PowerPoint-Pr

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Chorea Huntington Morbus Huntington Juv. form
Westphal variant 1872 described by George
Huntington Frequency/prevalence 0,6 o in
white people less in black people Equally in
males and females 3000 8000 in Germany

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Symptoms Motor Hyperkinetic hypoton
uncontrolled movements, distally
accentuated like in a confused or embarrassed
state Dancing like movements (Veitstanz) grimacin
g Tongue, speech, swallowing Mental Schizophreni
a-like psychotic symptoms Dementia
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Time course Occurence Beyond the age of 30 -
50 years after the
reproductive phase Irrestable
progressive Leading to death after 5- 20 years
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Cause A dominant gene with 100
penetrance Inheritance Autosomal dominant No sex
differences 1 parent bears the gene 50 of the
children will fall ill 1983 HD locus on the
short arm of chromosome 4 1995 HD a
polyglutamine disease Protein Huntingtin
enhanced CAG repeat frequency CAG
triplett repeat normal 11 -34
in HD 37 86
correlation between repeat frequency and
onset of the diesease
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Morphology A disease of the basal ganglia /
striatum In HD the spiny I neurons of the
striatum degenerate (GABAergic,
ENKergic) Predominantly the neurons giving rise
to the indirect pathway Neurochemistry GABAergic
projection to the GPe
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The neurons of the indirect pathway
(ENK/GABA) In the striatum not affected Aspiny
neurons Somatostatin containing neurons NP-Y
neurons NADPH-Diaphorase/NO-Synthase containing
neurons
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CORTEX
GLU
GLU
GLU
THAL
GABA
GABA
STRIATUM
SNr
ACH
D1()
GPi
GPe
D2(-)
GABA
GABA
GABA
DA
GABA
GABA
GLU
SNc
STN
GLU
DA
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Therapy No causal therapy available GABA
agonism is too unselective Unspecific
therapy Sedative drugs neuroleptics
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Animal models Destruction of striatal spiny
neurons Sparing interneurons containing Somatosta
tin Neuropeptid Y NADPH-diapohrase/NO synthase
positive neurons Tools Excitotoxin Quinolinic
acid Transgenic animals