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Quantitative motor phenotype assessment in pre-manifest and symptomatic Huntington's disease: tongue force analysis differentiates between disease stages and provides high phenotype correlation. Cross sectional results from the TRACK-HD Study
Conference proceeding   Peer reviewed

Quantitative motor phenotype assessment in pre-manifest and symptomatic Huntington's disease: tongue force analysis differentiates between disease stages and provides high phenotype correlation. Cross sectional results from the TRACK-HD Study

M Say, N Bechtel, A Sturrock, S van den Bogaard, C Jauffret, S Bohlen, D R Langbehn, J A Mills, T P Archarya, H Johnson, …
Aktuelle Neurologie, Vol.36(S 02)
Abstracts Freier Vorträge und Poster der Jahrestagung der DGN 2009, 2009 (Nürnberg)
10/07/2009
DOI: 10.1055/s-0029-1238518

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Abstract

Background: Assessment of motor phenotype and diagnosis of Huntington's Disease (HD) are based on the Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS), a categorical clinical scale. Therefore, results of clinical trials are limited by (1) subjective error, (2) sensitivity of the categorical scale, and (3) insensitivity in pre-manifest subjects. More objective and quantitative measures of motor phenotype are warranted. In a pilot study, we found increased variability of tongue force (TF) in pre-manifest and symptomatic HD, and correlation with genotype and UHDRS-TMS (Reilmann et al. 2005). Objective: To assess whether analysis of TF distinguishes between controls, pre-manifest and symptomatic subjects and exhibits correlation with disease phenotype and genotype in a blinded multi-center study. Methods: 123 controls, 120 pre-manifest HD gene carriers (UHDRS≤5) and 123 symptomatic HD subjects were assessed (study sites: Leiden, London, Paris and Vancouver). Isometric tongue protrusion force was measured with subjects resting their chin on a height-adjustable base. A force transducer was mounted 2cm in front of their lips. Subjects were instructed to match a target force level presented on a screen for 30s after a cueing tone. 4 trials were performed at “low“ (0.25 N) and “high“ (0.50 N) target force levels. Data were recorded using WINSC (University Umea, Sweden). Analysis was performed blinded, using automated algorithms. Primary outcome measures were variability of TF and contact time. Results: TF variability and contact time distinguished controls from pre-manifest and symptomatic subjects at both target force levels (p<0.0001). Further subdivision in early and late pre-manifest and symptomatic groups was best assessed by contact time in the high force condition. TF variability exhibited the highest effect sizes in detecting early motor phenotype. Both measures correlated with probability of onset of HD and with the coefficient of striatal to intracranial volume (p<0.0001). Conclusions: Blinded analysis of tongue force provides a quantitative objective measure for severity of motor phenotype in pre-manifest and symptomatic HD. A trajectory of deficits from pre-manifest to symptomatic subjects was observed suggesting that these measures may be able to track motor phenotype progression. Acknowledgment: TRACK-HD is supported by the CHDI and High Q Foundation, a not for profit organization dedicated to finding treatments for HD.

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