2. Definition
• Myasthenia Gravis (MG) is a neuromuscular
autoimmune disorder characterized by
Weakness of skeletal muscles, in which IgG
autoantibodies interact with the postsynaptic
acetylcholine receptors (AChR) at the nicotinic
neuromuscular junction (NMJ)
• On average MG patients have 30% of the
normal number of functional AChR
6. History of MG
Myasthenia (Greek – muscle
illness)
Gravis (Latin – “grave or
serious”)
First description in the 17th
century
Sir Thomas Willis
“a woman who spoke freely and
readily enough for a while, but after
a long period of speech was not
able to speak a word for one or two
hours”
8. First thymectomy, 1939
• Alfred Blalock
• 21 year old woman with
“cystic thymic tumor” and MG
• Able to stop prostagmine
• No recurrence of symptoms
over 3 year follow-up period
•“We wish to emphasize again the
absence of conclusive proof that the
improvement noted in our patient is
due to removal of the tumor..”
9. Epidemiology
Prevalence: 100 per 100 000 population
incidence: 2-4 per 100 000 per year
All age groups
Women in 20-30’s
Men in 40-60’s
W:M--- 3:2
Mortality/Morbidity: In the past, untreated
MG had a mortality rate of 30-70%, now
most patients with MG have a near-normal
life expectancy
BIMODAL PEAK
10. Pathophysiology
Autoantibodies against AChR at the neuromuscular
junction (NMJ) of skeletal muscles: 85 % of patients
with generalized myasthenia and 60% of those with
ocular myasthenia shows AChR Antibodies
Anti-MuSK Ab(40% of seronegative cases) An immune
response to muscle-specific kinase (MuSK) can also
result in myasthenia gravis, possibly by interfering
with “AChR clustering
.
11. Pathophysiology
The AChR antibodies reduce the number of
functional receptors by:
binding and activation of complement at the NMJ;
accelerated degradation of AChR molecules by
internalization of the antibody-labeled receptor; and
functional AChR block that prevents functional binding of
Ach
90 % of patients with MG have some degree of thymus
abnormality (eg, hyperplasia in 85% , thymoma in 15% ).
Autoimmune disorders such as thyroiditis, pernicious
anemia, and systemic lupus erythematosus are
common in patients with myasthenia gravis.
15. CLINICAL FEATURES
The incidence is age and sex-related, with one peak
in the second and third decades affecting mostly
women and a peak in the sixth and seventh decades
affecting mostly men
The cardinal features are weakness of skeletal
muscles
The weakness tends to increase with repeated
activity and improve with rest.
17. OCULAR MUSCLE WEAKNESS
• ASYMMETRIC
• Usually affects more than one extraocular muscle
and is not limited to muscles innervated by one
cranial nerve
• Ptosis is caused by Levator palpebrae weakness
• Diplopia is very common
• Bright sunlight aggravate the ocular signs and
COLD improves them
18. Facial muscle weakness is almost always present
Bilateral facial muscle weakness
Sclera below limbus may be exposed due to weak
lower lids
Muscles of facial expression & characteristic flattened
smile
19. BULBAR MUSCLE WEAKNESS
Bulbar muscle weakness ( more in Anti MuSK Ab
positive cases)
Palatal muscles
• “Nasal voice”, nasal regurgitation
• Chewing may become difficult
• Severe jaw weakness may cause jaw to hang open
• Swallowing may be difficult and
• Aspiration may occur with fluids—coughing and
choking while drinking
Neck muscles
• Neck flexors affected more than extensors
20. LIMB MUSCLE WEAKNESS
• Upper limbs more common than lower limbs
• Proximal > than distal muscles
• Usually asymmetric weakness
Upper Extremities
Deltoids
Wrist extensors
Triceps > Biceps
Lower Extremities
Hip flexors (most common)
Quadriceps
Hamstrings
Foot dorsiflexors
Plantar flexors
21. RESPIRATORY MUSCLE WEAKNESS
• Weakness of the intercostal muscles and the diaphragm
may result in CO2 retention due to hypoventilation
• If weakness of respiration becomes severe enough to
require mechanical ventilation, the patient is said to be in
crisis
• Weakness of pharyngeal muscles may collapse the upper
airway
• Monitor negative inspiratory force, vital capacity and tidal
volume
• Do NOT rely on pulse oximetry
• Arterial blood oxygenation may be normal while CO2 is
retained
22. CO-EXISTING AUTOIMMUNE DISEASES
1. Hashimoto’s thyroiditis/thyrotoxicosis
Occurs in 5-10% MG patients
Weakness may not improve with treatment of MG alone
in patients with co-existing hyperthyroidism
2. Rheumatoid arthritis
3. Scleroderma
4. Lupus erythematosus,
5. Mixed connective tissue disease
6. Anticardiolipin antibody
7. Polymyositis
23. Drugs to be avoided in MG
Myasthenic
Weakness
exaggerated
Erythromycin
Azithromycin
Local
anesthetic
xylocaine
Streptomycin
Ciprofloxacin
Levofloxacin
Ofloxacin
Gatifloxacin
Non depolarizing
muscle relaxants –
Propranolol
atenolol
Quininine
Magnesium
penicilliamine
24. CLASSIFICATION OF MG
(OSSERMAN)
Grade I – only eyes affected,
Grade IIa – mild generalised MG responding
well to therapy,
Grade IIb – moderate generalised MG
responding less well,
Grade III – severe generalised disease,
Grade IV – myasthenic crisis requiring
mechanical ventilation
25. Tensilon Test
Before After
Up to 10mg Edrophonium is administered IV is
standard test.
