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The applause sign in frontotemporal lobar degeneration and related conditions

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Abstract

The applause sign, i.e., the inability to execute the same amount of claps as performed by the examiner, was originally reported as a sign specific for progressive supranuclear palsy (PSP). Recent research, however, has provided evidence for the occurrence of the applause sign in various conditions. The aim of this study was to determine the prevalence of the applause sign and correlate its presence with neuropsychological and MRI volumetry findings in frontotemporal lobar degeneration and related conditions. The applause sign was elicited with the three clap test (TCT), with a higher score indicating poorer performance. Data were recorded from 272 patients from the cohort of the German consortium for frontotemporal lobar degeneration (FTLDc): 111 with behavioral variant frontotemporal dementia (bvFTD), 98 with primary progressive aphasia (PPA), 30 with progressive supranuclear palsy Richardson’s syndrome, 17 with corticobasal syndrome (CBS) and 16 with amyotrophic lateral sclerosis with frontotemporal dementia (ALS/FTD). For comparison, 29 healthy elderly control subjects (HC) were enrolled in the study. All subjects underwent detailed language and neuropsychological assessment. In a subset of 156 subjects, atlas-based volumetry was performed. The applause sign occurred in all patient groups (40% in PSP, 29.5% in CBS, 25% in ALS/FTD, 13.3% in PPA and 9.0% in bvFTD) but not in healthy controls. The prevalence was highest in PSP patients. It was significantly more common in PSP as compared to bvFTD, PPA and HC. The comparison between the other groups failed to show a significant difference regarding the occurrence of the applause sign. The applause sign was highly correlated to a number of neuropsychological findings, especially to measures of executive, visuospatial, and language function as well as measures of disease severity. TCT scores showed an inverse correlation with the volume of the ventral diencephalon and the pallidum. Furthermore the volume of the ventral diencephalon and pallidum were significantly smaller in patients displaying the applause sign. Our study confirms the occurrence of the applause sign in bvFTD, PSP and CBS and adds PPA and ALS/FTD to these conditions. Although still suggestive of PSP, clinically it must be interpreted with caution. From the correlation with various cognitive measures we suggest the applause sign to be indicative of disease severity. Furthermore we suggest that the applause sign represents dysfunction of the pallidum and the subthalamic nucleus, structures which are known to play important roles in response inhibition.

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Abbreviations

ALS/FTD:

Amyotrophic lateral sclerosis with frontotemporal dementia

bvFTD:

Behavioral variant frontotemporal dementia

CDR-SOB:

Clinical Dementia Rating Scale Sum of Boxes

CBS:

Corticobasal syndrome

FTLD:

Frontotemporal lobar degeneration

HC:

Healthy control

LI:

Laterality index

PPA:

Primary progressive aphasia

PSP:

Progressive supranuclear palsy

SPM12:

Statistical parametric mapping 12

STN:

Subthalamic nucleus

TCT:

Three clap test

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Funding

The study was supported by grants from the German Federal Ministry of Education and Research (project: FTLDc 01GI1007A), the JPND network PreFrontAls (01ED1512), the EU (FAIR-PARK II 633190), the German Research Foundation/DFG (SFB1279), the foundation of the state Baden-Württemberg (D.3830), Boehringer Ingelheim Ulm University BioCenter (D.5009) and the Thierry Latran Foundation.

Author information

Authors and Affiliations

  1. Neurologische Klinik und Poliklinik, Ludwig Maximilians Universität München, Munich, Germany

    Sonja Schönecker, Franz Hell, Kai Bötzel, Elisabeth Wlasich, Nibal Ackl, Christine Süßmair, Johannes Levin & Adrian Danek

  2. Department of Neurology, University of Ulm, Ulm, Germany

    Markus Otto, Sarah Anderl-Straub, Albert Ludolph & Jan Kassubek

  3. Swiss Epilepsy Clinic, Klinik Lengg, Zurich, Switzerland

    Hans-Jürgen Huppertz

  4. Department of Psychiatry and Psychotherapy, Technical University of Munich, Munich, Germany

    Janine Diehl-Schmid, Lina Riedl & Carola Roßmeier

  5. Department of Neurology, Saarland University, Homburg, Germany

    Klaus Fassbender & Epameinondas Lyros

  6. Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany

    Johannes Kornhuber & Timo Jan Oberstein

  7. Department for Neurodegenerative Diseases and Geriatric Psychiatry, University Hospital Bonn, Bonn, Germany

    Klaus Fliessbach & Anja Schneider

  8. German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

    Klaus Fliessbach & Anja Schneider

  9. Max Planck Institute of Human Cognitive and Brain Sciences (MPG), Leipzig, Germany

    Matthias L. Schroeter

  10. Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany

    Matthias L. Schroeter

  11. Department of Neurology, Rostock University Medical Center, Rostock, Germany

    Johannes Prudlo

  12. German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany

    Johannes Prudlo

  13. Department of Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany

    Martin Lauer

  14. Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Holger Jahn

  15. AMEOS Klinikum Heiligenhafen, Heiligenhafen, Germany

    Holger Jahn

  16. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany

    Johannes Levin

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  1. Sonja Schönecker
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  2. Franz Hell
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German FTLD Consortium

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Correspondence to Sonja Schönecker.

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Schönecker, S., Hell, F., Bötzel, K. et al. The applause sign in frontotemporal lobar degeneration and related conditions. J Neurol 266, 330–338 (2019). https://doi.org/10.1007/s00415-018-9134-y

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  • DOI: https://doi.org/10.1007/s00415-018-9134-y

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