MYASTHENIA GRAVIS

Pakamas Pasogpakdee,MD
 Introduction

•  The most common primary disorder of neuromuscular

transmission

•  Usual cause is an acquired immunological abnormality , some

cases result from genetic abnormality at the NMJ

•  Women : 2nd and 3rd decades , Men : 6th decades

•  USA : M>F (5th decades)

Neurology in Clinical Practice , 5th Edition , 2008

Immunopathology of MG

LEMS!
 Immunopathology of MG

•  80% of MG pts. , weakness result from the effects of

circulating anti-AChR Ab (T cell dependent)

•  destruction of the folds , accelerated internalization &

destruction of AChR , block Ach-AchR binding

•  10% of MG pts. have circulating Ab to MuSK

•  Remaining = seronegative

Neurology in Clinical Practice , 5th Edition , 2008

 Immunopathology of MG

AChR Ab neg
Antititin
Ab to ryanodine receptor

AChR Ab +ve
Anti
MUSK
AntiRapsyn
 Clinical Presentation

•  65%  ptosis & diplopia

•  15%  difficult chewing , swallowing , talking

•  10%  limb weakness

•  rare  single muscle group weakness

•  Typically fluctuates during the day , usually being least in the

morning and worse as the day progresses , esp. after prolonged
use of affected muscles

Neurology in Clinical Practice , 5th Edition , 2008

 Clinical Presentation

•  Careful questioning often reveals evidence of earlier myasthenic

manifestration

•  - frequent purchases of new eyeglasses

•  - avoidance of foods that became difficult to chew or swallow

•  - cessation of activities that require prolonged use of specific

m.

•  - friends may have noted a sleepy or sad facial appearance

•  caused by ptosis or facial weakness

Neurology in Clinical Practice , 5th Edition , 2008

 Physical Findings

•  pattern of muscle involvement

•  Ocular muscle
•  - eye movements
•  - Eye lid

•  Oropharyngeal muscle
•  - "myasthenic snarl“
•  - nasal speech , difficulty chewing , difficulty swallowing
• choking on liquids !

•  Limb muscle
•  - Limb muscle weakness , Fatiguability

Neurology in Clinical Practice , 5th Edition , 2008

 EYE & MG

•  Ptosis
•  - usually asymmetrically
•  - allow soap or water in the eyes during bathing

•  Diplopia
•  - Asymmetric weakness of several muscle in both eyes
•  - Pattern of weakness is not characteristic of lesions of
one or more nerves
•  - Pupillary responses are normal
•  - Weakness is most frequent & usually most severe in MR
•  should raise suspicion of MG in the combination of ptosis ,
ophthalmoparesis , weak eye closure

Neurology in Clinical Practice , 5th Edition , 2008

 Eyelid manifestation

•  Levator palpebrae
•  - Ptosis - Upper eyelid retraction
•  - Lid fatigue test - Enhancing ptosis
•  - Cogan lid twitch sign - Ice test
•  - Sleep test - Rest test

•  Orbicularis oculi muscle

•  - Forced eye closure: buried eyelashes
•  - Open the eyes against forced eyelid closure
 Upper eyelid retraction

Left upper eyelid retraction contralateral to a ptotic right

upper eyelid
 Lid fatigue test

(A)  On initial upgaze, minimal left upper eyelid ptosis is evident

(C)  After 2 minutes of sustained upgaze, the degree of left

upper eyelid ptosis is significantly increased owing to levator
muscle fatigue
 Cogan lid twitch sign

•  looks down for at least 10 to 20 seconds  makes

an upward saccade back to primary gaze

•  transient overshoot of the upper eyelid , which may

be followed by nystagmoid twitches of the upper
eyelid and then downward drifting of the eyelid to a
normal or ptotic position
Ice test

Preceding the test

An ice pack is applied to the

closed left eye for 2 minutes

Right upper eyelid ptosis is

significantly improved
 Sleep test

(A) before the test (B) After 30 minutes of sleep

(lying down in a quiet and dimly
lit room), the ptosis is
noticeably improved in both
eyes
 Rest test

