Huntington disease

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Huntington disease (HD), also known as Huntington chorea, is an autosomal dominant neurodegenerative disease 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. 

Epidemiology

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, so-called 'juvenile' form, which appears to be a variant of the usual adult form, with a different pattern of symptoms. In juvenile cases having inherited the disease from the father is far more common 3.

Clinical presentation

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. 

Pathology

It is a autosomal dominant with complete penetrance and genetic anticipation (i.e. next generation will have more repeats of CAG hence moreand 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 trineucleotide repeat. The usual 10-30 copies are amplified to greater than> 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. 

Radiographic features

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. 

MRI

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 an number of measurements:

Additionally in juvenile form putamen are also atrophied, and demonstrate increased T2 signal 4. In some case basal ganglia may show decrease 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 decrease in NAA/creatine ratio in keeping with neuronal loss in basal ganglia.

PET/CT 

PET scan demonstrates hypometabolism by decrease FDG uptake in basal ganglia and frontal cortex even before noticeable caudate nucleus volume loss 6.

Treatment and prognosis

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. 

History and etymology

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

Differential diagnosis

  • -<p><strong>Huntington disease (HD)</strong>, also known as <strong>Huntington chorea</strong>, is an autosomal dominant neurodegenerative disease caused by a loss of GABAergic neurons of the <a href="/articles/basal-ganglia">basal ganglia</a>, especially atrophy of the <a href="/articles/caudate-nucleus">caudate nucleus</a> and <a href="/articles/putamen">putamen</a>. Huntington disease is clinically characterised by progressive unintentional choreoathetoid movements, subcortical type dementia, behavioural changes, and psychosis which starts in midlife. </p><h4>Epidemiology</h4><p>Huntington disease has a prevalence of 5-10 per 100,000 and is typically diagnosed between 30 and 50 years of age <sup>3</sup>. 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 <sup>3</sup>.</p><p>In approximately 1-6% symptoms occur before the age of 20, so-called 'juvenile' form, which appears to be a variant of the usual adult form, with a different pattern of symptoms. In juvenile cases having inherited the disease from the father is far more common <sup>3</sup>.</p><h4>Clinical presentation</h4><p>Presentation is typically with progressive rigidity, choreoathetosis, dementia, psychosis and emotional lability <sup>2</sup>.</p><p>The juvenile form has a different presentation, with cerebellar symptoms, rigidity and hypokinesia being prominent. </p><h4>Pathology</h4><p>It is a autosomal dominant with complete penetrance and genetic anticipation (i.e. next generation will have more repeats of CAG hence more severe course of the disease or show symptoms earlier) particularly if inherited mutated allele is paternal. The mutation responsible is on chromosome 4p16:3, and consists of a CAG <a href="/articles/trineucleotide-repeat">trineucleotide repeat</a>. The usual 10-30 copies are amplified to greater than 36, and the greater the number of repeats the earlier the age of onset <sup>3</sup>. Microscopically, there are Huntington nuclear inclusion bodies <sup>8</sup>. Both deep grey matter and to a lesser degree white matter are involved in HD. </p><h4>Radiographic features</h4><p>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. </p><h5>MRI</h5><p>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 <sup>2-4</sup>. This can be quantified by an number of measurements:</p><ul>
  • +<p><strong>Huntington disease (HD)</strong>, also known as <strong>Huntington chorea</strong>, is an autosomal dominant neurodegenerative disease caused by a loss of GABAergic neurons of the <a href="/articles/basal-ganglia">basal ganglia</a>, especially atrophy of the <a href="/articles/caudate-nucleus">caudate nucleus</a> and <a href="/articles/putamen">putamen</a>. Huntington disease is clinically characterised by progressive unintentional choreoathetoid movements, subcortical type dementia, behavioural changes, and psychosis which starts in midlife. </p><h4>Epidemiology</h4><p>Huntington disease has a prevalence of 5-10 per 100,000 and is typically diagnosed between 30 and 50 years of age <sup>3</sup>. 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 <sup>3</sup>.</p><p>In approximately 1-6% symptoms occur before the age of 20, so-called 'juvenile' form, which appears to be a variant of the usual adult form, with a different pattern of symptoms. In juvenile cases having inherited the disease from the father is far more common <sup>3</sup>.</p><h4>Clinical presentation</h4><p>Presentation is typically with progressive rigidity, choreoathetosis, dementia, psychosis and emotional lability <sup>2</sup>.</p><p>The juvenile form has a different presentation, with cerebellar symptoms, rigidity and hypokinesia being prominent. </p><h4>Pathology</h4><p>It is a 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 <a href="/articles/trineucleotide-repeat">trineucleotide repeat</a>. The usual 10-30 copies are amplified to &gt; 36, and the greater the number of repeats the earlier the age of onset <sup>3</sup>.</p><p>Microscopically, there are Huntington nuclear inclusion bodies <sup>8</sup>. Both deep grey matter and to a lesser degree white matter are involved in HD. </p><h4>Radiographic features</h4><p>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. </p><h5>MRI</h5><p>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 <sup>2-4</sup>. This can be quantified by an number of measurements:</p><ul>
  • -<a href="/articles/wilsons-disease">Wilson disease</a><ul><li>more commonly involves white matter, thalamus, cerebellum and brainstem <sup>3</sup>
  • -</li></ul>
  • +<a href="/articles/wilsons-disease">Wilson disease</a>: more commonly involves white matter, thalamus, cerebellum and brainstem <sup>3</sup>
  • -<a href="/articles/leigh-disease">Leigh disease</a><ul><li>more commonly involves white matter, thalamus, cerebellum and brainstem</li></ul>
  • -</li>
  • +<a href="/articles/leigh-disease">Leigh disease</a>: more commonly involves white matter, thalamus, cerebellum and brainstem</li>

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