Myasthenia Gravis is an autoimmune neuromuscular disorder characterized by muscle weakness and fatigability. It is caused by antibodies that block acetylcholine receptors at the neuromuscular junction, preventing muscle contraction. Symptoms vary widely and can include weakness of the eye muscles, facial muscles, limbs, and respiratory muscles. Diagnosis involves physical exams, blood tests to detect antibodies, and electrodiagnostic tests. Treatment options include acetylcholinesterase inhibitors, immunosuppressants, plasmapheresis, intravenous immunoglobulin, and thymectomy.

1. Tikal Kansara
Baroda Medical College (BMC)

2. Photo Courtesy - http://www.beverlyhillsneurology.com/myastheniagravis-
symptoms.html

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.

4.  Epidemiology
 Pathophysiology
 Clinical Features
 Diagnosis
 Treatment

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

10. http://jama.ama-assn.org/content/298/1/29/embed/graphic-1.jpg

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.

14. Image Courtesy -
http://www.nanosweb.org/i4a/pa
ges/index.cfm?pageID=3286
Image Courtesy -
http://daily--
alerts.blogspot.com/201
1/06/myasthenia-
gravis.html

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.

21. Photo Courtesy - http://www.eacog.org/2011/06/myasthenia-gravis-photos-and-
pictures/

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).

23.  Repetitive nerve stimulation test.
 Electromyography.

24. More used to differenciate myasthenic crises from cholinergic crises.
Paralysed Muscle
Myasthenic Crises Temporary Improvement
Edrophonium
Chloride
Cholinergic Crises No improvement

26.  Chest X-Ray
 Detection of thymoma.
 To detect lung cancer for alternate diagnoses i.e. lambert-
Eaton Syndrome.
 CT-Scan
 MRI Scan

27. http://radpod.org/wp-
content/uploads/2006/
12/malignant_thymom
a_sml.JPG

28. http://upload.wikimedia.org/wikipedia/commons/3/3f/Tumor_Thy
moma1.JPG

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

32.  AchE Inhibitors
 Immunomodulatory Therapies
 Plasma Exchange
 Thymectomy

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.

37.  Thymectomy
 Surgical removal of thymus.

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.

39. 1. Isbister CM, Mackenzie PJ, Anderson D, et al. Co-occurrence of multiple sclerosis and
myasthenia gravis in British Columbia: a population-based study [abstract]. Neurology
2002;58(suppl 3):A185-A186
2. Phillips LH. The epidemiology of myasthenia gravis. Ann N Y Acad Sci 2003;998:407-412
3. Phillips LH, Torner JC. Epidemiologic evidence for a changing natural history of
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
7. Werner P, Kiechl S, Löscher S, et al. Distal myasthenia gravis: frequency and clinical
course in a large prospective series. Acta Neurol Scand 2003;108:209-210

40.  Epidemiology :-
 http://www.medscape.com/viewarticle/482694
 Pathophysiology
 http://en.wikipedia.org/wiki/Myasthenia_gravis#cite_note-5
 Clinical Features
 http://estudiantesdemedicina.wordpress.com/
 Diagnosis
 http://en.wikipedia.org/wiki/Myasthenia_gravis#cite_note-5
 Treatment
 http://estudiantesdemedicina.wordpress.com/
 http://www.slideshare.net/drshama65/mysthenia-gravisppt

41. TIKAL KANSARA
INTERN
CIVIL HOSPITAL
AHMEDABAD