UGC NET Paper 1 Mathematical Reasoning & Aptitude.pdf
botox presentation (1).pptx
1. Botulinum Toxin for Focal Hand
& Cervical Dystonia
Dr. Shobhit Gupta
GMC KOTA
2. • Dystonia is defined as an involuntary
contraction of the agonistic and antagonistic
muscles, which can lead to repetitive
involuntary movements and/or abnormal
positions.
3. Cause Of Dystonia
• Exact cause yet elucidated,
• Behavioral, genetic, gestural, environmental, and
psychological factors plays a role.
• Excessive activation of antagonists,
• overflow into synergists,
• prolongation of muscle activation
• deficiency of premotor cortical network
inhibition.
• Decreased levels of the inhibitory
neurotransmitter gamma-aminobutyric acid
(GABA) are present
4. Medical Management
• Drugs targets neuromuscular transmission
include:
• Anticholinergics, Baclofen and
benzodiazepines dopamine related
medications
• Botulin Toxin directly into the muscle cause
relaxation, and in many cases stop muscle
contractions that cause abnormal postures
5. Physiotherapy Management
• several approaches and will be dependent on
symptoms but the most common interventions
are:
• Sensomotor Training
• Muscle Strengthening
• Stretching
• Relaxation Techniques
• Home exercises
• Ergonomic changes at the instrument (Musician's
dystonia)
• Behavioral training
6. Immobilization
• shown to have a positive effects on focal
dystonia
• rational for improvement is the plastic
changes that occur at cortical level.
• SE: Immediately after immobilisation signs of
weakness, clumsiness and poor limb control,
• symptoms temporary and in most cases
improved within 4 weeks.
7. Surgery
• Indicated if symptoms are severe, have not
responded to other interventions
• Insertion of electrodes into the brain which
are connected to a generator, sends signals to
the brain which can control muscle
contractions and movement.
• Sever the nerves that control muscle spasm,
this is known as Selective Denervation Surgery
8. BOTOX
• 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
9. Botulism
o Poisoning that causes a fatal paralytic disease
o Probably known since humans have stored food
o Justimius Kerner
• Poet and Physician
• 1817-1822 publications correlating toxic agent in
improperly prepared and stored sausages----numerous
sausage poisonings reported in southwestern Germany
o Botulism
• From latin word botulus meaning sausage
• Sausage poisoning
• Causes a rapidly progressive profound weakness resulting
in death due to paralysis of respiratory muscles
10. • In 1988, drugmaker Allergan acquired the
rights to distribute Scott’s batch of botulinum
toxin type A (or Oculinum, as it was then
known) and a year later, the FDA approved
botulinum toxin type A for the treatment of
both strabismus and blepharospasm.
• Shortly thereafter, Allergan acquired Scott’s
company and changed the drug’s name to
compact, catchy “Botox.”
11. Further Development
o Bo NT considered for use as a weapon in WW I and II.
o 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
ToxicologyUniversity of WI
•
12. 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
13. MECHANISM OF ACTION
• The light chain cleaves
components of SNARE including
SNAP 25, VAMP/synaptobrevin ,
or syntaxin
• Prevents the fusion of
acetylcholine synaptic vesicle
with the plasma membrane.
• Blocks the release of the
neurotransmitter into the
synaptic cleft
14. Potency Of BoNT-A
• Measured in mouse units (MU).
• One MU of BoNT-A is equivalent to the
amount of toxin that kills 50% of a group of 20
g Swiss-Webster mice within 3 days of
intraperitoneal injection (LD50).
• 1 nanogram of toxin contains approximately
20 U of BOTOX® (ie, 1 U of BOTOX® is equal to
approximately 0.05 nanogram of the toxin).
15. • Requires 24-72 hours to take effect,
• Rarely some individuals require 5 days for the
full effect
• Peak effect at 10 days,
• the effect lasts nearly 8-12 weeks.
16. CONTRAINDICATIONS
• Patients afflicted with a preexisting motor
neuron disease, myasthenia gravis, Eaton-
Lambert syndrome, neuropathies,
psychological unstability.
