Magnetization transfer imaging in 'premanifest' Huntington's disease.
To investigate whether magnetization transfer imaging (MTI) is a useful detector of diffuse brain abnormalities in 'premanifest' carriers of the Huntington's disease (HD) gene mutation. Furthermore we examined the relations between MTI, clinical measures and CAG repeat length. Sixteen premanifest carriers of the HD gene without motor manifestation and 14 non-carriers underwent a clinical evaluation and a MRI scan. MTI analysis of whole brain, grey matter and white matter was performed producing magnetization transfer ratio (MTR) histograms. A lower peak height of the grey matter MTR histogram in carriers was significantly associated with more UHDRS motor abnormalities. Furthermore, a lower peak height of the whole brain, grey and white matter was strongly associated with a longer CAG repeat length. MTI measures themselves did not differ significantly between carriers and non-carriers. In premanifest HD mutation carriers, a lower MTR peak height, reflecting worse histological brain composition, was related to subtle motor abnormalities and higher CAG repeat length. Although we could not detect altered MTI characteristics in carriers of the HD gene mutation without clinical manifestations, we did provide evidence that the MTR peak height might reflect genetic and subclinical disease burden and may be of value in monitoring further disease progression and provide insight in clinical heterogeneity.
Jurgens
Caroline K
CK
Department of Neurology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands. C.K.Jurgens@lumc.nl
Bos
Reineke
R
Luyendijk
Jasper
J
Witjes-Ané
Marie-Noëlle W
MN
van der Grond
Jeroen
J
Middelkoop
Huub A M
HA
Roos
Raymund A C
RA
D000328:Adult; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins