Botulinum toxin (Botox) is a neurotoxin produced by the bacterium Clostridium botulinum that is used medically to treat various medical conditions. It was first used to treat eye muscle disorders and facial wrinkles. It is now commonly used to treat movement disorders like blepharospasm, hemifacial spasm, and cervical dystonia. Botox works by blocking nerve impulses from reaching the muscles, weakening them temporarily. When injected in precise doses into specific muscles, it can provide relief from involuntary muscle contractions and spasms. Common side effects are minor and temporary, including eyelid drooping and weakness of nearby muscles.

1. BOTOX ( Botulinum Toxin )
Dr M D Mohire MD, DM
Neurology Centre & Research, Kolhapur

2. Laurent Tatu et al. Neurology 2017;89:84-87
© 2017 American Academy of Neurology
The botulinum toxin legend of Reinhard Heydrich's death
High-ranking German Nazi
Reinhard Heydrich (1904–
1942) was one of the main
organizers of the mass murder
of Jews during the Second
World War. He died on June 4,
1942, in Prague after having
been wounded by sten gun
bullet containing Botulinum
Toxin

3. History
In 1820, Justinus Kerner, German gave first description of
clinical botulism so-called “sausage poisoning”.
(Botulus is Latin for sausage)
Canned Food
Seafood

4. Claustridium Botulinum
Gram-positive, rod-shaped, anaerobic, spore-forming, motile
bacterium with the ability to produce the neurotoxin botulinum
Food Poisoning
Deadliest Poison
Bioterrorism
Wound Infection

5. In 1895 Robert Koch, described Clostridium botulinum as the
bacterial source of the toxin.
Robert Koch (1843-1910)

6. A 14-year-old with botulism. Note the weakness of his eye muscles and the drooping
eyelids in the image to the left, and the large and non moving pupils in the right image.
This youth was fully conscious.

7. Clinicians frequently think of the symptoms of botulism in terms of a classic triad: bulbar
palsy and descending paralysis, lack of fever, and clear senses and
mental status ("clear sensorium").
Triad of Botulism

8. •Respiratory difficulty arises from airway obstruction and diaphragmatic weakness. Diplopia,
dysarthria, dry mouth, and generalized weakness are among the most common presenting
symptoms. Other symptoms that have been associated with botulism include ptosis, dysphagia,
sore throat, dysphonia, nystagmus, ataxia, paresthesias, paralytic ileus, severe constipation,
urinary retention, and orthostatic hypotension.
•Pupils are dilated or unreactive (ophthalmoplegia) in 50% of patients. Unless secondary
complications such as respiratory failure develop, patients are alert and mental function is
unimpaired
Descending GBS is Botulism

9. Finally, inspired by Daniel Drachman’s at Johns Hopkins, Alan B
Scott and colleagues injected botulinum toxin into monkey
extraocular muscles.
Daniel Drachman-1923-2016Allen Scot
In 1977 In 1980

10. Dystonia is a disorder characterized by involuntary sustained
muscle contractions resulting in twisting and repetitive movements
or abnormal postures.
Dystonic is improved markedly since the introduction of botulinum
toxin (BTX) therapy in the late 1980s, become the standard therapy
for dystonias.
Dystonia

11. Classification by distribution
Type Distribution
Focal Localized to one muscle or muscle group
Segmental Affecting several muscles or adjacent muscle groups
Multifocal Affecting several discrete muscles or muscle groups
Generalized Affecting many muscles all over the body
Unilateral Affecting only one side of the body
(Hemidystonia)
Generalized dystonia usually begins in childhood, as a focal dystonia
that gradually progressive to other parts of the body.
Adult-onset dystonia is rarely progressive

12. Classification by etiology
Classification Sub-group Description
Primary or idiopathic Hereditary Usually begins in childhood and is
progressive, often starting in one leg before
spreading to the trunk and the other limbs
Non-hereditary Includes the focal dystonias, usually non-
or Sporadic progressive, of adult onset and/or dystonias
limited to adjacent muscles groups
(segmental dystonia)
Secondary or Symptomatic Includes hemidystonia (affecting only one
side of the body), secondary to a local brain
lesion or cerebral hemi-atrophy
Associated with other hereditary neurological
syndromes e.g. Huntington’s chorea, Wilson’s
Disease
Environmental Due to trauma, infection, vascular disease,
toxins, drugs(tardive dyskinesia)

13. First described by Gowers in 1884
Fifth or sixth decades, almost always unilaterally
Begins with brief clonic movements of the orbicularis oculi
Over years to other facial muscles (corrugator, frontalis, orbicularis
oris, platysma, zygomaticus).
Chronic irritation of the facial nerve due to vascular compression
F > M, Fifth and sixth decade, Incidence is 1/1000,000, Prevalence is
11 cases per 100 000.
Hemifacial Spasm

14. Hemifacial Spasm

15. Blepharospasm
Involuntary eye closing aggravated by bright lights,wind, pollution,
smoke, emotional stress, fatigue.
Recurrent eye closing interfere with reading, driving, watching
television, and other visual activities,
May be associated with other dystonic disorders, such as
oromandibular or cervical dystonia.
Occurs in the 5th to 7th decades of life.
Prevalence is 5/100,000

16. Blepharospasm

17. •Blepharospasm
•Oromandibular dystonia
•Facial nerve tic
•Hemimasticatory spasm
•Focal seizures
•Synkinesias after facial nerve paralysis
Differential Diagnosis of Hemifacial Spasm

18. Posterior inferior cerebellar artery indenting facial nerve
Ventrolateral medullary compression in hypertensive patients with hemifacial spasm
Workup for Hemifacial Spasm

19. Medications used to treat focal dystonia
BenzodiazepinesClonazepam
Lorazepam
Diazepam
Baclofen
AnticholinergicsTrihexyphenidyl
Benztropine
Dopamine-depleting agentsTetrabenazine
Clozapine

20. Dec 1989 approved by FDA

21. BOTOX® is dispensed in small vials containing 100 units (U),
Dysport contains 500 U.
The relative potency of BOTOX® units to Dysport units is
approximately 1:4. BOTOX®
Available

22. The 7 distinct serotypes, A, B, C, D, E, F, and G, are of similar sizes
and structures.
They differ in their potency, duration of action.
Types A and B have been shown to be safe and effective for the
treatment of dystonia.
BOTOX® (USA), Dysport (UK).
Types of Botox

23. OnabotulinumtoxinA (Botox)
AbobotulinumtoxinA (Dysport)
IncobotulinumtoxinA (Xeomin)
RimabotulinumtoxinB (Myobloc)
BOTOX - Brands

24. Therapeutic Uses of Botulinum Toxin
Axillary, Palmer Hypersweating

25. Botulinum toxin type B for dystonia
Myobloc (Elan Pharmaceuticals) was approved by the FDA in
December 2000
Those who developed resistance to BTX-A.
.

26. The administration of BTX therapy for the focal dystonias requires a
thorough understanding of the toxin itself,
Practical knowledge of typical dosages and anatomy, and
Physiology.
Requirments for Botox Administration

27. N Engl J Med 1999; 341:118-120July 8, 1999

28. Hemifacial spasm
Common movement disorders.
Characterized by unilateral muscle contractions of the face.
Involve any combination of orbicularis oculi, frontalis, risorius,
zygomaticus major, and platysma muscles.
Caused by irritation of cranial nerve VII by an artery compressing the
nerve as it exits the brain stem.

29. Dilution by 4 ml of Distilled Water

30. 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
Optimum goals of treatment with botulinum toxin

31. No absolute contraindications.
Relative contraindications include myasthenia gravis , motor neuron
disease.
Patients who are pregnant or lactating may not be appropriate
candidates for BTX therapy.
Contraindications

34. Nerve Supply of Facial Muscles

36. Supine Position

38. Treatment may be started with 10 U of BOTOX® per eyelid, injecting
a total of 20 U per patient.
The most common effective dose is 25 U per eye. Diluting the
BOTOX® with 4 mL of isotonic saline is recommended.
The principle is to avoid the mid portion of the upper eyelid into the
levator palpebrae superiores, which would lead to undesirable
ptosis.
Injection into the medial lower lid also is avoided.
Dose Per Eyelid

39. Complications
Blepharospasm 10 % of patients develop ptosis, which improves
spontaneously in less than 2 weeks.
Other complications include blurring of vision, tearing, and local
hemorrhage.
Lower face injections may result in facial weakness and asymmetry,
face and mouth droop, drooling, and loss of facial expression.

40. The lethal dose of BOTOX® in humans is not known, although it has
been estimated to be about 3000 U.
Lethal Dose of Botox

41. Hemifacial Spasm
Before After

42. Hemifacial Spasm
Before After

43. AfterBOTOX
Blepharospasm
Before BOTOX