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Show Variable Ptosis after Botulinum Toxin Type A Injection with Positive Ice Test Mimicking Ocular Myasthenia Gravis Ahmad M. Alaraj, MD, Darren T. Oystreck, MMedSci, Thomas M. Bosley, MD Abstract: We describe a patient who received cosmetic botulinum toxin type A injections to the brow and sub-sequently developed unilateral ptosis that was variable during examination and was transiently improved after the ice pack test. Ptosis gradually resolved spontaneously over approximately 3 months. This is the third patient to have variable ptosis documented after botulinum toxin type A injection to the brow and the second to have a positive ice test. The ice test is not completely specific for myasthenia gravis but may, at times, improve ptosis resulting from other defects at the neuromuscular junction. Wound botulism now is much more common because of illicit drug use, and the ice test also might be positive in this setting. Journal of Neuro-Ophthalmology 2013;33:169-171 doi: 10.1097/WNO.0b013e31828bb19b © 2013 by North American Neuro-Ophthalmology Society Botulinum toxin injections (Botox; Allergan, Inc, Irvine, CA) (Dysport; Medicis Aesthetics, Inc, Scottsdale, AZ) (Myobloc; Elan, Inc, San Francisco, CA) are the most common minimally invasive facial procedures performed in the United States and probably worldwide (1,2). We describe a patient with unilateral ptosis following cosmetic botulinum toxin type A injections to the brow that mim-icked myasthenia gravis (MG), including having a positive ice test (3,4). This patient highlights the issues regarding diagnostic difficulties in the setting of ptosis following bot-ulinum toxin type A injection and regarding the specificity of the ice test for myasthenic ptosis. CASE REPORT A 52-year-old woman presented with a 1-week history of a drooping right upper eyelid. She denied diplopia, pain, dysphagia, dysarthria, dyspnea, generalized weakness, or any other focal neurologic symptoms, and initially, she did not mention receiving cosmetic botulinum toxin injections. Medical history was significant for diabetes mellitus and hypertension, and her medications were glibenclamide and amlor. Family history was unremarkable. Visual acuity was 20/20 in the right eye and 20/40 in the left eye. She had 3 mm of right upper eyelid ptosis (Fig. 1A) with fatigability of the right levator on sustained upgaze and a positive Cogan lid twitch sign. The left upper eyelid was normal, as was examination of the pupils. Ocular motility was full, and funduscopy was normal. The remainder of her neurologic examination was unremarkable without dysar-thria or midline or appendicular weakness. A 5-minute ice test was performed resulting in transient improvement in ptosis of .2 mm (Fig. 1B). General physical examination and chest x-ray were normal. Acetylcholine receptor antibody titer was within the normal limits. On a follow-up visit, the patient admitted receiving cosmetic botulinum toxin type A injection to the right eyebrow 3 days before the onset of right ptosis. There was complete resolution of ptosis over 12 weeks (Fig. 1C). DISCUSSION Our patient developed unilateral upper lid ptosis shortly after cosmetic botulinum toxin type A injections to the ipsilateral brow and forehead. Initial clinical examination mimicked MG with variable lid position, Cogan lid twitch sign, and transient resolution of ptosis after cooling of the involved lid with an ice pack (3,4). The patient did not have diplopia, limited ocular motility, or any other systemic signs or symptoms of generalized MG, and acetylcholine receptor Department of Ophthalmology (AMA), College of Medicine, Qassim University, Buraidah, Saudi Arabia; Department of Ophthalmology (DTO, TMB), College of Medicine, King Saud University, Riyadh, Saudi Arabia; and Division of Ophthalmology (DTO), Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa. The authors report no conflict of interest. Address correspondence to Darren T. Oystreck, MMedSci, King Abdulaziz University Hospital, PO Box 245, Riyadh 11411, Saudi Arabia; E-mail darrenoystreck@gmail.com Alaraj et al: J Neuro-Ophthalmol 2013; 