EXTERNAL MOVEMENT PROBLEMS                                 1

BRADYKINESIA-Greek for "slow movement":        In PD, it's not a
mere habit that can be overcome by attention, but true inability
to move at normal speed. Research has found, it's not due to
caution or timidity in the PWP, but a basic deficit in control.
Curiously, visual guidance cues do play a part, and sometimes
when they are present, bradykinesia momentarily vanishes. It
doesn't, however, respond well to the usual PD therapy.

Slowness:                              Bradykinesia is one of
the "classic triad" of prominent motor symptoms in PD. As a
rule of thumb, two out of the three justifies a hasty (but tentative)
diagnosis of PD. A remarkable feature of the brain
is its adaptability in case of trouble. When a normal pathway
for neural signals is impaired, the brain automatically seeks
out or creates an alternate, or "detour" pathway. This "detour"
is likely to be longer, and therefore slower, than the primary path. Any
therapy which tends to restore the primary path
function will probably reduce the bradykinesia.

Poverty Of Motion:                   By this is meant the loss
of normal animation that continually changes position of body,
limbs, or facial expression, conscious or otherwise. The patient
may be perfectly attentive and alert, but tends to sit
motionless until some purposeful movement is intended. A most common
feature is failure or inability to swing the arms when walking. Trying
to hide that by conscious effort fails, because
the opposing motion is hard to learn.

EXTERNAL MOVEMENT PROBLEMS (cont.)                         2

RIGIDITY:           Generally results when muscles cannot attain
their normal relaxed state. Muscles only pull, not push, and the
arrangement for skeletal motion usually involves two or more in
opposition. When both directions are tensed, a fixed resistance
develops. When only one direction is affected, the result will
be something like curled toes, clawed hand, or flexed elbow.
Disabling, drug-resistant rigidity and/or dyskinesia may as a
last resort be treated by surgery, where a few cubic mm deep in
the brain are either destroyed, or stimulated by an implanted
electrode. The site of choice is not the substantia nigra, where
failure of dopamine production is thought to cause PD, but a
part of the globus pallidus, where imbalance of signal feedback
is a more immediate cause of PD symptoms.

Persistent Tension:                           In extreme cases,
the patient may become "stiff as a board" and unable to move.
More commonly, one or more skeletal muscles remain tensed, due
to failure of the "feedback" signal to relax. The biceps muscle, for
example, may feel firm to the touch, while the triceps
feels loose and floppy. The neurologist will extend or flex the
patient's elbow to look for "cogwheel" rigidity, which is the
product of muscle tension with a superimposed tremor.

Blank Expression:                       PWP are noted for blank
facial expression and fixed stare. Expression of emotion such
as pleasure or anger may require conscious attention.

Stooped Posture:                    Many illustrations show the
PWP leaning forward with stooped shoulders and bent knees. I
suspect this is a habit arising from imbalance of calf muscle
strength that causes more weight to be borne on the toes.
Frequent conscious reminders to straighten knees, force head
and shoulders back, may be helpful.

SELECTIVE WEAKNESS:         The PWP will notice as the disease
progresses that habitual acts requiring some strength, such
as climbing a stair, opening a jar, etc. become difficult.
This is due not to loss of muscle itself but to a deficit in
its control system, and is little affected by therapy. Doctors
always advise more exercise, to maintain strength as long as
possiblle. Semi-autonomous functions such as breathing are
affected as well as voluntary ones, and a common cause of
mortality that follows late-stage PD is either suffocation
or pneumonia from inhaled food or liquid.

Swallowing Weakness:                        The swallowing act
requires coordination of several muscles that are partly under
reflex (autonomous) control. PWP must be more careful than
others to avoid trying to swallow while talking, and to pause between
mouthfuls, despite inability to eat as fast as table companions.
Late-stage PWP may lose ability to swallow
altogether.

Limb Weakness:                  The arm, wrist, hand, or leg
opposite to the side with most pronounced tremor may become
weaker, making it harder, for example, to open twist-tops.

