What Is Parkinson's Disease?
Parkinson's disease is a fairly common age-related and progressive disease of brain cells (brain disorder) that affect movement, loss of muscle control, and balance. Usually, the first symptoms include a tremor (hand, foot, or leg), also termed a "shaking palsy." It is estimated that approximately one million North Americans suffer from Parkinson’s disease.
Men are about 1.5 times more likely to develop Parkinson's disease than women; however, although the majority of all patients that get the disease are over 60, the total chance of getting the disease is about 2% to 4% in this age group (i.e. over 60). Consequently, the disease is not rare but the chances of someone age 60 or over developing the disease is not high.
Men are about 1.5 times more likely to develop Parkinson's disease than women; however, although the majority of all patients that get the disease are over 60, the total chance of getting the disease is about 2% to 4% in this age group (i.e. over 60). Consequently, the disease is not rare but the chances of someone age 60 or over developing the disease is not high.
Signs and Symptoms
The progression of symptoms in PD may take 20 years or more. In some people, however, the disease progresses much more quickly. PD is a devastating and complex disease that interferes with movement more and more as time goes on. It also produces a wide range of other problems for patients. No one can predict which of these symptoms will affect a particular patient, and the intensity of the symptoms varies from person to person. None of these secondary symptoms is fatal, although swallowing problems can cause choking.
Symptoms of the disease vary somewhat, but they may include problems with swallowing and chewing, speech impairments, urinary problems or constipation, excessive sweating and other skin problems, depression and other emotional changes, and difficulties with sleep. Three key symptoms that develop early in Parkinson's disease are a tremor, usually on one side of the body (hand, foot, arm, or other body part) when the person is at rest. The second symptom is rigidity, or resistance to movement when someone tries to move the person's joint or when the person has difficulty going from a sitting to a standing position. The third symptom is termed bradykinesia, or slowness, and small movements. Bradykinesia is seen in people that have small handwriting (micrographia) and decreased facial expression (the person often only has a somber or serious expression under most circumstances). This condition is termed a "masked face."
Symptoms of the disease vary somewhat, but they may include problems with swallowing and chewing, speech impairments, urinary problems or constipation, excessive sweating and other skin problems, depression and other emotional changes, and difficulties with sleep. Three key symptoms that develop early in Parkinson's disease are a tremor, usually on one side of the body (hand, foot, arm, or other body part) when the person is at rest. The second symptom is rigidity, or resistance to movement when someone tries to move the person's joint or when the person has difficulty going from a sitting to a standing position. The third symptom is termed bradykinesia, or slowness, and small movements. Bradykinesia is seen in people that have small handwriting (micrographia) and decreased facial expression (the person often only has a somber or serious expression under most circumstances). This condition is termed a "masked face."
Pathophysiology of Parkinson's Disease
Humans have approximately 220,000 dopaminergic neurons in the substantia nigra of each hemisphere. This specialized set of neurons sends signals in the form of a neurotransmitter called dopamine. The signals travel to the striatum via long fibers called axons. The activity of this pathway controls normal movements of the body. When neurons in the substantia nigra degenerate, the resulting loss of dopamine causes the nerve cells of the striatum to fire excessively. This makes it impossible for people to control their movements, leading to the primary motor symptoms of PD. Many Parkinson's patients eventually lose 80 percent or more of their dopamine-producing cells.
Unfortunately, the ultimate cause of Parkinson's disease, the reason that the cells in the brainstem become altered and die, is not known but researchers suggest that a combination of both genetic and environmental factors cause about 90% of all Parkinson's disease.
Figure 3. The dopamine containing neurons are in the substantia nigra and appear black in the picture. The upper picture is from a normal brain and the lower from someone with Parkinson's Disease. Note that there is loss of the dopamine neurons in the Parkinson's diseased brain as indicated by the less blackened areas.
The fiber connections of the corpus striatum form the basis for its function. The input is via the nuclei of the neostriatum and the major source is from the cerebral cortex, particularly the frontal lobes. Almost the entire cortex projects to the caudate and putamen (corticostriate projections), although there are differences between the connections of the two nuclei. The primary motor, premotor, supplementary motor and somatosensory areas of cortex project mainly to the putamen whereas the association cortex of the prefrontal and parietal lobes project to the caudate preferentially. Projections from the cortex to the striatum are excitatory mediated by the neurotransmitter Glutamate (Glu).
The neostriatum also receives important afferent projections from the Substantia Nigra. These use the transmitter dopamine and provide post-synaptic inhibition at their site of termination within the striatum. This projection system is important in the genesis of Parkinsonism.
Then, the signal (in a form of GABA) sequentially goes through the external Globus Pallidus, the internal Globus Pallidus, and Thalamus, and reaches motor cortex, from which the processed signals go to the rest of the body.
Parkinson's disease results in loss of dopaminergic innervation to the striatum (and other basal ganglia) and a cascade of subsequent consequences.
The neostriatum also receives important afferent projections from the Substantia Nigra. These use the transmitter dopamine and provide post-synaptic inhibition at their site of termination within the striatum. This projection system is important in the genesis of Parkinsonism.
Then, the signal (in a form of GABA) sequentially goes through the external Globus Pallidus, the internal Globus Pallidus, and Thalamus, and reaches motor cortex, from which the processed signals go to the rest of the body.
Parkinson's disease results in loss of dopaminergic innervation to the striatum (and other basal ganglia) and a cascade of subsequent consequences.
While the neurons' underlying cause of death remains uncertain, researchers have identified several cellular characteristics that are common in this disease and appear to play a role in the neuronal degeneration. Chief among these characteristics is the presence of Lewy bodies (or aggregation of proteins) in neurons of the substantia nigra, the brainstem, and other parts of the brain. Defects that cause increased aggregation of a protein known as alpha-synuclein, or a-synuclein, leads to harmful ring-like or pore-like structures in human membranes. Although the function of alpha-synuclein is not fully understood yet, researches suggest that the protein is involved in maintaining supply of synaptic vesicles in presynaptic terminals. It is hypothesized that the lack of suppy of synaptic vesicles results in the degenaration of the neurons in the Substantia Nigra.
Another cellular characteristic of PD is the presence of Lewy neurites – swollen nerve fibers containing alpha-synuclein and other proteins. The accumulation of alpha-synuclein in these nerve fibers may interfere with transmission of nerve signals or other important neuronal functions.
Another cellular characteristic of PD is the presence of Lewy neurites – swollen nerve fibers containing alpha-synuclein and other proteins. The accumulation of alpha-synuclein in these nerve fibers may interfere with transmission of nerve signals or other important neuronal functions.