Botulinum Toxin

General information about Botox

Botulinum toxin type A, or Botox, is a therapeutic muscle-relaxing agent that reduces the rigidity of muscles or unwanted spasms in a specific muscle. Botox is produced from the bacteria (Clostridium Botulinum) that causes food poisoning and provides relief for muscle stiffness at the site of injection. Though high doses of Botox can be deadly, the very small doses used in cerebral palsy cases. Over the past ten years, the use of Botox has shifted from wrinkle reduction to successfully treating muscle spasticity in children with cerebral palsy. Botox is produced by Clostridium Botulinum as a complex of proteins containing the neurotoxin itself and other nontoxic proteins. There are 7 Botulinum serotypes (A, B, C, D, E, F, and G), all of which inhibit acetylcholine release although their intracellular target proteins and potencies vary substantially.

Mechanism of Botox

Botox blocks signal transmission at the neuromuscular junction by preventing the release of acetylcholine from the presynaptic terminal. The effect is reversed when the preterminal neurite sprouts and reinnervates the muscle. The level of chemical denervation is dependent upon the amo++unt of Botox injected into the muscle. Thus, muscle relaxation with Botox is both graded and reversible.

Conditions treated by Botox

Botox have been used to manage a variety of disorders involving muscles hyperactivity, including focal dystonia, dysphonia, spasticity, achalasia, tremors, and cerebral palsy. In case of cerebral palsy Botox can be used for releasing tightness at:

The lower limbs

Hip level : adducted hip / flexed hip / internally rotated hip / externally rotated hip

Knee level : flexed knee/ hyperextended knee / stiff knee

Ankle level : equines foot / equinovarus foot / valgus foot / claw toes / stratial toes

The upper limbs

Shoulder level : adducted shoulder / internally rotated shoulder / externally rotated shoulder

Elbow level : flexed elbow / pronated arm

Wrist level : flexed wrist / clenched fist / thumb-in-palm pattern

Selection of right candidate for Botox therapy

Botox may be appropriate for use in children with focal spasticity who meets the following criteria

Criteria for Botox Treatment in Children with Focal Spasticity

Dynamic deformity interfering with function, producing pain, and/or contributing to progressive deformity

• Equinus (equinovarus or equinovalgus) foot deformity
• Hamstring spasticity-crouch gait
• Psoas spasticity-crouch gait
• Adductor spasticity-scissoring posture,
• early spastic hip displacement
• Cervical muscle spasticity-torticollis
• Upper extremity spastic postures/deformity,

e.g., elbow flexion, forearm pronation, wrist flexion, thumb-in-palm

> Painful spasms
> Pain control

• Postoperatively
• Post cast application

Symptomatic focal limb or cervical dystonia

Diagnostic trial for surgery

Drooling reduction

Contraindications for Botox therapy

The clinical contraindications for Botox use in patients include the following:

• Allergic reaction to the neurotoxin or its vehicle
• Resistance to neurotoxin effects
• Significant muscle weakness
• Concurrent use of amino glycoside antibiotics
• Failure to respond to injections
• Inability to achieve the desired outcome
• Presence of fixed joint or muscle contracture.
• The child is less than 18 months.
• If the child has diffuse hypertonia.

Side effects

Treatment with Botox is well tolerated by most children with cerebral palsy. Some children may experience side effects especially during the first few weeks following injection. Generally these side effects are mild and temporary. A fever may occur for 1-3 days, though this is rare. Too high a dose may cause excessive weakness and temporary loss of function. Temporary pain, local irritation and bruising may occur but are not significant enough to influence the choice of therapy.

Specialized injection technique

Developing proficiency with the injection of Botox requires significant time commitment and skill development on the part of the injector. In a busy clinical practice, any technique that can improve the efficiency and efficacy of such a treatment is valuable. Electromyography (EMG) and electrical stimulation (ES) are two such techniques used to improve the effectiveness of treatment with Botox.

Optimal dose calculation

There is a specific dosing guideline available.

