Simple diameters, accurate stages:a practical approach to HD-ISS staging.

BACKGROUND

Huntington's disease (HD) is a neurodegenerative disorder caused by CAG repeat expansions. The Huntington's Disease Integrated Staging System (HD-ISS) classifies disease stages (0-3) using clinical, biological, and imaging assessments, with caudate and putamen volumes serving as key early biomarkers. Conventional automated volumetric methods typically require specialized software and experienced operators, limiting broader accessibility. Simple linear measurements, such as the bicaudate ratio (BCR) and bifrontal-to-bicaudate ratio (FCR), may provide a practical alternative for assessing striatal atrophy.

METHODS

Reference caudate and putamen volumes were measured using automated segmentation (FreeSurfer). Linear measurements (frontal horn width, intercaudate distance, inner table width) were used to calculate BCR and FCR in a training cohort of 44 HD mutation carriers. Regression models predicting caudate and putamen volumes based on FCR were developed and validated in an independent test cohort of 11 HD mutation carriers. Interrater reliability was assessed via intraclass correlation coefficients (ICC).

RESULTS

Interrater reliability was excellent. Among linear measurements, FCR had the strongest correlation with caudate (r = 0.866; R2 = 0.749) and putamen volumes (r = 0.897; R2 = 0.805). Predictive equations derived from FCR-based regression models accurately estimated volumes, resulting in identical HD-ISS staging classifications compared to actual volumetric measurements for all test cohort participants.

CONCLUSION

FCR-based linear estimation of caudate and putamen volumes provides accurate and reliable HD-ISS staging. This simplified method offers a practical and time-efficient alternative to conventional volumetry, potentially facilitating wider application of HD-ISS staging in clinical practice and non-specialist research settings.