(A) Before rest (B) After only 5 minutes of

gentle eye closure, the ptosis
is much improved in both eyes
 Orbicularis oculi muscle

severe bilateral orbicularis weakness bilateral lagophthalmos

secondary lower eyelid retraction

Not “bury” the eyelashes during weak orbicularis muscle in the right eye during
forced eye closure forced eye closure
 Ocular finding in myasthenia gravis

Weakness usually involves one or more ocular muscles w/o overt pupillary abnormality
Weakness is typically variable , fluctuating , fatigable
Ptosis that shifts from one eye to the other is virtually pathognomonic of MG
With limited ocular excursion , saccades are superfast , producing ocular “quiver”
After downgaze , upgaze produces lid overshoot “lid twitch”
Pseudo-internuclear ophthalmoplegia-limited adduction is present w/ nystagmoid jerks in abducting
eye
In asymmetrical ptosis , covering the eye w/ the ptotic lid may relieve contraction of the opposite
frontalis
Passively lifting a ptotic lid may cause the opposite lid to fall
Edrophonium may improve only one of several weak ocular muscle , other may become weaker
Edrophonium may relieve asymmetric ptosis & produce retraction of the opposite lid from frontalis
contraction
The opposite lid may droop further as the more involved lid strengthens after edrophonium
Cold applied to the eye may improve lid ptosis
Neurology in Clinical Practice , 5th Edition , 2008
 Oropharyngeal Muscles

•  Changes in voice
•  - nasal voice
•  - asking high-pitched “EEEEEEEEE” sound
•  Difficulty chewing and swallowing
•  Inadequate maintenance of the upper airway
•  Alter facial appearance
•  - myasthenic snarl

Neurology in Clinical Practice , 5th Edition , 2008

 Myasthenic Snarl

Rest Smile

Contraction of medial
portion of upper lip
Corner of mouth
droop downward

No upward curling
 Trunk & limb muscles

•  Neck muscle
•  Upper extremities
•  - Out stretched arms test
•  - Grip fatigue can be measured with a dynamometer that
the patient grasps repetitively
•  - Repetitive exercise test
•  Lower extremity
•  - step up and down from a footstool as if climbing stairs
•  - progressively more difficult and the patient begins to
push off their knee with their arm in order to help the
weakening quadriceps

• * Neck flexors , Deltoids , Triceps , WE , FE , ankle

dorsiflexors *
 Diagnostic test

•  Clinical diagnosis
•  Investigation
•  Anticholinesterase test
•  Autoantibodies
•  Electridiagnosting Testing
•  repetitive nerve stimulation
•  single-fibre electromyography

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

1. Anticholinesterase test

Edrophonium Chloride (Tensilon) Test

- Rapid onset(30sec), short duration(5min)
- 2 mg IV if no change add 8 mg IV

Neostigmine test
- Neostigmine 1-2 mg,IM
- Effects seen within 20-40 min
- Should have measurable parameter eg. Ptosis

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

1. Anticholinesterase test

False positive Edrophonium test

- Lambert-Eaton syndrome (37%positive)
- Botulism (27% positive)
- Congenital end-plate acetylcholine receptor deficiency
- Guillain-Barré syndrome
- Amyotrophic lateral sclerosis
- Brain stem glioma

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

2. Auto- Ab

•  serum antibodies that bind human AChR

•  70-90% generalized myasthenia
•  50-75% ocular myasthenia
• 
•  AChR binding antibodies conc. sometimes increased in
patients w/
•  SLE , inflammatory neuropathy , ALS , RA taking D-
penicillamine , thymoma w/o MG , normal relatives of
patients with MG

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

2. Auto-Ab

•  Positive AChR Ab plus clinical = confirm diagnosis

•  Negative AChR Ab can not be rule out
•  no correlation between disease severity and antibody titre
•  clinical improvement: associated with a fall in Ab titre

Biodrugs 2001 March; 15 (3): 173-83

N Engl J Med 1994; 330 (25): 1797-810
 Diagnostic test

2. Auto-Ab

•  Anti-MUSK Ab

•  Antistriational muscle Ab : predicting thymoma (60% of

pts. w/ MG w/ onset before age 50 have thymoma)

