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Three Part Question

In [patients presenting with bilateral ptosis] is [the ice-pack test effective] at [diagnosing myasthenia gravis]?

Clinical Scenario

A 57-year-old man attends the Emergency Department with bilateral ptosis. You only have a short time in order to ascertain the cause of the ptosis and therefore refer appropriately. The ED SHO wonders if there is a simple bedside test to distinguish whether Myasthenia Gravis is the cause of this presentation.

Search Strategy

OVID Medline 1966-2015
HDAS EMBASE 1974-2015
The Cochrane Library issue 9, 2015


[exp Ice/ OR Ice-Pack] AND [exp Myasthenia/ OR Myasthenia Gravis]

Search Outcome

Medline: 11 papers found, 2 relevant
EMBASE: 29 papers found, 5 relevant
Cochrane: 4 papers found, 3 relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Fakiri OM et al 2013 Netherlands	31 patients presenting with ptosis	Retrospective cohort study	Sensitivity	92%	Subjective reporting of ptosis improvement Time that ice cube was applied not standardized
			Specificity	79%
Sethi KD et al 1987 USA	10 myasthenic patients 7 patients with nonmyasthenic ptosis	Randomised controlled trial	Sensitivity	80%	Small sample Possible selection bias
			Specificity	100%
Kubis KC et al 2000 USA	10 subjects with ptosis from previously undiagnosed MG 15 subjects with nonmyasthenic ptosis	Randomised noninterventional trial	Sensitivity	90%	Open to observer bias Small sample size
			Specificity	100%
Lertchavanakul A et al 2001 Thailand	20 patients with MG ptosis 20 patients with non-MG ptosis	Prospective, nonrandomized comparative study	Sensitivity	95%	Not randomized or blinded
			Specificity	100%
Liu Y et al 2006 China	32 patients with ptosis from newly diagnosed MG 33 subjects with nonmyasthenic ptosis	Randomised noninterventional trial	Sensitivity	78%	Subjective reporting of improvement in ptosis
			Specificity	100%
Ramirez-Antunez AG et al 2013 Spain	18 patients with MG 18 patients with nonmyasthenic ptosis	Observational non-randomized study	Sensitivity	83%	Non-randomized, non-blinded
			Specificity	100%
da Fonseca Jr. NL et al 2010 Brazil	40 patients with MG 30 patients with nonmyastenic ptosis	Prospective cohort study	Sensitivity	100%	Open to observer bias
			Specificity	100%
Chatzistefanou KI et al 2009 Greece	89 patients with recent onset blepharoptosis, diplopia or both	Prospective cohort study	Sensitivity	92.3%	Variability in cooling time
			Specificity	98.3%
Czaplinski A et al 2003 Switzerland	5 patients with undiagnosed MG ptosis 5 patients with non-MG ptosis	Prospective cohort study	Sensitivity	100%	Small study Not blinded
			Specificity	100%
Tabassi A et al 2005 Iran	156 patients presenting with ptosis	Prospective cohort study	Sensitivity	100%	Possible confounding due to simultaneous Tensilon testing
			Specificity	100%

Comment(s)

There are a number of differential diagnoses for a patient presenting with bilateral ptosis, such as myasthenia gravis (MG), Lambert-Eaton myasthenis syndrome, demyelinating neuropathy, Guillan-Barré or an acute neurological event (Browning J, 2011). MG itself may present with a diverse range of symptoms such as skeletal muscle weakness, dysphagia, diplopia or respiratory compromise. The majority of patients develop some form of ocular myasthenia and ptosis is the initial presentation in 50% of patients. This is due to the involvement of the levator palpebrae superioris and may be unilateral or bilateral (Nair AG, 2014). There are a number of investigations currently available for the diagnosis of MG, including serum acetylcholine (ACh) receptor antibodies, repetitive nerve stimulation, Tensilon test, neostigmine test and the rest test. Serological testing requires a specialist laboratory and thus takes time to process. In addition, seropositivity has been reported to be as low as 59.4% (Bindu PS, 2008). The Tensilon test is the most commonly used bedside test at present and involves administration of edrophonium (an acetylcholinesterase inhibitor) and is contraindicasted in cardiac disease or asthma and requires resuscitation equipment to be immediately available. The ice-pack test is performed by placing ice chips in a glove or towel and holding it on the eyelid for 2 minutes. A positive test is deemed as >2mm increase in distance between upper and lower eyelid margins. The ice test works due to the biochemical basis principle of low temperatures enhancing neuromuscular transmission due to its effect on calcium influx into the nerve terminal, release and binding of ACh and reduced hydrolysis of ACh by acetylcholinesterase (Witoonpanich, 2010). Cooling below 22°C, however, may result in complete failure of neuromuscular transmission (Ricker K, 1977). Drawbacks of the ice-pack test are discomfort for the patient if the glove is applied for more than 2 minutes, and cooling below 22°C resulting in false negatives (Rajasekharan C, 2011). It is otherwise a very safe test. Bindu PS, N. N. (2008). Myasthenia gravis and acetylcholine receptor antibodies: A clinico immunological correlative study on South Indian patients. Ann Indian Acad Neurol , 11 (4), 242-244. Browning J, W. M. (2011). Bedside testing for myasthenia gravis: the ice-test. Emerg Med J , 28, 709-711. Nair AG, P.-C. P. (2014). Ocular myasthenia gravis: A review. Indian J Ophthalmol , 62 (10), 985-991. Rajasekharan C, A. V. (2011, Jul). Ice pack test: is it obsolete? BMJ Case Rep . Ricker K, H. G. (1977). Influence of temperature on neuromuscular transmission in myasthenia gravis. J Neurol , 216 (4), 273-82. Witoonpanich, R. (2010). Physiology of myasthenia gravis: Effect of temperature on neuromuscular transmission. Clinical Neurophysiology , 121 (S79), 1388-2457.

Clinical Bottom Line

The ice-pack test is a quick, low-cost test with moderate sensitivity and specificity that can be used to determine if ptosis is of myasthenic origin. It is especially useful in the emergency department, where time and resources may be lacking. Although not diagnostic of MG itself, it is a valuable adjunct and can ensure prompt referral and treatment.

References

1. Fakiri OM, Tavy DLJ, Hama-Amin AD et al. Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis Muscle & Nerve 2013; 48(6):902-904.
2. Sethi KD, Kapil D, Rivner MH, Swift TR. Ice pack test for myasthenia gravis Neurology 1987; 37(8):1383-1385.
3. Kubis KC , Danesh-Meyer HV , Savino PJ, Sergott RC. The ice test versus the rest test in myasthenia gravis. Ophthalmology 2000; 107(11):1995.
4. Lertchavanakul A, Gamnerdsiri P, Hirunwiwatkul P. Ice test for ocular myasthenia gravis. Journal of the Medical Association of Thailand 2001; 84(1):131.
5. Liu Y, Gu X, Zhang L, Ye X, Sadun AA. Ice test - Assessing this as a tool for the diagnosis of myasthenia gravis. Laboratory Ophthalmology and Visual Research 2006; 47.
6. Ramirez-Antunez AG, Garcia-Ramos G ,Estanol-Vidal B et al. Validation of the ice pack test in ophthalmoparesis due to myasthenia gravis. Revista de Neurologia 2013; 57(9):385-395.
7. da Fonseca Jr. NL, Lucci LMD, Rehder JRCL. Ice pack test in the diagnosis of myasthenia gravis. Arquivos Brasileiros de Oftalmologia 2010; 73(2) 161-164.
8. Chatzistefanou KI, Kouris T, Iliakis E et al. The ice pack test in the differential diagnosis of myasthenic diplopia. Ophthalmology 2009; 116(11):2236-2243.
9. Czaplinski A, Steck AJ, Fuhr P. Ice pack test for myasthenia gravis: A simple, noninvasive and safe diagnostic method. Journal of Neurology 2003; 250(7)883-884.
10. Tabassi A, Dehghani A, Saberi B. The ice test for diagnosing myasthenia gravis. Acta Medica Iranica 2005; 43(1) 60-62.