“Pre‐symptomatic” Huntington's Disease

Abstract

Publication of the human genome has accelerated the paradigm shift in medicine from treatment of disease following diagnosis to the prediction and prevention of disease in healthy persons. Huntington's disease (HD), an autosomal dominant progressive neurological disease with an identified gene mutation (Huntington's Disease Collaborative Research Group, 1993), could prove to be a useful model in preparing for preventive clinical trials in other neurodegenerative diseases because individuals with the gene expansion can be identified years before diagnosis through genetic testing. This chapter will review current diagnostic procedures for HD, with a focus on recent developments in the identification of the earliest signs and symptoms of pre-diagnosed individuals carrying the gene expansion for HD. Additionally, we will highlight some clinical information that could be used to select these individuals in preparation for preventive clinical trials.

Early detection of Huntington‘s disease

“…For instance, recent results suggest that obsessive compulsive symptoms in prHD emphasize worrying and checking and rarely reach the levels of severity associated with diagnoses of obsessive compulsive disorders [101] until later in HD following clinical diagnosis [113]. Similarly, an analysis of the depression phenotype in prHD suggests that cognitive difficulties (poor concentration), suicidal thoughts, and low energy characterize this syndrome [21, 102, 115]. Although the range of scores on traditional depression assessment seen in prHD was often as broad as that seen in Major Depressive Disorder (MDD), the profile of these scores was poorly related to overall severity of depressive symptoms (suggesting poor discriminative properties) and appeared distinct from that seen in MDD [117].…”

Family carer personal concerns in Huntington disease

“…Several aspects of HD may also give insights into concerns of family carers, and how some concerns may not be shared by carers in other conditions. Manifestations of HD in the earliest phases of the condition, prior to the onset of motor symptoms, have only recently been described (Duff et al. 2008, Paulsen et al.…”

“…Several aspects of HD may also give insights into concerns of family carers, and how some concerns may not be shared by carers in other conditions. Manifestations of HD in the earliest phases of the condition, prior to the onset of motor symptoms, have only recently been described (Duff et al 2008, and the impact of changes in the cognitive and behavioural domains may be apparent in dayto-day functioning long before actual diagnosis. This is difficult for family members who search for explanations of changes in behaviour such as irritability or forgetfulness, but don't know if these are due to HD, other health problems, or a result of something that the family member did to upset the person .…”

Tractography of the Corpus Callosum in Huntington’s Disease

“…Many studies have documented the deleterious effect HD has on the brain, (for review see: [3]). Furthermore, it has been shown that presymptomatic (Pre-HD) subjects may have brain atrophy up to 10 years before disease manifestation [4], [5]. However, less is known about the effects of HD on white matter (WM) fibers.…”