•  Others : Antititin Ab
•  Anti ryanodine Ab

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

3. Electrodiagnostic test

•  Repetitive Nerve Stimulation (RNS)

•  - Decrement of > 10% at 3 Hz: highly probable
•  - more often in proximal muscles, such as
the facial muscles, biceps, deltoid, and trapezius than in
hand muscles
•  - Anti-ChE medications should withheld 12
hours (24 hours) prior to testing
•  - Yield of RNS : Ocular MG 30-40%
•  Generalized MG 70-80%

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

3. Electrodiagnostic test

•  Single Fiber EMG (SFEMG)

•  - most sensitive clinical test of neuromuscular
transmission
•  - shows increased jitter in some muscles in
almost all patients with myasthenia gravis
•  - positive in 95-99% of pts. with generalized MG

Neurology in Clinical Practice , 5th Edition , 2008

 Diagnostic test

•  Anticholinesterase test : often Dx in pts. w/ ptosis or

ophthalmoparesis , less useful in assessing other muscles

•  Autoantibodies : presence of AChR-Ab , anti-MUSK Ab ensures

the Dx of MG , but absence dose not exclude

•  Electrodiagnosting Testing
•  repetitive nerve stimulation : confirm impaired
neuromuscular transmission , but frequently normal in
mild or purely ocular disease
•  single-fibre electromyography : normal jitter in weak
muscle excludes MG
•  Neither EDx is specific for MG
Neurology in Clinical Practice , 5th Edition , 2008
 Sensitivity of tests in MG

Tests Ocular MG Generalized MG

Edrophonium test 80-90% 80-90%
Ice pack / sleep test Criteria poorly defined Criteria poorly defined

AChR Ab 30-50% 80-90%

MuSK Ab Rare 30-40% of seronegative
Antistriatal Ab 80% in pt. w/ thymoma 80% in pt. w/ thymoma
30% in pt. w/o thymoma 30% in pt. w/o thymoma

RNS 30-60% 90%

Single fiber EMG 90-95% 90-95%
 DDx : Ocular MG

•  Mitochondrial disorder : CPEO

•  Oculopharyngeal muscular dystrophy

•  Thyroid ophthalmopathy

•  Brainstem lesion

•  Local eyelid disorder

 DDx : Generalized MG

•  NMJ disorder
•  - LEM
•  - Congenital myasthenic syndrome
•  - Neurotoxins eg. Botulism

•  Myopathies

•  Demyelinating polyneuropathies
 Assessment

•  Associated disorder
•  - Disorder of thymus : Thymoma , Hyperplasia
•  - Other autoimmune disorder : Hashimoto thyroiditis ,
Grave’s disease , RA , SLE

•  Disorder or circumstance that may exacerbate MG

•  - Hyperthyroidism , Occult infection
•  - Medical Rx of other condition (aminoglycoside,
quinidine, antiarrhythmic drug)

•  Disorder that may interfere therapy

•  - TB , DM , PU , GI bleed , Asthma , osteoporosis
 Classification (modifications of Osserman)

Class I - Ocular myasthenia

Class IIA - Mild generalized myasthenia with slow progression;

no prominent bulbar signs; no crisis; drug responsive

Class IIB - Moderate generalized myasthenia; severe skeletal

and bulbar involvement but no crisis;
drug response than satisfactory

Class III - Acute fulminating myasthenia; rapid progression of

severe symptoms with respiratory crisis and poor
drug response; high incidence of thymoma; high mortality

Class IV - Late severe myasthenia; same as III but progress

over two years from class I to II !
 Classification (MGFA)

Class I - Any ocular muscle weakness

- May have weakness of eye closure
- All other muscle strength is normal

Class II - Mild weakness affecting other than ocular muscles

- May also have ocular muscle weakness of any severity
IIa - Predominantly affecting limb , axial muscles , or both
- May also have lesser involvement of oropharyngeal musc
IIb - Predominantly affecting oropharyngeal ,respiratory
muscles or both
- May also have lesser or equal involvement of limb , axial
muscles or both!
 Classification (MGFA)

