Huntington disease

Dr Dan J Bell and A.Prof Frank Gaillard et al.

Huntington disease (HD), also known as Huntington chorea, is an autosomal dominant neurodegenerative disease, and one of the trinucleotide repeat disorders and caused by a loss of GABAergic neurons of the basal ganglia, especially atrophy of the caudate nucleus and putamen. Huntington disease is clinically characterised by progressive unintentional choreoathetoid movements, subcortical type dementia, behavioural changes, and psychosis which starts in midlife.

On imaging, it is classically characterised by atrophy of the caudate nucleus with concomitant enlargement of the frontal horns of the lateral ventricles.

Huntington disease has a prevalence of 5-10 per 100,000 and is typically diagnosed between 30 and 50 years of age 3. Incidence is equal in both genders, although there appears to be an effect depending on the gender of the parent from whom the defect was inherited: if inherited from the father, presentation is earlier. The cause for this effect is as yet uncertain 3.

In approximately 1-6%, symptoms occur before the age of 20 years, the so-called 'juvenile' form, which appears to be a variant of the usual adult form, with a different pattern of symptoms. In juvenile cases, paternal inheritance is far more common 3.

Presentation is typically with progressive rigidity, choreoathetosis, dementia, psychosis and emotional lability 2.

The juvenile form has a different presentation, with cerebellar symptoms, rigidity and hypokinesia being prominent.

It is autosomal dominant with complete penetrance and genetic anticipation (i.e. next generation will have more repeats of CAG and a more severe course of the disease or show symptoms earlier) particularly if the inherited mutated allele is paternal. The mutation responsible is on chromosome 4p16:3, and consists of a CAG trinucleotide repeat. The usual 10-30 copies are amplified to >36, and the greater the number of repeats the earlier the age of onset 3.

Microscopically, there are Huntington nuclear inclusion bodies 8. Both deep grey matter and to a lesser degree white matter are involved in HD.

Although all modalities capable of structural brain imaging will demonstrate morphological changes of Huntington disease, MRI has the greatest spatial and contrast resolution and is thus preferred.

The most striking, and best known, feature is that of caudate head atrophy resulting in enlargement of the frontal horns, often giving them a box-like configuration 2-4. This can be quantified by a number of measurements:

Additionally in juvenile form the putamina are also atrophied, and demonstrate increased T2 signal 4. In some cases the basal ganglia may show decreased T2 signal and blooming on SWI in keeping with iron deposition 7. Generalised age-inappropriate cortical volume loss is also recognised 4.

MR spectroscopy may demonstrate elevation of lactate in the occipital cortex and basal ganglia which correlates with duration of symptoms. There is also a decrease in the NAA/creatine ratio in keeping with neuronal loss in the basal ganglia.

PET scan demonstrates hypometabolism as decreased FDG uptake in the basal ganglia and frontal cortex even before visible caudate nucleus volume loss is noticeable  6.

No treatment is currently generally available 4.

The adult onset form is slower in its course and inevitably leads to death in 14-15 years, whereas the juvenile form has a more rapidly progressive course, with death occurring in in 7-8 years 3.

It is named after George Huntington, an American physician (1850-1916) 1.

Neurodegenerative diseases

Neurodegenerative diseases are legion and their classification just as protean. A useful approach is to divide them according to underlying pathological process, although even using this schema, there is much overlap and thus resulting confusion.

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Article information

rID: 1465
Synonyms or Alternate Spellings:
  • Huntington's disease

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Cases and figures

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    FH IT CC

    Figure 1: FH/CC and CC/IT ratios
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    Huntington's dise...
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