• History of reaction to toxin or albumin.
• Pregnancy and lactating females.
• Infection at the injection site.
17. RELATIVE CONTRAINDICATIONS
• Some medications decrease neuromuscular
transmission, generally should be avoided in
patients treated with botulinum toxin. Includes :
• aminoglycosides (may increase effect of
botulinum toxin)
• penicillamine, quinine, chloroquine and
hydroxychloroquine (may reduce effect)
• calcium channel blockers, and blood thining
agents eg. warfarin or aspirin (may result in
bruising)
18. Counseling and Informed Consent
• Detailed counseling with respect to the
treatment, desired effects, and longevity of
the results should be discussed .
• A detailed consent form needs to be
completed by the patient. Should include the
type of botulinum toxin, longevity expected,
need for repeated treatments and possible
postoperative complications.
• Preoperative photography is mandatory.
19. Precautions after botulinum toxin
injection
• Pt. should be instructed to contract the
injected area for approximately 90 minutes to
two hours, which will help in the uptake of the
toxin.
• Avoid bending for a few hours after treatment
to avoid potential diffusion.
• One should go home immediately and rest
after Botox®.Do nothing strenuous for one or
two days.
20. Electromyograph monitoring
Technique involves uses 27-gauge (1.5 in) polytef-
coated EMG needle connected to an EMG
recorder by an alligator clip on its shaft.
• The patient asked to contract the muscle .
• injection is placed where the maximal EMG
recording can be found within the muscle.
• technique ensures injection at muscle point that
contributing most
• EMG-guided injections remain a useful adjunct in
patients who have residual function after their
initial injection
21. Side-effects/Safety
o Unintentional weakness
• Depends on location of injections
o Injection site reaction, bruising
o Development of antibodies
o Some spread of toxin to distant locations
• not clinically relevant in with expert use
o Expensive!!!!!!
• Manufactured biologically from refined strains of clostridium
botulinum
22. Hand dystonia
• Dystonia Medical Research Foundation
defines hand dystonia as a focal
dystonia characterized by excessive,
involuntary muscle contractions in the fingers,
hand, forearm, and sometimes shoulder.
25. • Initially, there will be marked tightness in muscles
responsible for the action being performed,
followed by the involvement of surrounding
muscles.
• Causes abnormal movements characteristic of
dystonia which may worsen with prolonged
activity of the involved muscles
• Initially appear to be task-specific dystonias and
progress over time into being less specific.
26. Clinical subtypes
• Simple writer’s cramp involves difficulty with
only writing. The abnormal postures and
involuntary movements begin soon after you pick
up a pen. It only affects your ability to write.
• Dystonic writer’s cramp moves beyond the one
task. Symptoms will show up not only during
writing, but also when doing other activities with
hands — like shaving or applying makeup.
27. Botulinum toxin therapy
• The first step is careful evaluation and selection
of muscles for injection
• The patient should be examined at
1. Rest and
2.During movements that specifically activate
the dystonia
• Patients should be asked to write without trying
to compensate
• Writing with the nondominant hand, which can
evoke dystonia in the dominant, resting hand
(mirror dystonia)
28. • botulinum toxin delivery better ensured by
use of specialized electromyographic (EMG)
needles with a hollow core
• Electromyographic guidance is especially
recommended where deeper muscles are
targeted
29. Outcome Measures
• Arm Disability Disability Scale
• Tubiana-Chamagne Scale (used for Musician's
dystonia)
• Writer's Cramp Rating Scale
31. Focal flexor subtype
• up to two fingers involved.
• Mov: thumb or the index
finger flexes with the
writing activities
• M/S: FPL or FPB in the
thumb flexion. Individual
fascicles of FDS or FDP can
also be involved.
32. Generalized flexor subtype
• hand has the tendency to flex after
the start of the writing.
