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


METHODS
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 9-51 years) and 44 controls (12-49 years) underwent T2 multi-echo sequence in a 3T scanner. Twenty-three patients (12-50 years) and 19 controls (14-49 years) were reassessed after 1 year. T2 was evaluated using specialized software (Aftervoxel) and severity of disease was quantified with the Friedreich Ataxia Rating Scale (FARS).


RESULTS
T2 of both DNC was significantly shorter in the FRDA group at baseline (right, 58.6 ± 8.3 ms vs. 63.7 ± 8.1 ms, P = 0.013; left, 56.7 ± 7.7 ms vs. 62.6 ± 6.8 ms, 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 1 year. DNC T2 change over time correlated with GAA expansions and clinical deterioration (expressed by a change in FARS scores).


CONCLUSIONS
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.
Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas - UNICAMP, Campinas, SP, Brazil.
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Bonilha da Silva
Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas - UNICAMP, Campinas, SP, Brazil.
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Bergo
Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas - UNICAMP, Campinas, SP, Brazil.
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D'Abreu
Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas - UNICAMP, Campinas, SP, Brazil.
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Cendes
Department of Medical Genetics, Faculty of Medicine, University of Campinas - UNICAMP, Campinas, SP, Brazil.
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Lopes-Cendes
Department of Neurology and Neuroimaging Laboratory, Faculty of Medicine, University of Campinas - UNICAMP, Campinas, SP, Brazil.
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França
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D002529:Cerebellar Nuclei; D002648:Child; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005621:Friedreich Ataxia / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D055815:Young Adult
D015415:Biomarkers
Friedreich's ataxia; MRI; T2 relaxometry; dentate nuclei