Huntington’s chorea Flashcards
What is Huntingtons
Cause of chorea and is a neurodegenerative disorder characterised by the LACK of the inhibitory neurotransmitter GABA
What is chorea
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.
Inheritance pattern of huntingtons
Autosomal dominant (full penetrance)
When does presentation start
What are initial symptoms
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
Epidemiology
5 per 100,000
Aetiology
Mutation on chromosome 4 resulting in repeated expression of CAG sequence
Risk factors
Family history
Having a parent with Huntingtons
If a parent has Huntingtons, what is risk of child getting it
50%
Pathophysiology
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
Repeats of CAG if adult or child onset
More CAG repeats, earlier symptom onset:
Most adult onset have 36-55 repeats
Early onset i.e. from childhood have >60 repeats
What results from GABA deficiency
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
Where is GABA produced
Striatum
Where is progressive cerebral atrophy and loss of neurones in Huntingtons
Caudate nucleus and Putamen of Basal ganglia
Loss of the corpus striatum GABA-nergic and Cholinergic neurons
Clinical presentation
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
Clinical presentation of chorea
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
How long until death after diagnosis
15 yrs
Usually from an intercurrent illness e.g. infection
Example of psychiatric problems in clinical presentation
Depression/anxiety
Behavioural change - aggression, addictive behaviour, apathy and self-neglect
True or False:
Huntingtons is the most common cause of chorea
True
Other causes of chorea
- Sydenham’s chorea (Rheumatic fever)
- Creutzfeldt-Jakob Disease (prion)
- Wilson’s disease
- SLE
- Stroke of basal ganglia
Diagnosis
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)
Treatment - conservative
No treatment to prevent progression
Conservative:
Counselling to patient and family
Genetic counselling to any children of patients
Treatment - medical
No treatment to prevent progression Symptomatic management of chorea Antidepressants Antipsychotic medication such as neuroleptics Treat aggression using Risperidone
Symptomatic treatment of chorea
BENZODIAZEPINES
SULPIRIDE - neuroleptic - depresses nerve function
TETRABENAZINE - dopamine depleting agent
Example of antidepressants
Selective serotonin reuptake inhibitors (SSRI’s) e.g. SEROXATE
Example of antipsychotic medication
Neuroleptics e.g. HALOPERIDOL
