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Algorithm For The Management Of Parkinson's Disease 10

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Table 2. Causes of excessive daytime sleepiness associated with Parkinson's disease

Drug-induced

Levodopa

Anxiotytics

Antidepressants

Selegiline-induced insomnia

Primary sleep disorder

Obstructive sleep apnea

Restless leg syndrome

Periodic limb movements of sleep REM behavior disorder

Endocrine dysfunction (eg hypoparathyroidism)

Circadian cycle disruption with dementia PD, lack of zeitgebers

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Dementia. Disruption of normal circadia rhythms occurs with the dementia of PD when patients lose the normal environmental an temporal clues, or "zeitgebers" about time passage.[156] This problem is common in nursing homes and other institutional settings. In all patients, sleep hygiene should be reviewed. For some, restoration of consistent schedules (eg lights out, meals, medication times, exposure to sunlight) is adequate for normalizing circadian cycles.

Idiopathic. Nighttime insomnia should be corrected if possible. Other primary sleep disorders, such as obstructive sleep apnea[157] or narcolepsy should be evaluated with appropriate PSG and mean sleep latency testing studies. Treatment with methylphenidate, 5 to 10 mg one to two times daily, or selegiline, 5 mg at morning and noon, can be beneficial. Occasionally, caffeine (as coffee or tablets, 100 to 200 mg per day) produces increased alertness. Hypothyroidism and other metabolic causes for excessive daytime sleepiness should he investigated.

Nightmares. Nightmares can be induced by medications, a precursor of dementia, or idiopathic (breakout 25). Medication induced. Dopaminergic medications frequently induce vivid dreams. In fact, patients with PD often note a return of previously absent dreaming shortly after initiation of carbidopa-levodopa therapy. It is only after several years of treatment, with higher dosages of levodopa, that vivid dreams become problematic, Simple reductions in nighttime dopaminergic drugs should alleviate the nightmares, Elimination or reduction of tricyclic medications also can be beneficial. A distinction between vivid dreams and RBD may be important in certain patients, Manifestations of the former are reported by the patient, whereas complaints relating to RBD typically are voiced by the bed partner.

Dementia. Increasing nightmares are harbingers of cognitive impairment and possible daytime drug-induced psychosis. If optimal motor function can only be obtained with dopaminergic dosages that produce psychosis, treatment with low-dose clozapine may produce a striking benefit.[158,159] This drug is associated with a 1 to 2% risk of neutropenia (and death from overwhelming infection), Therefore, weekly monitoring of the white blood count is mandatory.[160] The dosage of clozapine is much lower than that used for schizophrenia. Typically, 12.5 mg is prescribed nightly. The maximum dose is 75 mg nightly but most patients do quite well in the 12.5- to 25-mg range. Some patients require treatment only three to four nights per week, The most common side effects associated with clozapine are lethargy and hypotension, with the former most often seen in patients with frank dementia. Alternative antipsychotics can be employed. Those with the least specific D2 receptor blockade produce less exacerbation of parkinsonism. Molindone, 5 to 25 mg nightly, or thioridazine, 10 to 50 mg nightly has been used for many years to this end, Little experience has been gained with the recently released drug risperidone.

Idiopathic. If aggressive behavior or wandering occurs during sleep PSG may confirm RBD and appropriate treatment can be started, If RBD is not present on PSG, then reduction of dopaminergic medications is often necessary.

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.[161] 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 (breakout 26). Medication-related. RLS seems distinct from akathisia, which is most often related to underdosage or "wearing off" of the levodopa effect.[162] 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.[163] 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).[161] 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. [164] However, the specific neuronal systems involved have yet to be determined.[165] 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 studies. Treatment with methylphenidate or selegiline can be beneficial. Occasionally caffeine produces increased alertness.

REFERENCES

1. Duvoisin, RC. Parkinson's disease: a guide for patient and family. 3rd ed. NY: Raven Press, 1991.

2. Lieberman A. An integrated approach to patient management in Parkinson's disease. Neurol Clin 1992;10:553-556.

3. Diamond SG, Markham CH, Hoehn MM. Effect of age at onset on progression and mortality in Parkinson's disease. Neurology 1989;39:1167-1190.

4. Hoehn MM. The natural history of Parkinson's disease in the pre-levodopa post-levodopa eras. Neurol Clin 1992;1O(suppl 2): 331-339.

5. Lesser RP, Fahn S,, Snider SR. Analysis of the clinical problems in parkinsonism and complications of long-term levodopa therapy. Neurology 1979;29:1253-1260.

6. Markham CH, Diamond SG. Evidence to support early levodopa therapy in Parkinson's disease. Neurology 1981;31:125-131.

7. Rajput AN,Rozdilsky B, Rajput A. Levodopa efficacy and pathological basis of parkinson syndrome. Clin Neuropharmacol 1990;11:553-558.

8. Koller WC. How accurately can Parkinson's disease be diagnosed? Neurology l992;42:(suppl 1):6-16.

9. Stacy M, Jankovic J. Differential diagnosis of Parkinson's disease and the Parkinsonism Plus Syndrome. Neurol Clin 1992;10(suppl 2): 341-359.

10. The Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1989;321:1364-1371.

11. The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1993;328:176-183.

12. Mayeaux R, Chen J, Mirabello E. et al. An estimate of the incidence of dementia in idiopathic Parkinson's disease. Neurology 1990;40: 1513-1517.

13. Biggins CA, Boyd JL, Harrop FA, et al. A controlled, longitudinal study of dementia in Parkinson's disease. J Neurol Neurosurg Psychiatry 1992;55:566-571.

14. Koller WC. Disturbance of recent memory function in Parkinson's disease. Cortex 1984;20:307-311.

15. Pate DS, Margolin DI. Cognitive slowing in Parkinson's and Alzheimer's patients: distinguishing bradyphrenia from dementia. Neurology 1994;44:639-674.

16 Birkmayer W. Knoll J, Riederer P. Improvement of life expectancy due to l-deprenyl in Parkinson's disease; a long-term study. J Neurol Transm 1985;65: 113-127.

17. Heikkila RE. Manzino L, Cabbat FS. Protection against the dopaminergic neurotoxicity of 1-methyl-4-phenyl.1,2,3,6- tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311;467-469.

18. Olanow CW, Calne D. Does selegiline monotherapy in Parkinson's disease act by symptomatic or protective mechanisms? Neurology 1992;42(suppl 4):13-26.

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