Intravenous Neostigmine Test for Diagnosis of Ocular Myasthenia Gravis

Dong Ik Kim; Byung Joo Lee; Kim Seong-Joon

doi:10.3341/jkos.2017.58.1.74

Journal List > J Korean Ophthalmol Soc > v.58(1) > 1010798

Go to TopGo to Top Go to BottomGo to Bottom

TOOLS

Kim, Lee, and Seong-Joon: Intravenous Neostigmine Test for Diagnosis of Ocular Myasthenia Gravis

Original Article

J Korean Ophthalmol Soc 2017;58(1):74-78.

Published online: 30 August 2017

DOI: https://doi.org/10.3341/jkos.2017.58.1.74

Intravenous Neostigmine Test for Diagnosis of Ocular Myasthenia Gravis

Dong Ik Kim, M.D, Byung Joo Lee, M.D, Kim Seong-Joon, 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

Received 13 October 201624 October 2016 Accepted 29 December 2016

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.

Keywords: Neostigmine, Ocular myasthenia gravis, Ptosis, Strabismus

References

1. Viets HR, Schwab RS. Prostigmin in the diagnosis of myasthenia gravis. N Engl J Med. 1961; 66:111–24.

2. Tether JE. Intravenous neostigmine in diagnosis of myasthenia gravis. Ann Intern Med. 1961; 66:111–24.

3. Calvey TN, Wareing M, Williams NE, Chan K. Pharmacokinetics and pharmacological effects of neostigmine in man. Br J Clin Pharmacol. 1961; 66:111–24.

4. Sommer N, Melms A, Weller M, Dichgans J. Ocular myasthenia gravis. A critical review of clinical and pathophysiological aspects. Doc Ophthalmol. 1961; 66:111–24.

5. Osserman KE. Ocular myasthenia gravis. Invest Ophthalmol Vis Sci. 1961; 66:111–24.

6. Luchanok U, Kaminski HJ. Ocular myasthenia: diagnostic and treatment recommendations and the evidence base. Curr Opin Neurol. 1961; 66:111–24.

7. Costa J, Evangelista T, Conceição I, de Carvalho M. Repetitive nerve stimulation in myasthenia gravis--relative sensitivity of dif-ferent muscles. Clin Neurophysiol. 1961; 66:111–24.

8. Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology. 1961; 66:111–24.

9. Ellis FD, Hoyt CS, Ellis FJ, et al. Extraocular muscle responses to orbital cooling (ice test) for ocular myasthenia gravis diagnosis. J AAPOS. 1961; 66:111–24.

10. Chatzistefanou KI, Kouris T, Iliakis E, et al. The ice pack test in the differential diagnosis of myasthenic diplopia. Ophthalmology. 1961; 66:111–24.

11. Oey PL, Wieneke GH, Hoogenraad TU, van Huffelen AC. Ocular myasthenia gravis: the diagnostic yield of repetitive nerve stim-ulation and stimulated single fiber EMG of orbicularis oculi mus-cle and infrared reflection oculography. Muscle Nerve. 1993; 16:142–9.

12. Padua L, Stalberg E, LoMonaco M, et al. SFEMG in ocular myas-thenia gravis diagnosis. Clin Neurophysiol. 1961; 66:111–24.

13. Vincent A, Newsom-Davis J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry. 1961; 66:111–24.

14. Lindstrom JM, Seybold ME, Lennon VA, et al. Antibody to ace-tylcholine receptor in myasthenia gravis Prevalence, clinical corre-lates, and diagnostic value. J Neurology. 1998; 51:933.

15. Oda K, Ito Y. Myasthenia gravis: antibodies to acetylcholine receptor in ocular myasthenia gravis. J Neurol. 1961; 66:111–24.

16. Jacob S, Viegas S, Leite M, et al. Presence and pathogenic relevance of antibodies to clustered acetylcholine receptor in ocular and generalized myasthenia gravis. Arch Neurol. 1961; 66:111–24.

17. Meriggioli MN, Sanders DB. Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity. Lancet Neurol. 1961; 66:111–24.

Table 1.

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.

Table 2.

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

Table 3.

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

Figure 1.

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.

Figure 2.

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.

Figure 3.

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.

TOOLS

Similar articles