Total maximum body dose per visit = lesser of 12 units per kg or 400 units
Maximum dose per large muscle per visit=3-6 units per kg
Maximum dose per small muscle per visit= 1-2 units per kg
Maximum dose per injection site= 50 units
Reinjection not before three months

Localization of a muscle for injection

The target muscle is localized by the knowledge of surface anatomy and with the help of electromyography (EMG)

Precaution necessary for dilution and handling

Botox is supplied in 100 U vials (Now-a-days in 50 U also) and can be diluted to a variety of concentrations. For most muscle of average size, a concentration of 5-10 U/0.1mL is appropriate with a volume of up to 0.5 mL per site.

Botox is reconstituted in the vial with normal saline without preservative. The vial is gently swirled, but not shaken or agitated.

Number of injection sites

The choice of the number of injection sites per muscle is a function of muscles size and ease of access.

Possible goals of Botox therapy in the management of spasticity

Following are the possible goals:

1. Improved function
   
   > Mobility (ambulation, normalization of gait patterns)
   
   > Transfers
   
   > Seating and positioning
   
   > Balance
   
   > Wheelchair management and mobility
   
   > Sexuality
   
   > Energy demand reduction
   
2. Increased ease of care
   
   > Dressing
   
   > Feeding
   
   > Hygiene and bathing
   
   > Positioning
   
   
3. Increased comfort
   
   > Pain reduction
   
   > Sleep improvement
   
   > Orthoses fit improvement
   
   
4. Prevention or treatment of musculoskeletal complications
   
   > Delay or prevention of contracture
   
   > Increased efficacy of and reduced need for casting
   
   > Prevention of spasm
   
   > Prevention of subluxation
   
   > Pressure sore reduction
   
   
5. Cosmoses
   
   > Improved body image
   
   > Increased choice of and tolerance for regular footwear.
   

Optimal efficacy

The minimum duration of the effect is 90 days and the maximum duration of effect varies from 6 months to 18 months. In maximum cases there is no need to re-inject Botox if there is a good post Botox therapy available.

Possibility of antibody formation

Development of resistance to Botox is an important clinical issue. Resistance is characterized by absence of any beneficial effect. Antibodies against the toxins are presumed to be responsible for most cases of resistance. There is no correlation between the number of injection repetition and antibody production has been established. If a lack of therapeutic benefit continues, the possibility of antibody mediated resistance must be considered. The prevalence of neutralizing antibodies has been estimated at approximately 5% of all children receiving Botox depending on dose and duration of therapy.

Post Botox therapy

The general goal of post Botox therapy treatment is to improve function by increasing range of motion, selective control, strength, motor planning, coordination, agility and other components of motor performance. Following are the components of a good post Botox therapy programme.

 
1. Therapeutic exercises
2. Multimodal developmental therapy and functional training
3. Modalities
4. Splinting, serial casting, orthoses
5. Positioning
6. Home programme
7. Safety issues

Patient / parent education

Educating the parents is essential for carrying over of the therapeutic programme, whether it is when way from the clinic or when home after discharge. It is essential that the child understands and avoid previous compensations and positions that may reinforce spasticity. The consultant can make recommendations and provide guidance for using positions that favor more normal movement and may further inhibit spasticity. Such parent / patient education may include ideal positions for ADL, sitting, transfers, sleeping, and body mechanics.

Availability of Botox / Cost of each vial

BTX-A is marketed worldwide under the name of BOTOX (Allergan) and DYSPORT (Speywood). Now-a-days a few other companies also manufactured BTX-A in the name of INTAS and BIO-MED.

Company	Units	Cost
Allergan	100	App. Rs 13,650
Dysport	500 3 units of Dysport is equivalent to 1 unit of Allergan	App Rs 25,000
Intas	100	App Rs 9000
Bio-med	100	App Rs 6000

Description	Dose dependent Botox	Phenol
Titration effect	Dose dependent	Dependent on number of motor branches
Onset	24-72 hours; peak at 21-28 days	Immediate
Optimal location for injection	Small muscles- fine control	Large muscles such as lower limb
Local toxicity	No irritation	Potential edema, necrosis
Systemic toxicity	If total quantity > 800 U	If intravascular or intrathecal injection