The ice test for diagnosis of Myasthenia Gravis
Date First Published:
November 13, 2015
Last Updated:
December 2, 2015
Report by:
Jonathan Kentley, Anna Morgan (checker), SHO, ED consultant (Whipps Cross University Hospital ED Department)
Search checked by:
Jonathan Kentley, Whipps Cross University Hospital ED Department
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
HDAS EMBASE 1974-2015
The Cochrane Library issue 9, 2015
Search Details:
[exp Ice/ OR Ice-Pack] AND [exp Myasthenia/ OR Myasthenia Gravis]
Outcome:
Medline: 11 papers found, 2 relevant
EMBASE: 29 papers found, 5 relevant
Cochrane: 4 papers found, 3 relevant
EMBASE: 29 papers found, 5 relevant
Cochrane: 4 papers found, 3 relevant
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis Fakiri OM, Tavy DLJ, Hama-Amin AD 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% | ||||
| Ice pack test for myasthenia gravis Sethi KD, Kapil D, Rivner MH, Swift TR. 1987 USA | 10 myasthenic patients 7 patients with nonmyasthenic ptosis |
Randomised controlled trial | Sensitivity | 80% | Small sample Possible selection bias |
| Specificity | 100% | ||||
| The ice test versus the rest test in myasthenia gravis. Kubis KC , Danesh-Meyer HV , Savino PJ, Sergott RC. 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% | ||||
| Ice test for ocular myasthenia gravis. Lertchavanakul A, Gamnerdsiri P, Hirunwiwatkul P. 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% | ||||
| Ice test - Assessing this as a tool for the diagnosis of myasthenia gravis. Liu Y, Gu X, Zhang L, Ye X, Sadun AA. 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% | ||||
| Validation of the ice pack test in ophthalmoparesis due to myasthenia gravis. Ramirez-Antunez AG, Garcia-Ramos G ,Estanol-Vidal B 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% | ||||
| Ice pack test in the diagnosis of myasthenia gravis. da Fonseca Jr. NL, Lucci LMD, Rehder JRCL. 2010 Brazil | 40 patients with MG 30 patients with nonmyastenic ptosis |
Prospective cohort study | Sensitivity | 100% | Open to observer bias |
| Specificity | 100% | ||||
| The ice pack test in the differential diagnosis of myasthenic diplopia. Chatzistefanou KI, Kouris T, Iliakis E et al. 2009 Greece | 89 patients with recent onset blepharoptosis, diplopia or both | Prospective cohort study | Sensitivity | 92.30% | Variability in cooling time |
| Specificity | 98.30% | ||||
| Ice pack test for myasthenia gravis: A simple, noninvasive and safe diagnostic method. Czaplinski A, Steck AJ, Fuhr P. 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% | ||||
| The ice test for diagnosing myasthenia gravis. Tabassi A, Dehghani A, Saberi B. 2005 Iran | 156 patients presenting with ptosis | Prospective cohort study | Sensitivity | 100% | Possible confounding due to simultaneous Tensilon testing |
| Specificity | 100% |
Author Commentary:
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.
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.
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:
- Fakiri OM, Tavy DLJ, Hama-Amin AD et al.. Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis
- Sethi KD, Kapil D, Rivner MH, Swift TR.. Ice pack test for myasthenia gravis
- Kubis KC , Danesh-Meyer HV , Savino PJ, Sergott RC.. The ice test versus the rest test in myasthenia gravis.
- Lertchavanakul A, Gamnerdsiri P, Hirunwiwatkul P.. Ice test for ocular myasthenia gravis.
- Liu Y, Gu X, Zhang L, Ye X, Sadun AA.. Ice test - Assessing this as a tool for the diagnosis of myasthenia gravis.
- Ramirez-Antunez AG, Garcia-Ramos G ,Estanol-Vidal B et al.. Validation of the ice pack test in ophthalmoparesis due to myasthenia gravis.
- da Fonseca Jr. NL, Lucci LMD, Rehder JRCL.. Ice pack test in the diagnosis of myasthenia gravis.
- Chatzistefanou KI, Kouris T, Iliakis E et al.. The ice pack test in the differential diagnosis of myasthenic diplopia.
- Czaplinski A, Steck AJ, Fuhr P.. Ice pack test for myasthenia gravis: A simple, noninvasive and safe diagnostic method.
- Tabassi A, Dehghani A, Saberi B.. The ice test for diagnosing myasthenia gravis.