Chorea

Veitstanz, m. St. Vitus s dance, chorea. Vektorengleichung,/. vector equation. Vektorgeriist, n. vector diagram, vektorieil, a. vectorial. 

Basal ganglia are a group of subcortical nuclei which are essential for the coordination of movements (so-called extrapyramidal system). They include the caudate nucleus, putamen, globus pallidus, and lenti-form nucleus. Damage of the basal ganglia results in involuntary movements, as are observed in Parkinson s disease and Huntington s chorea. 

Trinucleotide sequences that increase in number (microsateUite instability) can cause disease. The unstable p(CGG) repeat sequence is associated with the fragile X syndrome. Other trinucleotide repeats that undergo dynamic mutation (usually an increase) are associated with Huntington s chorea (CAG), myotonic dystrophy (CTG), spinobulbar muscular atrophy (CAG), and Kennedy s disease (CAG). 

Another indication of the importance of DA in motor control is the observation that in humans its precursor levodopa, and DA agonists like bromocriptine, not only overcome the akinesia of Parkinsonism but in excess will actually cause involuntary movements, or dyskinesia (Chapter 14). Also it is well known that DA antagonists like chlorpromazine and haloperidol produce Parkinsonian-like symptoms in humans (and catalepsy in animals) and, as indicated above, reduce the dyskinesia of Huntington s Chorea. Thus DA seems to sit on a knife edge in the control of motor function (Fig. 7.8). 

Figure 7.8 Dopamine and motor function. When nigrostriatal dopamine activity is normal so is motor function. Any reduction in this DA activity, as in Parkinson s disease, results in reduced motor activity, i.e. akinesia. By contrast, too much DA activity, as in Huntington s Chorea, produces abnormal motor function, i.e. dyskinesia. The latter may be controlled by neuroleptic drugs (DA antagonists) but they can swing the balance in DA activity sufficiently to produce akinesia (Parkinsonism). DA agonists (and levodopa) may overcome akinesia but can induce DA overactivity and dyskinesia (peak dose effect) (see Chapter 15)...

Response fluctuations occur with disease progression as the patient s dopamine reserves are depleted in the brain and as a complication of PD treatment. Motor fluctuations include delayed peak response, early wearing off, random unpredictable on-off, and freezing. Dyskinesias include chorea, dystonia, and diphasic dyskinesia. Wearing off can be visualized by imagining the therapeutic window of dopamine narrowing over time. The therapeutic window is defined as the minimum effective concentration of dopamine required to control PD symptoms (on without dyskinesia) and the maximum concentration before experiencing side effects from too much dopamine (on with dyskinesia). Early in the disease, a dose of... 

Chorea A type of dyskinesia with rhythmic dance-like movement. The increase in motor activity may be associated with fidgeting, twitching, or flinging movements. 

Dyskinesia Abnormal involuntary movements, which include dystonia, chorea, and akathisia. 

Ibogaine protects the N-methyl-D-aspartate neuron receptors against excessive release of excitatory amino acids and represents, therefore, a potential therapeutic agent for the treatment of Alzheimer s disease, Huntington s chorea, and other... 

RFLPs are often a reflection of individual genetic diversity and are not related to a clinical phenotype, but occasionally they can be diagnostic of an inherited disease. This technique is relatively new yet, it has been applied to the prenatal detection of sickle cell anemia, thalassemia, phenylketonuria, a,-antitrypsin deficiency, Huntington s chorea, Duchenne muscular dystrophy, hemophilia A and B, cystic fibrosis, and several other, diseases. 

Symptomatic treatment. The chorea of Huntington s disease responds (partially) to treatment with neuroleptics, which, through blockade of D2 receptors, may help to increase basal ganglia output to more normal levels. Dopamine-depleting agents, such as reserpine or tetra-benazine have also been used. At best, these agents are only moderately effective and they should only be used if the chorea truly interferes with activities of daily living or produces social embarrassment. Neuroleptics and... 

Huntington disease (HD) is the prototypic disease caused by expansion of unstable GAG repeat. It primarily affects striatal neurons. It is a mid-life onset disorder characterized by unvoluntary movements (chorea), personality changes and dementia that progress to death within 10-20 years of onset. There are currently no treatment to delay or prevent appearance of the symptoms in the patients. Other diseases in this class include spinocerebellar ataxias (SCA) 1, 2, 3 (also known as Machado-Joseph disease, MJD), 6, and 7, DRPLA, and spinobulbar muscular atrophy (SMA, also known as Kennedy s disease) (Zoghbi and Orr 2000). 

Huntington s disease, an autosomal dominant disorder, has a mean age-of-onset of 43-48 years. Symptoms appear gradually and worsen over a period of about 15 years until death occurs. Mood disturbance, impaired memory, and hyperrefiexia are often the first signs, followed by abnormal gait, chorea (loss of motor control), dystonia, dementia, and dysphagia. Cases of juvenile onset (<10 years old) are more severe and most frequently occur when the defective allele is inherited paternaily. About 25% of cases have late onset, slower progression, and milder symptoms. 

Huntington s chorea is a rare, dominantly inherited, progressive disease characterised by chorea (brief involuntary jerky muscle contractions) and dementia. It has an insidious onset and usually occurs between 30 and 50 years of age. Symptoms include uncontrolled movements, personality disorders, severe depression and anxiety. 

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