Mg Handout

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Introduction

MYASTHENIA GRAVIS

•  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)

Pakamas Pasogpakdee,MD

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Neurology in Clinical Practice , 5th Edition , 2008

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Immunopathology of MG

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

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LEMS!

Neurology in Clinical Practice , 5th Edition , 2008

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Immunopathology of MG

Clinical Presentation

AChR Ab neg •  65%  ptosis & diplopia

Antititin Ab to ryanodine receptor

•  15%  difficult chewing , swallowing , talking •  10%  limb weakness

AChR Ab +ve AntiRapsyn

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Anti MUSK

•  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

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Neurology in Clinical Practice , 5th Edition , 2008

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Clinical Presentation

Physical Findings • 

•  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. •  •  6/28/09!

•  •  • 

Oropharyngeal muscle - "myasthenic snarl“ - nasal speech , difficulty chewing , difficulty swallowing

Limb muscle - Limb muscle weakness , Fatiguability Neurology in Clinical Practice , 5th Edition , 2008

Eyelid manifestation

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

Neurology in Clinical Practice , 5th Edition , 2008

Ocular muscle - eye movements - Eye lid

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•  Levator palpebrae •  - Ptosis •  - Lid fatigue test •  - Cogan lid twitch sign •  - Sleep test -

•  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

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•  •  • 

•  • 

EYE & MG

•  •  • 

involvement

• choking on liquids !

- friends may have noted a sleepy or sad facial appearance caused by ptosis or facial weakness Neurology in Clinical Practice , 5th Edition , 2008

pattern of muscle

Upper eyelid retraction Enhancing ptosis Ice test Rest test

•  Orbicularis oculi muscle •  - Forced eye closure: buried eyelashes •  - Open the eyes against forced eyelid closure

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Upper eyelid retraction

Left upper eyelid retraction contralateral to a ptotic right upper eyelid 6/28/09!

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Lid fatigue test

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

(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 6/28/09!

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Ice test

Sleep test

Preceding the test

An ice pack is applied to the closed left eye for 2 minutes (A) before the test Right upper eyelid ptosis is significantly improved 6/28/09!

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Rest test

(A) Before rest

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(B) After 30 minutes of sleep (lying down in a quiet and dimly lit room), the ptosis is noticeably improved in both eyes

Orbicularis oculi muscle

severe bilateral orbicularis weakness secondary lower eyelid retraction

bilateral lagophthalmos

Not “bury” the eyelashes during

weak orbicularis muscle in the right eye during forced eye closure

(B) After only 5 minutes of gentle eye closure, the ptosis is much improved in both eyes

forced eye closure 6/28/09!

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Ocular finding in myasthenia gravis

Oropharyngeal Muscles

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

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

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 6/28/09!

Neurology in Clinical Practice , 5th Edition , 2008

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Myasthenic Snarl Rest

Trunk & limb muscles

Smile

Contraction of medial portion of upper lip

Corner of mouth droop downward

Neurology in Clinical Practice , 5th Edition , 2008

•  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

No upward curling

• * Neck flexors , Deltoids , Triceps , WE , FE , ankle dorsiflexors * 6/28/09!

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Diagnostic test

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

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Neurology in Clinical Practice , 5th Edition , 2008

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Diagnostic test

Diagnostic test

1. Anticholinesterase test

1. Anticholinesterase test

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

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

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

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Neurology in Clinical Practice , 5th Edition , 2008

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Diagnostic test

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 Dpenicillamine , thymoma w/o MG , normal relatives of patients with MG Neurology in Clinical Practice , 5th Edition , 2008

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2. Auto-Ab •  •  •  • 

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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%

•  Anti-MUSK Ab •  Antistriational muscle Ab : predicting thymoma (60% of pts. w/ MG w/ onset before age 50 have thymoma)

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Biodrugs 2001 March; 15 (3): 173-83 N Engl J Med 1994; 330 (25): 1797-810

Diagnostic test

2. Auto-Ab

•  Others : • 

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

Antititin Ab Anti ryanodine Ab

Neurology in Clinical Practice , 5th Edition , 2008

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Neurology in Clinical Practice , 5th Edition , 2008

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Diagnostic test

Diagnostic test

•  Anticholinesterase test : often Dx in pts. w/ ptosis or ophthalmoparesis , less useful in assessing other muscles

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

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•  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

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Sensitivity of tests in MG

Tests

Ocular MG

Edrophonium test

80-90%

Generalized MG 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 30% in pt. w/o thymoma

80% in pt. w/ thymoma 30% in pt. w/o thymoma

RNS

30-60%

90%

Single fiber EMG

90-95%

90-95%

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DDx : Ocular MG

DDx : Generalized MG

•  Mitochondrial disorder : CPEO

•  NMJ •  •  • 

•  Oculopharyngeal muscular dystrophy •  Thyroid ophthalmopathy

•  Myopathies

•  Brainstem lesion

•  Demyelinating polyneuropathies

•  Local eyelid disorder

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

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Assessment

Classification (modifications of Osserman)

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

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

•  Disorder or circumstance that may exacerbate MG •  - Hyperthyroidism , Occult infection •  - Medical Rx of other condition (aminoglycoside, quinidine, antiarrhythmic drug)

Class III

•  Disorder that may interfere therapy •  - TB , DM , PU , GI bleed , Asthma , osteoporosis

drug

- Acute fulminating myasthenia; rapid progression of severe symptoms with respiratory crisis and poor 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 !

