IMPORTANCE Parkinson disease is the second most common neurodegenerative disease worldwide. Although no available therapies alter the underlying neurodegenerative process, symptomatic therapies can ...improve patient quality of life. OBJECTIVE To provide an evidence-based review of the initial pharmacological management of the classic motor symptoms of Parkinson disease; describe management of medication-related motor complications (such as motor fluctuations and dyskinesia), and other medication adverse effects (nausea, psychosis, and impulse control disorders and related behaviors); and discuss the management of selected nonmotor symptoms of Parkinson disease, including rapid eye movement sleep behavior disorder, cognitive impairment, depression, orthostatic hypotension, and sialorrhea. EVIDENCE REVIEW References were identified using searches of PubMed between January 1985 and February 2014 for English-language human studies and the full database of the Cochrane Library. The classification of studies by quality (classes I-IV) was assessed using the levels of evidence guidelines from the American Academy of Neurology and the highest-quality data for each topic. RESULTS Although levodopa is the most effective medication available for treating the motor symptoms of Parkinson disease, in certain instances (eg, mild symptoms, tremor as the only or most prominent symptom, aged <60 years) other medications (eg, monoamine oxidase type B inhibitors MAOBIs, amantadine, anticholinergics, β-blockers, or dopamine agonists) may be initiated first to avoid levodopa-related motor complications. Motor fluctuations may be managed by modifying the levodopa dosing regimen or by adding several other medications, such as MAOBIs, catechol-O-methyltransferase inhibitors, or dopamine agonists. Impulse control disorders are typically managed by reducing or withdrawing dopaminergic medication, particularly dopamine agonists. Evidence-based management of some nonmotor symptoms is limited by a paucity of high-quality positive studies. CONCLUSIONS AND RELEVANCE Strong evidence supports using levodopa and dopamine agonists for motor symptoms at all stages of Parkinson disease. Dopamine agonists and drugs that block dopamine metabolism are effective for motor fluctuations and clozapine is effective for hallucinations. Cholinesterase inhibitors may improve symptoms of dementia and antidepressants and pramipexole may improve depression. Evidence supporting other therapies for motor and nonmotor features is less well established.
A drug challenge test in Parkinson’s disease, such as the levodopa challenge test (LCT), is an easy and generally safe procedure, which has been used by clinicians for various indications. The ...results of the test have significant implications in the management of patients, from preoperative evaluation for deep brain stimulation to providing the basis for medication adjustments to address motor or non-motor fluctuations and dyskinesias. This paper reviews the different indications and protocols commonly used in an acute LCT. Potential complications of the procedure and an overview of levodopa responsiveness and unresponsiveness are also discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Levodopa‐induced dyskinesia is a common complication in Parkinson disease. Pathogenic mechanisms include phasic stimulation of dopamine receptors, nonphysiological levodopa‐to‐dopamine conversion in ...serotonergic neurons, hyperactivity of corticostriatal glutamatergic transmission, and overstimulation of nicotinic acetylcholine receptors on dopamine‐releasing axons. Delay in initiating levodopa is no longer recommended, as dyskinesia development is a function of disease duration rather than cumulative levodopa exposure. We review current and in‐development treatments for peak‐dose dyskinesia but suggest that improvements in levodopa delivery alone may reduce its future prevalence. Ann Neurol 2018;84:797–811
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Dystonia and Parkinson's disease are closely linked disorders sharing many pathophysiological overlaps. Dystonia can be seen in 30% or more of the patients suffering with PD and sometimes can precede ...the overt parkinsonism. The response of early dystonia to the introduction of dopamine replacement therapy (levodopa, dopamine agonists) is variable; dystonia commonly occurs in PD patients following levodopa initiation. Similarly, parkinsonism is commonly seen in patients with mutations in various DYT genes including those involved in the dopamine synthesis pathway. Pharmacological blockade of dopamine receptors can cause both tardive dystonia and parkinsonism and these movement disorders syndromes can occur in many other neurodegenerative, genetic, toxic and metabolic diseases. Pallidotomy in the past and currently deep brain stimulation largely involving the GPi are effective treatment options for both dystonia and parkinsonism. However, the physiological mechanisms underlying the response of these two different movement disorder syndromes are poorly understood. Interestingly, DBS for PD can cause dystonia such as blepharospasm and bilateral pallidal DBS for dystonia can result in features of parkinsonism. Advances in our understanding of these responses may provide better explanations for the relationship between dystonia and Parkinson's disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP