Dentate nuclei T2 relaxometry is a reliable neuroimaging marker in Friedreich's ataxia.

Abstract

In Friedreich's ataxia (FRDA), frataxin deficiency results in iron redistribution in the dentate nuclei (DNC). Clusters of iron cause inhomogeneities in a magnetic field and result in a reduction in T2 relaxation time (T2). T2 was prospectively evaluated in DNC, putamen, substantia nigra (SN), cerebellar white matter (CWM) and caudate and the correlation with clinical parameters was investigated. Thirty-five patients (range 9-51years) and 44 controls (12-49years) underwent T2 multi-echo sequence in a 3T scanner. Twenty-three patients (12-50years) and 19 controls (14-49years) were reassessed after 1year. T2 was evaluated using specialized software (Aftervoxel) and severity of disease was quantified with the Friedreich Ataxia Rating Scale (FARS). T2 of both DNC was significantly shorter in the FRDA group at baseline (right, 58.6±8.3ms vs. 63.7±8.1ms, P=0.013; left, 56.7±7.7ms vs. 62.6±6.8ms, P=0.001). No significant difference was found between groups regarding the SN, putamen, CWM and caudate T2. DNC T2 values correlated with age, FARS total score and FARS III subscore on both sides. Prospectively, there was a significant reduction of T2 in FRDA patients in right and left DNC (P=0.001 and 0.009) but not in other structures. Amongst controls, none of the regions significantly changed after 1year. DNC T2 change over time correlated with GAA expansions and clinical deterioration (expressed by a change in FARS scores). DNC T2 values are abnormal in FRDA, progress over time and correlate with ataxia severity. These results strongly suggest that DNC relaxometry can be a useful neuroimaging marker in FRDA.