Class III- Moderate weakness affecting other than ocular muscles

- May also have ocular muscle weakness of any severity
IIIa - Predominantly affecting limb , axial muscles , or both
- May also have lesser involvement of oropharyngeal muscl
IIIb - Predominantly affecting oropharyngeal ,respiratory
muscles or both
- May also have lesser or equal involvement of limb , axial
muscles or both!
 Classification (MGFA)

Class IV- Severe weakness affecting other than ocular muscles

- May also have ocular muscle weakness of any severity
IVa - Predominantly affecting limb , axial muscles , or both
- May also have lesser involvement of oropharyngeal muscl
IVb - Predominantly affecting oropharyngeal ,respiratory
muscles or both
- May also have lesser or equal involvement of limb , axial
muscles or both
Class V - Defined by intubation , w/ or w/o mechanical ventilation
except when employed during routine postoperative
management

The use of a feeding tube w/o intubation places the patients in class IVb !
 Classification (MGFA)

Class IV- Severe weakness affecting other than ocular muscles

- May also have ocular muscle weakness of any severity
IIIa - Predominantly affecting limb , axial muscles , or both
- May also have lesser involvement of oropharyngeal musc
IIIb - Predominantly affecting oropharyngeal ,respiratory
muscles or both
- May also have lesser or equal involvement of limb , axial
muscles or both
Class V - Defined by intubation , w/ or w/o mechanical ventilation
except when employed during routine postoperative
management

The use of a feeding tube w/o intubation places the patients in class IVb !
Clinical subtypes

•  Early onset cases

•  Late onset cases
•  Ocular myasthenia
•  Seronegative MG
•  Thymoma associated MG
•  Positive antititin antibodies
•  Neonatal MG
 Early onset cases

•  Female

•  Onset before age 40

•  AChR Ab-positive

•  Usually do not Ab to muscle Ag

•  Hyperplasia of thymus gland

•  60% of cases : HLA-D8 , HLA-DRw3

 Late onset cases

•  Men slightly more than female

•  Onset after age 40

•  Associated with HLA-B7 , HLA-DRw2

 Ocular myasthenia

•  AChR Ab positive only 40-60% of cases

•  Represent mild cases of autoimmune generalized MG

•  50-60% develop generalized weakness in 1-2 years

•  40% remain ocular MG

•  Pts. w/ pure ocular symptoms for 2 yrs. have less

chance to develop generalized MG
 Seronegative MG

•  Clinicla similar to MG with AChR Ab

•  Many evidence suggest autoimmune in origin

•  Development of neonatal MG in babies born to
seronegative mother
•  Response to plasma exchange

•  A good proportion of cases have autoantibodies to a

muscle specific receptor tyrosine kinase (MuSK)
 Thymus & MG

•  more mature T cells than normal Thymus

•  70% of pt. have lymphoid follicular hyperplasia

•  > 10% of pt. have a thymoma

•  30–60% of thymomas associated with MG

Neurology in Clinical Practice , 5th Edition , 2008

 TREATMENT

•  Controlled clinical trials : rare

•  Objectives :
•  Directly target autoimmune response
•  Modify Ab production or modify immune mediated damage
to NMJ
•  Modify natural history of disease
•  Strategy : induce remission , maintain remission
 TREATMENT

•  CSR : no s/s of MG ≥ 1 yr. & has received no therapy for MG

during that time , isolated weakness of eyelid closure is accept
•  PR : same criteria of CSR except that the pts. continue to take
some from of therapy of MG. Pts. taking
cholinesterase inh. are excluded from this category because their
use suggests the presence of weakness

• CSR = complete stable remission , PR = pharmacologic remission

 TREATMENT

•  MM : no symptoms of functional limitation from MG , some

weakness on examination of some muscles
•  MM-0 : no MG treatment ≥ 1 yr.
•  MM-1 : receive some form of immunosuppression , no ChE
inhibitor or other symptomatic therapy
•  MM-2 : receive low dose of ChE inhibitor(<120 mg) ≥1 yr.
•  MM-3 : receive ChE inhibitor or other symptomatic therapy
& some form of immunosuppression during the
past yr.
• MM = minimal manifestations
 TREATMENT