EXTERNAL MOVEMENT PROBLEMS (cont.)                         3

TREMOR:       A rhythmic reciprocating motion which may or may
not be noticed, or voluntarily suppressed, by the PWP. All
tremors result from failure of the feedback loop, that is, imbalance or
mis-timing between a signal that tells a muscle
to act and the corresponding signal that tells it when to stop.
In engineering terms, the system oscillates. Some PWP report
internal tremors in various parts of the body. Tremor is one
of the 3 cardinal symptoms of PD, evidently arising from a
defect in supply or employment of dopamine. It often abates
or disappears under therapy, either medicinal or surgical.
Tremor of a different kind also appears in dyskinesia, to be
discussed later, resulting from an excess of dopamine. When
disabling tremor is of primary concern and does not respond
to drug therapy, surgery is a last resort. Since tremor seems
to originate in the thalamus, or more precisely the subthalamic
nucleus, that is the site of choice for the electrode, either
for ablation (destruction) or for chronic deep-brain
stimulation.

Resting Tremor:    Of the 3 named kinds, resting tremor was once
considered exclusive to PD. It appears most often as a 5-7 hz torsional
vibration of a hand when hanging loosely, or of a
foot when relaxed, and is easily suppressed when it is noticed
by the patient. The tremor of dyskinesia, discussed elsewhere,
is not subject to such voluntary control. Resting tremor usually appears
as the current dose of levodopa or other medicine wears off, and
disappears as the new dose takes effect.

Intention Tremor:             This is the tremor of muscle under
load, as when holding a parcel or when the neurologist tells
you to "make a fist". It once was thought to distinguish PD
from the less-well-understood Essential Tremor, because it
is suppressed (briefly) by alcohol or the antitremor drugs
primidone and propranolol, while resting tremor is not.

Action Tremor:             This is the tremor that occurs during
movement, as when drawing or writing. A common and easy test of tremor
prominence at a given moment is to draw, with either hand,
a circular closely-spaced spiral. Tremor prominence is affected
by stress, fatigue, or the status of medication.

Dyskinesic Tremor:           This kind of tremor may be forcible,
and is akin to other involuntary motion caused by too much free dopamine
following immediately after a medication dose. Likewise, it is
unaffected by alcohol, but susbsides as the medication
wears off.

EXTERNAL MOVEMENT PROBLEMS (cont.)                         4

FLUCTUATIONS:         Motor fluctuations are drastic, sometimes
sudden, changes in mobility, rigidity, tremor, energy, and
symptoms such as dyskinesia. They are all related to the level
or the availability in the brain of dopamine, one of numerous
so-called neurotransmitter chemicals that are made and used by nerve
cells to transmit signals between themselves. Dopamine is
the dominant neurotransmitter whose deficiency results in PD,
and all drugs for PD are designed to increase either the supply or the
efficient use of dopamine. In the simplest terms, insufficient dopamine
leads to the immobilizing symptoms of PD, and an excess leads to
unwanted, involuntary movement. In a healthy system, the
level of dopamine is regulated by several elegant mechanisms. When
dopamine is deficient, as in PD, the problem of drug medication is to
keep between the bounds of too much or too little.

