Evidence of thalamic dysfunction in Huntington disease by proton magnetic resonance spectroscopy

Abstract

Our objective was to investigate thalamic neuronal dysfunction in patients with Huntington disease (HD). We performed localized single-voxel proton magnetic resonance spectroscopy (MRS) of the thalamus in 22 HD patients and 25 healthy individuals. The mean age of patients was 48.5 years (ranging from 32 to 71 years). Age at onset varied between 20 and 66 years (mean 38.9 years). The expanded CAG repeat ranged from 40 to 52 (mean 45.2) CAGs. The mean age of control group was 35.4 years, ranging from 19 to 67 years. N-acetylaspartate (NAA) relative to creatine (NAA/Cr) values in the thalamus of HD patients were decreased when compared with controls (P = 0.0001). The spectroscopic findings were not correlated with motor impairment. However, there was a positive correlation between duration of disease and motor impairment (P = 0.02, r = 0.48), and a tendency for positive correlation between duration of disease and NAA/Cr (P = 0.059, r = 0.4). We found decreased NAA/Cr values in the thalamus of patients with HD, indicating neuronal loss or dysfunction. This is in agreement with previous studies that indicated the involvement of mitochondrial dysfunction in the neurodegenerative process of HD.

Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease

“…H magnetic resonance spectroscopy (MRS) has previously been evaluated as a biomarker modality in premanifest and early HD. [4][5][6][7][8][9][10][11] However, the literature is conflicted with regard to the utility of metabolites such as total N-acetylaspartate (tNAA), a measure of neuronal integ-*These authors contributed equally to this work. References e1-e7 are available on the Neurology Web site at www.neurology.org.…”

“…[4][5][6][7][8][9][10][11] However, the literature is conflicted with regard to the utility of metabolites such as total N-acetylaspartate (tNAA), a measure of neuronal integ-rity, 12 as potential biomarkers in HD. In an attempt to address these discrepant findings, arising in part from small subject numbers, poorly comparable outcome measures and heterogeneity within patient cohorts, we sought to determine the potential of MRS as an HD biomarker using large numbers of subjects in defined, homogeneous clinical cohorts and examined MRS outcome measures normalized to unsuppressed water rather than metabolites such as total creatine (tCr) which are affected in HD.…”

“…In an attempt to address these discrepant findings, arising in part from small subject numbers, poorly comparable outcome measures and heterogeneity within patient cohorts, we sought to determine the potential of MRS as an HD biomarker using large numbers of subjects in defined, homogeneous clinical cohorts and examined MRS outcome measures normalized to unsuppressed water rather than metabolites such as total creatine (tCr) which are affected in HD. 6,11 TRACK-HD is an observational HD study that is taking place in Europe and 1 location in North America (Vancouver). Eighty-four individuals (30 controls, 25 pre-HD, and 29 early HD individuals) from the University of British Columbia (UBC), Vancouver, Canada, cohort underwent cross-sectional MRS examination of the left putamen and immediately surrounding white matter.…”

Reduced thalamic N-acetylaspartate in idiopathic normal pressure hydrocephalus: a controlled 1H-magnetic resonance spectroscopy study of frontal deep white matter and the thalamus using absolute quantification

“…The motor and cognitive symptoms may, from a strict neuroanatomical point of view, originate from the thalamus. In schizophrenia as well as in Huntington's disease, thalamus has been examined with MRS, and NAA has found to be decreased 33 34…”

Exploratory 7-Tesla magnetic resonance spectroscopy in Huntington’s disease provides in vivo evidence for impaired energy metabolism

“…In one study, a lower level of N -acetylaspartate (NAA) was confirmed post-mortem in the putamen and cortex in manifest HD [7]. In vivo altered levels of NAA, creatine, choline, and glutamate have been reported in both premanifest and manifest HD in several brain structures, such as the striatum and thalamus using MRS [9, 11, 12, 24, 25, 31, 32]. However, in contrast, other studies using localized MRS did not detect changes in these metabolite levels in either manifest or premanifest HD [6, 21, 35].…”