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I want to talk clinically about

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Huntington's disease.

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I've got an axial FLAIR

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showing some of the ratios

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that will measure the intercaudate

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distance as part of that ratio.

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The interfrontal distance as part of that ratio,

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and the intertable to intertable

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distance as part of that ratio,

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measures one or two slices

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below the lower aspect

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of the body of the ventricles,

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or at the level of the third and lateral ventricles.

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Then we come over to the middle because this

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patient has a movement abnormality.

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And your first thought is, okay, PD,

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Parkinson's disease.

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And you look,

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you've got red nucleus separated

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from substantia nigra.

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They have not bled together as one structure,

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as you might see with PD or Parkinson's disease.

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And in the coronal projection,

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the caudate nucleus head and body,

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just too small,

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allowing the ventricles to bow out and assume

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this inferior pointy configuration.

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There's your internal capsule and there is your

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relatively small putamen with the external capsule

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claustrum extreme capsule and centrosylvian cortex.

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Not specifically defined,

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but in this region.

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And as you come forward a little bit,

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you see the subthalamic nucleus inferiorly.

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Now, Huntington's disease

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is an autosomal dominant,

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progressive neurodegenerative disorder,

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typically characterized by chorea,

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cognitive decline and behavioral changes,

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leading to relentless increasing disability,

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and unfortunately,

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an untimely death.

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Often the first presentation is

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simply behavioral changes.

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And sometimes,

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it's nothing more than disinhibition,

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you know,

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excessive emotionality, doing things that you

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otherwise might not expect from this person.

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Neurodegeneration and Huntington's disease,

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most prominently affects the striatum with loss of

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medium-sized spiny neurons and large neurons

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in layers three, four, and five,

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predominantly in the frontal cortex.

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But it also affects the supplementary motor area,

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or SMA.

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The cytopathological hallmarks of Huntington's

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disease are intranuclear inclusions,

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consisting of amyloid-like fibrils.

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So amyloid is not just seen in angiopathic disease,

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amyloid angiopathy,

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it's seen in Alzheimer's disease,

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it's seen in Huntington's disease,

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and it's seen in other neurodegenerative conditions.

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Often, mutant huntingtin ubiquitin

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is present with synuclein and other proteins.

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So, abnormal proteins accumulate in the cell.

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This is a cell-level abnormality.

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The prevalence of Huntington's disease in the

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European and North American studies is between

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three and seven people per 100,000,

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whereas the annual incidence is between

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two and seven per million.

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You've already heard that there's an increased

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incidence of this disease in Scots people

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of Scottish descent and people from Venezuela.

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Huntington's disease is caused by

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a trinucleotide CAG repeat, expansion in the

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gene encoding of huntingtin on chromosome 4p16.3.

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So, we know this is a disorder of chromosome four.

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This CAG repeat on DNA analysis is

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a hallmark of the disease.

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Now,

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healthy individuals will have this CAG cytosine

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adenine, guanine repeat fewer than 35 times.

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But repeats of 40 or more are associated with

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Huntington's disease with complete penetrance.

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Individuals with 36 to 39 of these repeats

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can also develop Huntington's disease,

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but the penetrance to the offspring is incomplete.

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So, this affects your assessment of the overall

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genetics of that patient and / or that family.

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So, it may not be imminently clear that this is an

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autosomal dominant, inherited condition.

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Now, I'm also introducing the CAG repeat

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or cytosine adenosine...

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adenine guanine repeat,

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because the number of repeats affects when

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the individual will get the disease.

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This is a 67-year-old with

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late-onset Huntington's.

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So, the number of repeats in this individual's

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family is going to be relatively low.

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It's going to be somewhere in the 36 to 37 range,

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whereas somebody who gets it at age 25

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is going to have 40, 45, 47 repeats.

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So, unfortunately, or fortunately,

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not only can you make the diagnosis

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by DNA analysis,

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you can generally predict how severe and when

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the onset of the disease will occur

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individual by individual,

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family by family.

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Let's move on, shall we?