AILESBURY MEDICAL: 'The uses of Botox in Neurology' by Dr. Patrick Treacy

Botulinum toxin is a medication and a neurotoxic protein produced by the bacterium Clostridium botulinum. The terms Botox (Cosmetic), Vistabel, Dysport, Myobloc, Neurobloc and Xeomin are trade names
By: Ailesbury Media
 
June 21, 2009 - PRLog -- As I said last week, there is growing evidence that BOTULINUM TOXIN A is going to revolutionise the way that conventional medicine is practised in the Western world and as each day passes, new cases are found for its use. This is largely because over the past twenty years, the ingenuity of medical researchers has slowly transformed the lethal toxin of Clostridium botulinum into a modern day therapeutic medicine, which has proven to be a safe and effective therapy for a variety of somatic and autonomic motor disorders. The pharmaceutical has certainly come a long way since the first cases botulinum poisoning from sausages was described in Germany in the late 1700’s. It took until 1897, a full two years after the death of Louis Pasteur, until Professor Emile van Ermengem isolated the assassin, Clostridium botulinum, from a contaminated ham that had killed three people at a remembrance ceremony of the Ellezelle Music Society. (van Ermengem E: Ueber einen neuen anaeroben Bacillus and seine Beziehungen zum Botulisms. Ztsch Hyg Infekt. 1897; 26 1). We should remember that this was the dawn of the scientific age, Pasteur had just identified the causes of rabies, anthrax, chicken cholera, and discredited the myth of spontaneous generation. When the German Romantic physician and scientist, Justinus Kerner published data on 230 cases of botulism, the illness became known for a period as “Kerner’s disease” (Dickson EC: Botulism. A clinical and experimental study. Rockefeller Inst Med Res Mong. 1918; 8:) but few now remember the fact that he  also suggested with amazing foresight that very small doses of the “sausage poison” could be used in the treatment of hypermotility disorders such as ‘St. Vitus Dance’ (Grusser O-J Die ersten systematischen Beschreibungen and tierexperimentellen Untersuchungen des Botulismus. Sudhoffs Archiv 1986). But, those were the days before Allergan and Ipsen and Kerner was happy to make his fortune by allowing Richard Schumann to set his lyrics to music in the now almost forgotten series of “Kerner-Lieder”. In the course of his studies, Kerner also documented the symptoms and signs of botulism, which include limb paralysis, ophthalmoplegia, dysarthria, dysphagia, dyspnoea, constipation, facial weakness, and urinary retention. It is these effects that have been harnessed to cause purified botulinum toxin (BTX) to undergo one of the most dramatic role reversals in modern medicine and to turn the toxin into the wonder drug of the 21st century. In 1949, Burgen et al discovered that BTX blocks neuromuscular transmission and unwittingly laid the theoretical foundation for the development of the toxin as a therapeutic tool. (The action of botulinum toxin on the neuromuscular junction. JPhysiol 1949; 109:10-24). There is little doubt that the exponential interest in BTX in the past two decades is related to its therapeutic usefulness and safety. The second part of the series is a bit more academic as it tends to review the clinical evidence relating to BTX-A in the treatment of medical conditions.


NEUROLOGY

In 1949, Burgen et al discovered that botulinum toxin blocks neuromuscular transmission, so it not surprising that botulinum toxin found its first use in neurology. In 1973, Alan B Scott, MD, of Smith-Kettlewell Eye Research Institute used BTX-A in monkey experiments and for the first time in humans to treat strabismus in 1980. Since then Botox therapy has found its way into headache management, epilepsy, multiple sclerosis, Parkinson's disease, movement disorders, neuromuscular disorders, and neuro-immune disorders.
(a) Treatment of Spasticity in Children with Cerebral Palsy


Since its introduction in 1989, BTX-A has been used in neurological problems in children, including the treatment of spasticity in children with cerebral palsy. (Edgar TS. Clinical utility of botulinum toxin in the treatment of cerebral palsy: comprehensive review. J Child Neurol 2001;16:37-46.) Injections are usually given into the gastrocnemius-soleus muscle complex to improve walking in children with equinus gait, but may also be given into the hip adductors and hamstrings to improve positioning in nonambulatory children. There are over a dozen studies, including 7 randomized, double-blind, placebo-controlled trials that have documented the beneficial effects of BTX-A on lower limb spasticity. Koman et al demonstrated significant improvement in gait function and range of motion after using BTX-A on 114 children (Koman LA, Mooney JF, Smith BP, et al. Botulinum toxin type A neuromuscular blockade in the treatment of lower extremity spasticity in cerebral palsy: J Pediatr Orthop 2000;20:108-15). Baker et al showed the same improvement after using BTX-A (Dysport®) on 125 children. (Baker R, Jasinski M, Maciag-Tymecka I, et al. Botulinum toxin treatment of spasticity in diplegic cerebral palsy: Dev Med Child Neurol 2002;44:666-75). The use of BTX-A has become an accepted addition to standard antispasmodic medications in children with lower limb spasticity and it has been shown to improve upper extremity function in children with hemiplegic cerebral palsy.


(b) Treatment of Muscular Spasms

Scott et al successfully used BTX-A to treat blepharospasm and strabismus in the early 1980’s. Blepharospasm is the involuntary forceful closure of the eyelids resulting initially in uncontrollable blinking and eventually the eyelids remain closed all the time and the patient becomes functionally blind. (Scott AB: Botulinum toxin injection of eye muscles to correct strabismus. Trans Am Ophthalmol Soc. 1981; 79: 734) Jankovic et al later used it for focal dystonias, muscle spasms and spasticity, (Jankovic J, Schwartz K, Donovan DT: Botulinum toxin in the treatment of cranial-cervical dystonias and hemifacial spasm. J. Neurol. Neurosurg. Psychiatry. 1990;53: 633). The FDA approved BTX type A (Botox®, Allergan) for the treatment of strabismus, blepharospasm, and hemifacial spasm in 1989 and BTX-B (Myobloc™, Elan) for clinical use in cervical dystonia patients later. Hemifacial spasm causes sudden, simultaneous contraction of the muscles on one side of the face and it can occur several times a day. BTX-A is also used for spasmodic torticollis of the neck and oromandibular dystonia, which involves continuous, bilateral spasms of the face, jaw, neck, tongue, larynx, and in severe cases, the respiratory system.

(c ) Treatment of spasmodic dysphonia and other speech problems
Spasmodic dysphonia is a focal dystonia affecting the laryngeal musculature, most commonly treated with localized injections of botulinum toxin A (Botox). These injections temporarily weaken the muscles, thereby decreasing dystonic laryngeal muscle activity. Duration of weakness varies from patient to patient and often from injection to injection. Murray and Woodson suggested that behavioural voice therapy used in combination with Botox increases effectiveness and duration of Botox injection therapy. Botox has proven effective in alleviating symptoms and restoring speech fluency, although one kind of spasmodic dysphonia (Abductor Spasmodic dysphonia) poses an airway obstruction risk if certain muscles are injected. Stuttering and vocal tremor may also be treatable with Botox. Most common disorders resulting in dysphonia include Parkinson disease, essential tremor (ET), and spasmodic dysphonia (SD). Unfortunately, there is little literature concerning the efficacy of voice therapy with other neurological disorders.

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