• BOTULINUM TOXIN
• A "toolbox" for clinicians.