The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients

Andreas Thieme; Jennifer Faber; Patricia Sulzer; Kathrin Reetz; Imis Dogan; Miriam Barkhoff; Janna Krahe; Heike Jacobi; Julia Elisabeth Aktories; Martina Minnerop; Saskia Elben; Raquel van der Veen; Johanna Müller; Giorgi Batsikadze; Jürgen Konczak; Matthis Synofzik; Sandra Roeske; Dagmar Timmann

doi:10.1007/s00415-022-11071-5

The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients

Andreas Thieme, Jennifer Faber, Patricia Sulzer, Kathrin Reetz, Imis Dogan, Miriam Barkhoff, Janna Krahe, Heike Jacobi, Julia Elisabeth Aktories, Martina Minnerop, Saskia Elben, Raquel van der Veen, Johanna Müller, Giorgi Batsikadze, Jürgen Konczak, Matthis Synofzik, Sandra Roeske, Dagmar Timmann

Kinesiology

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Background: A brief bedside test has recently been introduced by Hoche et al. (Brain, 2018) to screen for the Cerebellar Cognitive Affective Syndrome (CCAS) in patients with cerebellar disease. Objective: This multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia. Methods: A German version of the CCAS-Scale was applied in 30 SCA3, 14 SCA6 and 20 FRDA patients, and 64 healthy participants matched for age, sex, and level of education. Based on original cut-off values, the number of failed test items was assessed, and CCAS was considered possible (one failed item), probable (two failed items) or definite (three failed items). In addition a total sum raw score was calculated. Results: On a group level, failed items were significantly higher and total sum scores were significantly lower in SCA3 patients compared to matched controls. SCA6 and FRDA patients performed numerically below controls, but respective group differences failed to reach significance. The ability of the CCAS-Scale to diagnose CCAS in individual patients was limited to severe cases failing three or more items. Milder cases failing one or two items showed a great overlap with the performance of controls exhibiting a substantial number of false-positive test results. The word fluency test items differentiated best between patients and controls. Conclusions: As a group, SCA3 patients performed below the level of SCA6 and FRDA patients, possibly reflecting additional cerebral involvement. Moreover, the application of the CCAS-Scale in its present form results in a high number of false-positive test results, that is identifying controls as patients, reducing its usefulness as a screening tool for CCAS in individual patients.

Original language	English (US)
Pages (from-to)	4363-4374
Number of pages	12
Journal	Journal of Neurology
Volume	269
Issue number	8
DOIs	https://doi.org/10.1007/s00415-022-11071-5
State	Published - Aug 2022

Bibliographical note

Funding Information:
Open Access funding enabled and organized by Projekt DEAL. This work was supported by the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und Förderer der Neurologie der Universitätsmedizin Essen” and a scholarship of UMEA/DFG (University Medicine Essen Clinician Scientist Academy—a program funded by Deutsche Forschungsgemeinschaft, German Research Foundation; FU356/12-1) awarded to A.T. The study was also supported by the DFG grant N° 441409627, as part of the PROSPAX consortium under the frame of EJP-RD, the European Joint Programme on Rare Diseases, under the EJP-RD COFUND-EJP N° 825575 awarded to M.S. and D.T. as an associated partner. A.T. received research grants from the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und Förderer der Neurologie der Universitätsmedizin Essen” and a scholarship of UMEA/DFG (University Medicine Essen Clinician Scientist Academy—a program funded by the German Research Foundation; FU356/12-1). J.F. None. P.S. None. K.R. has received grants from the German Federal Ministry of Education and Research (BMBF 01GQ1402, 01DN18022), the German Research Foundation (IRTG 2150), Alzheimer Forschung Initiative e.V. (NL-18002CB), Friedreich’s Ataxia Research Alliance (FARA) and honoraria for presentations or advisory board from Biogen and Roche. I.D. None. M.B. None. J.Kr. None. H.J. None. JE.A. None. M.M. received a research grant from Deutsche Forschungsgemeinschaft (DFG; German Research Foundation). S.E. None. R.VdV. None. J.M. None. G.B. None. J.Ko. None. M.S. received consultancy honoraria from Ionis Pharmaceuticals (Carlsbad, California, USA), Jansen Pharmaceuticals (Beerse, Belgium) and Orphazyme Pharmaceuticals (Copenhagen, Denmark). S.R. None. D.T. received research grants from Deutsche Forschungsgemeinschaft (DFG; German Research Foundation), the European Union, and the Bernd-Fink-Foundation.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Bedside test
Cerebellum
FRDA
SCA3
SCA6

PubMed: MeSH publication types

Journal Article
Multicenter Study

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10.1007/s00415-022-11071-5

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Thieme, A., Faber, J., Sulzer, P., Reetz, K., Dogan, I., Barkhoff, M., Krahe, J., Jacobi, H., Aktories, J. E., Minnerop, M., Elben, S., van der Veen, R., Müller, J., Batsikadze, G., Konczak, J., Synofzik, M., Roeske, S., & Timmann, D. (2022). The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients. Journal of Neurology, 269(8), 4363-4374. https://doi.org/10.1007/s00415-022-11071-5

Thieme, A, Faber, J, Sulzer, P, Reetz, K, Dogan, I, Barkhoff, M, Krahe, J, Jacobi, H, Aktories, JE, Minnerop, M, Elben, S, van der Veen, R, Müller, J, Batsikadze, G, Konczak, J, Synofzik, M, Roeske, S & Timmann, D 2022, 'The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients', Journal of Neurology, vol. 269, no. 8, pp. 4363-4374. https://doi.org/10.1007/s00415-022-11071-5

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title = "The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients",

abstract = "Background: A brief bedside test has recently been introduced by Hoche et al. (Brain, 2018) to screen for the Cerebellar Cognitive Affective Syndrome (CCAS) in patients with cerebellar disease. Objective: This multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia. Methods: A German version of the CCAS-Scale was applied in 30 SCA3, 14 SCA6 and 20 FRDA patients, and 64 healthy participants matched for age, sex, and level of education. Based on original cut-off values, the number of failed test items was assessed, and CCAS was considered possible (one failed item), probable (two failed items) or definite (three failed items). In addition a total sum raw score was calculated. Results: On a group level, failed items were significantly higher and total sum scores were significantly lower in SCA3 patients compared to matched controls. SCA6 and FRDA patients performed numerically below controls, but respective group differences failed to reach significance. The ability of the CCAS-Scale to diagnose CCAS in individual patients was limited to severe cases failing three or more items. Milder cases failing one or two items showed a great overlap with the performance of controls exhibiting a substantial number of false-positive test results. The word fluency test items differentiated best between patients and controls. Conclusions: As a group, SCA3 patients performed below the level of SCA6 and FRDA patients, possibly reflecting additional cerebral involvement. Moreover, the application of the CCAS-Scale in its present form results in a high number of false-positive test results, that is identifying controls as patients, reducing its usefulness as a screening tool for CCAS in individual patients.",

keywords = "Bedside test, Cerebellum, FRDA, SCA3, SCA6",

author = "Andreas Thieme and Jennifer Faber and Patricia Sulzer and Kathrin Reetz and Imis Dogan and Miriam Barkhoff and Janna Krahe and Heike Jacobi and Aktories, {Julia Elisabeth} and Martina Minnerop and Saskia Elben and {van der Veen}, Raquel and Johanna M{\"u}ller and Giorgi Batsikadze and J{\"u}rgen Konczak and Matthis Synofzik and Sandra Roeske and Dagmar Timmann",

