In 1965, Cogan (1) first described the now eponymous lid twitch as a sign of myasthenia gravis (MG). This sign is elicited by instructing the patient to maintain downward gaze for 15 seconds and then gaze upward, finally returning to primary gaze. In patients with a positive sign, the observer will notice that the upper lid produces a definite upward twitch, or overshoot, soon after the patient has returned to primary gaze. This sign has been considered part of the standard battery of clinical tests used to diagnose ocular MG (2), a condition that is seropositive for acetylcholine receptor antibodies in only 65% of patients (3). At the time of our investigation, only 1 study evaluating the sensitivity and specificity of the Cogan lid twitch (CLT) had been published (4), and we felt further study was warranted.
We received institutional review board (IRB) approval through the Lancaster General Hospital IRB and a waiver of consent due to the low risk of this research and followed appropriate Health Insurance Portability and Accountability Act of 1996 guidelines. CLT testing was performed prospectively on 117 consecutive adult patients evaluated by a neuro-ophthalmologist (ELS). The examiner was not masked to the patients' symptoms or diagnosis. This study was conducted over a period of 2 weeks. The patients were instructed to look straight ahead, up, down, and straight ahead again. The upper eyelids were carefully evaluated immediately following this movement for the presence of a brief upward twitch of the upper eyelid, which would indicate a positive CLT test. The test was repeated as needed.
We evaluated the findings from the ophthalmic examination along with data from each patient's medical record, including results of serologic testing (including tests for acetylcholine receptor blocking, binding and modulating antibodies, antistriated muscle antibodies and muscle-specific receptor tyrosine kinase [MuSK] antibodies), MRI of the brain, CT of the chest, nerve conduction studies, response to intravenous edrophonium, and confirmation of suspected cases by a neurologist specializing in neuromuscular disease. In our patient population, the sensitivity and specificity of the CLT were calculated, as well as the false-positive rate.
Of the 117 patients evaluated, 19 displayed a positive CLT. Of these 19 patients, 18 had clinically certain MG. Further, of the 117 patients, 24 had clinically certain MG. Therefore, for the 98 patients who did not display a positive CLT, 6 had clinically certain MG (Table 1). We calculated that the specificity of the CLT for diagnosing MG in this sample of patients was 99%, while the sensitivity was 75%. Further, in our sample, the false-positive rate for the test was 1%. Of interest, none of the patients in our cohort had symptomatic ptosis.
We found that the CLT test appears to be a sensitive and reasonably specific test for the diagnosis of MG. Van Stavern et al (4) published the only other study evaluating these metrics for the CLT and suggested that this test was not as useful as our data would suggest. It is difficult to compare the 2 studies because the patient populations were very different. All 35 of the patients Van Stavern et al evaluated were selected because they had isolated symptomatic ptosis, a finding suspicious for MG, while our 117 patients were chosen at random. The aim of the report by Van Stavern et al was to determine whether CLT was useful in excluding etiologies of ptosis other than MG, while that of our study was to evaluate the utility of CLT in identifying MG, without any preselection bias.
The physiologic mechanisms underlying CLT are unknown. It is counterintuitive that patients with MG would have muscle overreactivity, as suggested by the fact that during a positive Cogan twitch, the eyelid retractors overshoot as the eye returns from downward gaze to primary gaze. The study by Van Stavern et al suggested that CLT was not particularly common in patients with ptosis. This might suggest that ptotic eyelids are insufficiently innervated or otherwise mechanically unable to overshoot. Interestingly, dysthyroid patients are known to suffer lagophthalmos and eyelid retraction, and patients suffering MG more often harbor antithyroid antibodies than the general population (5). Despite this, autoimmune thyroid dysfunction is not more common in myasthenic patients than in the general population (6). It might be worthwhile to determine whether the presence of CLT in patients with MG varied depending on the presence of antithyroid antibodies.
We are aware of a number of limitations of our study. Given that the prevalence of MG in the general population is up to 20/100,000 (7), our patient cohort was clearly highly selected. In addition, the examiner was not blinded to the patients' symptoms or diagnostic evaluation. Finally, we realize this is only a pilot study, and the results suggest further research is needed. Of particular interest would be to evaluate the timing of when the diagnosis of MG is established compared to discovery of the CLT. This should include patients both with and without ptosis. In addition, further study is required to understand the etiology and physiology of the CLT.
1. Cogan DG
. Myasthenia gravis: a review of the disease and a description of lid twitch as a characteristic sign. Arch Ophthalmol. 1965;74:217-221.
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, Newman NJ, Biousse V, eds.Walsh and Hoyt's Clinical Neuro-Ophthalmology, 6th edition. Philadelphia, PA: Lippincott, 2005.
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, Bhatt A, Haviland J, Black EH. A prospective study assessing the utility of Cogan's lid twitch sign in patients with isolated unilateral or bilateral ptosis. J Neurol Sci. 2007;256:84-85.
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, Cojocaru M, Musuroi C. Study of anti-striational and anti-thyroid antibodies in patients with myasthenia gravis. Rom J Intern Med. 2000-2001;38-39:111-120.
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, Mayr N, Zeitlhofer J. Clinical significance of autoimmune thyroid disease in myasthenia gravis. Exp Clin Endocrinol Diabetes. 2000;108:63-65.
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, Cardwell CR, McCarron PO, McConville J. A systemic review of population based epidemiological studies in myasthenia gravis. BMC Neurol. 2010;10:46-55.