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DYSKINESIAS Dyskinesias can be drug or disease-related. If they include a prominent component of chorea, medications are implicated. If they are exclusively dystonic, this could either be caused by a disease-related condition or secondary to medications. Thus, dyskinesias an more appropriately addressed by separating them into those that are choreiform/choreodystonic vs those that are exclusively dystonic. Choreiform /choredystonic. Chorea in the context of PD is invariably related to medications, Frequently, a prominent dystonic component is seen in conjunction with the chorea; hence the term, "choreodystonic." These choreodystonic dyskinesias occur in two patterns. The most common form is seen at the time of peak levodopa effect. This has been termed "peak-dose dyskinesia" (or I-D-I response, a shorthand for "improvement-dyskinesia-improvement"). The first and most obvious approach to this problem is to modestly lower the individual uses of carbidopa-levodopa (eg, 25-mg decrements). Unfortunately, many patients have a very narrow therapeutic window, and even a small levodopa decrement can result in transition from a dyskinetic state to a relative "off" state. In this circumstance, one may consider adding or increasing a dopamine agonist medication (bromocriptine or pergolide), which allows a slightly tighter titration of the response. Patients who swing dramatically from severe dyskinesia and who have a short-duration response to the "off" state may find liquid carbidopa-levodopa to be a better option, with benefits and drawbacks as described above. Choreodystonic dyskinesias are also seen in a second distinct pattern, in which these adventitious movements occur just at the beginning and again at the end of the levodopa response cycle. This has been termed "diphasic dyskinesia" or D-I-D response, a shorthand for "dyskinesia-improvement-dyskinesia"). This pattern is much less common than peak-dose dyskinesia and is often difficult to diagnose because the pattern may not he obvious, either to the patient or the clinician, The end-of-dose period of dyskinesias is typically more prolonged and troublesome than the initial dyskinetic period of the levodopa cycle. Although this D-I-D pattern can be very difficult to treat, it may respond to simple measures if the dyskinesias are relatively mild. First, more frequent dosing of carbidopa-levodopa may allow a more continuous "on" state without periodically cycling through the dyskinetic phases. Obviously the timing of the doses should he based on the carbidopa-levodopa response duration. In a similar strategy to the one for treating "wearing-off" problems, a sustained-release formulation of carbidopa-levodopa may be substituted for the standard formulation. The addition of dopamine agonist therapy close titration, using liquid carbidopa-levodopa, may be options for some patients. Finally, subcutaneous apomorphine may provide a route of escape from the dyskinetic phase. The use of subcutaneous apomorphine (as described before) allows time for the next dose of carbidopa-levodopa to become clinically effective. Occasional patients experience severe choreodystonic dyskinesias with a diphasic pattern, this can be very difficult to treat effectively. The initial descriptions of this clinical pattern documented the failure of carbidopa- levodopa dosages administered at short intervals around the clock to effectively treat this problem. Although several carbidopa-levodopa doses at short intervals can successfully defer the end-of-dose dyskinetic period, this strategy fails after approximately tour to five overlapping doses. At this point, patients typically begin to experience a sense of drug intoxication and, furthermore, note a decreasing threshold for dyskinesias with an inability to suppress them, despite even larger doses of carbidopa-levodopa. For the diphasic dyskinesia pattern to become obvious, the levodopa dose must be adequate; too low a dose will simply result in dyskinesias, whereas a higher dose allows the full pattern to develop. The usual dosages of carbidopa-levodopa used to treat conventional parkinsonian motor problems are adequate for demonstration of the diphasic dyskinesia pattern (ie, 100 to 250 mg of levodopa). Typically, it is the end-of-dose dyskinetic period rather than the initial dyskinetic phase that is the more troublesome and sustained. It tends to occur at a fairly well-defined portion of the levodopa response cycle, usually 2 to 8 hours after a single dose of carbidopa-levodopa. One treatment strategy is to overlap four to five doses of carbidopa-levodopa at intervals that are just long enough to preclude the development of the dyskinetic phase at the end of each dosage cycle. After the last dose, however, patients will cycle through the dyskinetic phase but at a relatively predictable time. Thus, they can arrange to be at home - and perhaps self administer a mild, short-acting tranquilizer such as alprazolam - during the time the dyskinetic period is expected. Once they have cycled through this dyskinetic period, patients typically experience adequate control of their parkinsonian motor symptoms for the remainder of the day, although control is not quite as good as during the time of peak levodopa response. This control typically continues overnight and into the next morning. If left untreated, patients usually start to experience increasing motor manifestations of parkinsonism by mid to late morning, at which time they can again restart their levodopa cycle, taking four to five overlapping doses. Thus, with this strategy patients can attain good control of their parkinsonian symptoms for several midday hours and adequate control during other portions of the day, once they have cycled through their last dyskinetic period. An alternative strategy for treating the severe diphasic choreodystonic dyskinesias is to switch the patient to dopamine agonist monotherapy (bromocriptine or pergolide). The transition can be difficult, as the dopamine agonist must be slowly introduced and the carbidopa-levodopa dosages concomitantly decreased. Eventually, as patients make the transition to bromocriptine or pergolide alone, they often will find that their parkinsonism is not as well controlled as with carbidopa-levodopa. The dyskinetic periods may be absent or substantially reduced in severity, however. To be effective, the bromocriptine or pergolide doses usually need to be higher than those employed when these drugs are used as adjunctive therapy with carbidopa-levodopa. For monotherapy, the usual range is 30 to 60 mg of bromocriptine or 3.0 to 6.0 mg of pergolide as monotherapy. Exacerbated