note = "Funding Information: Open Access funding enabled and organized by Projekt DEAL. This work was supported by the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und F{\"o}rderer der Neurologie der Universit{\"a}tsmedizin Essen” and a scholarship of UMEA/DFG (University Medicine Essen Clinician Scientist Academy—a program funded by Deutsche Forschungsgemeinschaft, German Research Foundation; FU356/12-1) awarded to A.T. The study was also supported by the DFG grant N° 441409627, as part of the PROSPAX consortium under the frame of EJP-RD, the European Joint Programme on Rare Diseases, under the EJP-RD COFUND-EJP N° 825575 awarded to M.S. and D.T. as an associated partner. A.T. received research grants from the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und F{\"o}rderer der Neurologie der Universit{\"a}tsmedizin Essen” and a scholarship of UMEA/DFG (University Medicine Essen Clinician Scientist Academy—a program funded by the German Research Foundation; FU356/12-1). J.F. None. P.S. None. K.R. has received grants from the German Federal Ministry of Education and Research (BMBF 01GQ1402, 01DN18022), the German Research Foundation (IRTG 2150), Alzheimer Forschung Initiative e.V. (NL-18002CB), Friedreich{\textquoteright}s Ataxia Research Alliance (FARA) and honoraria for presentations or advisory board from Biogen and Roche. I.D. None. M.B. None. J.Kr. None. H.J. None. JE.A. None. M.M. received a research grant from Deutsche Forschungsgemeinschaft (DFG; German Research Foundation). S.E. None. R.VdV. None. J.M. None. G.B. None. J.Ko. None. M.S. received consultancy honoraria from Ionis Pharmaceuticals (Carlsbad, California, USA), Jansen Pharmaceuticals (Beerse, Belgium) and Orphazyme Pharmaceuticals (Copenhagen, Denmark). S.R. None. D.T. received research grants from Deutsche Forschungsgemeinschaft (DFG; German Research Foundation), the European Union, and the Bernd-Fink-Foundation. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = aug,

doi = "10.1007/s00415-022-11071-5",

language = "English (US)",

volume = "269",

pages = "4363--4374",

journal = "Journal of Neurology",

issn = "0340-5354",

publisher = "D. Steinkopff-Verlag",

number = "8",

}

TY - JOUR

T1 - The CCAS-scale in hereditary ataxias

T2 - helpful on the group level, particularly in SCA3, but limited in individual patients

AU - Thieme, Andreas

AU - Faber, Jennifer

AU - Sulzer, Patricia

AU - Reetz, Kathrin

AU - Dogan, Imis

AU - Barkhoff, Miriam

AU - Krahe, Janna

AU - Jacobi, Heike

AU - Aktories, Julia Elisabeth

AU - Minnerop, Martina

AU - Elben, Saskia

AU - van der Veen, Raquel

AU - Müller, Johanna

AU - Batsikadze, Giorgi

AU - Konczak, Jürgen

AU - Synofzik, Matthis

AU - Roeske, Sandra

AU - Timmann, Dagmar

N1 - Funding Information: Open Access funding enabled and organized by Projekt DEAL. This work was supported by the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und Förderer der Neurologie der Universitätsmedizin Essen” and a scholarship of UMEA/DFG (University Medicine Essen Clinician Scientist Academy—a program funded by Deutsche Forschungsgemeinschaft, German Research Foundation; FU356/12-1) awarded to A.T. The study was also supported by the DFG grant N° 441409627, as part of the PROSPAX consortium under the frame of EJP-RD, the European Joint Programme on Rare Diseases, under the EJP-RD COFUND-EJP N° 825575 awarded to M.S. and D.T. as an associated partner. A.T. received research grants from the German Heredo-Ataxia Society (Deutsche Heredo-Ataxie-Gesellschaft e.V.), “Freunde und Förderer der Neurologie der Universitätsmedizin Essen” and a scholarship of UMEA/DFG (University Medicine Essen Clinician Scientist Academy—a program funded by the German Research Foundation; FU356/12-1). J.F. None. P.S. None. K.R. has received grants from the German Federal Ministry of Education and Research (BMBF 01GQ1402, 01DN18022), the German Research Foundation (IRTG 2150), Alzheimer Forschung Initiative e.V. (NL-18002CB), Friedreich’s Ataxia Research Alliance (FARA) and honoraria for presentations or advisory board from Biogen and Roche. I.D. None. M.B. None. J.Kr. None. H.J. None. JE.A. None. M.M. received a research grant from Deutsche Forschungsgemeinschaft (DFG; German Research Foundation). S.E. None. R.VdV. None. J.M. None. G.B. None. J.Ko. None. M.S. received consultancy honoraria from Ionis Pharmaceuticals (Carlsbad, California, USA), Jansen Pharmaceuticals (Beerse, Belgium) and Orphazyme Pharmaceuticals (Copenhagen, Denmark). S.R. None. D.T. received research grants from Deutsche Forschungsgemeinschaft (DFG; German Research Foundation), the European Union, and the Bernd-Fink-Foundation. Publisher Copyright: © 2022, The Author(s).

