Nervous system ORGAN SYSTEMS

Huntington disease (HD)

Neurodegenerative disorder characterized by involuntary choreatic movements with cognitive and behavioral disturbances.


Neurodegenerative disorder characterized by involuntary choreatic movements with cognitive and behavioral disturbances.

  • Autosomal dominant inheritance


In 1872 George Huntington described the disorder in his first paper “On Chorea” at the age of 22.

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.


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
In Huntington disease, the length of CAG repeat is inversely related to age of onset. This relationship is shown with approximations of age of onset based on repeat length. JHD, juvenile Huntington disease | Nopoulos P. C. (2016). Huntington disease: a single-gene degenerative disorder of the striatum. Dialogues in clinical neuroscience, 18(1), 91–98.


Basal ganglia:

Most striking cell loss occurs in the basal ganglia but other areas of the brain including the cortex are also affected.
Photographs of the cut surfaces of the brain of an age-matched control (left) and a patient with Huntington’s disease (right). The massive loss of the basal ganglia (esp. caudate nucleus) is apparent. | Harper, 1991,

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.

Location of the nuclei comprising the basal ganglia. This coronal section through the brain is slanted anteroposteriorly in order to show all the structure on one section. Note the two parts of the globus pallidus. The two subdivisions of the substantia nigra (pars reticulate and pars compacta) are not shown in this figure. The connections from the caudate nucleus and putamen to the substantia nigra are shown terminating in the pars reticulate. The dopaminergic connection from the pars compacta is not shown. | (2020) Huntington’s disease | Neupsy Key. Retrieved November 10, 2020, from
The Calgary Guide |
The Calgary Guide |

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.

Primary physiotherapy aims and the continuum of Huntington’s disease. | Walker et al., Huntington’s Disease. Lancet 2007;369 (9557): 218-28, with permission from Elsevier.

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.
(2020) Stages of Huntington’s Disease – HOPES Huntington’s Disease Information. Retrieved November 10, 2020, from

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.
(2020) Stages of Huntington’s Disease – HOPES Huntington’s Disease Information. Retrieved November 10, 2020, from

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.
(2020) Stages of Huntington’s Disease – HOPES Huntington’s Disease Information. Retrieved November 10, 2020, from


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.
The Total Functional Capacity (TFC) Scale | (2020) Huntington’s disease | Neupsy Key. Retrieved November 10, 2020, from

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.
Illustration of the WHO ICF domains and coding to the Huntington’s disease triad. Bold text indicates areas that are key components of the physiotherapy assessment. | Ufo Themes. (2020) Huntington’s disease | Neupsy Key. Retrieved November 10, 2020, from

MRI (brain):

Coronal section from an MR brain scan of a patient with HD, showing atrophy of the heads of the caudate nuclei, enlargement of the frontal horns of the lateral ventricles (hydrocephalus ex vacuo), and generalized cortical atrophy | By Frank Gaillard – Own work, CC BY-SA 3.0,

Brain biopsy:

HD is characterized by abnormal protein deposits containing mutant huntingtin. (A) Huntingtin immunoreactivity in neuronal intranuclear inclusions (hNIIs) and dystrophic neurites in HD brain. Cortex of a juvenile patient shows numerous hNIIs prominently stained. (B and C) Cortical pyramidal neurons in a different juvenile patient shown with Nomarski optics contain one (B) and two (C) hNIIs. The nucleolus in each cell is unlabeled. (D–E) Huntingtin aggregates in human postmortem cerebral cortex and striatum from a presymptomatic case. Light micrographs are from the insular cortex (D) and dorsal striatum (E). Large numbers of EM48-immunoreactive aggregates of a wide variety of shapes and sizes are visible in cortex. All of these aggregates are in the neuropil. In contrast, striatal aggregates are exceedingly uncommon. Scale bar, 70 µm. | A–C: DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277: 1990–1993 | D–E: Gutekunst C-A, Li S-H, Yi H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li X-J 1999. Nuclear and neuropil aggregates in Huntington’s disease: Relationship to neuropathology. J Neurosci 19: 2522–2534


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

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