Huntington's Disease (HD)

Primer

Huntington's Disease (HD) is a hereditary, neurodegenerative illness characterized by a triad of symptoms including motor disturbance, cognitive impairment, and psychiatric symptoms. It is an autosomal dominant disorder caused by an expanded trinucleotide repeat (CAG) mutation in the coding region of the huntingtin gene on chromosome 4.

Prevalence

The worldwide prevalence is estimated to be 2.7 per 100,000. The prevalence of Huntington's disease in North America, Europe, and Australia is 5.7 per 100,000. The prevalence is much lower in Asia, and is 0.40 per 100,000. The average age at diagnosis of Huntington's disease is approximately 40 years, although this varies widely. Age at onset is inversely correlated with CAG expansion length.

Prodrome

Psychiatric and cognitive abnormalities can predate the motor abnormality by at least 15 years. Initial symptoms requiring care often include irritability, anxiety, or depressed mood. Other behavioural disturbances may include pronounced apathy, disinhibition, impulsivity, and impaired insight, with apathy often becoming more progressive over time.

Diagnosis

A diagnosis of definite Huntington's disease is given in the presence of unequivocal, extrapyramidal motor abnormalities in an individual with either a family history of Huntington's disease or genetic testing showing a CAG trinucleotide repeat expansion in the huntingtin (HIT) gene, located on chromosome 4.

Major or Mild Neurocognitive Disorder Due to Huntington’s Disease

Criterion A

The criteria are met for major or mild neurocognitive disorder.

Criterion B

There is insidious onset and gradual progression.

Criterion C

There is clinically established Huntington’s disease, or risk for Huntington’s disease based on family history or genetic testing.

Criterion D

The neurocognitive disorder is not attributable to another medical condition and is not better explained by another mental disorder.

Pathophysiology

The pathophysiology and neurochemical bases of Huntington's are poorly understood. Dopamine and glutamate transmission is hypothesized to be affected, leading to striatal and cortical changes resulting in motor dysfunction such as chorea.

Symptoms

Psychiatric

There are four main clusters of psychiatric symptoms:

  1. Depression and anxiety (including low mood, suicidal ideation)
  2. Drive and executive function impairment (perseveration, compulsions, apathy)
  3. Irritability and aggression
  4. Psychosis (delusions and hallucinations)

Apathy is one of the most prevalent behavioural symptoms, occurring in close to 70% of symptomatic cases.[1] Progressive cognitive impairment is a core feature of Huntington's. There are early changes in executive function (i.e. - processing speed, organization, and planning) rather than learning and memory.

Neurologic

Cognitive and associated behavioural changes often precede the emergence of the motor abnormalities. Chorea, dystonia, bradykinesia, and oculomotor dysfunction can all occur.

Treatment

Motor

Chorea is one of the core symptoms of Huntington's, and when there is significant motor dysfunction, this needs to be treated. Untreated chorea can worsen weight loss and increase falls risk. Tetrabenazine (up to 100 mg/day), amantadine (300–400 mg/day), or riluzole (200 mg/day) can be prescribed. Adverse effects such as depression, suicidality, parkinsonism (with tetrabenazine), and elevated liver enzymes (with riluzole) should be monitored for.

Psychiatric

References

1) Krishnamoorthy, A., & Craufurd, D. (2011). Treatment of apathy in Huntington’s disease and other movement disorders. Current treatment options in neurology, 13(5), 508.