PT - JOURNAL ARTICLE AU - Akin Nihat AU - Tze How Mok AU - Hans Odd AU - Andrew Geoffrey Bourne Thompson AU - Diana Caine AU - Kirsty McNiven AU - Veronica O'Donnell AU - Selam Tesfamichael AU - Peter Rudge AU - John Collinge AU - Simon Mead TI - Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease AID - 10.1136/jnnp-2021-327722 DP - 2022 Jan 11 TA - Journal of Neurology, Neurosurgery & Psychiatry PG - jnnp-2021-327722 4099 - http://jnnp.bmj.com/content/early/2022/01/11/jnnp-2021-327722.short 4100 - http://jnnp.bmj.com/content/early/2022/01/11/jnnp-2021-327722.full AB - Objective To use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.Methods Rasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008–December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility.Results The Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated.Conclusions These two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up.Data are available on reasonable request. Anonymised data are available on reasonable request to the corresponding author.