Huntington's disease

Question 1

Define Huntington’s disease.

Answer 1

Huntington’s disease is an autosomal dominant neurodegenerative disorder

Question 2

What is the aetiology of Huntington’s disease?

Answer 2

Pathology:

Atrophy and neuronal loss of striatum and cortex. Chorea results from striatal dysfunction.

Genetic basis:

Expanded CAG repeats on Chr. 4 N-terminus of the gene that codes for the huntingtin protein. If _>_40 CAG repeats then certain to develop Huntington’s.

Question 3

What are the risk factors for Huntington’s disease?

Answer 3

• FH
• Expanded CAG repeat length at N-terminal of huntingtin gene

Question 4

When does Huntington’s usually present?

Answer 4

Often presents in mid-life (35-45yrs) but may appear at any age.

Question 5

How common is Huntington’s? M:F? Typical onset?

Answer 5

• In Europe - 6/100,000
• Incurable, progressive - duration of disease is approx 20 years from time of diagnosis to death
• M:F 1:1
• Typical onset is 35-45 years

Question 6

What are the two variants of Huntington’s?

Answer 6

1. Rigid form: children or young adults present with rigidity and may not have chorea.
2. Choreic form: patients have chorea as a significant initial presenting feature. This is the most common phenotype.

Question 7

What are the clinical features of Huntington’s?

Answer 7

Starts with cognitive changes (e.g. reduced performance), then behavioural issues (e.g. irritability and impulsivity) then motor symptoms last (e.g. chorea, twitching, bradykinesia, rigidity)

• concentration impairment reducing performance at work or school
• depression
• incoordination (dropping things, stumbling, or RTA)
• irritability
• impulsivity
• lack of attention to hygiene
• personality change
• chorea
• restlessness
• bradykinesia/rigidity
• depression
• obsessions and compulsions

O/E:

• twitching/restlessness,
• loss of fine motor coordination (finger tapping),
• slowed saccadic eye movements,
• motor impersistence (e.g. when asked to squeeze for 10sec intensity varies),
• impaired tandem gait

Question 8

Define chorea.

Answer 8

Neurological disorder characterized by jerky involuntary movements affecting especially the shoulders, hips, and face.

Question 9

What should patients without Huntington’s be able to do on physical examination?

Answer 9

• Recite serial 7s seated, with eyes closed, without adventitious movements of fingers or toes.
• Tap finger 25 times in 2 seconds (with equal speed, regularity)
• Look quickly (saccade) between two index fingers, shoulder width apart.
• Maintain tongue protrusion/lid closure/grip tightly with same intensity for 10 seconds (HD = milkmaid’s grip)
• Walk heel to toe (tandem gait)

Question 10

What investigations would you do for Huntington’s?

Answer 10

• No initial tests - clinical diagnosis
• Consider: testing for CAG repeats, MRI/CT may show caudate/striatal atrophy

Question 11

Which parts of the brain does Huntington’s disease mostly affect?

Answer 11

Striatal dysfunction –> cognitive impairment, behavioural change, loss of coordination (→ chorea)

Damage is also seen in cortical and sub cortical structures.

Question 12

What is the management of Huntington’s?

Answer 12

MDT approach

Counselling for patient and family, carer support

Depression (and anxiety) - the most treatable symptom with SSRI or SNRI, reduces risk of suicide

Irritability and aggression - benzodiazepines, anticonvulsants, antipsychotics

Chorea - haloperidol or trifluoperazine (antipsychotics), tetrabenazine (VMATi)

Bradykinesia/rigidity - levodopa/carbidopa

Physiotherapy - improves motor fitness, motor function and gait

Question 13

What are the complications of Huntington’s disease?

Answer 13

• Weight loss due to dysphagia
• Falls
• Suicide risk
• Incontinence - end-stage

Question 14

What is the prognosis with Huntington’s?

Answer 14

Chorea sometimes reduces in severity with progression of the disease

Diagnosis to death is usually 20 years

Depression should improve with therapy