BACKGROUND

Huntington disease (HD) is characterized by striatal atrophy that begins long before the onset of motor symptoms.

OBJECTIVE

To determine when striatal atrophy begins, the extent and rate of atrophy before diagnosis of motor symptoms, and whether striatal atrophy can predict when symptom onset will occur.

METHODS

Caudate and putamen volumes were measured on MRI scans of 19 preclinical subjects with the HD gene expansion who were very far (9 to 20 years) from estimated onset, and on serial scans from 17 preclinical subjects, six of whom were diagnosed with HD within 5 years after the initial scan.

RESULTS

Striatal volumes were significantly smaller for the subjects who were very far from estimated onset than for age-matched control subjects. Statistical models fit to the longitudinal data suggest that rate of caudate atrophy becomes significant when subjects are approximately 11 years from estimated onset and rate of putamen atrophy becomes significant approximately 9 years prior to onset. In the six incident cases, caudate and putamen were approximately one-third to one-half of normal volume at diagnosis, and caudate volume alone was able to predict with 100% accuracy those subjects who would be diagnosed within 2 years of imaging.

CONCLUSIONS

Striatal atrophy begins many years prior to diagnosable HD, and assessment of atrophy on MRI may be very useful in both predicting HD onset and in tracking progression in future therapeutic trials in preclinical subjects.