Huntington s chorea

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)...

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. 

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. 

In Huntington s chorea, tetrabenazine is used to control movement disorders. It probably causes a depletion of nerve endings of dopamine. However, it has a useful action in only a proportion of patients and its use may be limited by the development of depression, a symptom that may already be present due to the underlying disease itself. 

A great many physical and mental disorders develop because of a malfunction in the nervous system. Some examples are Alzheimer s disease, schizophrenia, Parkinson s disease, Huntington s chorea, and bipolar disorder. Most of the effects produced by recreational drugs, such as alcohol, heroin, and cocaine, are also a result of changes in the way the nervous system functions. Today, scientists have a reasonably good understanding of the way in which the nervous system operates and how many types of chemicals affect this operation. 

Substance P 11 Levels of substance P are reduced in Huntington s chorea ... 

Stance P in the substantia nigra are markedly reduced in the neurological disease Huntington s chorea. 

Unlabeled Uses Treatment of Huntington s chorea, nausea or vomiting associated with cancer chemotherapy... 

Haloperidol Blockade of D2 receptors >> 5HT2A receptors Some a blockade, but minimal M receptor blockade and much less sedation than the phenothiazines Schizophrenia (alleviates positive symptoms), bipolar disorder (manic phase), Huntington s chorea, Tourette s syndrome Oral and parenteral forms with metabolism-dependent elimination Toxicity Extrapyramidal dysfunction is major adverse effect... 

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