33: 169-171 169 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. antibody levels were normal. Ptosis resolved spontaneously over 3 months. It seems most likely that ptosis was the result of botulinum toxin type A injections in the area above the right upper lid (5). Two similar patients have been reported with variable ptosis mimicking MG after cosmetic botulinum toxin type A injections. Sunness and Kelman (6) described a 70-year-old woman with variable right upper lid ptosis and diplopia associated with esotropia and hypertropia. A tentative diag-nosis of ocular MG was made, and an ice test improved ptosis but not ocular motility. At the second visit, the patient admitted that she had received cosmetic botulinum toxin type A injections around the lids 6 days before the onset of symptoms. Ptosis resolved within 2 weeks and diplopia some time later. Parikh and Lavin (7) encountered a 58-year-old woman with unilateral ptosis after a botulinum toxin type A "party" during which she received a relatively high dose. She also had fatigability of the lid, but an ice test was negative. Ptosis completely resolved in 12 weeks. All 3 patients with ptosis following botulinum toxin type A injections had clin-ical evidence of neuromuscular junction impairment with fatigability and Cogan lid twitch sign, and 2 had a positive ice test. Ptosis in all 3 resolved within 2-12 weeks. Reports describing ptosis as a side effect of therapeutic botulinum toxin type A injection generally have not mentioned variability, but the patients described in previous reports (6,7) and in the present study indicate that variability may occur. This may create potential confusion regarding the diagnosis of MG, particularly if the patient is not questioned about or initially denies botulinum toxin type A injections (6). The etiology of improvement in ptosis following lid cooling is unknown (8-10). Cooling may decrease cholin-esterase activity (11) and/or increase acetylcholine efficiency at the postsynaptic junction (12,13). In patients with myas-thenic ptosis, ice applied to a ptotic lid improves ptosis more than 2 mm in most (3,14) or all (4,15) individuals. Decreasing temperature seems superior to rest alone (4,15), while heat may have the reverse clinical effect (16). Cooling also improves myasthenic facial weakness (17), decremental response to repetitive nerve stimulation (9,17), and in most (15,17), but not all (6,8), instances of restricted ocular motility. Improvement of ptosis after cooling of an eyelid for 2 minutes has been reported to be both sensitive and specific for MG (3,14). A positive response is considered to be specific for MG because a number of studies have described no improvement in ptosis (3,4,18,19) or ocular motility restriction (19) of nonmyasthenic origin. However, the ice test has been found to be positive in patients with the congenital myasthenic syndrome caused by CHRNE mutations (20), as well as in patients with ptosis resulting from the cosmetic use of botulinum toxin type A. No study has specifically investigated the effect of cooling on ptosis resulting from neuromuscular junction defects that are not autoimmune in origin (15). While botulism in general is uncommon, wound botulism has become much more common because of an increase in the subcutaneous injection of illicit drugs (18,21,22). At times, the responsible wound is not men-tioned nor is it apparent on physical examination (19). Patients commonly present with bilateral ptosis and facial weakness, dysarthria, and difficulty swallowing (21,22). A positive ice test in this setting might be interpreted incor-rectly as diagnostic of MG. REFERENCES 1. Jankovic J, Brin MF. Therapeutic uses of botulinum toxin. N Engl J Med. 1991;324:1186-1194. 2. Brin MF, Boodhoo TI, Pogoda JM, James LM, Demos G, Terashima Y, Gu J, Eadie N, Bowen BL. Safety and tolerability of onabotulinum toxin A in the treatment of facial lines: a meta-analysis of individual patient data from global clinical registration studies in 1678 participants. J Am Acad Dermatol. 2009;61:961-970.e1-e11. 3. Golnik KC, Pena R, Lee AG, Eggenberger ER. An ice test for the diagnosis of myasthenia gravis. Ophthalmology. 