L2 Huntingdon's disease Flashcards
how is HD inherited
autosomal dominant CAG triplet repeat expansion
what is the average age of onset and when does death happen
37 years
15-25 years after onset
what are movement features of HD
chorea in 90% adult onset
motor incoordination
dystonia
oculomotor disturbance
what are cognitive features of HD
difficulties with
planning, judgement, impulse control, flexibility, multi-tasking, emotional processing
what are psychiatric features of HD
irritability depression anxiety suicide aggression compulsions psychosis hypersexuality - combination of pscyhiatric and cognitive features cause the greatest disability, functional decline and distress to relatives - area most poorly catered for in our society because they fall in between psychiatry and neurology
what happens in juvenile onset
early stage of disease
more aggressive, rigidity, dystonia, rapid cognitive decline
general restlessness, fidgety movements during stress
what happens in mid course disease
extrapyramidal signs
oculomotor disturbance
impairment of voluntary motor function, clumsiness, disturbances in fine motor control, motor speed
gait disturbance
dysarthria (speech), dysphagia (swallowing)
what happens during advanced stage disease
patients die of other causes associated with the disease
dominated by hypokinesia, rigidity, dystonia
mutism and severe dysphagia
severe eye movement abnormalities
agitation common
weight loss and emaciation
assisted suicide
what does anti sense oligonucleotide do in the trial
interferes with the production of a protein
what is a biomarker
a
characteristic that is objectively measured
and evaluated as an indicator of normal
biologic processes, pathogenic processes,
or pharmacologic responses to a
therapeutic intervention.”
what do we need in a biomarker
sensitive to disease effects - early HD - premanifest stages reproducible within and between sites track change over time link to clinically meaningful measure of function
what is a clinical rating scale used
unified HD rating scale
for total functional capacity, total motor score
what was the purpose of the TRACK-HD study
multi-national, longitudinal
develop biomarkers for future trials
baseline 12,24,36 month assessments in clinical, 3T MRI, quantitative motor, oculomotor, cognition, neuropsychiatry
123 controls, 120 premanifest gene carriers, 123 early HD
what are types of quantitative motor tasks
oculomotor, speeded tapping tasks, tongue force
how does imaging help
track disease progression
understand history of disease before clinical onset
