ocular myasthenia gravis: past, present, and future
TRANSCRIPT
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Ocular Myasthenia Gravis: Past, Present, and Future
Victoria S. Pelak, MDDepartments of Neurology and OphthalmologyUniversity of Colorado Health Sciences Center
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Ocular Myasthenia Gravis
1. Definition and Natural History2. Epidemiology3. Anatomy & Pathophysiology4. Clinical features & Differential Dx5. Diagnostic tests 6. Treatment7. Future Options
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Definition
⢠Weakness and fatigability of cranial, limb, respiratory musclesâ âgeneralizedâ
⢠Levator palpebrae superioris, EOMs, and orbicularis oculiâ âocularâ
⢠15% purely âocularâ
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Natural History
Ocular symptoms in Myasthenia Gravis:
⢠50% present solely with
⢠75-80% have on presentation
⢠90% eventually develop
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Natural History (Grob et al. â81)
⢠~2/3 will generalize⢠Who?⢠When?
â first 7 monthsâ OMG @ 1 year: 84% will NOT â OMG @ 2 years: 88%â OMG @ 3 years: 92%
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Historical Perspective
⢠Thomas Wills 1672⢠Samuel Wilks 1877⢠Ernst Sauerbrch 1912⢠Mary Walker 1934⢠C.E. Chang 1962⢠1970s
Thomas Wills
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Epidemiology: Incidence
⢠Incidence MG:4-14/100,000age and gender related⢠generalized: early peak late peak ⢠ocular: late peak
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0
20
40
60
80
100
120
140
1st 2nd 3rd 4th 5th 6th 7th 8th
womenmen
n=868
Generalized Myasthenia (Grob et al. â81)
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0
5
10
15
20
25
30
35
1st 2nd 3rd 4th 5th 6th 7th 8th
womenmen
Ocular Myasthenia (Grob et al. â81)
n=168
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Epidemiology: Mortality (Grob et el. â87)
1915-34: 70%
1935-39: 40%
1940-57: 33%
1958-65: 14%
1966-85: 7%
1934: anticholinesterase
1939: assisted ventilation
1960: pressure or volume
1966: steroid use
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Epidemiology: Associated Conditions
⢠Thyroid dysfunction
⢠Rheumatoid Arthritis
⢠Ankylosing spondylitis
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Anatomy & Pathophysiology
⢠Anatomyâ Neuromuscular junction
⢠Pathophysiologyâ Causesâ Autoimmune
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Anatomy
⢠Central nervous system⢠Peripheral nerve⢠Neuromuscular junction⢠Muscle⢠Combination
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Neuromuscular Junction
Electrical impulse
Chemical impulse
Electrical impulse
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Neuromuscular Junction Disorders
⢠Myasthenia Gravis⢠Lambert Eaton-Myasthenic Syndrome (LEMS)⢠Toxic or Metabolic
â Botulismâ Hypermagnesemiaâ Drugs (D-Penicillamine)â Organophosphate toxicityâ Snake, spider, scorpion bites
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Pathophysiology: Causes
⢠Autoimmune
⢠Neonatal
⢠Congenital
⢠Drug-induced
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Neonatal Myasthenia Gravis
⢠Passive transfer of IgG
⢠10 â 30% mothers with MG
⢠0 â 3 d after birth
⢠Transient: 1-6 weeks
⢠Weak cry, poor suck, hypotonia
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Congenital Myasthenia Gravis
⢠Genetic defects
⢠Birth or infancy
⢠Ocular +/- generalized
⢠Fluctuate, stable
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Neonatal MG
Congenital MG
Maternal MG
(+)
(-)
Onset 0-3 days postnatal
birth - infancy
Weakness generalized
ocular +/- generalized
Time Course
remission 1-6 wks
fixed
Antibodies usually (+) no
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Drug-induced Myasthenia Gravis
⢠D-Penicillamine
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Autoimmune Myasthenia Gravis
1. Postsynaptic disorder
2. Decreased acetylcholine receptors
⢠Immune-mediated
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Pathophysiology
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Clinical Features: OMG
⢠Ptosis
⢠Diplopia
⢠Orbicularis oculi weakness
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Ptosis⢠Isolation or with ophthalmoplegia⢠Fluctuates and shifts⢠Usually asymmetric⢠Examination:
â Fatigabilityâ âCoganâs lid twitchââ Curtainingâ Eyelid retraction
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Ocular Motility Deficits
⢠Any pattern â pseudo INOâ pseudo 3rd, 4th, 6th
â pseudo cavernous sinus syndromeâ Exam changes
⢠Medial rectus
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Orbicularis Oculi Weakness
⢠Common⢠Most commonly affected muscles:
1. levator palpebrae superioris2. EOMs3. orbicularis oculi4. proximal limb 5. facial expression, mastication, speech6. neck extensors
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Differential Diagnosis
⢠Ocular Myastheniaâ PEOâ Oculopharyngeal
dystrophyâ Thyroid eye diseaseâ Intracranial mass lesionâ âSenileâ ptosis
⢠Bulbar Dysfunctionâ Motor neuron syndromesâ Oculopharyngeal dystrophyâ Polymyositis
⢠Generalized Myastheniaâ Lambert-Eaton syndromeâ Botulismâ Myopathy
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Diagnostic Tests
⢠Anti-Acetylcholine Receptor Antibodies
⢠Tensilon Test
⢠Electromyography
⢠Response to mestinon
⢠Ice test
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Anti-Acetylcholine Receptor Antibodies
⢠Present in 80-90% of generalized
⢠Present in 50% of ocular
⢠No difference in severity, response, or prognosis
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Tensilon Test
⢠OMG: + 75%
⢠False positive
⢠Onset in 30s, lasts 1- 5 minutes
⢠Heart disease and elderly
⢠Atropine available
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Electromyography
⢠Repetitive nerve stimulationâ 60-90% generalizedâ 20-30% OMG
⢠Single fiber EMGâ 90-100% generalizedâ 80-90% OMG
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Mestinon Response
⢠Poor in OMG
⢠Ptosis
⢠Motility
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Ice Test
⢠Ice pack on more ptotic lid x 2 minutes
⢠Ptosisâ 92% in MGâ 0 non MG
⢠Substitute for tensilon
Borenstien et al. â75
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Ice Test: Case of 75 year old woman
⢠Negative antiacetylcholine receptor antibodies⢠Negative RNS and SFEMG ⢠Negative Tensilon test x 2⢠No response to mestinon
⢠Ice pack at home when âeyeâ closed shut
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Treatment
⢠Cholinesterase inhibitors (Mestinon)⢠Immunosuppresion:
â prednisoneâ cyclosporineâ azathioprine (Imuran)
⢠Thymectomy⢠Acute therapies
â IVIgâ Plasmapheresis
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Cholinesterase Inhibitors (Mestinon)
⢠Response often incompleteâ ptosisâ diplopia
⢠Onset 30â, half life of 3-4 hours⢠SE: diarrhea⢠Caution: cardiac conduction defects
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Prednisone
⢠OMG: good response
⢠Maintain high dose ~ 3 months or stable
⢠Lowest effective doseâ once determined alternate day therapyâ majority need indefinitely
⢠Caution: steroid-induced exacerbation
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Cyclosporine and Azathioprine
⢠Occasionally used in OMG
⢠Toxicity
⢠Indications:â resistant to steroidsâ need to reduce steroid dose
⢠>50 mg qod⢠significant SE
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Thymectomy
⢠Definite indications:1. Generalized: puberty â 60 years2. Thymoma (15%)
⢠OMG w/o thymoma: not rec
⢠Response: months-years
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Acute Therapies: IVIg and Plasmapheresis
⢠Short term â transient (days to weeks)
⢠Not indicated in OMG
⢠Indications in GMG
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Alternatives to Medical Treatment
⢠Ptosisâ ptosis crutchesâ ptosis surgery: not recommended
⢠Diplopiaâ patchâ prisms: too variableâ strabismus surgery: poor outcome
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Drug PrecautionsAntibiotics: aminoglycosides, neomycin, streptomycin,
kanamycin, gentamicin, tobramycin, netilmicin, amikacin,
Other: tetracycline, ciprofloxacin, erythromycin
Anticonvulsants: dilantin
Antimalarials: chloroquine, quinine
Cardiovascular: quinidine, procainamide, verapamil, timolol, propanolol
Ophthalmic: betaxolol, timolol
Psychotropic: lithium, chlorpromazine
Rheumatologic: D-penicillamine, chloroquine
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Most Common Problems
⢠Aminoglycosides
⢠Beta blockers
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Studies in OMG
⢠Thyroid function tests⢠CT Chest⢠Review patient drug list
⢠Tuberculin skin test⢠Rheumatologic screen
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Future Options
⢠Vaccine
⢠Early immunosuppresionâ injury to NMJ occurs during years 1-3
maximum weakness generalizationprednisone treated OMG
â trial: early IVIg
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Future Options
⢠Vaccineâ Araga and Blalock â94â Anti-idiotypic antibodiesâ Prevention of experimental autoimmune
myasthenia gravis
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Future
⢠Early immunosuppresion
â injury to NMJ: year 1-3 maximum weakness generalizationprednisone treated OMG
â trial: early IVIg?