Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies against acetylcholine receptors at the neuromuscular junction. It causes muscle weakness and fatigability. It most commonly affects young women and older men. Symptoms include drooping eyelids, double vision, difficulty speaking and swallowing. Diagnosis involves testing for autoantibodies, electrophysiology and response to medication challenges. Treatment includes anticholinesterases, immunosuppression, thymectomy and management of exacerbations. Anesthetic management focuses on optimizing the patient, using regional techniques when possible and careful airway management and extubation planning due to risk of respiratory failure.

1. MYASTHENIA GRAVIS-
anaesthetic concerns
Dr.Malaka Munasinghe
Registrar in Anaesthesia
2015.12.02

2. Outline
 Introduction
 Epidemiology
 Pathophysiology
 Classification
 Clinical features
 Differential Diagnosis
 Treatement
 Anaesthetic considerations

3. History
 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”

4. Myasthenia Gravis
 Chronic autoimmune condition
 Autoantibodies –NMJ post junctional Ach
receptors
Skeletal muscle weakeness and fatigability

5. Epidemiology
 Incidence
2-4 per 100,000 per year
 Prevalence
100 per 100,000
 Young women(20-30) and Older men(60-
70)

6. Pathophysiology
Neuromuscular junction

9. Anti-AChR
Abs
T
T
T
T
B
Plasma cellAPC
Nerve Terminal
Postsynaptic membrane
AChR
MuSK
Rapsyn
AChase
ACh
Voltage-gated
Na+ channel
Voltage-gated
Ca+ channel
Ca++Ca++
AChR
MuSK

10. Autoantibodies
 Ach receptor antibody(AchR)-IgG
( Positive in 85% of patients)
 Muscle specific tyrosine kinase antibody
( MuSK)

11. Anti Ach antibodies
 Reduce the number of functional
receptors
1. Blockade of Ach molecule binding to
receptor
2. Increase rate of Ach receptor
degredation
3. Complement induced damage to NMJ

12. Thymus and Myasthenia
• Abnormal in 85% of patients
-85% Hyperplasia
-15% Thymoma
 Myoid cells in Thymus express Ach
Receptors
T and B cells in Thymus get sensitized
produce Antibodies

13. Osserman’s classification
Type
I Ocular signs and symptoms only
11A Generalized mild muscle weakeness responding well to
therapy
IIB Generalized moderate muscle weakeness responding less
well to therapy
III acute fulmination presentation and/or respiratory
dysfunction
IV Myasthenic crisis requiring arteficial ventilation

14. Presentation
 Fatigability and weakeness
 Diplopia/Ptosis
 Disabled chewing
 Dysphagia
 Dysphonia/dysarthria/Nasal speech
 muscle weakeness- Neck
- Limb girdle
- Respiratory
 No AUTONOMIC features
 No SENSORY features
 15% Of patients- extraocular muscle involvement only

15. Ptosis

16. D/D
 Neuromuscular junction diorders
- Lambert-Eaton syndrome
- Botulism
- Acquired Neuromyotonia
- Congenital myasthenia
- Drug induced myasthenia gravis
 Metabolic and toxic myopathies
 Brain stem
diseases(ischaemic/inflammatory/neoplastic)

17. Diagnosis
 History
 Examination( Absence of autonomic and sensory fx)
 Ix
- Serological (Autoantibodies)
- Electrophysiological ( Decremental motor response to
repetitive stimulation of motor nerves)
- Pharmacological ( Tensilon test)
- Imaging (CT/MRI chest+neck)

18. IV 10 mg Edrophonium injected-after 30 seconds
Improved muscle power for up to 5 minutes
Tensilon Test
Before After

19. Associated conditions
 Thyroid disorders(Hypo/hyper)
 Rheumatoid arthritis
 Pernicious anaemia
 SLE
 Sarcoidosis
 Polymyositis
 Ulcerative colitis
 Sjogren’s disease

20. Treatement
Anticholinergic drugs
- Pyridostigmine/Neostigmine
Immune-directed treatments
• Short-term
Plasmapheresis, IV Immunoglobulin
• Long-term
- Corticosteroids
- Immunosuppressive drugs( Azathioprine/Cyclosporine)
- Thymectomy( 25% complete remission)