Most pts show marked improvement after 30sec
and lasts 5min
26. Antibody test
AChR antibody test:
Positive in 85% of MG patients
Negative test does not exclude MG
Measured levels does not correlate with severity of MG
Fall in Ab on treatment –clinical improvement .
MuSK antibodies in 40% of AChR negative, generalized MG
27. Electrical tests
Repetitive nerve stimulation (RNS)
Anti Ach E medication to be stopped before 6-24 hrs.
Weak and proximal muscles to be tested.
Deliver shocks at 2-3 sec
Normally amplitude does not change
In MG 10-15% DECREASE
DECREMENTAL RESPONSE
28. Imaging
A chest Xray is indicated to determine the presence of aspiration
or other pneumonias, which commonly occur in patients with
MG.
CT scan or MRI of the chest is highly accurate in detecting
thymoma and should be done in every new presentation.. Chest
radiography is relatively insensitive in screening for thymoma, as
it does not detect up to 30% of cases.
Thymoma
29. MYASTHENIC CRISIS
A rapid and severe deterioration of
myasthenia called “myasthenic crisis” causing
respiratory failure and quadriparesis in hours
Respiratory infection or a sedative medication with
NM block may be the reason
It can develop at any time after the diagnosis of
myasthenia
Anticipate if patient is restless, anxious with
diaphoresis and develops tremor.
Require respiratory support
30. CHOLINERGIC CRISIS
Cholinergic crisis results from an excess of cholinesterase
inhibitors (neostigmine, pyridostigmine, physostigmine)
and resembles organophosphate poisoning.
Excessive ACh stimulation of striated muscle at nicotinic
junctions produces flaccid muscle paralysis that is
clinically indistinguishable from weakness due to MG
cholinergic crisis may cause bronchospasm with
wheezing, bronchorrhea, respiratory failure, diaphoresis,
and cyanosis.
Miosis and the SLUDGE syndrome (salivation, lacrimation,
urinary incontinence, diarrhoea, GI upset and
hypermotility, emesis) also may mark cholinergic crisis
# from myasthenic crisis, edrophonium test
31. Management of myasthenic crisis
1. Acetylcholine esterase inhibitors
Physostigmine 8–24 mg/day IV
2. Glucocorticosteroids
Up to 500 mg methylprednisolone IV (with gradual reduction
on remission)
3. Plasma separation techniques
Plasmapheresis (non-selective) or additional immune
adsorption (semi-selective),
Exchange of 1–2 plasma volumes 2–3 × weekly for 2 weeks
4. Immunoglobulins IV
0.4 g/kg on 5 consecutive days
5. Immunosuppressive long term therapy Begin as soon
as possible or continue at a higher dose/combination
32. DIFFERENTIAL DIAGNOSIS
o Presynaptic disorder .
o Proximal muscles of lower limbs mostly affected.
o Ptosis -70% cases
o or absent reflexes.
o Autonomic features present
o Incremental response on repetitive nerve stimulation.
o P/Q type Ca channels at motor nerve terminals -85%
cases.
o Usually associated with Small Cell Ca Lung.
o Rx – Plasmapheresis, immunosuppression
o 3,4 diaminopyridine –blocks K channels- inc Ach release
o Pyridostigmine –prolongs Ach actions
Lambert Eaton Myasthenic Syndrome:
33.
34. TREATMENT
Four methods of treatment are currently in use:
Enhancement of neuromuscular
transmission with anticholinesterase agents
Surgical thymectomy,
Immunosuppression, and
Short-term immunotherapies, including
plasma exchange and intravenous
immune globulin
35. Anticholinesterase medications
• At least partial improvement
• PYRIDOSTIGMINE (Mestinon) :most widely used drug
• Onset within 15-30 min
• Lasts for 3-4 hrs
• 30-60 mg tid
• Max dose 120 mg 3 hrs daytime
• Muscarnic side effects –diarrhea, abdominal cramps
salivation –atropine, lopermaide
37. Immunomodulatory therapy
[Short-term]
Plasmapheresis:
6 sessions, every other day.
Improvement during treatment and the 1st
week after treatment.
Improvement last 1-2 months.
IVIG
0.4 mg/kg for 3 or 5 consecutive days.
Effect seen 4 days to 2 weeks after Rx and lasts
1-2 months.
When acute temporary improvement is
needed.