• complains of pain and aching either
on the palm or flexor forearm muscle
group
• M/S: FCR and FCU often involved and
increased activations (FDS, FDP) and
palmaris longus
• When severe, pronator muscle group
may also be activated.
33. Focal extensor subtype
• M/S: (EPL) and
extensor indicis
proprius (EIP) are
involved
• With continuous use of
the dystonic hand,
further worsening may
lead to the generalized
extensor subtype
34. Generalized extensor subtype
• hand extends with
writing
• The patient
compensates by flexing
the fingers to hold the
pen.
• Intermittently different
fingers will extend
leading to dropping of
the pen
35. Arm abduction subtype
• the upper abducted with attempted
writing
• could be compensatory to
accommodate the dystonic
contraction of the generalized flexor
subtype.
• Sometimes the abduction of the arm
is the primary dystonic posture. In
these cases the deltoid muscle is
also involved.
36. Methods for muscle localization
(1) passive movement of the joint with
observation of needle,
(2) stimulation through the needle with
observation of movement, and
(3) ultrasound.
37. FPL
origin: anterior surface of the
middle half of the radius
insertion: palmarsurface of the distal phalanx of the
thumb.
The needle is inserted between the
middle and the distal third of the forearm.
Needle is verified by the patient flexing the distal
phalanx of the thumb.
Prior to needle insertion, the
radial artery palpated
• FPB has two heads.
• Origin: One head from flexor retinaculum,
trapezium, and trapezoid, other one is from
the second and third metacarpals.
• Insertion: lateral side of the base of the
proximal phalanx of the thumb.
• The needle inserted into the medial half of
the thenar eminence.
• The muscle is verified by the patient flexing
the thumb
38. FDP origin :proximal anterior surface
of the ulnar and the anterior interosseous membrane.
Insertion: palmar surface of the distal phalanges of the
second to fifth finger.
Localization: patient’s hand supinated
and the elbow flexed, the needle is inserted
at the middle of the forearm, passing through the
FCU and advanced tangentially toward the radial
side.
Each of the muscle fascicles can be identified by flexing
the distal phalanx of the second to fifth finger individually
• FDS origin: medial epicondyle and
coronoid process of the ulnar.
• Insertion: middle phalanges, second to
fifth digit. Localization: Patient’s arm
supinated, the needle is inserted at the
mid forearm, layer between PL &FCU
• Each fascicle of the FDS identified by
flexing the respective finger at middle
phalanx
40. FCR origin: medial epicondyle of
the humerus.
Insertion : second metacarpal
bone.
Localization: The needle is inserted at about
a third of
the distance from the medial epicondyle and
the
needle tip is verified by asking the patient to
flex
and adduct the wrist.
• PL origin: in the medial
epicondyle
• insertion : palmar aponeurosis
and flexor
• retinaculum.
• Localization: Needle is inserted
into the proximal upper third of
the line between the middle of
wrist and the medial
epicondyle.
• Caution: not to insert needle
too deeply FDP.
41. • The FCU origin: medial epicondyle of the
humerus
• Insertion :pisiform and hamate bone and the
fifth metacarpal bone.
• Localization: Needle inserted into the middle
of the muscle.
• The needle tip, verified by the patient flexing
with ulnar deviation of the wrist or by simply
flexing and abducting the fifth finger
42. Pronator quadratus origin: anteromedial aspect at
the distal part of the ulna
Insertion: Anteromedial aspect of the distal
part of the radius.
Localization:Forearm pronated, the
needle is inserted 3cm proximal to the ulnar styloid
close to the surface of the ulna.
Another approach dorsal surface of the distal
forearm, the needle is advanced through the
interosseous membrane to the pronator quadratus.
Pronation of forearm verifies the needle position.
Pronator teres origin: medial epicondyle
of the humerus and coronoid process of the
ulna.
Insertion: Lateral surface of the radius.
Localization: Forearm supinated, the
needle is introduced medial to the cubital fossa
about two fingers below the elbow.
Position is verified by the patient pronating the
forearm with slight elbow fle
43. EIPorigin: dorsal surface of the
ulna
Insertion : second finger.
