Parkinson's disease is a degenerative disorder of the central nervous system, which progresses slowly and is characterized by typical motor deficits, which result from the depletion of the neurotransmitter dopamine. The reason for dopamine depletion is unknown, but it is known to be linked to the death of a very specific group of cells found deep in the brain in an area called the substantia nigra. The characteristic motor deficits of Parkinson's disease include a slowing of physical movement, muscle rigidity, involuntary resting tremor, postural instability and gait distrubances. The disease is due to abnormal functioning of the basal ganglia, structures deep within the brain that control the automatic aspects of movement, precisely and without conscious control.
Normally, basal ganglia neurons release the neurotransmitter dopamine, which is vital to motor control. In Parkinson's disease, either dopamine release or dopamine receptors are compromised.
In the progressive stages of the disease, motor disturbances extend to the control of speech and swallowing. Speech becomes slow and soft, and in severe cases is reduced to little more than a whisper as patients experience difficulties in forcing air through their windpipes (which is necessary in order for them to raise their voices).
An estimated 1-2% of the population suffers from Parkinson's disease, with an estimated 1 million patients in the U.S. alone. In Israel, there is no centralized registry of Parkinsonian patients. Based on estimates of the prevalence of the disease in the general population, there are between 60,000 and 100,000 patients in Israel. The average age of onset of Parkinson's disease is 57-58, and the prevalence of the disease increases with age.
The exact causes of Parkinson's disease are unclear, although a number of genetic factors have been proposed as relevant to the disease. In a small number of patients, poisoning with heavy metals such as manganese has been implicated in the disease. An additional factor that may be implicated in the disease is an impairment of the liver's detoxification ability: exposure of people with compromised detoxification abilities to sulfur-containing compounds increases their risk of harm from neurotoxins. Prolonged exposure of such people to neurotoxins can lead to damage that would eventually manifest as a clinical disease. Additional risk factors include age, as the average age of onset of the disease is 57, and family history of the disease.
Conventional treatments: Various drug therapies are available that act by artificially introducing dopamine into the body, and these can ease the symptoms of the disease. However, these treatments produce various side effects, such as nausea (especially at the beginning of treatment), involuntary movements, confusion or hallucinations caused by an overdose. Another type of drug, of which Seligiline is an example, can slow the progression of the disease if it is taken during early stages of the disease. Still another type of drug, of which Amantadine is an example, stimulates the release of dopamine from neurons, but may cause confusion. Drugs such as Bromocriptine replace dopamine by releasing a substance that mimics its activity. The greatest challenge of drug therapy is in finding the proper balance. A Parkinsonian patient who does not take enough medication may have trouble moving. On the other hand, an overdose may lead to unwanted movements. Moreover, the body's reaction time to the drugs is variable, which makes it difficult to determine the right dosage. Additionally, as the disease progresses, the drugs become less and less effective. Another drug, Azilect, has demonstrated the potential to slow the progression of the disease.
Deep brain stimulation (DBS) - a surgical intervention that involves electrical stimulation of a deep brain area called the subthalamic nucleus - is considered to have good prospects, but is only suitable for about 10% of patients, and it does not cure the disease, but only improves motor symptoms. Naturally, this procedure also entails all the risks inherent in brain surgery. A number of TMS studies have shown beneficial effects on the motor symptoms of the disease.
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