Chorea Huntington Morbus Huntington Juv. form: Westphal variant

1. 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

2. Symptoms Motor: Hyperkinetic hypoton uncontrolled movements, distally accentuated like in a confused or embarrassed state Dancing like movements (Veitstanz) grimacing Tongue, speech, swallowing Mental: Schizophrenia-like psychotic symptoms Dementia

3. Time course Occurence: Beyond the age of 30 - 50 years after the reproductive phase Irrestable progressive Leading to death after 5- 20 years

4. 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

5. 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

6. 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

7. CORTEX GLU GLU GLU GABA GABA THAL STRIATUM ACH SNr D1(+) GPi GPe D2(-) GABA GABA GABA DA GABA GABA GLU SNc STN GLU DA

8. Therapy No causal therapy available GABA agonism is too unselective Unspecific therapy: Sedative drugs neuroleptics

9. Animal models Destruction of striatal spiny neurons Sparing interneurons containing: Somatostatin Neuropeptid Y NADPH-diapohrase/NO synthase positive neurons Tools: Excitotoxin Quinolinic acid Transgenic animals