1. Botox and Its Role in Parkinson’s Disease
Laura Buyan Dent, MD, PhD
Associate Professor of Neurology
University of Wisconsin School of Medicine and Public Health

2. Intro Botulinum neurotoxin = Botox=BoNT
One of the most poisonous substances known to humans
Lethal dose of approximately 1 ng per kilogram body wt
Inhaled by a person, 1 g would certainly be lethal
1 g can theoretically kill 1,000,000 persons
Discuss the toxin itself
History of development
specific uses for certain symptoms/problems in PD

3. Botulism Poisoning that causes a fatal paralytic disease
Probably known since humans have stored food
Justimius Kerner
Poet and Physician
publications correlating toxic agent in improperly prepared and stored sausages----numerous sausage poisonings reported in southwestern Germany
Botulism
From latin word botulus meaning sausage
Sausage poisoning
Causes a rapidly progressive profound weakness resulting in death due to paralysis of respiratory muscles

4. Clostridium Botulinum
Emilio Pierre Marie von Ermengerm
microbiologist
received samples from an outbreak of botulism and identified the microorganism responsible
Intoxication, not infection
Toxin produced in food by bacteria
After digestion, toxin remains active
Toxin can be inactivated by heat
Now know that clostridium botulinum is found worldwide in soil, dust, marine sediments
Types of exposure
Improperly preserved food
Infant exposure via honey
Wound contamination

5. Clostridium Botulinuum
Anaerobic bacteria which produces a neurotoxin
Major effect of the neurotoxin is paralysis of muscles

6. Further Development
Bo NT considered for use as a weapon in WW I and II.
Military research at Fort Detrick helped to isolate and purify the toxin
1942–1946 Carl Lamanna and Edward Schantz
purify the toxin and prepare it in crystalline form
1946 Schantz
produces a large amount of this toxin
makes it available for clinical research
1972 Schantz
moved to Department of Microbiology and Toxicology at University of WI
Go Badgers !!!!!!!!!!!!!!!!!!!!!!!

7. Medical Development
1972 First experimental evidence of BoNT injection causing localized muscle weakness
1980’s injected into humans for treatment of strabismus (“crossed-eye”)
1989 FDA approved for treatment of strabismus, blepharospasm and hemifacial spasm
medical and cosmetic uses

8. Medical Use
Major effect of the neurotoxin is paralysis of muscles

9. How Does It Work?

10. Motor System Review Nervous System Muscle
Source: The Spinal Cord, Clinical Neuroanatomy, 28e
Citation: Waxman SG. Clinical Neuroanatomy, 28e; 2017
Copyright © 2017 McGraw-Hill Education. All rights reserved

11. Neuromuscular Junction
Source: Muscle Tissue, Junqueira's Basic Histology, 14e
Citation: Mescher AL. Junqueira's Basic Histology, 14e; 2016,
Available at:
Copyright © 2017 McGraw-Hill Education. All rights reserved

12. BoNT blocks neuromuscular transmission
Inhibits release of neurotransmitter (acetylcholine) at the neuromusclular junction
Interferes with proteins involved in vesicular release
Source: Clostridium, Peptostreptococcus, Bacteroides, and Other Anaerobes, Sherris Medical Microbiology, 6e
Citation: Ryan KJ, Ray C. Sherris Medical Microbiology, 6e; 2014 Available at:
Copyright © 2017 McGraw-Hill Education. All rights reserved

13. Formulations and Pharmacology
7 serotypes of BoNT (A,B,C1,D,E,F,G)
A & B available for medical use
onabotulinumtoxinA(Botox)
abobotulinumtoxinA (Dysport)
incobotulinumtoxinA(Xeomin)
RimabotulinumtoxinB (Myobloc, NeuroBloc)
Different formulations may affect different proteins in the pathway of synaptic release of acetylcholine

14. Medical uses
Used to treat a variety of conditions in which there is excessive muscle spasm
Also evidence that BoNT affects certain pain receptors directly
Can reduce some dysautonomic symptoms due to interfering with contraction of “smooth” muscle which is controlled by the autonomic nervous system

15. Uses specific to PD

16. Dystonia
Definition = specific type of muscle spasm, often with a twisting component resulting in an unusual posture
“On” vs “Off”
Painful
Risk of contractures
Can affect numerous body parts
Most common
Face
Feet
Neck
trunk

17. Foot spasms
Striatal toes
Toe curling

18. Eye Spasms Blepharospasm Apraxia of eyelid opening
Video from Jankovic and Tolosa Parkinson’s Disease & Movement Disorders, 5th ed, 2007

19. Eye Spasms Blepharospasm Apraxia of eyelid opening
Video from Jankovic and Tolosa Parkinson’s Disease & Movement Disorders, 5th ed, 2007

20. Facial Muscles

21. Facial Dyskinesia Bruxism= grinding of teeth
Facial grimacing usually from levodopa
Video from Jankovic and Tolosa Parkinson’s Disease & Movement Disorders, 5th ed, 2007

22. Facial Dyskinesia Bruxism= grinding of teeth
Facial grimacing usually from levodopa
Video from Jankovic and Tolosa Parkinson’s Disease & Movement Disorders, 5th ed, 2007

23. Sialorrhea
Drooling
Not due to excessive saliva production
Occurs due to decrease in automatic swallowing
Botox will interfere with the salivary glands releasing saliva

24. Other Tremor Bent spine / camptocormia Hyperactive bladder
Very limited success due to excessive weakness of arms/hands
Bent spine / camptocormia
Variable success
Hyperactive bladder
Done by Urology

25. Side-effects/Safety Unintentional weakness
Depends on location of injections
Injection site reaction, bruising
Development of antibodies
Some spread of toxin to distant locations
not clinically relevant in with expert use
Expensive!!!!!!
Manufactured biologically from refined strains of clostridium botulinum
Actually very safe. Diffuses only ~ 2 cm from injection site

26. Clinical visit and practical considerations
“art of medicine”
Procedure which is done in the office
No anesthesia necessary
Takes 3-10 days to notices effects
Can take days to weeks for side-effects to resolve
Effects wear off necessitating repeat treatments
Some variability in responses
EMG guidance possible

27. Questions?????