406
UNIT THREE
Surgery can alleviate Parkinson’s symptoms.
Fox underwent thalamotomy, in which an elec-
trode caused a lesion in his thalamus that calmed
violent shaking in his left arm. Another surgical
procedure, pallidotomy, causes lesions in the glo-
bus pallidus internus, a part of the basal nuclei,
and the approach is also used on an area poste-
rior to the thalamus. Deep brain implants of elec-
trodes may also control some symptoms.
Researchers are turning to cells in a patient’s
own body as sources of the dopamine needed in
PD. For example, cells at the back of the eye called
retinal pigment epithelium can be cultured with
biochemicals that stimulate them to produce
dopamine or levodopa. Researchers hope that
cells can be sampled from the patient without
impairing vision and implanted in the substantia
nigra. Neural stem and progenitor cells may also
be useful. Implants of fetal dopamine-producing
cells performed in the late 1990s had unexpected
ects—by 2008, a few patients had died, and the
implants showed signs of PD. Still, the implants alle-
viated symptoms in some patients for several years.
PD may have several causes. Symptoms have
been attributed to use of certain designer drugs,
exposure to pesticides, and frequent violent
blows to the head (²
g. 11D). Several genes may
increase risk of developing PD, but in most cases
it is not inherited. One gene that causes PD when
mutant encodes a protein called alpha-synuclein.
The abnormal protein folds improperly, forming
deposits in the brain (fig. 11E). Understanding
how the disease occurs in rare familial forms may
provide clues to helping the many others who
have this debilitating and common illness.
In PD, neurons in an area of the brainstem
called the substantia nigra degenerate.
Substantia
nigra
means “large black area,” for the dark pig-
ment that the neurons release as a by-product
of synthesizing the neurotransmitter dopamine.
When these neurons degenerate, less dopamine
reaches synapses with neurons in the striatum of
the basal nuclei. The decrease in dopamine causes
the motor symptoms of PD. Some patients also
develop nonmotor symptoms, including depres-
sion, dementia, constipation, incontinence, sleep
problems, and orthostatic hypotension (dizziness
upon standing).
So far, no treatments can cure or slow the
course of PD, but replacing or enhancing use of
dopamine can temporarily alleviate symptoms.
The standard treatment for many years has been
levodopa, a precursor to dopamine that can cross
the blood-brain barrier. Once in the brain, levo-
dopa is converted to dopamine. Levodopa provides
temporary relief from the twitching and rigidity.
Drug treatment for PD becomes less effec-
tive over time. By a feedback mechanism the
brain senses the external supply of dopamine and
decreases its own production, so that eventually
higher doses of levodopa are needed to achieve
the effect. Taking too much levodopa leads to
another condition, tardive dyskinesia, that pro-
duces uncontrollable facial tics and spastic exten-
sions of the limbs. Tardive dyskinesia may result
from effects of
excess dopamine
in brain areas other
than those a±
ected
in PD.
A
ctor Michael J. Fox was in his late twen-
ties when his wife, Tracy Pollan, noticed
the first sign of Parkinson disease
(PD)—he leaned when walking. When a finger
began twitching, Fox consulted a physician,
and so began the journey that would lead to his
diagnosis with the neurological disorder. Of the
approximately six million people worldwide who
know that they have PD, only 10% develop symp-
toms before the age of 40. Michael J. Fox was one
of them.
Fox kept his diagnosis private, but by the
late 1990s, his co-workers began to notice symp-
toms that emerged when medication wore o±
rigidity, a shu³
ing and o±
-balance gait, and poor
small motor control. It was difficult to ignore
Fox’s expressionless, masklike face, a character-
istic of PD called hypomimia. Fox had difficulty
communicating; it took a huge e±
ort to speak, a
symptom called hypophia. Even though his brain
could string thoughts into coherent sentences,
the muscles of his jaw, lips, and tongue could
not utter them. Oddest of all was micrographia,
the tendency of his handwriting to become
extremely small. PD also causes the sensation of
not being able to stay in one spot.
In 1998 Fox publicly disclosed his condi-
tion. In 2000, he founded the Michael J. Fox
Foundation for Parkinson’s Research, and contin-
ues to act occasionally in television programs.
11.5
CLINICAL APPLICATION
Parkinson Disease
FIGURE 11E
The chemical composition of Lewy bodies,
characteristic of the brains of people with Parkinson disease, may
provide clues to the cause of the condition. Lewy bodies include
alpha-synuclein, cytoskeletal elements, and other components.
FIGURE 11D
Professional boxers are at higher risk of developing
Parkinson disease (PD) from repeated blows to the head. Muhammed Ali
has PD from many years of head injuries. Michael J. Fox, an actor, not a
boxer, ²
rst experienced symptoms of PD at age 29, which is unusual.
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