Botox (botulinum toxin A)

Botox blocks release of acetylcholine by blocking cleavage of SNAP25 and hence binding of synaptosome to cell membrane, and release.

• Acts for 3-6 months. Recovery by axonal sprouting.
• ~10% of pts. develop neutralizing antibodies. Esp with large doses and brief intervals between doses.
• Released initially to treat strabismus, blepharospasm, and hemifacial spasm. Widely used in other focal dystonias also.
• Quite successful in spasmodic dysphonia (laryngeal dystonia). Occasional successes in writer's cramp, but more likely to help if obvious spasms in selected muscles and not just tight grip, lack of control, etc.
• Has been used in hand tremors.
• Has been used in very persistent tics.
• Relieves spasticity but limited in number of muscles that can be treated. Not very feasible if more than 3 or 4 muscles to be done. Studies generally positive, but more likely to help pain and range of motion and reduce spasms than it is to improve function. Basically an adjunct when select muscles are preferentially affected and drugs and therapy haven't sufficed.
• Achalasia reported to respond well.
• Injection of papilla of Vater provides relief in half of pts. with biliary symptoms without obstruction. Predicts who will gain longterm benefit from sphincterotomy.
• Reports of successful treatment of vaginismus.
• Reports of success in pts. with familial benign cramps and fasciculations.
• Injection of external urethral sphincter shown to help detrusor-sphincter dyssynergia.
• Parkinson's often complicated by constipation. Most are due to decreased parasympathetic tone plus effects of meds, inactivity and decreased fluids. But some involve spasm of pubo-rectalis, not relaxing to permit BM. Botox has helped relieve this.

Several studies have shown that injection of ext. anal sphincter allows healing of anal fissures, without surgery.

• 2 studies report improvement in dysphagia after injection of cricopharyngeal muscle, in pts. with hypertrophy or spasm of this muscle, or herniation of posterior pharyngeal wall.
• Tsui treated Parkinsonian drooling by injecting parotid glands. Mild effect noted but not very good, overall.
• Some reports of success in treating palatal myoclonus, but often temporary nasal regurgitation.
• Cosmetic uses : glabellar injections reduce creases; also some use for crow's feet
• Hyperhidrosis: sweating is mediated by sympathetic nervous system, but transmitter is acetylcholine. Botox injected intra-cutaneously reduces sweating.

Schulze-Bonhage et al reported using it in 3 pts. with gustatory sweating after trauma or surgery on parotid gland. 30 units in 15-20 sites provided good relief within 1-2 wks and lasted 6-8 months. Later reported for hyperhidrosis of hands and axilla.

• Recent reports suggest some utility in tension headache, and migraine.

Tension Headache and Botox

Relja studied 10 pts. with chronic tension headaches meeting IHS criteria. Present for 3-7 yrs. Had 15-26 headache days per month. 4 males and 6 females, mean age 43. Resistant to standard treatments. 12 week open-label study. Palpated frontalis, trapezius and sternomastoid muscle at mastoid process bilat., for tenderness. Injected 15-35 units, using most tender muscles. Off meds at baseline and injection. No mention thereafter. Headaches gone completely in 3 of 10 by 2 wks. Other 7 had some improvement. Tenderness scores decreased. By 8 wks, 2 headache free, and 6 in total still had some benefit. Waned by 12 wks.

Smuts and Porta reported placebo-controlled double blind study of 37 pts. with chronic tension headaches, not responding to standard treatments. 50 units injected into temporalis ( 2 sites, 7 units each side), and cervical muscles (4 sites, 18 units each side) 22 received Botox and 15 placebo. Significant decrease in monthly avge headache score from 2.7 to 1.9; increase in total headache-free days; and improvement in quality of life scores.

Migraine and Botox

Binder and Brin studied 96 pts. with frequent migraines, already attending Botox clinics for some other reason. Injected glabellar, corrugator, temporalis, and occipital muscles in areas that seemed involved. Mean dose 25 +/- 14 units. Open label and no control. 51% had complete resolution and lasted mean of 3.6 mths. 28% had partial response (> 50% reduction in severity or frequency of headaches) and lasted mean of 2.9 mths. 21% had no improvement (< 50% reduction)

Myofascial Pain and Botox

Cheshire reported on 6 pts. treated double-blind with Botox or saline. 30% reduction in pain scores, in 4 of 6 pts., but only lasted 2-4 wks.

Wheeler et al treated 33 pts. with chronic unilat. neck or upper thoracic pain and trigger points. Present over 3 mths. and no response to other treatments. Random allocation to placebo, 50 u Botox or 100u into worst trigger point. Blinded assessments. Botox gave no better response or more prolonged than placebo. All groups improved partially. with`