BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a

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.

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The Leiden REGISTRY cohort at baseline is mainly characterized by full penetrance gene expansion carriers who have been clinically diagnosed with HD but who remain relatively functionally independent. For the majority of these participants, disease onset was based on motor signs followed by psychiatric and cognitive signs.

BackgroundREGISTRY is the largest European observational study of Huntington’s disease (HD). The Leiden University Medical Centre (LUMC) in The Netherlands is the largest recruiting site.ObjectiveThe aim of this paper is to give an overview of the baseline characteristics of all Leiden participants from the start of the study in 2005 until the close of REGISTRY at the LUMC in September 2014.MethodsThe Leiden cohort is described in two different ways: CAG repeat length and presence of motor signs.ResultsDivision into groups based on prolonged CAG length revealed that the cohort consists of 4 intermediate – (27–35 CAG), 22 reduced penetrance – (36–39 CAG), 465 full penetrance – (> 39 CAG) and 60 control participants (< 27 CAG). The second way of dividing the participants based on present or absent of motor signs, showed that 170 pre-motormanifest – and 317 motormanifest participants were enrolled.ConclusionThe Leiden REGISTRY cohort at baseline is mainly characterised by full penetrance gene expansion carriers who have been clinically diagnosed with HD but who remain relatively functionally independent. For the majority of these participants, disease onset was based on motor signs followed by psychiatric and cognitive signs.