This message and the next five contain Bill Johnson's paper which he
volunteered to let us read. Bill is a graduate student and has obviously
gone to a great deal of effort to write this. Thanks, Bill
Barb
PARKINSON'S DISEASE
DIRECTED INDEPENDENT STUDY
AND SENIOR SEMINAR
by
Christopher William Johnson
University of North Florida
March, 1994
Clinical Features of Parkinson's Disease
The Role of MPTP in Research
Neuroanatomy of the Extrapyramidal System
Mesostriatal Circuitry
Pathology
Dopamine Reception and Regulation
Theories of Dopaminergic Neuronal Loss
Current Therapy References
Parkinson's disease is a neurological disorder
in which the neurotransmitter dopamine is depleted in
certain regions of the brain's extrapyramidal system,
presumably due to characteristic dopaminergic neuronal
degeneration. The cause of dopaminergic neuronal
degeneration is unknown (hence the term, idiopathic
Parkinson's disease) but many etiological hypotheses are
currently being researched. Parkinson's disease-like
symptoms have been induced by many environmental and
infectious sources. The various Parkinson's disease-like
disorders are all referred to as idiopathic parkinsonism.
Between 600,000 and 1,000,000 people throughout
the world have Parkinson's disease. The average age for
onset of the first clinical symptoms is 57.3 three years.
However, approximately 5% of Parkinson's disease patients
develop symptoms before the age of 40.
There is a wide variety of clinical
manifestations of Parkinson's disease. Some of these
symptoms can be attributed to pathological abnormalities
in the extrapyramidal system but many have unknown
pathogeneses. Because the cause of neuronal degeneration
is unknown, current drug therapy seeks to alleviate
clinical symptoms rather than reverse the pathological
abnormalities of Parkinson's disease.
In 1817 James Parkinson published a study on
the "shaking palsy," which he also referred to as
paralysis agitans, in which he described many of the
clinical abnormalities associated with the disease. For
140 years little progress was made in the study of
Parkinson's disease, until in 1957 Carlsson observed
similarities between parkinsonian symptoms and the side
effects of chronic treatment with reserpine, a known
monoamine depleting drug (Yurek and Sladek 1990). This
discovery prompted research into the functions of
monoamine neurotransmitters in parkinsonian and
asymptomatic subjects. In 1960 Ehringer and Hornykiewicz
observed that concentrations of striatal dopamine were
depleted in parkinsonian patients (Yurek and Sladek
1990).
The hallmark of idiopathic parkinsonism,
according to Yurek and Sladek (1990) is "severe reduction
of dopamine in all compartments of the basal ganglia."
They suggest two types of parkinsonism based on the
domination of particular clinical observations. One is
characterized by bradykinesia, postural instability, and
gait difficulties. The other is dominated by tremor.
Though most patients fall into one of these categories,
pathological differences between the two categories
remain unclear.
Parkinsonism is grouped into six Hoehn-Yahr
stages depending on the progression of the disease: (1)
stage 0- asymptomatic, (2) stage I- unilateral
involvement, (3) stage II- bilateral symptoms with
bilateral impairment, (4) stage III- bilateral symptoms
with some postural instabilities, (5) stage IV- severe
disability but able to walk or stand unassisted, and (6)
stage V- wheelchair-bound or bedridden unless aided
(Hoehn and Yahr 1967).
W. Poewe et al. (1990) studied premorbid social
and psychological factors of parkinsonian patients (those
with essential tremor) and controls. They found that
many parkinsonian patients share similar behavioral
characteristics. Seventy-five percent were pedantics,
seventy-one percent were workaholics, and forty-nine
percent were depressed. They also found that sixty-six
percent were nonsmokers but a study conducted by L. L.
Golbe (1990) suggests that the connection is due to the
parkinsonian patients' nonsmoking personality rather than
protective effects of tobacco. Studies by Poewe et al.
(1990) found that parents of dizygotic twins usually
noted that in early life the parkinsonian sibling tended
to be the follower, less confident, and more
self-controlled. Studies on age vulnerability have
produced conflicting results.
