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Hold Your Applause! A Critical Reappraisal of the Applause Sign
Abstract & Commentary
By Melissa J. Nirenberg, MD, PhD, Assistant Professor, Neurology and Neuroscience, Weill Cornell Medical College. Dr. Nirenberg reports that she has consulted for Biovail.
Synopsis: The applause sign is a nonspecific indicator of frontal lobe dysfunction and is not specific to Parkinsonian disorders.
Source: Luzzi S, Fabi K, Pesallaccia M, et al. Applause sign: Is it really specific for Parkinsonian disorders? Evidence from cortical dementias. J Neurol Neurosurg Psychiatry 2011; doi:10.1136/jnnp.2010.224394.
In 2005, a study published in Neurology demonstrated the usefulness of a simple bedside test, known as the "three clap test," in distinguishing progressive supranuclear palsy (PSP) from both frontotemporal dementia (FTD) and idiopathic Parkinson's disease (PD).1 The test consists of asking the patient "to clap three times as quickly as possible after demonstration of the examiner." When patients clap more than three times, an "applause sign" is present; this is felt to be a sign of motor perseveration and/or apraxia. The authors of this prior study found that the applause sign occurred commonly in PSP and was absent from those with PD or FTD, and therefore concluded that the test is useful for distinguishing between these disorders. A subsequent study concluded that the three clap test was not specific for PSP, but instead was a highly specific marker of Parkinsonian disorders in general.2
In the current study, the authors reexamined the applause sign, with the goal of determining whether the sign also may occur in neurodegenerative disorders that spare the basal ganglia, such as Alzheimer's disease (AD) or FTD without parkinsonism. The authors evaluated for the presence of the applause sign in 77 subjects10 with PSP, 15 with sporadic behavioral variant FTD, 29 with AD, and 23 healthy controls. Neurological diagnoses were determined based on standard clinical diagnostic criteria. A secondary goal of the study was to test the hypothesis that the applause sign is a marker for motor perseveration rather than apraxia; for this reason subjects with apraxia were excluded from enrollment. In addition, all studies underwent neuropsychiatric testing to determine the characteristics that correlated with the presence of an applause sign.
The authors found that the applause sign occurred in all of the neurodegenerative disorders that were examined (80% in PSP, 70% in FTD, and 31% in AD), and they were able to distinguish subjects with neurodegenerative disease from healthy controls. The three clap test also distinguished between PSP and AD. There were no statistically significant differences when comparing PSP with FTD, nor were there differences when comparing FTD with AD. The presence of an applause sign correlated with executive dysfunction on neuropsychiatric testing. Based on their findings, the authors conclude that the applause sign is a nonspecific sign of frontal lobe dysfunction that occurs not only in basal ganglia disorders, but also in cortical dementias such as AD.
Rapid, simple bedside testsparticularly those with high specificity and sensitivityare highly coveted tools in the field of neurology. For this reason, there was much excitement when it was originally reported that the three clap test could distinguish most cases of PSP from either FTD or PD. Unfortunately, subsequent studies have failed to fully replicate these initial compelling findings.
In the current study, the authors ask the straightforward question of whether the applause sign is specific to basal ganglia disorders. Their findings demonstrate that this sign also may occur in cortical dementias without apparent basal ganglia involvement, correlating mainly with executive dysfunction. However, the applause sign was of some utility in distinguishing between PSP and AD. Thus, although the applause sign is not 100% specific to basal ganglia disorders, it is a useful marker of executive dysfunction, which is often a prominent feature of PSP.
The authors' findings are interesting and clinically relevant, but the study itself has a number of important methodological limitations. The first is the fact neurodegenerative disorders were diagnosed clinically, such that some subjects may have been miscategorized. Second, the authors looked exclusively at sporadic behavioral variant FTD, which has more prominent executive dysfunction (and overlap with PSP) than other FTD subtypes; the findings therefore should not be extrapolated to other forms of FTD. Third, the sample size was low, such that the study may have lacked the necessary statistical power to demonstrate differences between groups. For this reason, further studies with a larger sample size and confirmatory diagnostic tests are warranted.
In summary, this study shows that the applause sign is a strong indicator of frontal lobe dysfunction that is present not only in basal ganglia disorders but also in cortical dementia. Further study is needed to clarify the sensitivity and specificity of this test in distinguishing between specific neurodegenerative disorders.
1. Dubois B, Slachevsky A, Pillon B, et al. "Applause sign" helps to discriminate PSP from FTD and PD. Neurology 2005;64:2132-2133.
2. Wu LJ, Sitburana O, Davidson A, et al. Applause sign in Parkinsonian disorders and Huntington's disease. Mov Disord 2008; 23:2307-2311.