1999;106:1282-1286. 4. Kubis KC, Danesh-Meyer HV, Savino PJ, Sergott RC. The ice test versus the rest test in myasthenia gravis. Ophthalmology. 2000;107:1995-1998. 5. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Semin Cutan Med Surg. 2001;20:109-120. 6. Sunness JS, Kelman S. Cosmetic Botox injection mimicking myasthenia gravis. Plast Reconstr Surg. 2004;113:1515. 7. Parikh R, Lavin PJ. Cosmetic botulinum toxin type A induced ptosis presenting as myasthenia. Ophthal Plast Reconstr Surg. 2011;27:470. 8. Saavedra J, Femminini R, Kochen S, deZarate JC. A cold test for myasthenia gravis. Neurology. 1979;29:1075. 9. Borenstein S, Desmedt JE. Local cooling in myasthenia. Improvement of neuromuscular failure. Arch Neurol. 1975;32:152-157. 10. Denys EH. AAEM minimonograph #14: the influence of temperature in clinical neurophysiology. Muscle Nerve. 1991;14:795-811. FIG. 1. One week following cosmetic botulinum toxin A injec-tion, there is 3 mm of right ptosis (A),which improved following ice test (B), and spontaneously resolved 12 weeks later (C). 170 Alaraj et al: J Neuro-Ophthalmol 2013; 33: 169-171 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 11. Thies RE. Neuromuscular depression and the apparent depletion of transmitter in mammalian muscle. J Neurophysiol. 1965;28:428-442. 12. Harris JB, Leach GD. The effect of temperature on end-plate depolarization of the rat diaphragm produced by suxamethonium and acetylcholine. J Pharm Pharmacol. 1968;20:194-198. 13. Hubbard JI, Jones SF, Landau EM. The effect of temperature change upon transmitter release, facilitation and post-tetanic potentiation. J Physiol. 1971;216:591-609. 14. Sethi KD, Rivner MH, Swift TR. Ice pack test for myasthenia gravis. Neurology. 1987;37:1383-1385. 15. Ellis FD, Hoyt CS, Ellis FJ, Jeffery AR, Sondhi N. Extraocular muscle responses to orbital cooling (ice test) for ocular myasthenia gravis diagnosis. J AAPOS. 2000;4: 271-281. 16. Movaghar M, Slavin ML. Effect of local heat versus ice on blepharoptosis resulting from ocular myasthenia. Ophthalmology. 2000;107:2209-2214. 17. Odabasi Z, Brooks JA, Kim DS, Claussen GC, Oh SJ. Ice-pack test in myasthenia gravis: electrophysiological basis. J Clin Neuromuscul Dis. 2000;1:141-144. 18. Werner SB, Passaro D, McGee J, Schechter R, Vugia DJ. Wound botulism in California, 1951-1998: recent epidemic in heroin injectors. Clin Infect Dis. 2000;31:1018-1024. 19. Pujar T, Spinello IM. A 38-year-old woman with heroin addiction, ptosis, respiratory failure, and proximal myopathy. Chest. 2008;134:867-870. 20. Salih MA, Oystreck DT, Al-Faky YH, Kabiraj M, Omer MI, Subahi EM, Beeson D, Abu-Amero KK, Bosley TM. Congenital myasthenic syndrome due to homozygous CHRNE mutations: report of patients in Arabia. J Neuroophthalmol. 2011;31:42-47. 21. Maselli RA, Ellis W, Mandler RN, Sheikh F, Senton G, Knox S, Salari-Namin H, Agius M, Wollmann RL, Richman DP. Cluster of wound botulism in California: clinical, electrophysiologic, and pathologic study. Muscle Nerve. 1997;20:1284-1295. 22. Brett MM, Hallas G, Mpamugo O. Wound botulism in the UK and Ireland. J Med Microbiol. 2004;53:555-561. Erratum A Mystery Case of Proptosis, Optic Neuropathy, and Peripheral Neuropathy: Erratum In the article that appeared on page 77 of the March 2013 issue of the Journal of Neuro-Ophthalmology, two hyperlinks were omitted which grant access to Supplemental Digital Content figures. To view Supplemental Digital Content 1, visit http://links.lww.com/WNO/A48; to view Supplemental Digital Content 2, visit http://links.lww.com/WNO/A49. Additionally, a typo appeared in the footnote regarding Supplemental Digital Content on the first page of the article. The correct journal web site is http://www.jneuro-ophthalmology.com, and the Supplemental Digital Content figures can be found accompanying the article online. REFERENCE 1. Keung BM, Shah LM, Eckart DE, Digre KB, Chin SS, Warner JEA. A mystery case of proptosis, optic neuropathy, and peripheral neuropathy. J Neuroophthalmol. 2013;33:77-82. Alaraj: J Neuro-Ophthalmol 2013; 33: 169-171 171 Clinical Observation Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
