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Simple diameters, accurate stages:a practical approach to HD-ISS staging.
Beatrice Heim1, Florian Krismer1, Greta Hemicker1
1Department of Neurology, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Journal of Neurology
|November 14, 2025
Summary
A new simplified linear measurement, the bifrontal-to-bicaudate ratio (FCR), accurately estimates brain volumes for Huntington's disease staging. This method offers a practical alternative to complex volumetric analysis, improving accessibility for clinical practice and research.
Area of Science:
- Neuroimaging
- Neurology
- Biomarkers
Background:
- Huntington's disease (HD) is a neurodegenerative disorder linked to CAG repeat expansions.
- The Huntington's Disease Integrated Staging System (HD-ISS) uses clinical, biological, and imaging data, with caudate and putamen volumes as key early biomarkers.
- Conventional automated volumetric methods for assessing these biomarkers are complex and require specialized expertise, limiting their widespread use.
Purpose of the Study:
- To evaluate simple linear measurements, specifically the bifrontal-to-bicaudate ratio (FCR), as a practical alternative for assessing striatal atrophy in HD.
- To determine if FCR can reliably predict caudate and putamen volumes for HD-ISS staging.
- To assess the feasibility of using FCR in clinical practice and non-specialist research settings.
Main Methods:
- Caudate and putamen volumes were initially measured using automated segmentation (FreeSurfer).
- Linear measurements, including frontal horn width and intercaudate distance, were used to calculate FCR in a training cohort (n=44).
- Regression models predicting volumes from FCR were developed and validated in an independent test cohort (n=11); interrater reliability was assessed.
Main Results:
- FCR demonstrated a strong correlation with both caudate (r=0.866) and putamen volumes (r=0.897).
- Predictive equations based on FCR accurately estimated caudate and putamen volumes.
- HD-ISS staging classifications derived from FCR-based estimations were identical to those from conventional volumetric measurements for all participants in the test cohort.
Conclusions:
- FCR-based linear estimation provides an accurate and reliable method for assessing caudate and putamen volumes for HD-ISS staging.
- This simplified approach is a practical, time-efficient alternative to traditional volumetric analysis.
- The FCR method has the potential to increase the accessibility and application of HD-ISS staging in diverse clinical and research environments.
