Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements

BACKGROUND: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. METHODS: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. RESULTS: There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. CONCLUSIONS: Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02069509

Functional impairment in patients with major depressive disorder: the 2-year PERFORM study

Lene Hammer-Helmich,1 Josep Maria Haro,2 Bengt J&ouml;nsson,3 Audrey Tanguy Melac,4 Sylvie Di Nicola,5 Julien Chollet,6 Dominique Milea,7 Beno&icirc;t Rive,8 Delphine Saragoussi4 1Real World Evidence and Epidemiology, H Lundbeck A/S, Valby, Denmark; 2Research and Teaching Unit, Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 3Department of Economics, Stockholm School of Economics, Stockholm, Sweden; 4Real-World Evidence and Epidemiology, Lundbeck SAS, Issy-les-Moulineaux, 5Biostatistics, Inferential, Paris, 6Clinical Operations, Lundbeck SAS, Issy-les-Moulineaux, France; 7Health Economics and Epidemiology, Lundbeck Singapore Pte. Ltd, Singapore, Singapore; 8Global Analytics, Lundbeck SAS, Issy-les-Moulineaux, France Background: The Prospective Epidemiological Research on Functioning Outcomes Related to Major depressive disorder (PERFORM) study describes the course of depressive symptoms, perceived cognitive symptoms, and functional impairment over 2&nbsp;years in outpatients with major depressive disorder (MDD) and investigates the patient-related factors associated with functional impairment.Methods: This was a 2-year observational study in 1,159 outpatients with MDD aged 18&ndash;65&nbsp;years who were either initiating antidepressant monotherapy or undergoing their first switch of antidepressant. Functional impairment was assessed by the Sheehan Disability Scale and the Work Productivity and Activity Impairment questionnaire. Patients assessed depression severity using the nine-item Patient Health Questionnaire and severity of perceived cognitive symptoms using the five-item Perceived Deficit Questionnaire. To investigate which patient-related factors were associated with functional impairment, univariate analyses of variance were performed to identify relevant factors that were then included in multivariate analyses of covariance at baseline, month 2, months 6 and 12 combined, and months 18 and 24 combined.Results: The greatest improvement in depressive symptoms, perceived cognitive symptoms, and functional impairment was seen immediately (within 2&nbsp;months) following initiation or switch of antidepressant therapy, followed by more gradual improvement and long-term stabilization. Improvement in perceived cognitive symptoms was less marked than improvement in depressive symptoms during the acute treatment phase. Functional impairment in patients with MDD was not only associated with severity of depressive symptoms but also independently associated with severity of perceived cognitive symptoms when adjusted for depression severity throughout the 2&nbsp;years of follow-up.Conclusion: These findings highlight the burden of functional impairment in MDD and the importance of recognizing and managing cognitive symptoms in daily practice. Keywords: major depressive disorder, functioning, functional impairment, depression, cognitio