21. Treatement
 Pyridostigmine
- Onset 15-30 min
- Peak effect 2h
- Duration 4hrs
- Dose 30mg tds – 90 mg 6hrly
- CHOLINERGIC CRISIS

22. Prednisolone
 Low dose 10-20mg/d- increment of 5mg every 3rd day
up to 60mg/d
 Gradual tailing off to a aminimum EOD dose

23. Azathioprine
-Dose 1-2mg/kg/d
S/E
-Bone marrow suppression/Liver toxicity/Idiosyncratic fly like
illness
Cyclosporine
- Dose 5mg/kg/d
S/E
- Nephrotoxicity/Hypertension

24. IV immunoglobulin
Indications
• Severe myasthenia gravis
• myasthenic crisis
• Intractable myasthenia
• Preop and post op period
• DOSE-400mg/kg for 5days
Plasmapheresis
- Quick onset
- Same efficacy

25. Thymectomy
• For patients of 15-60 years
• Total excision needed
• Indications
-Thymoma
- Thymic hyperplasia
- Myasthenia gravis

26. Drugs exacerbating MG
• Antibiotics-
Macrolides/aminoglycosides/tetracycline/Chloroquine
• Antidysrhythmic agents-
Beta-blockers/calcium channel
blockers/lidocaine/quinidine/procainamide
 Misc
Lithium/muscle relaxants/levothyroxine/ACTH

27. Anaesthetic considerations
 Respiratory reserves
 Optimization
- medication/ntrition/chest infection
 Premedication
- Depressants/Anticholinergics
 Steroid cover
 Mode of anaesthesia
 Prediction of need of post op ventilation

28. Mode of anaesthesia
 Regional and local anaesthesia preferred
 GA
o Monitoring( AAGBI+NM Monitoring+IABP)
o Intubation under inhalational induction
o Intubation with relaxants- DMR-Increased dose
- NDMR- Reduced dose
 Reversal not usually needed( risk of Cholinergic crisis)

29. Post operative management
 Confirm respiratory and bulbar muscle power before
extubation
 Identify patients who need post op ventilation
1. Duration of MG> 6 years (most influential)
12points
2. A history of chronic respiratory disease which is not
directly due to MG 10 points
3. A dose of pyridostigmine>750mg/d, 48 hrs before Sx
8 points
4. A preop vital capacity<2.9l 4 points
Total score>10-need post op ventilation

30. Myasthenic crisis
 Exacerbation of myasthenia leading to paralysis of
respiratory muscles requiring urgent repiratory support
- Poor cough
- RR
- VC<30ml/kg
 Increased generalized weakeness
 Progressive bulbar(speech/swallowing)weakeness

31.  Precipitants
- Infection
- Surgery
- Pregnancy and child birth
- Inadequate Rx
- Initial high dose steroid therapy
- Drugs

32. Cholinergic crisis
 Over treatement with anticholinergics
 Flaccid muscle weakeness
 Mieosis
 SLUDGE syndrome
- Salivation
- Lacrimation
- Urinary incontinence
- Diarrhoea
- GI upset
- Emesis

33. Mx of Cholinergic crisis
 Intubation and ventilation
 IV Immunoglobulin 400mg/kg/d for 5/365
 Plasmapheresis
 Immnomdulation
- Prednisolone 60-8-mg/d
- Azathioprine/cyclosporine
- Plan weaning from ventilation

34. Myasthenia and Pregnancy
 Remissions/exacerbations/no change
 Glucocorticoids/Azathioprine/cyclosporine- SAFE
 Magnesium/ CCB/Beta blockers to be avoided in
Hypertensive diseases
 2nd satge of labour needs assistance
 Anticholiesterases should be administered IV during labour

36. Questions
* 1996 August LEQ
-How would you manage a patient with Myasthenia Gravis
for elective abdominal surgery?
*2007 August LEQ
- Discuss the anaesthetic management of a 30 year old
female with myasthenia gravis presenting for a trans-
sternal thymectomy
*2009 August SAQ
- outline the main characteristic features of Myasthenic
syndrome
- How and why do they differ from those seen in Myasthenia
Gravis?

37. FRCA 2007
 What are the clinical features of acquired myasthenia
gravis?
 What tests are available to confirm the diagnosis?
 What are the important aspects of a patient with
generalised myashenia gravis presenting for laparoscopic
cholecystectomy?

38. Thank you!