Teaching slides on Myasthenia Gravis

1. Neuro-ophthalmology
Myasthenia Gravis
Dr M D Mohire, MD, DM
Neurology Centre & Research Kolhapur

2. Myasthenia Gravis
Highly Complex Phenotype for inexpirienced
Clarity of Clinical Features
Skill of iliciting Clinical Signs
Myasthenia Mimics & Differential Diagnosis
Excellent Model to learn Clinical Neurology & Neuroimmunology

4. Physostigmine for MG in 1934

5. John Simpson - 1922 - 2009
Autoimmune Theory of Myasthenia Gravis in 1960

6. Epidemiology
 Incidence 1/10,000 in US, 1/20000 in UK
 Females > Males
 In US 25000 cases
 In India 100,000 cases
 Peak age 2 nd & 3 rd decades,
 Second Peak 70 plus
Diagnosis is delayed for 2 yrs

7. Drachman D. N Engl J Med 1994;330:1797-1810
Normal (Panel A) and Myasthenic (Panel B) Neuromuscular Junctions
AChR antibodies impair the neuromuscular transmission
by complement-mediated focal muscle
membrane damage, accelerated degradation of
AChR,

8. Clinical Features
Weakness of Limb muscles, Lower & Upper
Weakness of Ocular & Bulbar Muscles
Weakness of Respiratory Muscles
Weakness of Neck & Trunk Muscles
Fatiquability with Diurnal Variation
Pure Motor Syndrome with DTR preserved

9. Class Distribution
I Ocular
II Mild generalized weakness, usually with ocular muscle weakness
III
Predominantly bulbar involvement, usually with mild generalized
weakness
IV Moderate generalized weakness
V Severe generalized weakness
Ann Thorac Surg 2006;82:1863-1869
Modified Osserman Classification

10. Diagnosis
Neurological Examination (Clinical)
Edrophonium Test / Ice Pack Test
Blood Analysis (Antibodies)
Neurophysiological (Repititive Nerve Stimulation / Single Fibre EMG
MRI of Chest for Thymoma
Respiratory Function Tests

11. 1- primary position, 2- upward gaze for >20 seconds, 3- primary position, 4- forced
lid closure, 5- eyes open in primary position. A short lived lid twitch sign is
encountered after re-opening.
Ptosis in myasthenia gravis: Extended fatigue and recovery bedside test
Klaus V. Toyka,

12. Tensilon Test
Arch Ophthalmol. 1965;74(2):217-221.
Before After

13. ICE Pack Test
It is performed by keeping Icepacks over eyes for 2-5
minutes & looking at improvement in Ptosis
Cooling improves Neuromuscular Transmission-

14. Chest X-ray showing Thymoma

15. Large mass in the left Ant Mediastinum, Histology revealed thymoma
CT Scan of Chest Showing Thymoma

16. Lange, D. J. Neurology 1997;48:18S-22S
Repetitive stimulation at 3 Hz in the medianthenar system in a patient with mild generalized
myasthenia gravis. A: Pre-exercise, showing decrement with U-shaped response. B: Immediately
after 10 seconds of maximal exercise, showing postactivation facilitation (note change in
amplitude). C: Three minutes after 1 min of maximal exercise, showing postactivation exhaustion.
A
B
C
Decrement . 10 %
Post activation Facilitation
Post activation Exaustion

17. Neuromuscular Junction and Key Elements for the Pathogenesis of Myasthenia Gravis.
Gilhus NE. N Engl J Med 2016;375:2570-2581

18. AchR Antibody Negative
Seronegative Patients

19. Antibodies in Myathenia Gravis
AchR Antibody Positive
Musk Antibody Positive
LRP-4 Antibody Positive
Cortactin Antibody Positive
Striational Antibodies-Titin, RyR and Kv1.4 Positive
Ach R Posititive in 85% of Myasthenia Gravis
Seropositive MG has more severe Disease
MuSK Positive require advanced Treatment, sometimes resistant

20. Subgroups of Myasthenia Gravis
Gilhus NE. N Engl J Med 2016;375:2570-
2581

21. Disorders Associated with Myasthenia Gravis
Thyroid Disorders
Collagen Vascular Disorders
Autoimmune Disorders
Diabetes Mellitus
More than 100 diseases are Associated with Myasthenia Gravis

22. Treatment Of Myasthenia Gravis
Anticholinesterases
Corticosteroids
Azathioprine
Mycophenolate Mofetil
Plasmapheresis
Gammaglobulines
Rituximab
Thymectomy

23. Thymoma
Task Force of the Medical Scientific Advisory Board of the
Myasthenia Gravis Foundation of America et al. Neurology
2000;55:16-23
©2000 by Lippincott Williams & Wilkins
During Thymecomy
Thymic nodules in
mediastinal
fat,retrothyroid,cervi
cal lobes & behind
innominate vein need
careful watch

24. An encapsulated cystic thymoma.
Enlarged Thymus

26. Crisis in Myasthenia Gravis

27. MuSK Positive MG
Female: Male Ratio, 3:1
Age of Onset, 6-68 yrs, 60% Under 40 Years.
Cranial & Bulbar Muscles severely involved
High frequency of Respiratory Crisis,
Limb Muscle involvement less Severe
Edrophonium test negative in 30 %
Response to Pyridostigmine Unsatisfactory
Thymus Atrophic, No Benefit from Thymectomy
PLEX & Immunosupression Good response
Remission & Exacerbation frequent
Mild Residual Weakness after Treatment
Sometimes Poor Response to all Treatment
AchR Positive MG
Female : Male Ratio, 2:1
Age of Onset, 2 nd & 3rd decade, late
Peak at 70 Plus
Respiratory Crisis Uncommon
Limb Muscle Weakness more severe
Edrophonium Test mostly Positive
Pyridostigmine Good Response
Thymus enlargrd-Thymoma
PLEX & Immunosupresants Good Response
Remission mostly, Less Exacerbation
No Residual Weakness after Treatment
Excellent Response to all Modalities

28. MuSK Ab Positive Myasthenia Gravis
Atrophic Triple furrowed tongue

29. Patient at age 34 years.
Triple Furrowed Tongue in MuSK Positive

30. Features of Myasthenia Gravis Subgroups.
Gilhus NE. N Engl J Med 2016;375:2570-2581

31. Drugs Used Most Frequently for the Treatment of Myasthenia Gravis.
Gilhus NE. N Engl J Med 2016;375:2570-2581

32. DD of Myasthenia Gravis
Botulism
AIDP (GBS)
CIDP
Hypokalemic PP
Myotonia Dystrophica
Mitochondrial Muscle Disease
Lambert Eaton Myathenic Syndrome
Top of the Basilar Syn
Snake bite, Tick bite, Scorpion bite
ALS
Organophosphorous Poisoning
Muscular Dystrophy
FSHD
LGMD
Oculopharyngeal MD
Polymyositis-Dermatomyositis Kennedy Syndrome
Miller Fisher Syndrome

33. Ach Recepror antibody Positive Myathenia Gravis

34. MuSK antibody Positive Myathenia Gravis

35. Miller Fisher Syndrome