Botulinum Therapy

Introduction
The Botulinum toxin is extracted from the bacteria (Clostridium Botulinum) that are responsible for food poisoning. There are seven (7) neurotoxins of which the most commonly used is Botulinum toxin type A. The other types of antigenically neurotoxins are B, C, D, E, F, F, and G. Human intoxication is primarily due to types A, B, E, and rarely F. 

• Botox is a trade name of Botulinum toxin manufactured by Allergan.
• Xeomin is a trade name of Botulinum toxin manufactured by Merz
• Neuronox  and Dysport  are the another two brands available 

Mechanism of Botulinum
Botulinum Toxin blocks signal transmission at the neuromuscular junction by preventing the release of acetylcholine from the pre-synaptic terminal. The effect is reversed when the pre-terminal neurite sprouts and re-innervates the muscle. The level of chemical denervation is dependent upon the amount of Botulinum injected into the muscle. Thus, muscle relaxation with Botulinum is both graded and reversible.

Conditions treated by Botulinum

• Cerebral Palsy-Brain damage due to a lack of oxygen
• Stroke
• Traumatic brain injury (TBI)
• Spinal cord injury (SCI)
• Encephalitis
• Meningitis
• Focal dystonia
• Dysphonia
• Spasticity
• Achalasia
• Tremors

In case of a person with Spasticity, Botulinum can be used for releasing tightness at: 

Hip level

• Adducted hip (Crossing the legs at hips and knees)
• Flexed hip / internally rotated hip / externally rotated hip

Knee level
Flexed knee/ hyper-extended knee / stiff knee

Ankle level
Equines foot (weight on toes while standing- walking) / equino-varus foot / valgus foot / claw toes / stratial toes

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  a right candidate for Botulinum therapy
Botulinum may be appropriate for use in a person with focal spasticity who meets the following criteria

Inclusion Criteria
In case Lower extremity
Dynamic deformity interfering with function, producing pain, and/or contributing to progressive deformity

• Equinus (equinovarus or equinovalgus) presentation
• Hallux Valgus
• Hamstring spasticity-crouch gait
• Psoas spasticity-crouch gait
• Adductor spasticity-scissoring posture,
• Early spastic hip displacement

In case of Upper extremity

• Elbow flexion,
• Forearm pronation,
• Wrist flexion,
• Thumb-in-palm
• Swan neck presentation

Others
Cervical dystonia

• Cervical muscle spasticity-torticollis
• Diagnostic trial for surgery
• Drooling reduction
• Painful spasms
• Pain control

Contraindications for Botulinum therapy
The clinical contraindications for Botulinum use in patients include the following:

• Diffuse hypertonia- Generalized Spasticity
• Presence of fixed deformity (joint) or muscle contracture
• Significant muscle weakness
• Inability to achieve the desired outcome
• Failure to respond to injections
• Resistance to neurotoxin effects
• Allergic reaction to the neurotoxin or its vehicle
• Concurrent use of amino glycoside antibiotics

Injection technique
To be proficient with Botulinum injection technique, one requires a lot of commitment and dedication. The skill is developed with stringent training as the injection technique is very much different from other injection techniques such as IM / IV / Spinal, etc. The injector should be confident in surface anatomy so that right muscle can be injected. The efficiency of the injection depends on right selection of muscles, right dilution of the drugs, formulation of right dosage according to the body weight and number of targeted muscles. Apart from surface anatomy, Electromyography (EMG) and Electrical stimulation (ES) are two such techniques which can be used to improve the effectiveness of treatment with Botulinum.

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
  

Re-injection 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) and Ultrasonography also

Precaution necessary for dilution and handling
Botulinum is supplied in 100 U vials (Now-a-days in 50 U and 200 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. 

Botulinum 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 Botulinum therapy in the management of spasticity
- Improved function

• Mobility (ambulation, normalization of gait patterns)
• Transfers
• Seating and positioning
• Balance
• Wheelchair management and mobility
• Sexuality
• Energy demand reduction

- Increased ease of care 

• Dressing
• Feeding
• Hygiene and bathing
• Positioning

- Increased comfort 

• Pain reduction
• Sleep improvement
• Orthoses fit improvement

- 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

- 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 Botulinum if there is a good post Botulinum therapy available.

Side effects
Treatment with Botulinum is well tolerated by most children with Spasticity / 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. Temporary loss of function may be observed in case of excessive weakness due to high dose of Botulinum. In a few cases, temporary pain, irritation at the injection site with bruising may be observed.   

Possibility of antibody formation
Development of resistance to Botulinum 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 Botulinum depending on dose and duration of therapy.

Post Botulinum therapy
The general goal of post Botulinum 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 Botulinum therapy program. 
Therapeutic exercises
Multimodal developmental therapy and functional training
Modalities
Splinting, serial casting, orthoses
Positioning
Home program
Safety issues

Patient / parent education
Educating the parents is essential for carrying over of the therapeutic program, 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.

Our experience
Our experience with Botulinum toxin therapy is always satisfactory.
ICD has been doing Chemodenervation with Botox (Botulinum toxin) for the last 17 years. In fact, ICD is the first pediatric habilitation Center in India where the first study was done in 2002 to 2004. The title of the study was “Role of Botulinum Toxin
(Botox-Allegan) in spasticity management with children with spasticity due to cerebral palsy”. The post Botulinum therapy protocol compiled by ICD is still in practice all over world.

The result of Chemodenervation with Botulinum toxin depends on the quality and quantity of post Botulinum therapy. There are three factors which determine the efficacy of the Botulinum toxin therapy

1. Selection of a right candidate with proper goal setting  selection of right muscles, appropriate amount of medicines, very specific weight, age and muscle oriented dosage, pre-botox parents counseling
2. Right injection protocol- dilution technique, appropriate dosage(targeted muscle oriented), injection location (surface anatomy or usage of EMG / US), number of site of injection, casting knowledge
3. Post Botulinum therapy protocol- Knowledge of what to do or what not to do immediately after injection, duration of the cast and exercises with the cast, usage of orthotic aids, written Exercise plan and ongoing assessment, parental training to carry an activity program in daily life.     

  
As ICD has knowledge and experience of past 17 years of practice, all the above factors are considered to get the best result with Botulinum therapy.

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