Nadya Pyatigorskaya, Presenter: Nothing to Disclose

Michael Sharman, Abstract Co-Author: Nothing to Disclose

Jean-Christophe Corvol, Abstract Co-Author: Speaker, H. Lundbeck A/S Speaker, Allon Therapeutics Inc Speaker, Biogen Idec Inc Speaker, Impax Laboratories, Inc Speaker, Novartis AG

Romain Valabregue, Abstract Co-Author: Nothing to Disclose

Alexis Brice, Abstract Co-Author: Nothing to Disclose

Stephane Lehericy MD, PhD, Abstract Co-Author: Nothing to Disclose

The goal of this work was investigating iron deposition in the basal ganglia and thalamus of the patients with affected and presymptomatic Leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson’s disease (PD) using T2* relaxometry. 

Twenty genetic PD subjects (4 symptomatic and 2 non-symptomatic Parkin subjects, 9 symptomatic and 5 non-symptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 Tesla using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), striatum, globus pallidus, and thalamus. 

In the SN, R2* values increased in IPD and mutation-carrying patients as compared to controls (p<0.0001) and in mutation-carrying patients as compared to IPD patients (p=0.0023). Asymptomatic mutation carriers showed R2* values higher than in controls (p = 0.021), but not significantly different from those in IPD patients (p = 0.58). Randomization-permutation methods allowed separate analysis of LRRK2 and Parkin groups, which showed significant increase of R2* in each group in both symptomatic (p = 0.003 for LRRK2 and Parkin) and asymptomatic (p= 0.003 for LRRK2 and p=0.01 for Parkin) mutation careers. There were no changes in the other structures or in R2 values. No significant correlation was found between clinical variables in IPD and symptomatic mutation carriers and between R2* obtained using the mean left and right SN values or the most affected hemisphere separately. As expected, in IPD patients, the HY disability score correlated significantly with age, disease duration, and the UPDRS score. The UPDRS score also correlated with disease duration.

The results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers; R2* measurements may be used to investigate nigrostriatal damage in preclinical mutation-carrying patients. Increased R2* in asymptomatic PD-mutation carriers and the lack of correlation with disease duration indicate iron deposition in the early pre-clinical phase of the disease, while the lack of clinical correlations suggest that R2* may not be a reliable marker of disease severity.

 R2* rate measured by MRI is suggested as a promising biomarker of nigrostriatal damage in mutation-carrying PD patients. Its causal relationships and prognostic values should be investigated in longitudinal studies. 

Pyatigorskaya, N, Sharman, M, Corvol, J, Valabregue, R, Brice, A, Lehericy, S, High Nigral Iron Deposition in LRRK2 and Parkin Mutation Carriers Measured Using MRI R2* Relaxometry.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14010361.html