Most physicians and lay people are not aware of PD's true impact: and do not realize that more people suffer from it than multiple sclerosis, muscular dystrophy and amyotrophic lateral sclerosis (Lou Gehrig's Disease) combined. Few diseases have remained so anonymous while affecting so many people.
There are several reasons for this lack of recognition:
Parkinson s Disease is a chronic illness. Currently, there are no specific tests for PD, though there are several methods of evaluating its presence. A diagnosis is based on a neurological examination, which includes evaluation of symptoms--and their severity. If the symptoms are significant, a trial test of antiparkinsonian drugs (primarily levodopa) may be used to further diagnose the presence of the disease. If the patient fails to benefit from levodopa, the diagnosis of Parkinson's Disease should be questioned. Computed tomography (CT) or magnetic resonance imaging (MRI) scans of the brain may be helpful in ruling out other diseases whose symptoms resemble PD.
Secondary symptoms of Parkinson's Disease may include: depression, senility, postural deformity, and difficulty in speaking. There are some other neurological disorders which may have both primary and secondary parkinsonian symptoms. When this occurs, the condition may be referred to as Parkinson's Syndrome, or Atypical Parkinson's. For example, parkinsonian symptoms can be caused by tumors in the brain, repeated head trauma, prolonged use of tranquilizing drugs, such as the phenothiazines (Thorazine), butyrophenones (Haldol) and reserpine; and with manganese and carbon monoxide poisoning. Even the commonly used drug, metaclopramide (Reglan), for stomach upset can cause parkinsonism.
In addition, many people who had minor illnesses during the epidemic developed PD many years later These patients were erroneously diagnosed as having post-encephalitic PD.
Recently, parkinsonian symptoms developed in several young people after they used an illegal drug (abbreviated MPTP) related to the narcotic pain killer, meperidine (Demerol). MPTP damaged the extra pyramidal nervous system. It is thought that the parkinsonian brain might, under certain circumstances, produce a substance similar to MPTP. This substance might in turn, damage the extra pyramidal nervous system resulting in PD. Knowledge of how MPTP causes parkinsonian symptoms will lead to a better understanding of PD.
Researchers have made significant progress in understanding what actually occurs in the brain of a parkinsonian patient. To visualize this process, picture the brain as the body's communications system. It receives stimuli from the sense organs and, in return, sends messages to various parts of the body. These messages transmit instruction which govern specific bodily functions. If, in any way, there is an interference in this transmittal process, then, like a damaged communications system, some breakdown occurs.
PD is associated predominantly with two areas of the brain: the substantia nigra and the striatum (the caudate nucleus and putamen). The substantia nigra (meaning "black substance") derives its name from its many pigmented cells. These cells contain neuromelanin, a pigment that resembles melanin (the pigment found in skin).
In PD, many of the cells of the substantia nigra, and a few cells in the striatum are damaged. These damaged cells may contain pink staining spheres called Lewy bodies. The Lewy body is a marker for PD. Why the Lewy body appears, and how it is involved in damaging cells is not known.
Paralleling the degree of cell loss in the substantia nigra is a loss of dopamine in the striatum. Loss of approximately 80 percent of the substantia nigra's pigmented cells and 80 percent of the striatum's dopamine content result in the appearance of the PD symptoms.
Initially, the brain may adjust to the loss of these cells in the substantia nigra through an increase in the activity of the remaining pigmented cells: or through an increase in the sensitivity of the cells in the striatum to the actions of dopamine. Additional amounts of dopamine may also be made by other cells in the striatum, cells which do not produce dopamine under ordinary conditions. Some of the compensatory mechanisms may delay the appearance of PD symptoms: however, eventually these mechanisms fail-and the symptoms appear.
The pigmented cells in the substantia nigra connect with at least two different kinds of receptors for dopamine in the striatum. One kind of receptor (called D1 ) is found on a subset of cells in the striatum. The other kind of receptor (D2) is found on another subset of cells in the striatum on elongated projections of cells that have their main bodies in the cortex (the highest part of the brain) and send out fibers which pass through the striatum. There are also dopamine receptors (D3) on the processes of the cells of the substantia nigra. Some antiparkinsonian drugs stimulate one of the three receptors, and some stimulate all three receptors. The role of each of the receptors is now being studied.
An important chemical transmitter, acetylcholine, is also found in the striatum. The content of acetylcholine is normal in patients with PD. However, in order for the striatum to function, a balance between dopamine and acetylcholine is necessary. As a result of PD's dopamine deficiency, the dopamine/acetylcholine balance is disturbed. The disturbance further aggravates the symptoms of the disease. The use of drugs (anticholinergics) which block the actions of acetylcholine, as well as drugs (levodopa) which increase dopamine, partially restores the balance.
In PD there may also be a deficiency of another chemical transmitter, norepinephrine, which is found mainly in two regions of the brain. These two regions (the locus ceruleous and the lateral tegmental area) are involved in governing the involuntary autonomic nervous system. The norepinephrine deficiency may be responsible for some of the secondary symptoms of PD. There are also decreases in other chemical transmitters, such as serotonin and gamma amino butyric acid (GABA). These deficiencies may contribute to some of the secondary symptoms.