Huntington Disease

 

Findings:

Diffuse cortical atrophy w/caudate nucleus and putamen most severely affected
Atrophy of caudate nucleus results in characteristic enlargement of the frontal horns, which take on a heart-shape configuration.

Huntington disease (HD), Huntington chorea

Autosomal dominant neuro degenerative disease with loss of GABAergic neurons of basal ganglia (BG)

Clinical triad: Early onset dementia, choreoathetosis, and psychosis.

Best diagnostic clue: 

Atrophy of caudate nucleus (Cn), loss of convex surface of caudate head, enlargement of frontal horns of lateral ventricles.

Location
o Primarily striatum (especially Cn, putamen)
o Cerebral cortex, globus pallidus (GP), thalamus
o Substantia nigra (SN), brainstem

CT / MRI
o Cn atrophy is measured on axial images at level of 3rd ventricle
• Intercaudate distance (CC) between most medial aspects of Cn
• CC compared with distance between most lateral aspects of frontal horns (FH)
• CC compared with distance between inner tables (IT) of skull at level of CC measurement
• Increase in CC relative to FH or IT
• Decrease in FH/CC ratio
• Increase in CC/IT ratio (bicaudate ratio): Most specific and sensitive measure for HD

MRS
increase in Lactate concentration in occipital cortex of symptomatic HD, also in BG in some patients
Lactate level correlates with duration of illness
Decrease in N-acetylaspartate/creatine in BG (neuronal loss)
Markedly increased Choline/creatine ratio in BG (gliosis)

Nuclear Medicine Findings
• PET
decrease in FDG uptake in BG before any detectable atrophy
Frontal lobe hypometabolism
• SPECT: Perfusion defects in motor cortex, prefrontal cortex, and BG correlate with clinical disease.

Clinical Issues
• Movement disorder
• Mean age of onset: 35-44 y in adult-onset HD

Pathology
CAG trinucleotide repeat disease affecting HD gene on chromosome 4p16.3
 Polyglutamine expansion =} Huntington accumulates in nucleus and cytoplasm =} cytoplasmic Huntington aggregates in axonal terminals, neuronal loss and gliosis.