Huntington's disease

Question 1

what are the primary causes of chorea?

Answer 1

inherited:
HD commonest,
other HD like disorders

Acquired:
Vascular,
infective,
post-infectious, drugs

Question 2

what should chorea be distinguished from?

Answer 2

tics,
dystonia,
myoclonus,
habit

Question 3

HD is a …

Answer 3

inherited trinucleotide repeat movement disorder,

Question 4

what are the thresholds for repeat expansions

Answer 4

up 35 CAG (glutamine) = normal,

36-39 grey zone.

> 40 = pathological

disease threshold generally considered 36

Question 5

age of onset for HD

Answer 5

varies, but typically 30-50.

correlation with number of repeats

Question 6

what are the two key features of HD

Answer 6

movement disorder symptoms ie chorea:

course often inverted U as progresses then ameliorates.

and psychiatric symptoms/personality change

Question 7

chorea treatment in HD

Answer 7

Sulpiride (watch for rigidity),

olanzapine (can also increase weight & treat psychosis),

tetrabenazine (depression & parkinsonionism)

haloperidol (last resort)

Question 8

what movement disorders can occur in HD other than chorea and how can they be managed

Answer 8

parkinsonionism ( l-dopa, reduce antipsychotics),

ataxia,

Dystonia (botox?)

Spasticity (Baclofen)

hemiballism (clonazepam)

Question 9

psychiatric features of HD

Answer 9

depression 35-65%

Anxiety (35-60%)

irritability (38-70%)

apathy (35-75%),

OCD-10-50%,

psychosis (5-15%)

Question 10

treatment of psychiatric disorders in HD

Answer 10

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

Question 11

what featurs can point toward differential diagnosis for HD

Answer 11

ataxia:

ie SCAs, Extrapyramidal signs: wilsons,

Myoclonus: mitochondrial disease,

Occulomotor abnormalities: SCAs, prion, orolingual

dystonia: acanthocytosis

Question 12

what genetic disease may closely mimic HD

Answer 12

spinocerebellar ataxia 17 (SCA17)

mid age onset, choreic and psychiatric problems and similar occulomotor phenotype

Question 13

what are the featues of SCA17

Answer 13

ataxia (commonest typical presentation),

Dementia,

promiment psychiatric features,

chorea,

dystonia,

oculomotor abnormalities common,

epilepsy

Question 14

what are some genetic causes of chorea

Answer 14

wilsons,

benign hereditary chorea,

friedrichs,

mitochondrial,

ataxia telengiectasia

Question 15

what is the genetic profile of SCA17

Answer 15

Autosomal Dominant,

Polyglutamate disorder like HD,

CAG repeat

ub the TBP-TATA binding protein,

> 43 repeats

Question 16

what MRI feature can distinguish SCA17 from HD

Answer 16

commonly shows cerebellar atrophy (T2)

Question 17

what prion disease can mimic HD

Answer 17

vCJD

Question 18

what is the main pathological feature of HD

Answer 18

severe atrophy of the striatum (caudate)

cortical atrophy,

astrogliosis and microglial activation,

Question 19

which neurons are most vulnerable in HD

Answer 19

GABAergic medium sizes spiny striatal neurones,

Large NADPH-diaphorase positive neurones relatively spared

Question 20

what is genetic anticipation mainly associated with?

Answer 20

paternal transmission in polyQ diseases

Question 21

what are some other polyglutamine disorders

Answer 21

spinobulbar muscular atrophy (SBMA)

or Kennedy’s Disease , SCA, types 1,2,3,6,7,17

Question 22

what are the common features of polyglutamine diseases?

Answer 22

autosomal dominant ,

genetic anticipation,

inverse relationship between CAG repeat and age of onset,

toxic “gain of function” mechanism,

protein accumulation and aggregation

Question 23

where are Huntingtin aggregates found in HD patients cells?

Answer 23

neurophil,

nucleus,

cell body