HUNTINGTON’S DISEASE

Hyperkinetic + Sad

Huntington’s Disease is the opposite of Parkinson’s disease -- it’s a hyperkinetic disease. Both Huntington’s and Parkinson’s are caused by damage to the basal ganglia (BG), but while Parkinson’s damages the excitatory dopaminergic neurons of the BG, Huntington’s damages the inhibitory neurons, which contain GABA and Acetylcholine. Both disorders are permanent and progressive.

Pathophysiology?

Autosomal dominant inheritance with trinucleotide CAG repeats on c4. Healthy people have about 19 repeats. Huntington’s patients have 40+. Their huntingtin protein (not a misspelling) will be dysfunctional, leading to oxidative damage of neurons. Like all trinucleotide repeat diseases, anticipation is a feature (your symptoms are worse than your parents). It typically onsets between ages 20 to 50.  The caudate degenerates → emotional inhibition lost. The putamen degenerates → motor inhibition lost → choreoathetosis

CAG: The Caudate nucleus dies, so there is less Acetylcholine and GABA. 

When you HUNT you put animals in a CAGe. There are 4 letters in cage (chromosome 4)

Symptoms?

The dominant symptom is chorea, or uncontrolled dance-like movements. The basal ganglia stores patterns of movement. In Huntington’s it’s almost as if broken patterns of movement are “leaking” out of the basal ganglia. Athetosis is also seen, it refers to snake-like writhing of the arms and legs. This is not a tremor or jerky movement. It’s smooth. They also suffer from depression and dementia in the later-stages. 

Diagnosis?

The diagnosis is based on genetic testing. On an MRI, the lateral ventricles look big -- because the heads of the caudate nuclei died, and they formed the lateral wall of the lateral ventricles. This is an example of hydrocephalus ex vacuo.