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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