•  Controlled clinical trials : rare

•  Objectives :
•  Directly target autoimmune response
•  Modify Ab production or modify immune mediated damage
to NMJ
•  Modify natural history of disease
•  Strategy : induce remission , maintain remission
 TREATMENT

•  Symptomatic treatment
•  Immunomodulating therapies/Thymectomy
•  Others : treatment of comorbidities

•  Improvement •  Unchanged
•  Minimal manifestation •  Worse
•  Pharmacologic remission •  Died
•  Complete stable remission
 SYMPTOMATIC TREATMENTS

•  Pharmacologic treatment
•  Cholinesterase inhibitor (first line medication)

•  Muscle training , weight control , lifestyle modification

 Cholinesterase inhibitor

•  retard the enzymatic hydrolysis of ACh at cholinergic

synapses  ACh accumulates at NMJ  prolonged effects
•  diagnostic test
•  early treatment , symptomatic treatment
•  response usually becomes less w/ chronic use
 Cholinesterase inhibitor

•  Pyridostigmine bromide (Mestinon) & neostigmine bromide

(Prostigmine)
•  initial oral dose = 30-60 mg every 4-6 hrs.
•  mestinon 60 mg , oral = neostigmine methylsulfate 0.5
mg , IV
•  no fixed dosage schedule suits all patients
•  varies from day to day & during the same day
•  different muscles response differently
 Cholinesterase inhibitor

•  Drugs schedule should be titrated to produce an optimal

response in muscles causing the greatest disability
•  Attempts to eliminate all weakness by increasing the
dose or shortening the interval causes overdose at the time
of peak effect
• “keep the dose low enough to provide definite
improvement in the most important muscle groups
w/in 30-45 min , expect the effect to wear off
before the next dose”
 Cholinesterase inhibitor

•  Adverse effect :
•  muscarinic receptor on smooth muscle &
autonomic glands
•  nicotinic receptor on skeletal muscle
•  common : GI  queasiness , nausea , vomiting ,
abdominal cramp , loose stool , diarrhea
•  suppress with loperamide hydrochloride(Imodium) ,
propantheline bromide(Pro-Banthine) ,
glycopyrrolate(Robinul) diphenoxylate hydrochloride w/
atropine(Lomotil)
IMMUNOMODULATION

•  Corticosteroids
•  Immunosuppressant drugs
•  Plasma exchange
•  Intravenous immunoglobulin
•  Thymectomy
 IMMUNOMODULATION

G2= perimitotic phase

CY

M= mitotic phase
CY

S= DNA synthesis CY , AZA Cell cycle

phase MMF , MTX

CY , AZA CY
MMF , MTX
G0=dormant phase
G1= resting phase
 IMMUNOMODULATION

S
Macrophage
T-cell receptor

Extracellular
T-cell receptor Intracellular

CSA
T cell
TAC Nucleus S
 Corticosteroids

•  Mechanism :
•  Blocking Ag processing
•  Decrease number of circulating T cells
•  Reducing trafficking of inflammatory cells
•  Reduce expression of inflammatory cytokines and adhesion
molecules
•  Never been studied in large RCT marked improvement or
complete relief of symptoms > 75% of pts.
•  onset : 6-8 weeks
•  remission : 3 months
•  good response : pts w/ recent onset of symptoms
 Corticosteroids

•  1.5-2.0 mg/kg/day until sustained improvement (2 wks.) 

