Introduction
Neurodegenerative disorder characterized by involuntary choreatic movements with cognitive and behavioral disturbances.
- Autosomal dominant inheritance
History:
George Huntington (April 9, 1850 – March 3, 1916) was an American physician from Long Island, New York who contributed the clinical description of the disease that bears his name — Huntington’s disease. Dr. Huntington wrote his paper “On Chorea” when he was 22 years old, a year after receiving his medical degree from Columbia University in New York. “On Chorea”was first published in the Medical and Surgical Reporter of Philadelphia on April 13, 1872.
Aetiology
Trinucleotide repeat disorder:
Caused by elongation of CAG repeats on the short arm of chromosome 4p16.3 in the HTT gene.
- ≥ 40 repeats: Disease expression
- 27-35 repeats: Not associated with disease expression but may expand in paternal transmission, resulting in the disease in descendants.
- ≤ 26 repeats: Normal
Pathophysiology
Basal ganglia:
Most striking cell loss occurs in the basal ganglia but other areas of the brain including the cortex are also affected.
Damage to the indirect pathway leads to overstimulation of the thalamo-cortical feedback and chorea (random purposeless movements), whereas loss of the direct pathway results in increased inhibition of the thalamus and less activity of the thalamo-cortical feedback producing bradykinesia and rigidity. Although both pathways degenerate, the balance between them is disturbed.
Clinical features
If a person has inherited the gene there will be a period of time where she/he is completely asymptomatic. In time, the neurones become dysfunctional.
Pre-manifest HD:
Onset of HD is insidious with non-specific problems such as mood change or being slightly forgetful, which can be attributed easily to other mundane causes. A person in this prodromal stage may become depressed, but a clinical diagnosis cannot be made confidently until motor signs, such as chorea, appear. These may be infrequent, of low amplitude and may not be noticed by the patient, family or clinician with limited experience of the condition. Indeed even at a time when the chorea is quite obvious it may be denied as a problem by the patient.
Early stage HD:
Symptoms become noticeable enough to warrant a diagnosis. Cognitive and behavioral symptoms particularly make it harder for people to work and perform at their usual level. However, at this stage, people are still able to maintain a fairly normal lifestyle and can generally continue to work, drive, and live independently.
Mid-stage HD:
Lose of ability to work and drive, and might be unable to perform household chores. Eating can become challenging, as patients have trouble performing the complicated series of muscle movements needed to swallow. Speech becomes slurred, and walking becomes staggered. However, many people are still able to eat, dress, and take care of hygiene with some help. Physical therapists can help patients control their voluntary movements; speech pathologists can help patients deal with swallowing and speaking; occupational therapists can help patients deal with changes in their thoughts.
Late-stage HD:
Patients require help in all aspects of life. They are generally unable to speak, and remain bedridden. Since it becomes more and more difficult to care for a patient as the disease progresses, patients often spend the last few years of life in a nursing home. Choking is a major concern; it becomes extremely difficult to swallow, so most late-stage patients need to be fed with a tube that is inserted surgically into the stomach or small intestine. Many patients have trouble urinating or become constipated, and some patients have trouble sleeping normally.
Diagnosis
Clinical diagnosis:
- Quasi-purposeful movements
- Abnormal movements that appear to have purpose
- Abnormal eye movements
- Inability to sustain movements
- Lack of coordination
Total Functional Capacity (TFC) scale:
Classifies HD into 5 stages of disease progression based on functioning for ADLs, domestic chores, finances, work and overall care level.
WHO International Classification of Functioning, Disability and Health (ICF) (WHO, 2001):
Aid in structuring assessment of a person’s functioning and participation and in allowing consideration of the triad of motor, cognitive and psychiatric symptoms that are often seen in HD.
MRI (brain):
Brain biopsy:
Management
There is no cure for HD. However, many therapeutic options exist for treating signs and symptoms with the aim of improving the quality of life.
Medical management:
- Choreic movements: Typical (haloperidol) and atypical (olanzapine) neuroleptics; benzodiazepines; or the monoamine-depleting agent tetrabenazine
- Anti-parkinsonian agents: Ameliorate hypokinesia and rigidity, but may increase chorea
- Psychiatric disturbances (depression, psychotic symptoms, and outbursts of aggression): Psychotropic drugs or some antiepileptic drugs
- Valproic acid: Improved myoclonic hyperkinesia in Huntington disease