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Classification (MGFA)

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 IIb - Predominantly affecting oropharyngeal ,respiratory muscles or both - May also have lesser or equal involvement of limb , axial

muscles

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 IIIb - Predominantly affecting oropharyngeal ,respiratory muscles or both - May also have lesser or equal involvement of limb , axial

muscles

muscles or both!

muscles or both! 6/28/09!

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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 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 !

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Classification (MGFA)

muscles

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 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

muscles

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

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Clinical subtypes

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

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Early onset cases

Late onset cases

•  Female •  Onset before age 40

•  Men slightly more than female

•  AChR Ab-positive

•  Onset after age 40

•  Usually do not Ab to muscle Ag

•  Associated with HLA-B7 , HLA-DRw2

•  Hyperplasia of thymus gland •  60% of cases : HLA-D8 , HLA-DRw3 6/28/09!

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Ocular myasthenia

Seronegative MG

•  AChR Ab positive only 40-60% of cases

•  Clinicla similar to MG with AChR Ab

•  Represent mild cases of autoimmune generalized MG

•  Many evidence suggest autoimmune in origin •  Development of neonatal MG in babies born to seronegative mother •  Response to plasma exchange

•  50-60% develop generalized weakness in 1-2 years •  40% remain ocular MG

•  A good proportion of cases have autoantibodies to a muscle specific receptor tyrosine kinase (MuSK)

•  Pts. w/ pure ocular symptoms for 2 yrs. have less chance to develop generalized MG

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Thymus & MG

•  more mature T cells than normal Thymus •  70% of pt. have lymphoid follicular hyperplasia

TREATMENT

•  Controlled clinical trials : rare •  Objectives : •  Directly target autoimmune response

•  > 10% of pt. have a thymoma

•  Modify Ab production or modify immune mediated damage to NMJ

•  30–60% of thymomas associated with MG

•  Modify natural history of disease •  Strategy : induce remission , maintain remission

Neurology in Clinical Practice , 5th Edition , 2008

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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

TREATMENT

•  MM : no symptoms of functional limitation from MG , some weakness on examination of some muscles •  MM-0 : no MG treatment ≥ 1 yr.

•  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

•  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.

• CSR = complete stable remission , PR = pharmacologic remission

• MM = minimal manifestations

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TREATMENT

TREATMENT •  Symptomatic treatment

•  Controlled clinical trials : rare

•  Immunomodulating therapies/ Thymectomy

•  Objectives :

•  Others : treatment of comorbidities

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

•  Improvement

•  Unchanged

•  Minimal manifestation

•  Worse

•  Pharmacologic remission

•  Died

•  Complete stable remission 6/28/09!

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Cholinesterase inhibitor

SYMPTOMATIC TREATMENTS

•  Pharmacologic treatment

•  retard the enzymatic hydrolysis of ACh at cholinergic synapses  ACh accumulates at NMJ  prolonged effects

•  Cholinesterase inhibitor (first line medication)

•  diagnostic test •  early treatment , symptomatic treatment

•  Muscle training , weight control , lifestyle modification

•  response usually becomes less w/ chronic use

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Cholinesterase inhibitor

Cholinesterase inhibitor

•  Pyridostigmine bromide (Mestinon) & neostigmine bromide (Prostigmine)

•  Drugs schedule should be titrated to produce an optimal response in muscles causing the greatest disability

•  initial oral dose = 30-60 mg every 4-6 hrs.

•  Attempts to eliminate all weakness by increasing the dose or shortening the interval causes overdose at the time of peak effect

•  mestinon 60 mg , oral = neostigmine methylsulfate 0.5 mg , IV •  no fixed dosage schedule suits all patients

• “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”

•  varies from day to day & during the same day •  different muscles response differently

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Cholinesterase inhibitor

IMMUNOMODULATION

•  Adverse effect : •  muscarinic receptor on smooth muscle & autonomic glands • 

•  Corticosteroids •  Immunosuppressant drugs

nicotinic receptor on skeletal muscle

•  Plasma exchange

•  common : GI  queasiness , nausea , vomiting , abdominal cramp , loose stool , diarrhea

•  Intravenous immunoglobulin •  Thymectomy

•  suppress with loperamide hydrochloride(Imodium) , propantheline bromide(Pro-Banthine) , glycopyrrolate(Robinul) diphenoxylate hydrochloride w/ atropine(Lomotil) 6/28/09!