PY - 2022/8

Y1 - 2022/8

N2 - Background: A brief bedside test has recently been introduced by Hoche et al. (Brain, 2018) to screen for the Cerebellar Cognitive Affective Syndrome (CCAS) in patients with cerebellar disease. Objective: This multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia. Methods: A German version of the CCAS-Scale was applied in 30 SCA3, 14 SCA6 and 20 FRDA patients, and 64 healthy participants matched for age, sex, and level of education. Based on original cut-off values, the number of failed test items was assessed, and CCAS was considered possible (one failed item), probable (two failed items) or definite (three failed items). In addition a total sum raw score was calculated. Results: On a group level, failed items were significantly higher and total sum scores were significantly lower in SCA3 patients compared to matched controls. SCA6 and FRDA patients performed numerically below controls, but respective group differences failed to reach significance. The ability of the CCAS-Scale to diagnose CCAS in individual patients was limited to severe cases failing three or more items. Milder cases failing one or two items showed a great overlap with the performance of controls exhibiting a substantial number of false-positive test results. The word fluency test items differentiated best between patients and controls. Conclusions: As a group, SCA3 patients performed below the level of SCA6 and FRDA patients, possibly reflecting additional cerebral involvement. Moreover, the application of the CCAS-Scale in its present form results in a high number of false-positive test results, that is identifying controls as patients, reducing its usefulness as a screening tool for CCAS in individual patients.

AB - Background: A brief bedside test has recently been introduced by Hoche et al. (Brain, 2018) to screen for the Cerebellar Cognitive Affective Syndrome (CCAS) in patients with cerebellar disease. Objective: This multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia. Methods: A German version of the CCAS-Scale was applied in 30 SCA3, 14 SCA6 and 20 FRDA patients, and 64 healthy participants matched for age, sex, and level of education. Based on original cut-off values, the number of failed test items was assessed, and CCAS was considered possible (one failed item), probable (two failed items) or definite (three failed items). In addition a total sum raw score was calculated. Results: On a group level, failed items were significantly higher and total sum scores were significantly lower in SCA3 patients compared to matched controls. SCA6 and FRDA patients performed numerically below controls, but respective group differences failed to reach significance. The ability of the CCAS-Scale to diagnose CCAS in individual patients was limited to severe cases failing three or more items. Milder cases failing one or two items showed a great overlap with the performance of controls exhibiting a substantial number of false-positive test results. The word fluency test items differentiated best between patients and controls. Conclusions: As a group, SCA3 patients performed below the level of SCA6 and FRDA patients, possibly reflecting additional cerebral involvement. Moreover, the application of the CCAS-Scale in its present form results in a high number of false-positive test results, that is identifying controls as patients, reducing its usefulness as a screening tool for CCAS in individual patients.

KW - Bedside test

KW - Cerebellum

KW - FRDA

KW - SCA3

KW - SCA6

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The CCAS-scale in hereditary ataxias: helpful on the group level, particularly in SCA3, but limited in individual patients

Abstract

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