The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias

Louisa P Selvadurai¹, Susan L Perlman², Tetsuo Ashizawa³, George R Wilmot⁴, Chiadi U Onyike⁵, Liana S Rosenthal⁶, Vikram G Shakkottai^{7

8}, Henry L Paulson⁷, Sub H Subramony⁹, Khalaf O Bushara¹⁰, Sheng-Han Kuo¹¹, Cameron Dietiker¹², Michael D Geschwind¹², Alexandra B Nelson¹², Christopher M Gomez¹³, Puneet Opal¹⁴, Theresa A Zesiewicz¹⁵, Trevor Hawkins¹⁶, Talene A Yacoubian¹⁷, Peggy C Nopoulos¹⁸, Sharon J Sha¹⁹, Peter E Morrison²⁰, Karla P Figueroa²¹, Stefan M Pulst²¹, Jeremy D Schmahmann²²

Affiliations

¹ Department of Neurology, Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Suite 2000, Boston, MA, 02114, USA.
² Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Neurology, Houston Methodist Research Institute, Houston, TX, USA.
⁴ Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁶ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁷ Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA.
¹⁰ Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
¹¹ Department of Neurology, Columbia University, New York, NY, USA.
¹² Department of Neurology, University of California, San Francisco, CA, USA.
¹³ Department of Neurology, University of Chicago, Chicago, IL, USA.
¹⁴ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁵ Department of Neurology, University of South Florida Ataxia Research Center, Tampa, FL, USA.
¹⁶ Department of Neurology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
¹⁷ Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁸ Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
¹⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
²⁰ Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
²¹ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
²² Department of Neurology, Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Suite 2000, Boston, MA, 02114, USA. jschmahmann@mgh.harvard.edu.

PMID: 38165578
PMCID: PMC11217149
DOI: 10.1007/s12311-023-01651-0

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias

Louisa P Selvadurai et al. Cerebellum. 2024 Aug.

. 2024 Aug;23(4):1411-1425.

doi: 10.1007/s12311-023-01651-0. Epub 2024 Jan 2.

Authors

Affiliations

¹ Department of Neurology, Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Suite 2000, Boston, MA, 02114, USA.
² Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
³ Department of Neurology, Houston Methodist Research Institute, Houston, TX, USA.
⁴ Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁶ Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁷ Department of Neurology, University of Michigan, Ann Arbor, MI, USA.
⁸ Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA.
¹⁰ Department of Neurology, University of Minnesota, Minneapolis, MN, USA.
¹¹ Department of Neurology, Columbia University, New York, NY, USA.
¹² Department of Neurology, University of California, San Francisco, CA, USA.
¹³ Department of Neurology, University of Chicago, Chicago, IL, USA.
¹⁴ Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁵ Department of Neurology, University of South Florida Ataxia Research Center, Tampa, FL, USA.
¹⁶ Department of Neurology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA.
¹⁷ Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁸ Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
¹⁹ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
²⁰ Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
²¹ Department of Neurology, University of Utah, Salt Lake City, UT, USA.
²² Department of Neurology, Ataxia Center, Cognitive Behavioral Neurology Unit, Laboratory for Neuroanatomy and Cerebellar Neurobiology, Massachusetts General Hospital and Harvard Medical School, 100 Cambridge Street, Suite 2000, Boston, MA, 02114, USA. jschmahmann@mgh.harvard.edu.

PMID: 38165578
PMCID: PMC11217149
DOI: 10.1007/s12311-023-01651-0

Abstract

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.

Keywords: Cerebellar cognitive affective syndrome; Cognition; Scale; Spinocerebellar ataxia.

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Conflict of interest statement

Conflict of Interest L.P.S. was funded by an Australian-American Fulbright Commission scholarship.

C.U.O. receives research support from Alector Inc. and Transposon Inc., and consults for Acadia Pharmaceuticals. He is also supported by the Robert and Nancy Hall for Brain Research, and the Joseph Trovato Fund.

L.S.R. is site PI for Biohaven Pharma and has consulted for Bial Biotech and Reata Pharmaceuticals. She receives research support from NINDS, Pfizer, the National Ataxia Foundation, Gordon and Marilyn Macklin Foundation, and the Daniel B and Florence E. Green Foundation.

M.D.G is site PI for Biohaven Pharma, receives funding from the NIH/NIA (R01 AG AG031189; R01AG062562; R56 AG055619) and is supported by the Michael J. Homer Family Fund.

J.D.S. is site PI for Biohaven Pharma, consults for Biohaven, and holds the copyright with the General Hospital Corporation to the Brief Ataxia Rating scale, Patient Reported outcome Measure of Ataxia, the Cerebellar Cognitive Affective / Schmahmann Syndrome Scale, and the Cerebellar Neuropsychiatric Rating Scale.

Figures

**Fig. 1**
Total CCAS-S a Raw score and b Fail score by diagnostic group. The dashed line at raw score = 82 indicates the score obtained when all CCAS-S items are passed with the minimum score. Error bars indicate Mean +/− 1 standard deviation

**Fig. 2**
Individual CCAS-S item raw scores by diagnostic group

**Fig. 3**
Scatterplots of the relationship between Age and a CCAS-S total raw score and b CCAS-S total fail score, and between Years of Education and c CCAS-S total raw score and d CCAS-S total fail score, among the Control and Symptomatic groups

**Fig. 4**
Scatterplots of the relationship between CCAS-S total raw score and a SARA score, b BARS score, and c Functional Staging of Ataxia score, by SCA type. *p < .05, SARA, Scale for the Assessment and Rating of Ataxia; BARS, Brief Ataxia Rating Scale

See this image and copyright information in PMC

References

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The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias

Affiliations

The Cerebellar Cognitive Affective/Schmahmann Syndrome Scale in Spinocerebellar Ataxias

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous