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Disclosures

Ocular Myasthenia: How to catch a slippery fish  I have no relevant financial relationships

Ryan D. Walsh, MD Assistant Professor Dept. of Ophthalmology and Visual Sciences Dept. of Neurology Medical College of Wisconsin

2017 Wisconsin EYE MD Symposium 10/7/17

“The Great Mimicker” —Basics

 Antibody‐mediated  Myasthenia Gravis (MG) is known for its ability to mimic any  Reduced availability of Ach Receptors at skeletal type of ocular misalignment NMJdefective NMJ transmissionweakness  Eyelids and extraocular muscles involved in 90% of patients with MG  50% present with and/or eye motility abnormalities ONLY  50% of these will remain “ocular myasthenics”  50% develop generalized dz (usually within 2 years)

Liu GT et al. Neuro‐ophthalmology Diagnosis and Management, 2nd Ed. 2010

Myasthenia Gravis—Basics Ice Pack Test

 Ptosis, , swallowing difficulties, extremity weakness, dysarthria, dysphagia  Weakness = variable, fatigable, diurnal variation  Lid Signs  Easy as 1‐2‐3  Ptosis  Fatigability  Cogan’s lid twitch  Curtaining/enhanced ptosis  Orbicularis oculi weakness  Lid hopping

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Ice Pack Test Serologic Testing

 Serum Antibodies ‐Sensitivity: 92%  receptor antibodies (binding, blocking, ‐Specificity: 79% modulating) ‐Positive Predictive  Muscle‐specific receptor tyrosine kinase (MuSK) antibodies Value: 73%  Striated muscle (striational) antibodies ‐Negative Easy as Predictive 1‐2‐3  Lipoprotein‐related protein 4 (LRP4) antibodies Value: 94%  Anti‐cortactin antibodies Fakiri MO et al. Muscle Nerve, 2013

Acetylcholine Receptor Antibodies Muscle‐specific receptor tyrosine (AChR‐Ab) kinase (MuSK) Antibodies

 AchR Binding Abs  Complement activationdamage to postsynaptic muscle membrane  MuSK=post‐synaptic NMJ protein  85‐90% of patients with generalized MG  Generalized MG patients negative for AchR‐Abs  50% of patients with ocular myasthenia  40% of these pts = +MuSK  AchR Blocking Abs  Rarely found in ocular MG  Impair binding of Ach to the AchR  More bulbar symptoms  Ocular MG patients may rarely be blocking Ab+ and binding Ab –  AchR Modulating Abs  Cross‐link AChR on the cell surfaceendocytosis and degradation of AChRs  Occasionally + in MG when AchR binding Abs are ‐

Chan KH et al. Muscle Nerve. 2007 Meriggioli M and Sanders D. Lancet Neurol. 2009 Kang S et al. Neurol Sci. 2015 Howard FM et al. Ann N Y Acad Sci. 1987

Other Antibodies (Tensilon) Test

 Edrophonium chloride=short‐acting acetyl‐cholinesterase inhibitor  Most useful if ptosis or a single obviously paretic extraocular muscle  Striated muscle (striational) Abs can be used as an endpoint  Target muscle cytoplasmic proteins  Cautions:  Increase in oral secretions  Titin, myosin, actin, ryanodine receptors  respiratory compromise in patients with significant oropharyngeal  weakness 75‐85% of pts with thymomatous MG  Bradycardia/syncope  Also seen in 50% of late‐onset non‐thymomatous MG  Rare but serious  Have atropine available  Also seen in without MG  Acute GI intolerance/diarrhea  Anti‐Lipoprotein‐related receptor protein 4 (LRP4) Abs  Sensitivity  Estimated 86% in ocular MG, 71.5‐95% in generalized MG  Anti‐cortactin Abs  Specificity  Not defined though likely higher in generalized than ocular

Meriggioli and Sanders. Lancet Neurol. 2009 Marino M et al. PLoS One. 2015 Stergiou C et al. J Neuroimmunol .2016 Pascuzzi RM. Semin Neurol. 2003 Cortes‐Vicente E et al. JAMA Neurol. 2016 Meriggioli and Sanders. Lancet Neurol. 2009

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Nerve Conduction Studies/EMG Thank you!!

 NCS with repetitive stimulation  Sensitivity ≈75% in generalized MG; <50% in ocular MG  Single fiber EMG  Sensitivity 95‐99% (if appropriate muscles examined)  Not entirely specific for MG (other nerve, muscle, or pathology can produce abnormal results)

Meriggioli and Sanders. Lancet Neurol. 2009

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