40. Surgical Thymectomy
Indicated for its therapeutic effect in
myasthenia gravis or to prevent the spread
of a thymoma
The goal of thymectomy as a treatment for
myasthenia gravis is to induce remission, or
at least improvement
The mechanism by which thymectomy
produces benefit in myasthenia gravis is still
uncertain. In general, acetylcholine-receptor
antibody levels fall after thymectomy
41. Pre operative assessment
Patients should be admitted 24-48h before surgery
Assessment of respiratory function (serial FVC on the ward) and bulbar
weakness (SALT)
Chest physiotherapy
Optimize immunosuppression and anticholinesterase therapy
Consider IV Ig or plasma exchange
Consider ITU bed, prolonged ventilation post op more likely if:
Stage III or IV disease
Chronic respiratory disease
FVC <2.9l
Long history of disease (>6 years)
Exclude associated thyroid disease or DM
Airway ?RA ?Thymic mass compressing
42. Premedication
Give anticholinesterases or not? Why?
Omit anticholinesterase therapy as this may prolong action
of sux, require increased doses of non depolarising
neuromuscular blocking drugs
Myasthenic patients may have little respiratory reserve and
hence depressant drugs for preoperative premedication
should be used with caution, and avoided in patients with
bulbar symptoms,
Anticholinergic may be useful.
Increased steroids, IV hydrocortisone
43. RESPONSE TO ANESTHETIC DRUGS
Nondepolarizing Neuromuscular Blockers
MG patient is typically sensitive to NDNMB: lower
number of receptors that need to be blocked in the
NMJ
Long acting NDNMB (pancuronium, pipecuronium,
doxacuronium) :avoided
Intermediate and short acting: used with careful
Vecuronium ED95: 40% - 55% of normal
Atracurium ED95: 58% of normal
Monitoring: BY EMG, MMG, AMG
Single twitch (0.1-1Hz), Train-of-four (2Hz), Tetany(50-
100Hz), Double-burst stimulation.
47. Depolarizing Neuromuscular Blocker
(Succinylcholine)
Unpredictable response to suxamethonium
MG patients show resistance to depolarizing
agents.( ED95 : 2.6 times of control )
MG patients are more likely to develop phase
II block , particularly with repeated doses of
succinylcholine
48. Potent Inhaled Anesthetic Agents
Isoflurane , enflurane: decrease TOF
responses
Sevoflurane at 2.5% depresses EMG
responses ( T1/Tc at 47%, T4/T1 at 57%).
A recent report found sevoflurane was
suitable as a sole anesthetic for a myasthenic
undergoing sternal split thymectomy,
implying that sevoflurane alone provided
adequate muscle relaxation
49. Intravenous Anesthetic Agents
Propofol
Anesthetic management using propofol without
untoward effects have been described.
Short duration, no effect on NM transmission.
Opioid
Do not appear to depress NM transmission in MG
muscle.
Central respiratory depression may be a problem.
Use of short-acting opioids : more titratable.
Remifentanil (elimination half-life:9.5min)
50. Regional Anesthesia
Potentiation of NM blockade by local anesthetics
has been reported.
Ester anesthetics, metabolized by cholinesterase,
may present particular problems in patients taking
anticholinesterases.
Use reduced doses of amide (lidocaine, bupivacaine)
to avoid high levels.
51. Anesthesia Management
The anesthetic management of the myasthenic patient
must be individualized to the severity of the disease and
the type of surgery
Several GA techniques have been proposed, none has
been proven to be superior.
General anesthesia can be performed safely, provided the
patient is optimally prepared and neuromuscular
transmission is adequately monitored during and after
surgery.
Use of Muscle Relaxants ?
The use of muscle-relaxants in patients with MG has been
associated with
o a higher rate of unsuccessful extubation at the end of surgery
o longer postoperative mechanical ventilation and hospital stay.
52. Anesthesia Management
Avoid muscle relaxants. Use inhaled agents both for
facilitating intubation and providing relaxation for surgery.
Titrate small doses (10-25% ) of intermediate-acting
muscle relaxants and titrated to effect by giving small
increments
It is recommended that the baseline neuromuscular block
be tested before inducing anesthesia and again before
administration of NDNMB
Patients with a decreased T1/T4 ratio before anesthesia is
administered are at increased risk for postoperative
weakness and the possibility of prolonged mechanical
ventilation
53. Anesthesia Management
TIVA for the management of myasthenics has
been reported.
When possible, many clinicians prefer
regional or local anesthesia
Regional techniques- reduce or eliminate the need
for muscle relaxants in abdominal surgery
54. Postoperative management
Ventilatory function must be monitored carefully after surgery.
Myasthenic patients may be at increased risk of developing
postoperative respiratory failure – following trans-sternal
thymectomy, up to 50% of patients require prolonged
postoperative ventilation
Adequate analgesia should be provided; however, oversedation
from narcotic drugs is undesirable
Differential diagnosis:
1.Myasthenic crisis
2. Residual effects of anesthetic drugs
3. Nonanesthetic drugs interfering neuromuscular
transmission
4.Cholinergic crisis.
55. Postoperative management
Four risk factors have been identified:
Duration of myasthenia gravis for longer than six years
(12 points).
A history of chronic respiratory disease other than
respiratory dysfunction directly due to MG (10 points).
A dose of pyridostigmine greater than 750 mg per day
(8 points).
A preoperative vital capacity < 2.9 L (4 points)