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Bilateral Ptosis from Ocular Myasthenia: The benefit of the ice and rest test

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Title: Bilateral Ptosis from Ocular Myasthenia: The benefit of the ice and rest test
Authors:  Shanna Swartwood, MD and Meagan Seay, DO
Photographer: Meagan Seay, DO
Date: 11/2019
Keywords/Main Subjects: Myasthenia gravis, ptosis, ice test, rest test
Diagnosis: Ocular myasthenia gravis

Introduction: Myasthenia gravis (MG) is an autoimmune disorder characterized by fluctuating weakness and fatigability of skeletal muscles due to dysfunction of the neuromuscular junction. The ocular, bulbar, limb and respiratory muscles are most often affected. When the symptoms of MG are isolated to the ocular muscles it is referred to as ocular MG (OMG). The classic presentation for OMG is the triad of ptosis, oculomotor paresis, and orbicularis oculi weakness.

Description of Case:  A 68-year-old male presents with one-week history of bilateral ptosis, left worse than right eye. The patient reported the sensation of heavy eyelids, worse at end of the day and improved upon awakening. He denied other ocular symptoms including diplopia, anisocoria and vision loss and denied systemic symptoms including generalized weakness in extremities. On exam, extraocular movements revealed mild left gaze palsy with small esotropia in right gaze. Bilateral fatigable ptosis that fluctuated throughout the exam, as well as bilateral orbicularis weakness, Cogan’s lid twitch and eyelid curtaining were observed. Visual acuity, pupils, visual fields, slit lamp and fundus exam were unremarkable. The ice pack and rest test were performed (Figure 1) with significant improvement after 5 minutes of ice pack application to left eye and rest of the right eye (Figure 2) raising suspicion for diagnosis of MG. Acetylcholine receptor antibody (AChR) testing sent and positive for AChR binding, blocking and modulating antibodies. Treatment for OMG initiated with acetylcholinesterase inhibitor pyridostigmine.

Figure 1: Bilateral ptosis in primary gaze, pre-ice pack test and rest test.

Figure 2: Post-ice pack test left eye, post-rest test right eye. Improved ptosis of both eyes, left greater than right.

Discussion: Myasthenia gravis is an autoimmune neuromuscular junction disease characterized by fatigable and fluctuating weakness of skeletal muscles. The triad of ptosis, oculomotor paresis, and orbicularis oculi weakness should raise suspicion for the purely ocular form of MG. Over one-half of patients with MG initially present with isolated ptosis, diplopia or both, and no signs or symptoms of weakness elsewhere1. Males are more often affected by OMG than females with a bimodal distribution in women with peaks at 30 and 60 years of age and a unimodal peak in men around 70 years of age1. If symptoms of pain, proptosis, perception loss or pupillary involvement are present an alternate diagnosis other than MG should be considered. Multiple exam maneuvers may be performed in clinic to help establish diagnosis of MG including Cogan’s lid twitch (video)2, characterized by an overshoot of the ptotic eyelid when patient sustains downgaze and saccades back to neutral gaze, and eyelid curtaining, present when one eyelid is manually elevated resulting in enhanced ptosis of the opposite eyelid. Both of these findings, if present, are highly suggestive of MG. 3 Non-pharmacologic tests may help raise suspicion for MG including the ice pack test and rest test.4 It has been hypothesized that improved ptosis after ice pack application is a result of resting the eyelids. Previously published literature has shown significant improvement of ptosis with ice pack test compared to rest test5 arguing there is an additional benefit of cooler temperatures on ptosis, possibly through improved neuromuscular transmission at lower muscle temperatures. Diagnostic testing for MG includes auto-antibody and electrophysiological testing. Acetylcholine receptor antibody (AChR) is the most frequently detected auto-antibody in both ocular and generalized MG; however, patients with OMG are more likely to be seronegative for AChR than patients with generalized MG.6 Other auto-antibodies present in MG include muscle-specific tyrosine kinase (MuSK) and low-density lipoprotein receptor-related protein 4 (LRP4). Patients positive for LRP4-Ab tend to have a milder disease course compared with AChR-positive, MuSK-positive or double positive patients (AChR/LRP4 Abs or MuSK/LRP4 Abs).7 Negative serologic testing for AChR, MuSK and LRP4 is present in 10% of patients with MG and is termed “triple negative.”8 Of triple negative patients, 15-50% will have other auto-antibodies, including agrin, collagen Q and non-junctional antibodies titin and ryanodine receptor (RyR).8  The presence of non-junctional antibodies is associated with a more severe disease course in all MG subgroups.9 Single-fiber electromyography (SFEMG) is the most useful electrophysiological test for patients with OMG, especially in the presence of autoantibody sero-negativity. In addition to being a useful diagnostic tool, SFEMG helps predict the severity of disease, more jitter correlates with a more severe disease course.10 Additional testing should include CT scan of the chest to assess for thymoma and serum testing for concurrent autoimmune disorders including autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis.11 First line treatment for MG/OMG is with acetylcholine esterase inhibitors. Prednisone is often used as a first-line immunosuppressive agent. Steroid-sparing agents that improve disease control while minimizing steroid-induced complications, including azathioprine and mycophenolate mofetil, are becoming used more frequently.12 Rituximab is an off-label treatment for refractory MG.13 Prognosis for MG is variable, increasing age at onset of symptoms is associated with greater risk for respiratory crisis or death caused by MG.14 Previously published literature has reported if disease remains purely ocular after two years there is roughly 80% chance that generalization will never occur.15 One study reported treatment with immunosuppressive agents and pyridostigmine are protective factors against conversion of OMG to GMG for AChR-positive patients.15

