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.

Recognition of Cognitive Dysfunction in Cerebellar Infarction: Validation of the Chinese Cerebellar Cognitive Affective Syndrome Scale

“…This study validated the Chinese version of CCAS-s in patients with acute cerebellar infarction and adjusted the pass/fail diagnostic cut-off scores for CCAS-s tests. The Chinese CCAS-s showed acceptable reliability and validity in cerebellar infarction, whereas with relatively lower speci city and sensitivity than those reported in previous studies 11 . Our analyses further demonstrated that CCAS-s raw scores were correlated with age, education, and ne motor skills.…”

“…Our study also indicated that the cut-off scores of CCAS-s tests may differ among cerebellar diseases. The passing score (sum of cut-off scores for each item of the scale) was 81 for our cerebellar infarction cohort in contrast to 95 for the German hereditary ataxia cohort 7 and 72 for the original validation cohort 4 . The severity of cognitive de cits following cerebellar damages may in part re ect the distinct patterns of disrupted connectivity between the cerebellum and cerebrum in these cerebellar disorders and their diverse clinical presentations 16 .…”

“…To improve the diagnosis of the CCAS in clinical practice, Hoche and colleagues developed and validated the CCAS scale (CCAS-s) in a heterogeneous cohort of patients with cerebellar diseases (i.e., complex cerebrocerebellar disease, isolated cerebellar disease, isolated cerebellar injury) and healthy controls 4 . CCAS-s has been further validated in patients with a range of cerebellar disorders and showed great speci city and sensitivity to detect cognitive de cits in these diseases [5][6][7][8] . However, CCAS-s was developed and validated in mixed samples of cerebellar disorders 4,9 .…”

Cerebellar degeneration impairs strategy discovery but not strategy recall

“…The inferences we can draw in terms of brain-behavior relationships is limited by the heterogeneity of our patient sample. Of note, our sample did include a large number of patients with SCA-3, a genetic variant that typically produces symptoms indicative of cerebellar and extra-cerebellar involvement (56) and is associated with depressed cognitive function (57). Note that 1) this subgroup did not stand out on our measures of strategy discovery or recall, suggesting that the impairment in strategy discovery is related to degeneration of the cerebellum; 2) the number of non-learners was similar in the CD and Control groups, arguing that the observed dissociation between discovery and recall is unlikely to be due to a general cognitive impairment in the CD group; and 3) our results have been corroborated by that of another unpublished dataset using a standard visuomotor rotation task (58).…”

Consensus Recommendations for Clinical Outcome Assessments and Registry Development in Ataxias: Ataxia Global Initiative (AGI) Working Group Expert Guidance

“…As a consequence of cerebellar dysfunction, ataxia patients may have a syndrome of impaired executive functions, visuospatial cognition, linguistic functions, and personality changes, named the Cerebellar Cognitive Affective Syndrome (CCAS) [ 22 ]. Consideration of the CCAS in clinical routine is facilitated by the availability of a validated bedside test, the CCAS scale [ 23 ], albeit showing limitations in its application for individual diagnostics [ 24 ].…”