1. Myasthenic crisis, a life-threatening worsening of MG symptoms, is treated with plasmapheresis (PLEX) or intravenous immunoglobulin (IVIg), along with corticosteroids to achieve sustained response. 2. Thymectomy, the surgical removal of the thymus gland, is an elective procedure for MG patients to potentially avoid long-term immunosuppression and should be performed when the patient is stable. 3. Measuring acetylcholine receptor antibody levels is not recommended as a marker for treatment response in MG patients. Limb and bulbar symptoms generally respond better to anticholinesterase drugs than ocular manifestations.

1. Myasthenia Gravis
Management Guidelines
Dr. Rahi kiran. B
SR Neurology
GMC Kota
International Consensus Guidance For Management Of Myasthenia Gravis- Executive Summary; Donald B. Sanders, MD
Et. Al. ; Neurology® 2016;87:419–425
UPTODATE. Com

2. Severity of attacks

3. Question 1- Symptomatic
• Pyridostigmine-initial therapy for mild to moderate MG, Dose
S/B adjusted based on symptoms
• not met Rx goals after an adequate trial of pyridostigmine -
Corticosteroids or IS therapy

4. • Impending crisis - Rapid clinical worsening , in the opinion of
the treating physician, could lead to crisis in the short term
(days to weeks).
• Manifest crisis - a serious life-threatening, rapid worsening of
MG and potential airway compromise from ventilatory or
bulbar dysfunction
• Although cholinergic crisis is rare, it cannot be completely
excluded as a cause of clinical worsening
Question 2- Myasthenic crisis

5. • hospital admission- to an ICU if it progresses to manifest crisis.
• PLEX and IVIg - mainstay of management
• Corticosteroids or other IS agents-started at the same time to
achieve a sustained response
• Clinical trials - IVIg= PLEX
• Expert consensus –PLEX> IVIg
Question 2- Myasthenic crisis

6. Respiratory assistance
1. MIP < 20 cm H2O,
2. tidal volume < 4 to 5 cc/kg
3. MBC less than three times the tidal volume
4. forced vital capacity is <15 cc/kg body weight.

7. • Significant steroid side effects, deemed by the pt. or the
treating physician
• Inadequate response to an adequate trial of corticosteroids
• Corticosteroid dose cannot be reduced d/t symptom relapse.
Question 3- Prophylactic - Nonsteroidal IS
agent

8. • Azathioprine- first-line IS agent in MG.
• Mycophenolate mofetil – not proven by RCT, but used widely
• Cyclosporine – RCT favour, but more s/e – less used
• Methotrexate - not proven by RCT
• Tacrolimus
Question 3- Prophylactic - Nonsteroidal IS
agent

9. Question 4- Treatment goals
• Minimal Manifestation Status (MMS) or better
• no more than grade 1 Common Terminology Criteria for
Adverse Events (CTCAE)
• MMS: no symptoms or functional limitations from MG but has
some weakness on examination of some muscles.
• CTCAE grade 1 medication side effects: asymptomatic or only
mild symptoms; intervention not indicated.

10. Question 5- Remission
• has no symptoms or signs of MG.
• Weakness of eyelid closure is accepted, but there is no
weakness of any other muscle.

11. Question 7 - Non responders
• Refractory MG
• unchanged or worse after CS and at least 2 other IS agents, used in
adequate doses for an adequate duration, with persistent
symptoms or side effects that limit functioning, as defined by
patient and physician.
• Agents used - Chronic IVIg >> chronic PLEX (d/t s/e)
• Cyp
• Rituximab, for which evidence of efficacy is building

12. • short-term treatment –
– with life-threatening signs such as respiratory insufficiency
or dysphagia
– In preparation for surgery in patients with significant bulbar
dysfunction one or two weeks before
– When a rapid response to treatment is needed;
– when other treatments are insufficiently effective
– Prior to beginning corticosteroids if deemed necessary to
prevent or minimize exacerbations
• maintenance therapy- refractory MG or for IS are c/I
Question 8- Indications for IVIG and PLEX

13. • choice depends on individual patient factors and the
availability of each.
• equally effective in the treatment of severe generalized MG.
• The efficacy of IVIg is less certain in milder or ocular MG.
• PLEX may be more effective than IVIg in MuSK-MG
Question 8- IVIG vs PLEX

14. Question 9 - When to stop treatment?
• corticosteroid - gradually tapered once treatment goals
achieved.
• Nonsteroidal IS - once goals achieved, maintain for 6 months
to 2 years and taper slowly
• Dosage adjustments should be made no more frequently than
every 3–6 months
• If relapse – increase the dose
• In some, long term IS needed - individualised

15. Question 10-Treatment of relapse
 Risk - higher in symptomatic or after rapid taper
 In some, maintainance is needed for many years, sometimes for
life - individualised
 Make upward adjustments in dose.

16. Question 11 - If complications occur?
• Changing to an alternative IS agent - if adverse effects and
complications are medically significant or create undue
hardship for the patient.

17. Question 12 - Dosages
• Pyridostigmine – start 30 mg three times for 2-3 days
if cholinergic s/e occur- glycopyrrolate 1 mg with each dose,
maximum dose is usually 120 mg every four hours while awake.
• children and younger adolescents, the initial dose is 0.5 to 1 mg/kg
every four to six hours, max 7mg/kg

18. Question 13 – Drugs Contraindicated
• Neuromuscular blocking
agents and Anesthetic
agents
• Aminoglycosides
• Clindamycin
• Fluoroquinolones
• Vancomycin
• Beta blockers
• Botulinum toxin
• Chloroquine
• Penicillamine
• Tetracyclines
• Macrolides
• Metronidazole
• Carbamazepine
• Ethosuximide
• Gabapentin
• Haloperidol, CPZ, Li
• Riluzole
• CS

19. Question 14 - Special situations –
Ocular myasthenia
• Pyridostigmine – symptomatic
• CS – effective, delay or reduce the frequency of progression to
generalized disease
• Start prednisone at an initial dose of 10–20 mg/day with
gradual increases every 3–5 days until achieving a clinical
response
• Thymectomy – c/I

20. • respond poorly to ChEIs,
• Respond well to CS and steroid-sparing agents.
• tend to remain CS dependent despite concomitant treatment
with steroid-sparing agents
• PLEX >> IVIg - less effective
• Rituximab - early therapeutic option in patients with MuSK-
MG who have an unsatisfactory response to initial
immunotherapy
Question 15 - Special situations –
MuSK antibodies

21. Question 16 - Special situations –
Pregnancy
• If under good control before pregnancy, majority will remain
stable throughout.
• If worsening occurs, more likely during the first trimester and
first month after delivery.
• objective -Spontaneous vaginal delivery.
• Eclampsia - Magnesium sulfate is c/i, Barbiturates or
phenytoin - useful

22. • first-line-Oral pyridostigmine
• IV ChEIs –c/I - produce uterine contractions
• Thymectomy - postponed , as benefit is unlikely during
pregnancy.
• IS agent of choice - Prednisone
Question 16 - Special situations –
Pregnancy

23. • nonsteroidal IS of choice- Azathioprine
• relatively safe - Azathioprine and cyclosporine
• MMF and MTX –c/I increased teratogenicity
• Rapid short term - PLEX or IVIg – risk vs benefit –
individualised, no consensus
Question 16 - Special situations –
Pregnancy

24. • babies born to myasthenic mothers- examined for evidence of
transient myasthenic weakness and should have rapid access
to neonatal critical care support.
• The maternal antibody level correlates with the frequency
and severity
• Decreased fetal movement as a possible indication for PLEX or
IVIg.
• Birth of a child with arthrogryposis should also prompt a
search for MG in the mother.
• hypotonic and feed poorly,
• Symptoms – 2-12 weeks
• Treatment- pyridostigmine, exchange transfusion, MV
Question 17 - Transient Neonatal
Myasthenia Gravis (TNMG)

25. • young children with only ocular symptoms of MG can be
treated initially with pyridostigmine - more likely than adults
to go into spontaneous remission.
• Immunotherapy can be initiated if goals of therapy are not
met.
• Maintenance PLEX or IVIg are alternatives to IS drugs in JMG
• Long term treatment with corticosteroids –if no response to
above – more chance of side effects
Question 18 - Juvenile MG