 

 

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References for further reading:

  1. Hendricks TM, Bhatti MT, Hodge DO, Chen JJ. Incidence, Epidemiology, and Transformation of Ocular Myasthenia Gravis: A Population-Based Study. Am J Ophthalmol. 2019 Sep; 205:99-105.
  2. Digre KB. Cogan’s Lid Twitch Moran CORE. Available at http://morancore.utah.edu/section-05-neuro-ophthalmology/cogans-lid-twitch-video-2/. Accessed November 8, 2019.
  3. Singman EL, Matta NS, Silbert DI. Use of the Cogan lid twitch to identify myasthenia gravis. J Neuroophthalmol 2011; 31:239-240.
  4. Garcia-Grimshaw M, Posadas-Pinto D. Myasthenia gravis: an icy diagnosis. Postgrad Med J. 2019 Oct; 95(1128):567.
  5. Kubis K, Danesh-Meyer H, Savino P, Sergott R. The ice test versus the rest test in myasthenia gravis. Ophthalmology2000; 107:1995-1998.
  6. Fortin E, Cestari DM, Weinberg DH. Ocular myasthenia gravis: an update on diagnosis and treatment. Curr Opin Ophthalmol. 2018 Nov; 29(6):477-484.
  7. Evoli A, Iorio R. Characteristics of myasthenia gravis with antibodies to muscle-specific kinase and low-density lipoprotein-related receptor protein 4. Clin and Exper Neuroimmunology. 2015; 6:40-48.
  8. Hong Y, Zisimopoulou P, Trakas N, Karagiorgou K, Stergiou C, Skeie GO, Hao HJ, Gao X, Owe JF, Zhang X, Yue YX, RomiF, Wang Q, Li HF, Gilhus NE, Tzartos SJ. Multiple antibody detection in ‘seronegative’ myasthenia gravis patients. Eur J Neurol. 2017 June; 24(6):844-850.
  9. Suzuki S, Utsugisawa K, Nagane Y, Suzuki N. Three types of striational antibodies in myasthenia gravis. Autoimmune Diseases. 2011 June.
  10. Padua L, Starberg E, Lomonaco M, et al. SFEMG in ocular myasthenia gravis diagnosis. Clin Neurophysiol 2000; 111(7):1203-1207.
  11. Tanovska N, Novotni G, Sazdova-Burneska S, Kuzmanovski I, Boshkovski B, Kondov G, Jovanovski-Srceva M, Kokareva A, Isjanovska R. Myasthenia Gravis and Associated Diseases. Open Access Maced J Med Sci. 2018 Mar 15; 6(3): 472-478.
  12. Palace J, Newsom-Davis J, Lecky B. A randomized double-blind trial of prednisolone alone or with azathioprine in myasthenia gravis. Neurology. 1998; 50:1778-1783.
  13. Tandan R, Hehir MK, Waheed W, Howard DB. Rituximab treatment of myasthenia gravis: A systemic review. Muscle Nerve. 2017 Aug;56(2):185-196.
  14. Bever CT, Aquino AV, Penn AS, Lovelace RE, Rowland LP. Prognosis of ocular myasthenia. Ann Neurol. 1983 Nov;14(5):516-519.
  15. Apinyawasisuk S, Chongpison Y, Thitisaksakul C, Jariyakosol S. Factors Affecting Generalization of Ocular Myasthenia Gravis in Patients with Positive Acetylcholine Receptor Antibody. Am J Ophthalmol. 2019 Sep 25. Available at https://www.ncbi.nlm.nih.gov/pubmed/31562855. Accessed November 10, 2019.

Faculty Approval by: Kathleen Digre, MD

Identifier: Moran_CORE_27089
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