by anxiety. Regardless of the type or pattern, choreodystonic dyskinesias can be unmasked or worsened by anxiety- provoking situations. If this is a frequent problem for the patient, intervention directed at neuropsychiatric issues may be appropriate. Dystonic movements. Dystonia in the absence of chorea is common in PD and can be caused by the disease process, per se, rather than a medication effect. Dystonia is commonly related to drug action, however. Prototypic is the isolated dystonic deviation of the toes or cramping of the legs that occasionally occurs in undertreated patients. Often, this will occur with other signs of undertreated parkinsonism. In this case, the usual strategies for improving PD motor control are appropriate. In certain patients, painful dystonia of the lower extremities is particularly a problem upon awakening in the morning (early morning foot dystonia), before the initial morning dose of carbidopa-levodopa can take effect. One option is to administer a dose of CR carbidopa-levodopa at bedtime. The effects may not be sufficiently long-lasting to carry the patient to the following morning, however. Administration of a dose of carbidopa-levodopa in the early morning, before the patient is scheduled to rise from bed, can be effective but requires the patient to set an alarm to awaken. The addition of bromocriptine or pergolide, with their longer-lasting effects, also may prove beneficial, particularly if one of the doses is administered at bedtime. Some patients experience painful or uncomfortable dystonia at the end of their levodopa response cycle. Several options are available, as described in the section "Optimal peak response but "wearing off." This is also one circumstance, apart from tremor, in which an anticholinergic drug may be helpful. Lithium may be helpful for painful "off"-period dystonia and can be tried when all other methods have failed. Botulinum toxin injection can be used to treat sustained focal dystonias of the foot. In some patients dystonia may be secondary to their medications. If it is present at the time of peak levodopa effect, a reduction in the individual doses of carbidopa-levodopa should result in resolution. If it occurs during the "off" period as a "wearing-off" phenomenon, strategies can be employed to increase "on" time (see the section "Optimal response but wearing off"). RESTLESS LEG SYNDROME AND PERIODIC LIMB MOVEMENTS OF SLEEP This primary sleep disorder has such high prevalence in the PD population that all clinicians should be aware of its varied manifestations. Restless leg syndrome (RLS) consists of uncomfortable sensations in the legs (eg parasthesias, aches cramping, and an overwhelming need to move or walk). Symptoms are at the worst in the evening or when the patient attempts to rest, and they transiently improve while the patient is walking, stretching, or exercising. RLS can be related to medications being taken, a symptom of PD itself, or idiopathic. Medication-related. RLS seems distinct from akathisia, which is most often related to underdosage or "wearing off" of the levodopa effect. If akathisia is suspected, then adjustment of antiparkinsonian medications is appropriate. Simply increasing carbidopa-levodopa doses at bedtime (the CR forms are particularly useful) maybe beneficial. It remains unclear whether or not PD- related leg restlessness should be considered idiopathic RLS. Clozapine has been reported to reduce akathisia. Differential diagnosis also should include nocturnal dyskinesia. This may be reduced by lowering bedtime doses of dopaminergic medications. Idiopathic. Approximately 50% of patients with RLS have associated periodic limb movements of sleep (PLMS). Termed "nocturnal myoclonus" in the past-perhaps inappropriately-this syndrome can be so mild as to be detectable only with PSG or so severe that it forces bed partners to sleep in separate rooms. The movements resemble fragments of the triple flexion or Babinski reflex. They last 0.5 to 6 seconds and occur every 20 to 40 seconds. These movements can profoundly disrupt normal sleep architecture and produce insomnia and excessive daytime sleepiness. The dramatic response to levodopa and dopaminometic medications implies reduced dopamine activity in the brain or spiral cord. However, the specific neuronal systems involved have yet to be determined. Regardless, it is clear that patient symptoms worsen with insufficient carbidopa-levodopa treatment and are relieved with increased medication. In particular, sustained-release carbidopa-levodopa can effectively halt RLS symptoms and markedly reduce PLMS. Unfortunately, overflow of RLS symptoms into the daytime is often a problem with levodopa therapy and requires additional doses during the waking hours. A long-acting dopamine agonist, such as pergolide, is an effective alternative in many patients. Other treatment options include low-dose clonazepam or opiates (eg, codeine, 30 to 60 mg nightly). Tricyclic agents may exacerbate RLS and PLMS. For nocturnal symptoms, direct attention to any Parkinson's disease symptoms or motor fluctuation. One of the long-acting levodopa preparations at bedtime may be an appropriate. Alternatively dopamine agonists may be employed. If dyskinesias interfere with normal sleep, bedtime dopaminergic dosages should be decreased. If insomnia is medication-induced and patients are taking selegiline twice daily, the second dose should be given no later than noon. If this is already the practice, consider elimination of the second dose or discontinuation of the drug altogether. Patients with insomnia should be questioned about possible depression and, if indicated, a treatment program initiated. The most simple form of daytime sleepiness to address is medication-induced. Use of anxiolytics or other sedating agents should be minimized during the day. Patients with moderate to advanced stages of Parkinson's disease may describe an overwhelming urge to sleep as a dose of levodopa takes effect. This effect can occasionally be reduced by switching from a CR to a short-acting form of carbidopa-levodopa during the daytime. Disruption of normal circadian rhythms occurs with the dementia of Parkinson's disease when patients lose the normal environmental and temporal clues about time passage. For some, restoration of consistent schedules is adequate for normalizing circadian cycles. Nighttime insomnia should be corrected if possible. Other primary sleep disorders should he evaluated with appropriate polysomnongraphy and mean sleep latency testing studies. Treatment with methylphenidate or selegiline can be beneficial. Occasionally caffeine produces increased alertness. janet [log in to unmask]