The cerebellar cognitive affective syndrome scale reveals early neuropsychological deficits in SCA3 patients

Abstract

Background The cerebellar cognitive affective syndrome scale (CCAS-S) was recently developed to detect specific neuropsychological deficits in patients with cerebellar diseases in an expedited manner. Objectives To evaluate the discriminative ability of the CCAS-S in an etiologically homogeneous cohort of spinocerebellar ataxia type 3 (SCA3) patients and to examine relationships between cognitive deficits and motor symptom severity. Methods The CCAS-S was administered to twenty mildly to moderately affected SCA3 patients and eighteen healthy controls matched for age, sex, and educational level. Disease severity was measured by the Scale for the Assessment and Rating of Ataxia (SARA), Inventory of Non-Ataxia Signs (INAS), 8 m walk test, nine-hole peg test (9HPT), and Patient Health Questionnaire-9 (PHQ-9). Results SCA3 patients had a lower total CCAS-S score (p < 0.001) and higher number of failed tests (p = 0.006) than healthy controls. Patients displayed impairments in semantic fluency, phonemic fluency, category switching, cube drawing, and affect regulation. Total CCAS-S score showed high discriminative ability (area under the curve [AUC]: 0.96) and was associated with disease duration, SARA score, walking speed, and dominant hand 9HPT performance. No correlations were observed with INAS count, repeat length, and PHQ-9 score. Discriminative capacity of the number of failed tests was moderate (AUC: 0.76). Conclusion Essentially all SCA3 patients exhibited some form of cognitive impairment. The CCAS-S differentiates SCA3 patients from healthy controls, detects neuropsychological deficits early in the disease course, and correlates with relevant ataxia severity measures.

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

“…Selectivity was good only for “CCAS definite” (three or more items failed): FRDA/SCA3/SCA6 controls: 95/87/86%. The present findings are in line with two other studies including controls (selectivity for CCAS possible/probable/definite: Maas et al [ 34 ]: 17/56/78%; Chirino-Pérez et al [ 36 ]: 32/68/91%). While selectivity was good for “CCAS definite”, sensitivity (the ability to detect true-positives) was poor (FRDA/ SCA3/SCA6: 25/37/36%).…”

“…The number of failed CCAS-Scale test items was significantly increased, and the total sum score was significantly reduced in SCA3 patients compared to matched controls confirming recent findings [ 34 ]. Findings in SCA6 and FRDA patients, however, were not significantly different from controls, although the number of failed items was numerically higher, and the total sum score was numerically lower.…”

“…In patients with SCA3, severity of CCAS, quantified by the CCAS-Scale, correlated with severity of the cerebellar motor syndrome, quantified by the Scale for Assessment and Rating of Ataxia (SARA), confirming recent findings by Maas et al [ 34 ]. In patients with SCA6 and FRDA, we did not observe such correlations.…”

“…While selectivity was good for “CCAS definite”, sensitivity (the ability to detect true-positives) was poor (FRDA/ SCA3/SCA6: 25/37/36%). Likewise, sensitivity (for “CCAS definite”) was moderate in previous studies testing SCA3 patients: 55% [ 34 ], FRDA patients: 63% [ 37 ], and chronic cerebellar strokes: 54% [ 36 ].…”

The Cerebellar Cognitive Affective Syndrome and the Neuropsychiatry of the Cerebellum

“…Its domains are semantic fluency, phonemic fluency, a category-switching fluency task, forward and reverse digit span, recall of a word list, go no-go task, cube draw and copy, similarities, and a set of questions about affect derived from the beta version of the cerebellar neuropsychiatric rating scale (Hoche et al 2016). The CCAS Scale has been useful in subsequent studies, including a validation analysis in a German cohort (Thieme et al 2020), and in defining cognitive challenges in patients with Friedreich's ataxia (Naeije et al 2020), SCA3 (Maas et al 2021) and those with chronic effects following cerebellar stroke (Chirino-Pérez et al 2021).…”