Objective: To measure, with NM-MRI, the integrity of neuromelanin-containing monoaminergic cells in the SN and LC in Huntington Disease Gene Expansion Carriers (HDGECs) and compare with age and sex-matched Healthy Controls (HCs).

Background: Huntington’s Disease (HD) is a neurodegenerative disease that affects primarily the Medium Spiny Neurons in the striatum. Neuropathological studies have demonstrated a late depletion of monoaminergic neurons in the Substantia Nigra (SN) and Locus Coeruleus (LC), which can mediate the late appearance of bradykinesia in these patients. However, no studies have investigated whether this degeneration is present in the early stages. Neuromelanin is a byproduct of the metabolism of monoaminergic cells and is a marker of integrity of both SN and LC cells. Neuromelanin-sensitive MRI (NM-MRI) is a recent neuroimaging technique that indirectly measures the in vivo neuronal integrity of these regions.

Method: 12 HDGECs (7 asymptomatic and 5 symptomatic, mean age 50.9±12.5, mean CAP score 90.9±25.1), and 12 age-and gender-matched healthy controls (HCs), undertook NM-MRI with a 3-Tesla MRI scanner. Areas and volumes of the SN and LC were calculated and left and right values were averaged. Clinical measures included UHDRS, MMSE, MoCA, TMT, PBA, HADS, and PPT. Statistical analysis included Mann-Whitney U test and Spearman test for correlation.

Results: Neuromelanin-positive SN and LC areas and volumes of HDGECs were significantly lower than HCs (P<0.0001 and P<0.001, respectively). Asymptomatic HDGECs showed decreased SN and LC compared with HCs (P<0.01). There was no significant difference between the area and the volume of SN and LC between the subgroups of asymptomatic and symptomatic HDGECs. Clinical-neuroimaging correlation showed an inverse correlation between LC areas and UHDRS chorea scores (rho=-0.588, P=0.04). No correlation was found with CAP score and p90 predicted age at onset.

Conclusion: NM-MRI demonstrates a reduction of monoaminergic neuromelanin-containing cells in HD since the asymptomatic stage. This abstract was also submitted for presentation at the 2019 European Academy of Neurology conference

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuromelanin-mri-detects-monoaminergic-cell-loss-in-huntington-disease-expansion-gene-carriers/