title: Composite cerebellar functional severity score: validation of a quantitative score of cerebellar impairment.
abstract: Reliable and easy to perform functional scales are a prerequisite for future therapeutic trials in cerebellar ataxias. In order to assess the specificity of quantitative functional tests of cerebellar dysfunction, we investigated 123 controls, 141 patients with an autosomal dominant cerebellar ataxia (ADCA) and 53 patients with autosomal dominant spastic paraplegia (ADSP). We evaluated four different functional tests (nine-hole pegboard, click, tapping and writing tests), in correlation with the scale for the assessment and rating of cerebellar ataxia (SARA), the scale of functional disability on daily activities (part IV of the Huntington disease rating scale), depression (the Public Health Questionnaire PHQ-9) and the EQ-5D visual analogue scale for self-evaluation of health status. There was a significant correlation between each functional test and a lower limb score. The performance of controls on the functional tests was significantly correlated with age. Subsequent analyses were therefore adjusted for this factor. The performances of ADCA patients on the different tests were significantly worse than that of controls and ADSP patients; there was no difference between ADSP patients and controls. Linear regression analysis showed that only two independent tests, the nine-hole pegboard and the click test on the dominant side (P < 0.0001), accounted for the severity of the cerebellar syndrome as reflected by the SARA scores, and could be represented by a composite cerebellar functional severity (CCFS) score calculated as follows: [Formula: see text]. The CCFS score was significantly higher in ADCA patients compared to controls (1.12 +/- 0.18 versus 0.85 +/- 0.05, P(c) < 0.0001) and ADSP patients (1.12 +/- 0.18 versus 0.90 +/- 0.08, P(c) < 0.0001) and was correlated with disease duration (P < 0.0001) but independent of self-evaluated depressive mood in ADCA. Among genetically homogeneous subgroups of ADCA patients (Spinocerebellar ataxia 1, 2, 3), SCA3 patients had significantly lower (better) CCFS scores than SCA2 (P(c) < 0.04) and the same tendency was observed in SCA1. Their CCFS scores remained significantly worse than those of ADSP patients with identified SPG4 mutations (P < 0.0001). The pegboard and click tests are easy to perform and accurately reflect the severity of the disease. The CCFS is a simple and validated method for assessing cerebellar ataxia over a wide range of severity, and will be particularly useful for discriminating paucisymptomatic carriers from affected patients and for evaluating disease progression in future therapeutic trials.
authors: AP-HP, Department of Biostatistics and Medical Informatics, Pitié-Salpêtrière Charles-Foix Clinical Research Unit, University Pierre et Marie Curie, Paris, France.
authors: Sophie Tezenas
authors: ST
authors: du Montcel
authors: Perrine
authors: P
authors: Charles
authors: Pascale
authors: P
authors: Ribai
authors: Cyril
authors: C
authors: Goizet
authors: Alice
authors: A
authors: Le Bayon
authors: Pierre
authors: P
authors: Labauge
authors: Lucie
authors: L
authors: Guyant-Maréchal
authors: Sylvie
authors: S
authors: Forlani
authors: Celine
authors: C
authors: Jauffret
authors: Nadia
authors: N
authors: Vandenberghe
authors: Karine
authors: K
authors: N'guyen
authors: Isabelle
authors: I
authors: Le Ber
authors: David
authors: D
authors: Devos
authors: Carlo-Maria
authors: CM
authors: Vincitorio
authors: Mario-Ubaldo
authors: MU
authors: Manto
authors: François
authors: F
authors: Tison
authors: Didier
authors: D
authors: Hannequin
authors: Merle
authors: M
authors: Ruberg
authors: Alexis
authors: A
authors: Brice
authors: Alexandra
authors: A
authors: Durr
mesh_terms: D000328:Adult; D000368:Aged; D002524:Cerebellar Ataxia / Q000503:physiopathology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010264:Paraplegia / Q000503:physiopathology* / Q000523:psychology; D011594:Psychometrics; D011596:Psychomotor Disorders / Q000209:etiology*; D011788:Quality of Life; D012720:Severity of Illness Index