Localization: hand is pronated
and the needle inserted into
the distal fourth of the
forearm lateral to the radial
side of the ulna.
Needle is verified by extension of
the index finger.
Caution : if needle inserted too
proximally, it will be in the EPL
44. Extensor pollicis longus/brevis (localization).
The EPL origin: posterior surface of the
middle third of the ulnar shaft and the posterior
interosseous membrane
Insertion : dorsal surface of the base of the distal
phalanx thumb.
Localization: The needle is inserted at the middle
third of the forearm along the radial side of the
ulna.
The position of the needle is verified by the
patient extending the thumb at the distal phalanx
45. Extensor digitorum communis (EDC) origin:
common extensor tendon
insertion: central slip into the middle
phalanges of fingers 2, 3, 4, 5 and two
collateral slips to the terminal phalanges of
the above four fingers.
Localization: The needle insertion point
is in the upper third on the line drawn
between the
lateral epicondyle and ulnar styloid
• The ECRL origin: distal third of
the lateral supracondylar ridge
of the humerus
• Insertion: dorsal surface and
base of the second metacarpal.
• Localization: forearm pronated,
extension and slightly abducts
the wrist radially, needle is
inserted 2–3cmdistal to the
elbow joint.
46. ECRB origin: lateral epicondyle
of the humerus and radial collateral ligament.
Insertion: dorsal surface of the base of the
third metacarpal bone.
Localization: Slightly distal and lateral to the
ECRL.
• The ECRL origin: distal third of the
lateral supracondylar ridge of the
humerus
• Insertion: dorsal surface and base of
the second metacarpal.
• Localization:With the forearm
pronated, extends and slightly
abducts the wrist radially,
• inserte the needle 2–3cmdistal to
the elbowjoint.
• The position verified by the patient
extending wrist toward the radial
side
47. APL origin: dorsal surface of the lower half of the ulna,
posterior interosseus membrane, and the middle third
of the radius.
Insertion: into the radial side of the base
of the first metacarpal bone.
Localization :The needle is inserted
at the junction of the middle and lower third of the
dorsal surface of the radial bone
49. Treatment of musicians’ focal dystonia
• Musicians’ focal dystonia is difficult to treat and
has uncertain results, requires a multidisciplinary
approach .
• Neurorehabilitation methods can be tried
include physical and psychological components
making a musician aware of their poor posture.
• BOTOX IS NOT EFFECTIVE IN MUSICIANS
DYSTONIA because of muscular weakness
• that follows botulinum toxin injection
50. Cervical dystonia
• Most Common form of focal dystonia
• characterized by involuntary, patterned
muscle contractions in the head and neck area
that cause the abnormal movements or
posturing
• may have tics to alleviate symptoms
• May be spasmodic or sustained.
• usually is a combination of the following head
positions
51. The clinical features of cervical
dystonia
• clinical presentation varies widely
• charactorized by involuntary, abnormal head
and neck movements and posturing
• upto 80%of patients have neck pain
• 30% of patients have head tremors
• Diagnosis often delayed more than 1 year
• mild cases may go undiagnosed
52. Cervical dystonia can be a lifelong
condition
• Frequently begins with pulling sensation in neck
or an involuntary twisting / jerking of the head.
• Neck pain at onset prominent.
• Symptoms typically progress, reaching
stabilization of symptoms after average of 3 to 5
years
• In about 33% of patients ,cervical dystonia
progresses to invove contagious parts
• Spontanious remissions occur in up to 20% of
patients,
- Usually occurs in first few years of onset
- Patients relapse within 5 years
53. Goal of Treatment
• Main goal of treatment is toi improve the
quality of life for the patient
- improve posture and jerky or tremulous
movement of head /neck
-decrease pain if present
- prevent development of secondary
complications
54. BoNT in CD
• Indicated in all forms CD.
