Huntington’s chorea

Question 1

What is Huntingtons

Answer 1

Cause of chorea and is a neurodegenerative disorder characterised by the LACK of the inhibitory neurotransmitter GABA

Question 2

What is chorea

Answer 2

A continuous flow of jerky, semi-purposeful movements, flitting from one part of the body to another.
They may interfere with voluntary movements but cease during sleep.

Question 3

Inheritance pattern of huntingtons

Answer 3

Autosomal dominant
(full penetrance)

Question 4

When does presentation start

What are initial symptoms

Answer 4

Middle age initially with a prodromal phase of mild symptoms e.g. irritability, depression and incoordination then progressing to psychiatric and cognitive symptoms.
The more CAG repeats, the earlier symptoms start

Question 5

Epidemiology

Answer 5

5 per 100,000

Question 6

Aetiology

Answer 6

Mutation on chromosome 4 resulting in repeated expression of CAG sequence

Question 7

Risk factors

Answer 7

Family history

Having a parent with Huntingtons

Question 8

If a parent has Huntingtons, what is risk of child getting it

Answer 8

50%

Question 9

Pathophysiology

Answer 9

Repeated expression of CAG sequence leads to the translation of an expanded polyglutamine repeat sequence in the huntingtin gene (expressed throughout the body), the protein gene product the function of which is unclear - the expansion is thought to be a toxic ‘gain-of-function mutation’.
Progressive cerebral atrophy with marked loss of neurones in the CAUDATE NUCLEUS & PUTAMEN of the basal ganglia - there is specifically loss of the corpus striatum GABA-NERGIC and CHOLINERGIC NEURONS
This results in DECREASED ACh & GABA SYNTHESIS in the striatum
GABA is the main INHIBITORY NEUROTRANSMITTER, loss of this will result in decreased inhibition of DOPAMINE release and therefore result in EXCESSIVE THALAMIC STIMULATION and thus EXCESSIVE MOVEMENTS - CHOREA

Question 10

Repeats of CAG if adult or child onset

Answer 10

More CAG repeats, earlier symptom onset:
Most adult onset have 36-55 repeats
Early onset i.e. from childhood have >60 repeats

Question 11

What results from GABA deficiency

Answer 11

GABA is the main INHIBITORY NEUROTRANSMITTER
Loss of this will result in decreased inhibition of DOPAMINE release and therefore result in EXCESSIVE THALAMIC STIMULATION and thus EXCESSIVE MOVEMENTS - CHOREA

Question 12

Where is GABA produced

Answer 12

Striatum

Question 13

Where is progressive cerebral atrophy and loss of neurones in Huntingtons

Answer 13

Caudate nucleus and Putamen of Basal ganglia

Loss of the corpus striatum GABA-nergic and Cholinergic neurons

Question 14

Clinical presentation

Answer 14

Prodromal phase of mild psychotic and behavioural symptoms
Chorea develops
Dysarthria (unclear speech), dysphagia and abnormal eye movements
Psychiatric problems - behavioural change, depression/anxiety
Dementia - impaired cognitive abilities and memory
Associated with seizures
Eventually to death

Question 15

Clinical presentation of chorea

Answer 15

Relentlessly progressive, jerky, explosive, rigidity INVOLUNTARY movements - CEASES when sleeping
Can’t sit still
May begin as general restlessness, unintentionally initiated movements and lack of coordination

Question 16

How long until death after diagnosis

Answer 16

15 yrs

Usually from an intercurrent illness e.g. infection

Question 17

Example of psychiatric problems in clinical presentation

Answer 17

Depression/anxiety

Behavioural change - aggression, addictive behaviour, apathy and self-neglect

Question 18

True or False:

Huntingtons is the most common cause of chorea

Answer 18

True

Question 19

Other causes of chorea

Answer 19

• Sydenham’s chorea (Rheumatic fever)
• Creutzfeldt-Jakob Disease (prion)
• Wilson’s disease
• SLE
• Stroke of basal ganglia

Question 20

Diagnosis

Answer 20

Mainly clinical
Genetic testing - shows many CAG repeats (>35)
CT/MRI - shows caudate nucleus atrophy and increased size of frontal horns of lateral ventricles (signs of brain matter destruction)

Question 21

Treatment - conservative

Answer 21

No treatment to prevent progression
Conservative:
Counselling to patient and family
Genetic counselling to any children of patients

Question 22

Treatment - medical

Answer 22

No treatment to prevent progression
Symptomatic management of chorea
Antidepressants
Antipsychotic medication such as neuroleptics
Treat aggression using Risperidone

Question 23

Symptomatic treatment of chorea

Answer 23

BENZODIAZEPINES
SULPIRIDE - neuroleptic - depresses nerve function
TETRABENAZINE - dopamine depleting agent

Question 24

Example of antidepressants

Answer 24

Selective serotonin reuptake inhibitors (SSRI’s) e.g. SEROXATE

Question 25

Example of antipsychotic medication

Answer 25

Neuroleptics e.g. HALOPERIDOL