Huntington's disease Flashcards
what are the primary causes of chorea?
inherited:
HD commonest,
other HD like disorders
Acquired:
Vascular,
infective,
post-infectious, drugs
what should chorea be distinguished from?
tics,
dystonia,
myoclonus,
habit
HD is a …
inherited trinucleotide repeat movement disorder,
what are the thresholds for repeat expansions
up 35 CAG (glutamine) = normal,
36-39 grey zone.
> 40 = pathological
disease threshold generally considered 36
age of onset for HD
varies, but typically 30-50.
correlation with number of repeats
what are the two key features of HD
movement disorder symptoms ie chorea:
course often inverted U as progresses then ameliorates.
and psychiatric symptoms/personality change
chorea treatment in HD
Sulpiride (watch for rigidity),
olanzapine (can also increase weight & treat psychosis),
tetrabenazine (depression & parkinsonionism)
haloperidol (last resort)
what movement disorders can occur in HD other than chorea and how can they be managed
parkinsonionism ( l-dopa, reduce antipsychotics),
ataxia,
Dystonia (botox?)
Spasticity (Baclofen)
hemiballism (clonazepam)
psychiatric features of HD
depression 35-65%
Anxiety (35-60%)
irritability (38-70%)
apathy (35-75%),
OCD-10-50%,
psychosis (5-15%)
treatment of psychiatric disorders in HD
Depression:
Antidepressants:
(Mirtazapine-sedating, Sedating-sleep issues
SSRIs- Stimulating (suicide)
Anxiety-
consider mirtazepine if mostly depressive,
consider mood stabiliser ie lamotragine if out of blue.
Irritability:
consider possibility of situational , depression, pain,
if none try: lamotragine, olanzapine.
Apathy:
consider depression, drug treatment???
Psychosis: olanzapine, assistance of psychiatrist
what featurs can point toward differential diagnosis for HD
ataxia:
ie SCAs, Extrapyramidal signs: wilsons,
Myoclonus: mitochondrial disease,
Occulomotor abnormalities: SCAs, prion, orolingual
dystonia: acanthocytosis
what genetic disease may closely mimic HD
spinocerebellar ataxia 17 (SCA17)
mid age onset, choreic and psychiatric problems and similar occulomotor phenotype
what are the featues of SCA17
ataxia (commonest typical presentation),
Dementia,
promiment psychiatric features,
chorea,
dystonia,
oculomotor abnormalities common,
epilepsy
what are some genetic causes of chorea
wilsons,
benign hereditary chorea,
friedrichs,
mitochondrial,
ataxia telengiectasia
what is the genetic profile of SCA17
Autosomal Dominant,
Polyglutamate disorder like HD,
CAG repeat
ub the TBP-TATA binding protein,
> 43 repeats
what MRI feature can distinguish SCA17 from HD
commonly shows cerebellar atrophy (T2)
what prion disease can mimic HD
vCJD
what is the main pathological feature of HD
severe atrophy of the striatum (caudate)
cortical atrophy,
astrogliosis and microglial activation,
which neurons are most vulnerable in HD
GABAergic medium sizes spiny striatal neurones,
Large NADPH-diaphorase positive neurones relatively spared
what is genetic anticipation mainly associated with?
paternal transmission in polyQ diseases
what are some other polyglutamine disorders
spinobulbar muscular atrophy (SBMA)
or Kennedy’s Disease , SCA, types 1,2,3,6,7,17
what are the common features of polyglutamine diseases?
autosomal dominant ,
genetic anticipation,
inverse relationship between CAG repeat and age of onset,
toxic “gain of function” mechanism,
protein accumulation and aggregation
where are Huntingtin aggregates found in HD patients cells?
neurophil,
nucleus,
cell body
