9/26/2017 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” Myasthenia Gravis—Basics Antibody‐mediated autoimmune disease Myasthenia Gravis (MG) is known for its ability to mimic any Reduced availability of Ach Receptors at skeletal type of ocular misalignment NMJdefective NMJ transmissionweakness Eyelids and extraocular muscles involved in 90% of patients with MG 50% present with ptosis 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, diplopia, 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 1 9/26/2017 Ice Pack Test Serologic Testing Serum Antibodies ‐Sensitivity: 92% Acetylcholine 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 activationdamage 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 surfaceendocytosis 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 Edrophonium (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 thymoma 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 2 9/26/2017 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 neuromuscular junction pathology can produce abnormal results) Meriggioli and Sanders. Lancet Neurol. 2009 3.