26. • Non-thymomatous MG –
– option to potentially avoid or minimize the dose or
duration of immunotherapy
– If patients fail to respond to an initial trial of
immunotherapy or
– have intolerable side-effects from that therapy
• Time - when the patient is stable and deemed safe to undergo
a procedure where postoperative pain and mechanical factors
can limit respiratory function
Question 19 - Thymectomy in MG

27. • Thymomatous MG - all patients should undergo surgery to
remove the tumor.
• Incompletely resected thymomas should be managed after
surgery with an interdisciplinary treatment approach
(radiotherapy, chemotherapy).
• may be considered in patients with generalized MG without
detectable AChR antibodies if they fail to respond adequately
to IS therapy, or to avoid/minimize intolerable adverse effects
from IS therapy.
• Current evidence does not support an indication for
thymectomy in patients with ocular MG, MuSK, LRP4, or agrin
antibodies.
Question 19 - Thymectomy in MG

28. Question 19 - Thymectomy in MG - Children
•In prepubertal patients – unclear
•Seropositive generalized MG – should be considered
1. If the response to pyridostigmine and IS therapy is
unsatisfactory
2. In order to avoid potential complications of IS therapy.
• Seronegative generalized MG - possibility of a congenital
myasthenic syndrome or other neuromuscular condition
should be entertained, and evaluation is of value prior to
thymectomy.

29. Question 20 - Diet and triggers

30. Question 21 - Immunizations
• annual seasonal influenza vaccination
– for all individuals receiving immunosuppressive therapy,
– for those with generalized MG,
– Ocular MG within three years of onset

31. Question 22 - Recent drugs
• Etanercept
• Eculizumab
• Belimumab
• Autologous stem-cell transplantation in refractory MG

32. Flow chart showing pharmacologic prophylaxis

33. • Which meal option would be the most appropriate for a
patient with myasthenia gravis?
• A. Fried potatoes and burger
• B. kachori and samosa
• C. mashed potatoes and daliya
• D. parantha and poori sabji

34. • A patient with myasthenia gravis will be eating lunch at 12pm.
It is now 10am and the patient is scheduled to take
Pyridostigmine. At what time should you administer this
medication so the patient will have the maximum benefit of
this medication?

35. • A 65 yr female symptomatic since 4 months diagnosed with
ocular MG, next best step for treatment –
• A. Pyridostigmine
• B. Pyridostigmine + CS
• C. wait and watch
• D. IVIG/ PLEX

36. • A 60yr male diagnosed with Gen MG, tried on max dose of
pyridostigmine+ CS for adequate duration, weakness
improved significantly, thymoma evaluation negative, ptosis
persisted…next step
• A . CST
• B. Increase the dose
• C. urgent IVIG/PLEX
• D. Shift to Stroke unit and mechanical ventilation

37. Thank you

38. • Crisis - Corticosteroids or other IS agents
• are often started at the same time to achieve a
sus
• tained
• clinical response. (Because corticosteroids
• may cause transient worsening of myasthenic
• weakness, it may be appropriate to wait several
• days for PLEX or IVIg to have a beneficial effect
• before starting corticosteroids).

39. • All thymus tissue should be removed along
with the tumor.
• Because of the long delay in
• onset of effect, thymectomy for MG is an
elective
• procedure. It should be performed when the
• patient is stable

40. • the acetylcholine receptor (AChR) antibody levels as a
marker
• for treatment response in MG is not recommended.
• In general,
• limb and bulbar symptoms (dysphagia, fatigable
chewing, and dysarthria) respond
• better to anticholinesterase drugs than the ocular
manifestations (ptosis and
• diplopia). Diplopia is particularly resistant to these
medications in many patients

41. • Long-acting pyridostigmine is not a
• good choice for daytime use because its
variable release and delayed absorption
• make it difficult to provide a consistent effect
and to regulate the overall
• pyridostigmine dose.

42. • .
• Cholinergic crisis is so rare that it should not be
the presumed cause of increasing
• weakness unless the doses taken are known to
significantly exceed total daily dose of ≤960 mg
• Otherwise, even in the presence of cholinergic
side effects, it should be assumed
• that the patient's underlying MG is worsening,
and appropriate treatment should be
• initiated