Botox > Dystonia

 
Dystonia Treatment:

Introduction
Dystonia is a disorder characterized by involuntary sustained muscle contractions resulting in twisting and repetitive movements or abnormal postures. Despite an incomplete understanding of the neurological mechanisms underlying dystonia, relief of dystonic posturing and associated pain and discomfort has improved markedly since the introduction of botulinum toxin (BTX) therapy in the late 1980s, so much so, it has become the standard therapy for focal dystonias.

BTX is one of the most potent biologic substances known. The 7 distinct serotypes, A, B, C, D, E, F, and G, are of similar sizes and structures. However, the serotypes differ in their potency, duration of action, and cellular target sites. Types A and B have been shown to be safe and effective in double-blind clinical trials for the treatment of dystonia. One formulation of BTX-A is marketed worldwide under the name BOTOX® (Allergan) for "the treatment of strabismus, blepharospasm, and focal spasms including hemifacial spasm" and more recently for the treatment of cervical dystonia.

The clinician must recognize that the various commercial formulations of BTX differ in the dosages used clinically owing to differences in potency and diffusion (see next 2 sections).


Botulinum toxin type A

BTX proteins have been studied since the early 1900s, initially to gain an understanding of botulism, a form of food poisoning. Later, they were studied because of the unique and specific muscle paralysis induced by minute amounts of the toxins. During the past 30 years of work on the use of the toxin for human treatment, selective procedures for the production, purification, and dispensing of the toxin have been developed to make it suitable for injection. Today BTX-A is employed and considered safe and effective for treatment of movement disorders and spasticity. One of the more common movement disorders treated with BTX-A is focal dystonia, the most frequently occurring types of which include cervical dystonia, blepharospasm, hand dystonia, oromandibular dystonia, occupational dystonia, and laryngeal dystonia.  

The administration of BTX therapy for the focal dystonias requires a thorough understanding of the toxin itself, preparation of various dilutions, and practical knowledge of typical dosages and anatomy, along with basic electromyographic skills. The optimal dose of botulinum toxin (BTX) is the least amount of BTX needed to achieve a predetermined outcome (eg, decreased muscle tone, improved range of motion, improvement of certain active function, improved hygiene) without causing an adverse effect, weakness.

This chemical denervation results in paralysis of the muscles, which usually peaks 2 weeks after the injection. Because of the molecular turnover within the neuromuscular junction and neuronal sprouting, neuronal activity begins to return at 3 months, with restoration of complete function at approximately 6 months.

Many factors affect the dose of botulinum toxin including severity and chronicity of the disease, number of muscles involved, previous response, concurrent other medical therapy used, and also the experience of the person performing the injection. Smaller doses are used in children, proportionate to the body mass.


Medications used to treat focal dystonia:

  1. Botulinum toxin injections
  2. Benzodiazepine
    • Clonazepam
    • Lorazepam
    • Diazepam
  3. Baclofen
  4. Anticholinergics
    • Trihexyphenidyl
    • Benztropine
  5. Dopamine-depleting agents
    • Tetrabenazine
    • Clozapine


Optimum goals of treatment with botulinum toxin
The ideal of BTX treatment is to achieve a balance between weakness sufficient to reduce spasm but insufficient to interfere with function. The best combination of reduction in dystonia and pain with optimization of function should be sought.

Most of the skeletal muscular system is arranged into groups of agonists and antagonist muscles that work in concert to provide efficient and controlled motion. This is achieved through the complex interaction of the musculoskeletal system with the pyramidal, extrapyramidal, and sensory components of the nervous system.

In gross anatomy, the nerves to skeletal muscles are branches of mixed peripheral nerves. The branches enter the muscles about one third of the way along their length, at motor points. Motor points have been identified for all major muscle groups for the purpose of functional electrical stimulation by physical therapists, in order to increase muscle power. Only 60% of the axons in the nerve to a given muscle are motor to the muscle fibers that make up the bulk of the muscle. The rest are sensory in nature, although the largest sensory receptors, the neuromuscular spindles, have a motor supply of their own.

A motor unit comprises a motor neuron in the spinal cord or brainstem together with the squad of muscle fibers it innervates. In large muscles (eg, the flexors of the hip or knee), each motor unit contains 1200 or more muscle fibers. In small muscles (eg, the intrinsic muscles of the hand), each unit contains 12 or fewer muscle fibers. Small units contribute to the finely graded contractions used for delicate manipulations. 


 
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