Huntington’s Disease (HD)

Huntington’s disease can affect everyone differently. It typically presents as a combination of cognitive, motor, and psychiatric symptoms.  Cognitive or behavioral changes may present very early in the disease course up to 15 years before the onset of motor symptoms. Motor symptoms typically begin as minor involuntary movements (chorea) that present early in the disease course and become more prominent over time. Chorea most commonly involves the fingers, hands, and face muscles. As time goes on, the arms, legs, upper body, or torso may also be affected. Later in the disease course, chorea may become severe but is more often replaced by other movement disorders, such as rigidity, bradykinesia (slowed movement), and loss of voluntary motor control.

Cognitive symptoms may include:

• Problems with learning, memory, and attention
• Difficulty with organization and planning
• Inability to interpret facial expressions
• Lack of awareness of time, place, or oneself
• Slowness in processing thoughts

Psychiatric and behavioral symptoms may include:

• Depression
• Irritability
• Impulsivity
• Impaired judgement
• Apathy (lack of emotion or interest)
• Perseveration and fixation (e.g. difficulty letting go of a particular idea or topic)
• Psychosis may occur in late stage disease with worsening cognitive decline

Involuntary movements associated with chorea can include:

• Dance-like twitching movement of the fingers and toes
• Inability to sustain a movement, such as holding a cup or shaking a hand
• Fidgeting or sudden jerky movements in the arms or legs
• Tongue moving in and out of the mouth
• Facial grimacing
• Slurred speech

A diagnosis of Huntington’s disease (HD) is typically based on family history, genetic testing,  and the observation of involuntary movements (chorea). The Unified Huntington’s Disease Rating Scale (UHDRS) is a validated research tool that can be used to assess the clinical features and disease course of HD. The UHDRS contains a subscale that assesses chorea symptoms across seven different regions of the body. Total score for this subscale ranges from 0-28, with a higher score indicating more severe chorea. Once HD is suspected, genetic testing of the huntingtin gene (HTT) can help to confirm a diagnosis.

There is currently no cure or treatment that can stop or slow the progression of Huntington’s disease. A combination of medications and non-medical care is commonly used to manage symptoms and improve quality of life for patients. Selective serotonin reuptake inhibitors (SSRIs), such as sertraline or citalopram, may be used in combination with cognitive behavioral therapy to treat symptoms of depression, anxiety, and irritability associated with HD. First and second-generation antipsychotics (e.g. haloperidol, olanzapine) may be used to treat psychosis and irritability. For patients with sleep disturbances, improving sleep hygiene can be helpful. Some ways to improve sleep include avoiding daytime naps, exercising regularly, limiting caffeine, and limiting screen time at night. As the disease progresses, medications such as melatonin and mirtazapine may be used to promote sleep at night, while modafinil may be helpful in restoring daytime alertness.

Chorea does not always require treatment. However, there are several types of medications that can help to relieve troublesome movement symptoms that interfere with daily life. Vesicular monoamine transporter 2 (VMAT2) inhibitors are the only medications that are FDA-approved specifically to treat chorea associated with Huntington’s disease. First and second-generation antipsychotics, which are often prescribed to manage the behavioral and psychological symptoms of HD, are also sometimes used off-label to reduce chorea. Other off-label medications that may be considered to reduce chorea in specific patients include amantadine and clonazepam.