Basal ganglia volume and clinical correlates in ‘preclinical’ Huntington’s disease

Jurgens, Caroline K.; Wiel, Lotte van de; Es, Ad C. G. M. van; Grimbergen, Yvette M.; Witjes-Ané, Marie-Noëlle W.; Grond, Jeroen van der; Middelkoop, Huub A. M.; Roos, Raymund A.C.

doi:10.1007/s00415-008-0050-4

Cited by 64 publications

(79 citation statements)

References 36 publications

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“…Kipps et al 10 suggest that cortical and white-matter atrophy may be more variable in location compared with the relatively concentrated striatal loss, making it more difficult to detect using voxel-based measurement techniques. The rate of globus pallidus atrophy was also significantly greater in the far and near groups than in the controls, consistent with cross-sectional reports of prodromal volume reduction in this area 22 23…”

Section: Discussionsupporting

confidence: 85%

Longitudinal change in regional brain volumes in prodromal Huntington disease

Aylward

Nopoulos

Ross

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

241

234

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Objective As therapeutics are being developed to target the underlying neuropathology of Huntington disease (HD), interest is increasing in methodologies for conducting clinical trials in the prodromal phase. This study was designed to examine the potential utility of structural MRI measures as outcome measures for such trials. Methods Data are presented from 211 prodromal individuals and 60 controls, scanned both at baseline and two-year follow-up. Prodromal participants were divided into groups based on proximity to estimated onset of diagnosable clinical disease: Far (>15 years from estimated onset); Mid (9–15 years); and Near (<9 years). Volumetric measurements of caudate, putamen, total striatum, globus pallidus, thalamus, total gray and white matter, and CSF were performed. Results All prodromal groups showed a faster rate of atrophy than Controls in striatum, total brain, and cerebral white matter (especially in the frontal lobe). Neither prodromal participants nor Controls showed significant longitudinal change in cortex (either total cortical gray or within individual lobes). When normal age-related atrophy (i.e., change observed in the Control group) was taken into account, there was more statistically significant disease-related atrophy in white matter than in striatum. Conclusion Measures of volume change in striatum and white matter volume, particularly in the frontal lobe, may serve as excellent outcome measures for future clinical trials in prodromal HD. Clinical trials using white matter or striatal volume change as an outcome measure will be most efficient if the sample is restricted to individuals who are within 15 years of estimated onset of diagnosable disease.

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Section: Discussionsupporting

confidence: 85%

Longitudinal change in regional brain volumes in prodromal Huntington disease

Aylward

Nopoulos

Ross

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

241

234

View full text Add to dashboard Cite

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“…Pillai et al (2012) reported a mean score of 23.7 (15-28) for cognitive impairments assessed using the MMSE in the moderate stages of in the severe stages. However, our MMSE results were very similar to those of other studies for the range of 42-46 CAG expanded alleles (Reedeker et al, 2010;Jurgens et al, 2008;Oliva et al, 1993;Dorsey et al, 2013). The results obtained assessing the UHDRS varied more when individuals bearing 42-46 CAG repeats were compared (Jurgens et al, 2008;Vaccarino et al, 2011).…”

Section: Discussionsupporting

confidence: 91%

“…Unsurprisingly, a longer disease duration has been found to be associated with higher scores on the UHDRS motor assessment in most patients (Kirkwood et al, 2001). A longer disease duration is also related to worse MMSE scores (Jurgens et al, 2008;Reedeker et al, 2010). A high degree of internal consistency between the motor, behavioral, cognitive and functional components of the UHDRS is observed.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic investigation of a Brazilian family with Huntington�s disease

Agostinho¹

2016

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SummaryThe aim of this study was to investigate a Brazilian family carrying full penetrance alleles for Huntington's disease (HD) in order to correlate each member's genetic and clinical features. To this end, the following scales were administered in each patient: the Beck Depression Inventory, the Mini-Mental State Examination (MMSE) and the Unified Huntington's Disease Rating Scale (UHDRS). The patterns of CAG and CCG polymorphic regions in the HTT gene were determined, the disease burden score was calculated, and genotypes were correlated with phenotypes within this family. We suggest that HD duration, the number of years of formal education, and UHDRS status variables can explain 96.6% of the MMSE variability in HD patients. A strong significant correlation was found between the disease burden score and the UHDRS (r = 0.76; p-value = 0.049) and the MMSE (r = −0.90; p-value = 0.006). The correlations between CAG allele size and the three clinical evaluations performed in the HD patients were not statistically significant.