EOD

•  reduced 20 mg/mo.    60 mg , EOD

•  reduced 10 mg/mo.     20 mg , EOD

•  reduced 5 mg q 3 mo   10 mg , EOD

•  not reduce the dose further than this unless another

immunosuppressant being given

•  weakness returns  increased dosage or add

immunosuppressant
 Corticosteroids

•  1/3 of pts. become weaker temporarily , usually in first 7-10

days

•  managed w/ ChE inhibitors

•  oropharyngeal weakness or respiratory insufficiency : plasma

exchange before started prednisone

•  should be hospitalized to start this treatment

 Corticosteroids

•  start 20 mg/day
• 
•  increase 10 mg q 1-2 wks.    maximum
improvement

•  reduced as above

•  reduced frequency or severity of corticosteroid-induced

exacerbations
 Corticosteroids

•  SE : hypercorticism , weight gain , HT , diabetes ,

anxiety / depression / insomnia “steroid psychosis” ,
glaucoma , osteoporosis , cataracts , ulcer/GI perforations ,
myopathy , opportunistic infections , avascular necrosis of
large joints

•  SE increased when high daily dose > 1 mo.

•  SE resolved when taper dose , <20 mg EOD

Azathioprine
onset action : 4-8 months
common SE : allergic reaction (flu-like syndrome)
less common SE : hepatic toxicity , leukopenia

Cyclosporine
onset action : 2-3 months
common SE : renal toxicity , HTN , multiple potential drug interactions

Cyclophosphamide
onset action : variable
common SE : leukopenia , hair loss , cystitis

Mycophenolate mofetil
onset action : 2-4 weeks
common SE : diarrhea , mild leukopenia

Neurology in Clinical Practice , 5th Edition , 2008

 Azathioprine

•  inhibiting purine synthesis & hence cell proliferation ( lymphocytes)

•  onset : 4-8 months
•  initial dose 50 mg/day  50 mg/day q 7 day  150-200 mg/day
•  discontinue or reduced below therapeutic level : symptoms almost
always recur in 3 mo.
•  start azathioprine & prednisone simultaneously
•  rapidly taper the dose of prednisone when azathioprine becomes
effective
 Azathioprine

•  prospective , randomized study

• “ azathioprine + prednisolone significant reduced the dose of

prednisolone required to maintain remission & reduced the
number of treatment failure ”

Palace et al. 1998

 Azathioprine

Side effects :
•  allergic reaction w/ flu-like symptoms occurs w/in 2 wks.  stop
•  GI irritation : divided dose , after meals , dose reduction
•  leukopenia or pancytopenia :
•  - CBC every wk. in 1st mo.
•  - CBC every mo. in 1st yr.
•  - every 3-6 mo. Thereafter
•  - WBC < 3500/mm3  temporarily reduced dose
•  - WBC < 1000/mm3  temporarily discontinued
 Azathioprine

Side effects :
•  increased liver enzyme :
•  enzyme > 2x  discontinue
•  restart when values become normal
•  pancreatitis : rare
•  potentially mutagenic  adequate contraception
 Cyclosporine (CYA)

•  Retrospective analyses :

•  “ improvement in most pts. taking CYA w/ or w/o

• corticosteroids ”

Ciafaloni et al. 2000

 Cyclosporine (CYA)

•  inhibits predominantly T-lymphocyte dependent immune

response
•  start at 5-6 mg/kg/day (divided 12 hr. apart)
•  measured serum level at 1 mo.
•  keep trough serum CYA concentration 75-150 ng/mL
•  monitor serum creatinine q 2-3 mo.
 Cyclosporine (CYA)

•  SE : renal toxicity , HTN

•  improve 1-2 mo. , maximum improvement after 6 mo.
•  after maximum response  gradually reduced CYA to
minimum that maintain improvement
 Cyclophosphamide

“ given IV in monthly pulsed doses has been used

effectively in severe , generalized MG that is refractory to
other therapy ”

De Feo et al ,2002 Drachman et al,2002

 Cyclophosphamide

•  IV : 500 mg/m2
•  oral : 150-200 mg/day  total dose 5-10 g
•  SE : alopecia , cystitis , nausea , vomiting , anorexia ,
• discoloration of nail & skin
 Mycophenolate mofetil (MM)