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IMMUNOMODULATION

IMMUNOMODULATION

G2= perimitotic phase

S

CY

Macrophage

T-cell receptor M= mitotic phase

CY

S= DNA synthesis phase

CY , AZA MMF , MTX

Extracellular T-cell receptor

Cell cycle

Intracellular

CSA

CY , AZA MMF , MTX

Nucleus

TAC

CY

S

T cell

G0=dormant phase

G1= resting phase

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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

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Corticosteroids

Corticosteroids

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

•  1/3 of pts. become weaker temporarily , usually in first 7-10 days •  managed w/ ChE inhibitors

•  reduced as above

•  oropharyngeal weakness or respiratory insufficiency : plasma exchange before started prednisone

•  reduced frequency or severity of corticosteroid-induced exacerbations

•  should be hospitalized to start this treatment

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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

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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

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Azathioprine

Azathioprine

•  inhibiting purine synthesis & hence cell proliferation ( lymphocytes) •  prospective , randomized study

•  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

• “ azathioprine + prednisolone significant reduced the dose of prednisolone required to maintain remission & reduced the number of treatment failure ”

•  rapidly taper the dose of prednisone when azathioprine becomes effective

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Palace et al. 1998

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Azathioprine

Azathioprine

Side effects : •  allergic reaction w/ flu-like symptoms occurs w/in 2 wks.  stop

Side effects :

•  GI irritation : divided dose , after meals , dose reduction

•  increased liver enzyme :

•  leukopenia or pancytopenia :

• 

enzyme > 2x  discontinue

• 

- CBC every wk. in 1st mo.

• 

restart when values become normal

• 

- CBC every mo. in 1st yr.

•  pancreatitis : rare

• 

- every 3-6 mo. Thereafter

•  potentially mutagenic  adequate contraception

• 

- WBC < 3500/mm3  temporarily reduced dose

• 

- WBC < 1000/mm3  temporarily discontinued

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Cyclosporine (CYA)

Cyclosporine (CYA)

•  inhibits predominantly T-lymphocyte dependent immune response

•  Retrospective analyses :

•  start at 5-6 mg/kg/day (divided 12 hr. apart) • 

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

•  measured serum level at 1 mo.

• corticosteroids ”

•  keep trough serum CYA concentration 75-150 ng/mL •  monitor serum creatinine q 2-3 mo.

Ciafaloni et al. 2000

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Cyclosporine (CYA)

Cyclophosphamide

•  SE : renal toxicity , HTN

“ given IV in monthly pulsed doses has been used

•  improve 1-2 mo. , maximum improvement after 6 mo.

effectively in severe , generalized MG that is refractory to

•  after maximum response  gradually reduced CYA to minimum that maintain improvement

other therapy ”

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De Feo et al ,2002 Drachman et al,2002

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Cyclophosphamide

Mycophenolate mofetil (MM)

•  inhibits the proliferation of B & T-lymphocyte clones , responding to antigenic stimulation •  suppresses the formation of Ab active in complementdependent lysis & cell-mediated cytotoxicity

•  IV : 500 mg/m2 •  oral : 150-200 mg/day  total dose 5-10 g

•  2 g/day in divided 12 hr. apart

•  SE : alopecia , cystitis , nausea , vomiting , anorexia ,

•  onset action : 2 wks.

• discoloration of nail & skin

•  SE : leukopenia , diarrhea •  refractory MG , as corticosteroid sparing agent when azathioprine has produced intolerable SE or has not been effective

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Mycophenolate mofetil (MM)

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Mycophenolate mofetil (MM)

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Plasma Exchange

Plasma Exchange

•  sudden worsening of myasthenic symptoms for any reason

•  remove 2-3 Liters of plasma , 3 times a wk. until improvement , usually 5-6 exchanges

•  rapidly improve strength before surgery

•  improvement usually begin after 2nd or 3rd exchange

•  concomitantly w/ starting high dose corticosteroids

•  improvement last for wks or months

•  chronic intermittent treatment for refractory MG

•  repeated exchange not produce a cumulative benefit •  SE : cardiac arrythmias , nausea , lightheadedness , chills , obscured vision , pedal edema

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Intravenous Immunoglobulin

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

Intravenous Immunoglobulin

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

•  C/I : selective IgA deficiency •  because may develop anaphylaxis to IgA in IVIg •  preperation

•  SE : headache , chills , fever , alopecia , aseptic meningitis , leukopenia , retinal necrosis , renal failure , cerebral infarction , myocardial infarction

•  A multicenter , randomized , controlled study comparing plasmapheresis with IVIg has demonstrated equal efficacy but significanly fewer and less severe SE for IVIg

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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

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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 ”

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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

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Thymectomy

Ocular MG

•  repeat thymectomy : •  chronic refractory disease •  all thymic tissue not removed at prior surgery •  good response to original surgery

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Special situations

MG (II,III,IV)

Factor that worsen myasthenic symptoms •  emotional upset •  systemic illness (esp. viral respiratory infections) •  hypothyroidism or hyperthyroidism •  pregnancy •  menstrual cycle •  Drugs •  Fever 6/28/09!

Special situations

•  Surgery : •  spinal block •  avoidance neuromuscular blocking agent

Special situations

“ Avoidance of situations in which neuromuscular transmission may be compromised ” Penicillamine , amiodarone , aminoglycosides

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

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Neurology in Clinical Practice , 5th Edition , 2008

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thyroid dysfunction may have direct effect on the NMJ

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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 6/28/09!

6/28/09!

Neurology in Clinical Practice , 5th Edition , 2008

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