3. Myasthenia Gravis (MG) is a neuromuscular disorder
characterized by weakness and fatigability of skeletal
muscles.
Key Concept :-
It is due to the decrease in the number of available
acetylcholine receptors (AchRs) at neuromuscular junctions
due to antibody mediated autoimmune attack.
5. Highest prevalence rate is 20.4 per 100,000
population.1
Prevalence of disease is increasing since 1950s.
2,3
Improved recognition
High sensitivity & specificity of the test.
Longer life-span due to effective treatment
More people in the ‘at risk’ group due to increased
life expectancy.
6. Currently, there are 60,000 patients with myasthenia
gravis in Unites States.2
The incidence & prevalence increases substantially
after the age of 55 years.4,5
The chances of “only ocular disease” increases after
the age of 55 years.6
Atypical presentation :-
Weakness in the distal extremity.
Different immunological & electrophysiological findings.
Prevalence 7% of patients.7
7. Autoimmune channelopathy
Genetic predisposition:
HLA B8 & DR3
DR1 specific for ocular myasthenia
75% patients have abnormality of thymus
10% have thymoma.
8. Autoantibodies against nicotinic
acetylcholinrereceptors (nAchRs)
These antibodies prevent binding of Ach to its
receptors
Other action:
Destruction of receptors
By complement activation
Elimination by endocytosis
9. AchR antigenic peptide fragment
+ TCR (T- Cell receptor)
Activation of T-Helper cells
B- cells converts to plasma cells
Production of antibodies
SYMPTOMS
12. Fluctuation weakness increasing trough the day &
relieved by rest.
Extra ocular muscle weakness
Present in 50% of patients initially.
Present in 90% of patients during the course of disease.
Disease remains ocular in 16% of patients.
13. Usually affects one extra ocular muscle
Ptosis
Not limited by innervations of one cranial nerve
Limited adduction of one eye with nystagmus of the
abducting eye on attempted lateral gaze
Diplopia common.
Sclera below limbus may be visible due to weak
lower eyelid.
15. Weakness of intercostal muscles and diaphragm
may lead to CO2 retention
Weakness of pharyngeal muscles may collapse the
airway.
O2 saturation can be normal while CO2 is retained.
So, pulse oximetry is not reliable to detect the
amount of paralysis.
16. Palatal muscle weakness
Nasal voice
Nasal regurgitation
Swallowing may be difficult & regurgitation of
foods can occur.
Coughing & choking while drinking.
Limb weakness can also be present
Initially proximal but may follow distal muscles also.
17. Hyperthyroidism
Weakness may not improve simply by treatment of
patients with MG; with co-existing hyperthyroidism.
Rheumatoid arthritis
Scleroderma
Lupus
18. NEONATAL: In 12% of the pregnancies with a mother with
MG, she passes the antibodies to the infant through the
placenta, causing neonatal myasthenia gravis. The symptoms
will start in the first two days and disappear within a few
weeks after birth. With the mother, it is not uncommon for the
symptoms to even improve during pregnancy, but they might
worsen after labor.
CONGENITAL: Children of a healthy mother can, very rarely,
develop myasthenic symptoms beginning at birth, congenital
myasthenic syndrome or CMS. Other than myasthenia gravis,
CMS is not caused by an autoimmune process, but due to
synaptic malformation, which in turn is caused by genetic
mutations. Thus, CMS is a hereditary disease. More than 11
different mutations have been identified, and the inheritance
pattern is typically autosomal recessive.
JUVENILE: myasthenia occurring in childhood, but after the
peripartum period
19. Physical examination
Blood tests
Neurophysiology
Edrophonium test
Imaging techniques
Pulmonary function tests
20. Looking upwards & sidewards for 30 seconds
For diplopia & ptosis
Looking at the feet while lying on the back for 30
seconds
Keeping arms stretched forward for 60 seconds
Ten deep knee bends
Wallking 30 steps on both the toes & heels
“Peek Sign” – After initial apposition of lid margins,
they quickly start to separate (in 30 seconds) & the
sclera start to show.
22. Detection of acetylcholine receptor antibodies.
Sensitivity of 80-96%
50% of patients with only ocular disease may lack in these
antibodies
In some cases, anti-MuSK protein antibodies.
Antibodies against voltage-gated calcium channels
to differenciate from Lambert-Eaton Myasthenic
Syndrome (LEMS).
24. More used to differenciate myasthenic crises from cholinergic crises.
Paralysed Muscle
Myasthenic Crises Temporary Improvement
Edrophonium
Chloride
Cholinergic Crises No improvement
25.
26. Chest X-Ray
Detection of thymoma.
To detect lung cancer for alternate diagnoses i.e. lambert-
Eaton Syndrome.
CT-Scan
MRI Scan
29. Forced Vital Capacity is monitored to detect any
gradual loss of respiratory functions.
Negative inspiratory force is useful to detect
adequacy of ventilation.
30. To detect IgG antibodies against neuromuscular
junction.
31. Class I: Any eye muscle weakness, possible ptosis, no other
evidence of muscle weakness elsewhere
Class II: Eye muscle weakness of any severity, mild weakness of
other muscles
Class IIa: Predominantly limb or axial muscles
Class IIb: Predominantly bulbar and/or respiratory muscles
Class III: Eye muscle weakness of any severity, moderate
weakness of other muscles
Class IIIa: Predominantly limb or axial muscles
Class IIIb: Predominantly bulbar and/or respiratory muscles
Class IV: Eye muscle weakness of any severity, severe weakness
of other muscles
Class IVa: Predominantly limb or axial muscles
Class IVb: Predominantly bulbar and/or respiratory muscles (Can also
include feeding tube without intubation)
Class V: Intubation needed to maintain airway
33. Pyridostigmine Bromide -
Starts in 30-60 mins & effect lasts 3-6 hours
Caution for cholinergic crises.
34. Most commonly used corticosteroid in US
Significant improvement is often seen after a
decreased antibody titer which is usually 1-4 months
No single dose regimen is accepted
Some start low and go high
Others start high dose to achieve a quicker response
Clearance may be decreased by estrogens or digoxin
Patients taking concurrent diuretics should be
monitored for hypokalemia
35. Drugs that alter the immune response can be used.
Commonly used drugs are
Azathioprine
Cyclosporine
Mycophenolate
36. Plasmapheresis
Filters out the antibodies from blood
Effect lasts only for a few weeks.
IV immuneglogulin
Provides body with antibodies
Binds to circulating antibodies.
38. Diet
Thickened liquids are preferred, when dysphagia arises to
counteract the fear of aspiration.
Asparagus should be taken as it contains steroid-like
substance.
Activity
Patients should be as active as possible but should take
rest in between.
Yoga exercises to stretch the weakened muscles should be
done.
This not only strengthens the muscles but also provides
oxygen & removes carbon dioxide from them.
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myasthenia gravis in British Columbia: a population-based study [abstract]. Neurology
2002;58(suppl 3):A185-A186
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myasthenia gravis. Neurology 1996;47:1233-1238
4. Kalb B, Matell G, Pirskanen R, Lambe M. Epidemiology of myasthenia gravis: a
population-based study in Stockholm, Sweden. Neuroepidemiology 2002;21:221-225
5. Phillips LH, Torner JC, Anderson MS, et al. The epidemiology of myasthenia gravis in
central and western Virginia. Neurology 1992;42:1888-1893
6. Jaretzke A, Barohn RJ, Ernstoff RM, et al. Myasthenia gravis. Recommendations for
clinical research standards. Neurology 2000;55:16-23
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