•  inhibits the proliferation of B & T-lymphocyte clones ,

responding to antigenic stimulation
•  suppresses the formation of Ab active in complement-
dependent lysis & cell-mediated cytotoxicity
•  2 g/day in divided 12 hr. apart
•  onset action : 2 wks.
•  SE : leukopenia , diarrhea
•  refractory MG , as corticosteroid sparing agent when
azathioprine has produced intolerable SE or has not been
effective
Mycophenolate mofetil (MM)
Mycophenolate mofetil (MM)
 Plasma Exchange

•  sudden worsening of myasthenic symptoms for any reason

•  rapidly improve strength before surgery

•  concomitantly w/ starting high dose corticosteroids

•  chronic intermittent treatment for refractory MG

 Plasma Exchange

•  remove 2-3 Liters of plasma , 3 times a wk. until

improvement , usually 5-6 exchanges

•  improvement usually begin after 2nd or 3rd exchange

•  improvement last for wks or months

•  repeated exchange not produce a cumulative benefit

•  SE : cardiac arrythmias , nausea , lightheadedness , chills ,

obscured vision , pedal edema
 Intravenous Immunoglobulin

•  2 g/kg (0.4 g/kg/day) infused over 2-5 days

•  improvement 50-100% , begin in 1 wk. , lasting for several

wks. or mo.

•  SE : headache , chills , fever , alopecia , aseptic meningitis ,

leukopenia , retinal necrosis , renal failure , cerebral
infarction , myocardial infarction
 Intravenous Immunoglobulin

•  C/I : selective IgA deficiency

•  because may develop anaphylaxis to IgA in IVIg
•  preperation

•  A multicenter , randomized , controlled study comparing

plasmapheresis with IVIg has demonstrated equal efficacy but
significanly fewer and less severe SE for IVIg
 Thymectomy

•  classic long-term treatment

•  effect is usually not apparent until after 1 yr , and the full

effect is not felt for 5 yr

•  never been demonstrated to be effective in a prospective ,

controlled study
 Thymectomy

Controversies
•  Effectiveness in late onset pts. (>50 year old)
•  Reduced effectiveness in MuSK +ve patients
•  Cost effectiveness
•  When to performed thymectomy
•  Which surgical techniques
 Thymectomy

•  American Academy of Neurology :

•  medication free remission : 2x
•  asymptomatic : 1.6x
•  show improvement : 1.7x

• “ For pts. w/ nonthymomatous autoimmune MG ,

thymectomy is recommended as an option to increase the
probability of remission or improvement ”
• 
 Thymectomy

•  recommended thymectomy for most pts. w/ MG whose

symptoms begin before age 60
•  good response : young people , women , early in course of
disease
•  advantage : induce sustained , drug-free remission , remove
thymoma
•  transthoracic approach
 Thymectomy

•  repeat thymectomy :
•  chronic refractory disease
•  all thymic tissue not removed at prior surgery
•  good response to original surgery
Ocular MG
MG (II,III,IV)
 Special situations

Factor that worsen myasthenic symptoms

•  emotional upset

•  systemic illness (esp. viral respiratory infections)

•  hypothyroidism or hyperthyroidism

•  pregnancy

•  menstrual cycle

•  Drugs

•  Fever
Neurology in Clinical Practice , 5th Edition , 2008
 Special situations

•  Surgery :
•  spinal block
•  avoidance neuromuscular blocking agent

•  Pregnancy :
•  improve-stable-worse
•  ChE inhibitor induce uterine contraction
•  immunosuppressant : only corticosteroids
•  transient neonatal myasthenia
 Special situations

“ Avoidance of situations in which neuromuscular transmission

may be compromised ”

Penicillamine , amiodarone , aminoglycosides

thyroid dysfunction may have direct effect on the NMJ

 Prognosis

•  course of disease : variable but usually progressive

•  ocular myasthenia  generalized myasthenia (2 years) , 1st year

maximum weakness (65%)

•  active stage : symptoms fluctuate over a relatively short period and

then become more severe

•  burnt-out stage : after 15-20 years , untreated weakness become

fixed , muscle atrophy

•  remission : may occur early on but rarely permanent

Neurology in Clinical Practice , 5th Edition , 2008