JKOS Journal of the Korean Ophthalmological Society J Korean Ophthalmol Soc 0378-6471 2092-9374 Korean Ophthalmological Society 10.3341/jkos.2017.58.1.74 jkos-58-74 Original Article Intravenous Neostigmine Test for Diagnosis of Ocular Myasthenia Gravis KimDong Ik M.D LeeByung Joo M.D Seong-JoonKim MD, PhD Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea Address reprint requests to Seong-Joon Kim, MD, PhD Department of Ophthalmology, Seoul National University Hospital, #101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: 82-2-2072-1979, Fax: 82-2-741-3187 E-mail: ophjun@gmail.com 08 2017 30 8 2017 58 1 74 78 13 10 2016 24 10 2016 29 12 2016 Copyright © 2017 Korean Ophthalmological Society 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Purpose

In the present study, we evaluated the validity of intravenous neostigmine administration combined with alternate prism cover test (APCT) measurement as a confirmatory diagnostic method for confusing cases of myasthenia gravis with ocular involvement.

 Methods

Neostigmine was administered intravenously in 26 suspicious myasthenic diplopia patients under electrocardio-graphic monitoring. Distance deviation at primary position was evaluated with APCT at 5, 10, 15, 20, and 30 minutes after intra-venous injection of neostigmine. Margin reflex distance was also evaluated at each time point.

 Results

Seven of 26 patients were diagnosed as myasthenic diplopia based on a positive neostigmine test. Among these pa-tients, 6 had strabismus at the primary position and 5 patients had ptosis. In patients who showed positive results, all 6 patients showed improvement of strabismus. However, ptosis was not improved in 1 patient. The improvement of strabismus and ptosis reached a peak at 10 to 15 minutes after neostigmine administration.

 Conclusions

Intravenous neostigmine administration combined with APCT is a rapid, objective and safe method in hard-to-diag-nose cases of myasthenia gravis with ocular involvement. When performing the neostigmine test for myasthenia gravis with ocu-lar involvement, not only the lid position but also strabismus should be evaluated quantitatively to avoid a false negative results.

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Clinical characteristics of patients who showed positive results in neostigmine test

Patient Sex Age DM HTN Initial diagnosis Brain MRI RNST Ach R Ab TFT
Case 1 F 31 (-) (+) MG, INO WNL (-) (+) WNL
Case 2 M 45 (+) (-) MG, ALS (-) (+) (+) WNL
Case 3 F 61 (-) (-) MG, TAO WNL (-) (+) WNL
Case 4 M 57 (-) (-) MG, TAO, MF variant WNL (+) (-) WNL (Hyperthyroidism on medication)
Case 5 M 37 (-) (-) Ocular MG (-) (-) (-) (-)
Case 6 M 70 (-) (-) Left 6th nerve palsy, MG, multiple cranial neuropathy WNL (-) (+) WNL
Case 7 F 69 (+) (-) Ocular MG WNL (-) (+) (-)

DM = diabetes mellitus; HTN = hypertension; MRI = magnetic resonance imaging; RNST = repetitive nerve stimulation test; Ach R Ab = acetylcholine receptor antibody; TFT = thyroid function test; MG = myasthenia gravis; INO = internuclear ophthalmoplegia; ALS = amyo-tropic lateral sclerosis; TAO = thyroid associated orbitopathy; MF = miller-fisher syndrome; WNL = within normal limits.

Onset and peak time of strabismus improvement after neostigmine injection (data of patients who had positive results in neo-stigmine test)

Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Mean
Onset (minutes) 5 20 5 5 5 5 7.5
Peak (minutes) 10 20 10 5 5 20 11.7

Onset and peak time of ptosis improvement after neostigmine injection (data of patients who had positive results in neo-stigmine test)

Case 2 Case 4 Case 5 Case 7 Mean
Onset (minutes) 5 5 5 5 5
Peak (minutes) 5 10 15 15 11.3
Figures

Degree of strabismus after neostigmine injection. Six patients showed positive results. The improvement of stra-bismus reached a peak at 11.7 minutes after neostigmine administration. PD = prism diopter.

Degree of ptosis after neostigmine injection in the right eye. Four patients showed positive results. The improve-ment of ptosis reached a peak at 11.3 minutes after neo-stigmine administration. MRD = margin reflex distance.

Degree of ptosis after neostigmine injection in the left eye. Four patients showed positive results. The improve-ment of ptosis reached a peak at 11.3 minutes after neo-stigmine administration. MRD = margin reflex distance.