Botulinum Toxin in Neurology
- 1. Botulinum Toxin in Clinical Practice; A Brief Review Ade Wijaya, MD February 2018
- 2. Introduction The potential for a therapeutic use for botulinum toxin was first recognised by Justinus Kerner in 1817 1989 FDA approved (Botox A) 2000 FDA approved (Botox B) Erbguth FJ, Naumann M. Historical aspects of botulinum toxin. Justinus Kerner (1786–1862) and the “sausage” poison.Neurology 1999;53:1850–3 Tintner R , Jankovic J. Focal dystonia: the role of botulinum toxin. Curr Neurol Neurosci2001;1:337–45. Brin MF, Hallett M, Jankovic J, eds. Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott Williams & Wilkins, 2002:1–507
- 3. Indication (FDA approved) Botox A strabismus, blepharospasm, and other facial nerve disorders, including hemifacial spasm Botox B cervical dystonia, and Botox Cosmetic for treatment of glabellar (frown) lines Brin MF, Hallett M, Jankovic J, eds. Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott Williams & Wilkins, 2002:1–507 Tintner R , Jankovic J. Focal dystonia: the role of botulinum toxin. Curr Neurol Neurosci2001;1:337–45.
- 4. Indication - Dystonia * Blepharospasm and lid apraxia * Oromandibular-facial-lingual dystonia * Cervical dystonia (torticollis) * Laryngeal dystonia (spasmodic dysphonia) * Limb dystonia * Task specific dystonia (eg, writer’s or other occupational cramps) * Other focal/segmental dystonias (primary, secondary) Tintner R , Jankovic J. Focal dystonia: the role of botulinum toxin. Curr Neurol Neurosci2001;1:337–45. Brin MF, Hallett M, Jankovic J, eds. Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott Williams & Wilkins, 2002:1–507
- 5. Indication – Other Involuntary Movements * Hemifacial spasm * Limb, head, voice, chin tremor * Palatal myoclonus * Motor and phonic tics (including coprolalia) * Nystagmus and oscillopsia * Myokymia Tintner R , Jankovic J. Focal dystonia: the role of botulinum toxin. Curr Neurol Neurosci2001;1:337–45. Brin MF, Hallett M, Jankovic J, eds. Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott Williams & Wilkins, 2002:1–507
- 6. Indication – Inappropriate Muscle Contractions Tintner R , Jankovic J. Focal dystonia: the role of botulinum toxin. Curr Neurol Neurosci2001;1:337–45. Brin MF, Hallett M, Jankovic J, eds. Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott Williams & Wilkins, 2002:1–507 * Spasticity (stroke, cerebral palsy, head injury, multiple sclerosis) * Painful rigidity * Strabismus * Bruxism and temporo-mandibular joint syndrome * Stuttering * Chronic tension (muscle contraction) headaches * Lumbosacral strain and back spasms * Radiculopathy with secondary muscle spasm * Myofascial pain syndromes * Achalasia (lower oesophageal sphincter spasm) * Spasm of the inferior constrictor of the pharynx * Spasm of the sphincter of Oddi * Spastic bladder, detrusor sphincter dyssynergia * Anismus * Vaginismus
- 7. Indication – Other Apllications Tintner R , Jankovic J. Focal dystonia: the role of botulinum toxin. Curr Neurol Neurosci2001;1:337–45. Brin MF, Hallett M, Jankovic J, eds. Scientific and therapeutic aspects of botulinum toxin. Philadelphia: Lippincott Williams & Wilkins, 2002:1–507 * Protective ptosis * Hyperlachrymation * Drooling (sialorrhoea) * Hyperhidrosis * Gustatory sweating * Anal fissure * Constipation * Obesity (distal stomach) * Cosmetic (wrinkles, brow furrows, frown lines, “crow’s feet”, platysma lines, facial asymmetry) * Tennis elbow and other sports injuries * Protective ptosis * Hyperlachrymation * Drooling (sialorrhoea) * Hyperhidrosis * Gustatory sweating
- 8. Mechanism of Action Activated botox, binds to the presynaptic plasma membrane of the motor axon terminal. The toxin complex is then internalised by energy dependent endocytosis The light chain (L), a zinc endopeptidase, is released into the cytoplasm The light chain cleaves various components of SNARE (indicated by vertical arrows), including SNAP 25 (botulinum toxin A), VAMP/synaptobrevin (botulinum toxin B), or syntaxin (botulinum toxin C), and thus prevents the fusion of acetylcholine synaptic vesicle with the plasma membrane. This blocks the release of the neurotransmitter into the synaptic cleft, causing local chemodenervation Jankovic, J. (2004). Botulinum toxin in clinical practice. Journal of Neurology, Neurosurgery & Psychiatry, 75(7), 951-957.
- 9. Mechanism of Action Jankovic, J. (2004). Botulinum toxin in clinical practice. Journal of Neurology, Neurosurgery & Psychiatry, 75(7), 951-957.
- 10. Botox Dosing Cervical dystonia: 200 U botox A ; 10000 U botox B Spasticity in CP: 20 mg/kg botox A Lumbar muscle spasm: 200 units botox A Hyperhidrosis: 100 to 200 units botox A Chronic anal fissure: 15 to 20 units botox B Neurogenic incontinence: 200 to 300 units botox A Jankovic, J. (2004). Botulinum toxin in clinical practice. Journal of Neurology, Neurosurgery & Psychiatry, 75(7), 951-957.
- 11. Analgesic effects of botulinum toxin : Inhibition of release of substances that sensitise muscle nociceptors; An effect on spindle afferents favourably altering the firing pattern of supraspinal projections and changing the central sensory processing; Suppression of neurogenic inflammation; Inhibition of substance P, glutamate, and other peptides and neurotransmitters involved in mediating pain. Jankovic, J. (2004). Botulinum toxin in clinical practice. Journal of Neurology, Neurosurgery & Psychiatry, 75(7), 951-957.
- 12. Summary Botulinum toxin in the treatment of a variety of neurological and non-neurological disorders Complication: local muscle weakness High cost Have a positive effect on health related quality of life