PEAK-DOSE EFFECTS:              A few decades ago, dopamine and
another neurotransmitter, acetylcholine, were thought normally
to be in a kind of balance, where dopamine enabled movement and
acetylcholine inhibited it. Since dopamine cannot pass from the blood
into the brain directly, therapists tried to restore
balance the other way, by limiting acetylcholine via so-called
anticholinergic drugs. Anticholinergics are still used, but
since the discovery that levodopa can enter the brain and then convert
to dopamine, not so popular anymore. The main problem
with dopamine and levodopa is that they both dissipate, or
convert to non-useful forms, rather quickly. I think of the dopamine
supply in the brain as having two parts: A long-term "baseline" level
which in PD declines gradually, until it is
insufficient to prevent the motor symptoms, and a "therapeutic" amount
added by any of several means, that declines according
to an exponential law. The latter is just a mathematical way of stating
that the rate of decline is proportional to the level
at any moment. So the time to sink from 100% to 50% is the same
as from 50% to 25%, and so on. This "half-life" for the
therapeutic dopamine is only from a half-hour to an hour or so.
Therefore, maintaining the desired level between an upper limit, where
dyskinesia appears, and the lower limit, where symptoms of
under-medicated PD appear, requires frequent dosage in small amounts,
just enough to raise the total level from the lower
limit to the upper one. Those limits are unchanged by progress
of the disease, but as the "baseline" level diminishes, an increasing
proportion of "supplemental" medication is needed.
Since the "supplemental" portion, in my theory, declines faster when it
is greater, it must be taken at ever shorter intervals
to keep the total available dopamine level within the desired
range. PWP cope with this problem by dividing the daily
medication into small doses taken every 4, 3, or even 2 hours.
At some point it becomes more convenient to mix the Sinemet with a
liquid such as orange juice, that can be sipped continually as needed.
Beyond that, it is possible to implant a tube through the
abdominal wall into the stomach, with a timed electric pump to ensure
continual infusion. Much work is done at present to
develop agonist drugs that prolong the half-life of dopamine, or
a skin patch that avoids the peaks and valleys of intermittent supply.

EXTERNAL MOVEMENT PROBLEMS (cont.)                         5

Dyskinesia:              Greek for "false motion" which appears
when the most recent dose of levodopa begins to take effect,
and the resulting concentration of dopamine is at a maximum.
It usually is an involuntary writhing motion of the arms, head, neck and
shoulders, and gradually subsides as the medication
wears off. Not necessarily disabling, it must still be disconcerting to
the patient and to onlookers. Dyskinesia may
be caused by a dopamine agonist alone, but the general term is
still "levodopa-induced dyskinesia". In theory, dyskinesia and
inherent PD symptoms such as dystonia don't occur together.

Drug-Induced Tremor:                    This is another form of
dyskinesia, quite different from the gentle tremor of untreated
PD. The dyskinetic tremor may be quite forcible pounding of a
hand or foot, possibly hard enough to be injurious.

END-OF-DOSE EFFECTS:          Dopamine that appears in the brain
as a product of levodopa medication somehow substitutes for the
dopamine emitted by individual nerve cells as they pass their
signals along. But free dopamine quickly breaks down to other
compounds, so it needs continual replenishment. Before the
discovery of levodopa therapy, PD patients generally became
completely catatonic and helpless, even while wide awake. As
the therapeutic dopamine declines, the patient approaches that
state. Needless to say, the clearest indication of an end-of-
dose effect is that it vanishes quickly after the next dose.

Wearing-Off:             The popular term for signs telling the
PWP or caregiver that time for another dose is approaching.
Besides a general loss of "ambition" or energy, the resting
tremor reappears, and (usually in bed) painful muscle cramps
announce that the autonomous feedback control is gone.

On-Off:             In more advanced PD, a troubling feature of
levodopa medication it that its effect doesn't wear off slowly,
but disappears suddenly and unpredictably, seeming to some
PWP like switching off a lamp. Those patients develop a clear
sense of "off" and "on" periods, which is used in clinical
research to evaluate various forms of therapy.

Dystonia (Cramp):               When a muscle gets an unlimited
signal to contract, not balanced by a corresponding signal to
stop or relax, it may become very painful. People without PD
may develop a "charley horse" in a leg muscle whose control
has been degraded by unaccustomed exertion, or disabling low
back pain caused by a "pinched nerve". In PD, one or more
such cramps may appear without warning anywhere, regardless of
any recent strain or abuse. Massage is ineffective, since
the muscle is getting an improper or unbalanced signal from the brain.
Dystonia of PD responds quickly (within minutes) to
levodopa medication, and there is a clinically recognized
condition of levodopa-responsive dystonia in the absence of PD.

Lethargy:                   An insidious feature of wearing-off,
especially if a schedule for medication at night is not strictly
followed. It may be tempting at those times to go back to sleep,
ignoring the future penalty for skipping or delaying a dose.
During daytime, however, many PWP find an afternoon nap to be
pleasant and beneficial.

Cheers,
Joe
--
J. R. Bruman   (818) 789-3694
3527 Cody Road
Sherman Oaks, CA 91403-5013