• Worsening of CD
1. Due to resistance of BoNT
2. Result of an actual increase in severity
3. Wrong muscles have been injected.
• BoNT should be initiated as early as possible,
• Prevents secondary changes to the muscles
involved –
-contractures
- Muscle hypertrophy
- cervical discs may occur with longstanding CD
55. Practical considerations for BoNT
treatment of CD
• The following questions must be answered
before BoNT therapy of CD is considered:
1. Is the abnormal posture of the head and of the
shoulder induced by dystonia or by another
abnormality that only imitates CD?
2. Is the CD the primary cause of disability?
3. Does the patient have myasthenia gravis or other
neuromuscular junction disorders?
4. Are there already secondary changes of muscles
or connective and bony tissues?
56. BoNT dosing in CD
- Total and individual muscle dose higher in younger patients.
- Women with small necks usually require smaller doses.
- In case bilateral injections dose is reduced to prevent neck
weakness
-sternocleidomastoid and infrahyoid muscles- 1/2 of the
regular dose.
-splenius capitis and semispinalis capitis muscles- 60%of
regular dose.
-Lower dose used initially in newly diagnosed CD
- the individual muscles sensitivity BoNT not known
- probability of developing side effects are not known.
57.
58. Injection site
1. Number of injection sites within muscle
ranges from 1to 8 depending on size
• Multiple injection has better results,
- limit diffusion and reduce side effects.
- less incidence of dysphagia
2. Muscle hypertrophy and involved muscle
patterns change over time,
-needs alteration of injection sites over the
course of repeated sessions.
59. EMG
• may be useful when response becomes
unsatisfactory determine-
• Whether injected muscles are denervated
• Assist in identifying overactive muscles that may not have
been injected.
• Needle EMG is needed for-
• deeper muscles,
• superficial muscles when are close together
64. Muscles of importance for genesis and
treatment of torticollis. The sternocleidomastoid muscle
is injected contralaterally whereas the other muscles are
injected on the ipsilateral side. The sign X denotes
approximate injection site.
66. response
• Common CD rating scales include –
-TWSTRS-
-Tsui scale.
• recommended for clinical trials, routine
evaluation of CD and of BoNT treatment.
67. References
• Blitzer, A., Brin, M. F., Fahn, S., Lange, D. & Lovelace, R. E.(1986). Botulinum toxin (BOTOX) for the
treatment of“spastic dysphonia” as part of a trial of toxin injections for the treatment of other
cranial dystonias.
• Laryngoscope, 96, 1300–1. Brooks, V. (2001). In L. R. Squire, ed., The History of Neuroscience in
Autobiography. Vol. 3. New York: Academic Press, pp. 76–116.
• Pickett, A., Panjwani, N., O’Keeffe, R. S. (2003). Potency of type A botulinum toxin preparations in
clinical use.40th Annual Meeting of the Interagency Botulism Research Coordinating Committee
(IBRCC), Nov. 2003, Atlanta, USA
• Brin, M. F., Lew, M. F., Adler, M.D., et al. (1999). Safety and
• efficacy of NeuroBloc® (botulinum toxin type B) in typ A-resistant cervical dystonia. Neurology,
53, 1431–8.
• Comella, C. L., Buchmann, A. S., Tanner, C. M., Brown-Toms, N. C. & Goetz, C. G. (1992).
Botulinum toxin injection for spasmodic torticollis: increased magnitu of benefit with
electromyographic assistance. Neurology,42, 878–82.
• Kessler, K. R., Skutta, M. & Benecke, R. (1999). Long-term treatment of cervical dystonia with
botulinum toxin A:efficacy, safety, and antibody frequency. J Neurology,246, 265–74.
• Karp, B. I. (2004). Botulinum toxin treatment of occupational and focal hand dystonia. Mov
Disord, 19(Suppl 8), S116–19.
• Lee, H. & DeLisa, J. (2000). Surface Anatomy for Clinical Needle Electromyography. New York, NY:
Demos MedicalPublishing.
• Levy, L. M. & Hallett, M. (2002). Impaired brain GABA in focal dystonia. Ann Neurol, 51, 93–101.