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“…Putaminal metabolite changes are pertinent since this is a site of early atrophy, identifiable years prior to clinical diagnosis. 29 Furthermore, putaminal atrophy correlates with psychomotor and motor deficits in premanifest HD 30 and early HD. 31 Our correlations suggest a possible role for MRS in evaluating the ability of an intervention to slow disease progression.…”

Section: Huntington Disease (Hd)mentioning

confidence: 99%

Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease

Sturrock¹,

Laule²,

Decolongon³

et al. 2010

Neurology

106

102

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Objectives: To evaluate in vivo brain metabolite differences in control subjects, individuals with premanifest Huntington disease (pre-HD), and individuals with early HD using 1 H magnetic resonance spectroscopy (MRS) and to assess their relationship with motor performance.Methods: Eighty-five participants (30 controls, 25 pre-HD, and 30 early HD) were recruited as part of the TRACK-HD study. Eighty-four were scanned at 3 T with single-voxel spectroscopy in the left putamen. Disease burden score was Ͼ220 among pre-HD individuals. Subjects underwent TRACK-HD motor assessment including Unified Huntington's Disease Rating Scale (UHDRS) motor scoring and a novel quantitative motor battery. Statistical analyses included linear regression and one-way analysis of variance. Results:Total N-acetylaspartate (tNAA), a neuronal integrity marker, was lower in early HD (ϳ15%) vs controls (p Ͻ 0.001). N-acetylaspartate (NAA), a constituent of tNAA, was lower in pre-HD (ϳ8%) and early HD (ϳ17%) vs controls (p Ͻ 0.05). The glial cell marker, myo-inositol (mI), was 50% higher in early HD vs pre-HD (p Ͻ 0.01). In early HD, mI correlated with UHDRS motor score (R 2 ϭ 0.23, p Ͻ 0.05). Across pre-HD and early HD, tNAA correlated with performance on a tongue pressure task (R 2 ϭ 0.30, p Ͻ 0.0001) and with disease burden score (R 2 ϭ 0.17, p Ͻ 0.005). Conclusions:We demonstrate lower putaminal tNAA in early HD compared to controls in a crosssection of subjects. A novel biomarker role for mI in early HD was also identified. These findings resolve disagreement in the literature about the role of MRS as an HD biomarker. We conclude that putaminal MRS measurements of NAA and mI are promising potential biomarkers of HD onset and progression. Neurology ® 2010;75:1702-1710 GLOSSARY AD ϭ Alzheimer disease; Cr ϭ creatine; DBS ϭ disease burden score; Glu ϭ glutamate; GPC ϭ glycerophosphocholine; HD ϭ Huntington disease; mI ϭ myo-inositol; MR ϭ magnetic resonance; MRS ϭ 1 H magnetic resonance spectroscopy; NAA ϭ N-acetylaspartate; NAAG ϭ N-acetylaspartylglutamate; PC ϭ phosphocholine; PCr ϭ phosphocreatine; pre-HD ϭ premanifest Huntington disease; SNR ϭ signal-to-noise ratio; tCho ϭ total choline; tCr ϭ total creatine; TE ϭ echo time; tNAA ϭ total N-acetylaspartate; TR ϭ repetition time; UBC ϭ University of British Columbia; UHDRS ϭ Unified Huntington's Disease Rating Scale; VBM ϭ voxel-based morphometry.The eventual development of Huntington disease (HD) symptoms can be predicted through detection of CAG trinucleotide repeat expansion in the HTT gene 1 in premanifest gene carriers. However, definitive HD biomarkers, able to objectively identify disease onset and progression, are lacking. Evaluation of potential biomarkers are the focus of longitudinal studies such as TRACK-HD 2 and PREDICT-HD. 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-ac...

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Basal ganglia volume and clinical correlates in ‘preclinical’ Huntington’s disease

Cited by 64 publications

References 36 publications

Longitudinal change in regional brain volumes in prodromal Huntington disease

Longitudinal change in regional brain volumes in prodromal Huntington disease

Clinical and genetic investigation of a Brazilian family with Huntington�s disease

Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease

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