Parkinson Disease: Ontario

Miyasaki JM, Shannon K, Voon V, Ravina B, Kleiner-Fisman G, Anderson K, Shulman LM, Gronseth G, Weiner WJ, Anonymous00046. · University of Toronto, Canada. · Neurology. · Pubmed #16606910 No free full text.

Abstract: OBJECTIVE: To make evidence-based treatment recommendations for patients with Parkinson disease (PD) with dementia, depression, and psychosis based on these questions: 1) What tools are effective to screen for depression, psychosis, and dementia in PD? 2) What are effective treatments for depression and psychosis in PD? 3) What are effective treatments for PD dementia or dementia with Lewy bodies (DLB)? METHODS: A nine-member multispecialty committee evaluated available evidence from a structured literature review using MEDLINE, and the Cochrane Database of Health and Psychosocial Instruments from 1966 to 2004. Additional articles were identified by panel members. RESULTS: The Beck Depression Inventory-I, Hamilton Depression Rating Scale, and Montgomery Asberg Depression Rating Scale should be considered to screen for depression in PD (Level B). The Mini-Mental State Examination and the Cambridge Cognitive Examination should be considered to screen for dementia in PD (Level B). Amitriptyline may be considered to treat depression in PD without dementia (Level C). For psychosis in PD, clozapine should be considered (Level B), quetiapine may be considered (Level C), but olanzapine should not be considered (Level B). Donepezil or rivastigmine should be considered for dementia in PD (Level B) and rivastigmine should be considered for DLB (Level B). CONCLUSIONS: Screening tools are available for depression and dementia in patients with PD, but more specific validated tools are needed. There are no widely used, validated tools for psychosis screening in Parkinson disease (PD). Clozapine successfully treats psychosis in PD. Cholinesterase inhibitors are effective treatments for dementia in PD, but improvement is modest and motor side effects may occur.

Irrcher I, Park DS. · Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada. · Sci Signal. · Pubmed #19351953 No free full text.

Abstract: The identification of the molecular mechanisms underlying neuronal survival continues to be the subject of intensive research efforts as the incidence of age-related neurodegenerative diseases rises. Amid a complex mélange of environmental and genetic factors that contribute to disease manifestation, much effort has been dedicated to understanding the underlying signaling mechanisms that regulate neuronal survival. A recent study by Yang et al. sheds new light on an intracellular quality-control system that regulates the constitutive abundance of a neuronal survival factor through chaperone-mediated autophagy and links the deregulation of this pathway to Parkinson's disease. Although the primary function of autophagy in most cell types has commonly been thought to be an adaptive response to starvation, it has been proposed that proper functioning of this system is essential for neuronal survival and that its deregulation leads to neurodegeneration.

Lang AE. · Toronto Western Hospital, University of Toronto, Canada. · Neurology. · Pubmed #19221313 No free full text.

Abstract: The questions of when and how to start treatment for Parkinson disease (PD) remain extremely challenging. A variety of treatment- and patient-related factors must be taken into account when making these decisions. Ideally, neuroprotective therapy would be started at the time of diagnosis. However, no treatment has been unequivocally shown to modify disease progression, and those that have some evidence for this effect all provide confounding symptomatic benefits, which may also be important to supplement faltering compensatory mechanisms within the basal ganglia. Dopamine agonists are clearly associated with a reduction in the incidence of dyskinesias in the early years, but it is not certain that this translates into long-term benefit. In addition, a number of nonmotor side effects are more frequently associated with dopamine agonists than with levodopa. This review will highlight these and other issues that must be considered when deciding on the early treatment of PD.

Brotchie J, Fitzer-Attas C. · Toronto Western Research Institute, University Health Network, Toronto, Canada. · Neurology. · Pubmed #19221312 No free full text.

Abstract: Parkinson disease (PD) is a disorder with a substantive period before the emergence of motor symptoms, during which significant dopaminergic neuronal loss is counterbalanced by endogenous compensatory mechanisms. Many potential compensatory mechanisms have now been proposed; these are both dopaminergic, focused on enhancing effects or exposure to existing dopamine, and nondopaminergic, being focused on reducing activity of the indirect striatal output pathway. Compensatory mechanisms can potentially postpone and reduce the severity of parkinsonian symptoms, and contribute to the benefit provided by a symptomatic therapy, thus offering targets for novel therapeutics. However, enhancement of certain compensatory mechanisms may produce problems when subsequent therapies are initiated, e.g., the development of motor complications with levodopa. Supporting endogenous compensatory mechanisms, to delay or reverse apparent disease progression, is a novel and attractive "disease-modifying" approach to PD. Such actions may contribute to the apparent disease-modifying benefit of initiating early treatment with levodopa or rasagiline, as suggested by the ELLDOPA and TEMPO studies.

Lim SY, Fox SH, Lang AE. · Movement Disorders Centre, Toronto Western Hospital, 399 Bathurst St, Toronto, Ontario M5T 2S8, Canada. · Arch Neurol. · Pubmed #19204152 No free full text.

Abstract: In recent years, there has been increasing recognition of the features of Parkinson disease that are not related to nigrostriatal dopamine deficiency. This review addresses selected clinical, anatomic, pathologic, and biochemical correlates of the early premotor symptoms of Parkinson disease, later nonmotor fluctuations, and advanced dopa-unresponsive motor and nonmotor features. The recognition of early features that predate classic motor symptoms will be important as effective neuroprotective therapy becomes available. Later-stage features often contribute markedly to disability and impaired quality of life and, therefore, represent an important future therapeutic challenge.

Lim SY, Evans AH, Miyasaki JM. · Movement Disorders Centre, Toronto Western Hospital, Toronto, Ontario, Canada. · Ann N Y Acad Sci. · Pubmed #18990123 No free full text.

Abstract: In the past decade, impulse control disorders, punding, and dopamine dysregulation syndrome (which we refer to collectively as disinhibitory psychopathologies) have been increasingly recognized in treated patients with Parkinson's disease. Practicing neurologists must understand these problems to limit potential harm. In this article, we summarize current knowledge regarding these behavioral disorders, including phenomenology, epidemiology, pathophysiology, and treatment.

Merims D, Freedman M. · Division of Neurology and Rotman Research Institute, Baycrest, Toronto. · Int Rev Psychiatry. · Pubmed #18925485 No free full text.

Abstract: Although Parkinson's disease (PD) has been considered to primarily affect motor abilities, increasing emphasis is being placed on cognitive and behavioural impairment in this disorder. Depression, dementia, psychosis and impulse control disorders have a major impact on quality of life for both patients and families. This article reviews cognitive and behavioural disturbances in PD and their relation to affective and motor symptoms, treatment of dementia associated with PD, and treatment approaches to psychosis in PD. We also discuss similarities between the dementia of PD and dementia with Lewy bodies.

Fox SH, Brotchie JM, Lang AE. · Movement Disorders Clinic, Division of Neurology, University of Toronto, Toronto, ON, Canada. · Lancet Neurol. · Pubmed #18848312 No free full text.

Abstract: Non-dopaminergic treatments are increasingly being recognised as part of the therapeutic armamentarium for Parkinson's disease (PD). Clinical and pathological studies have shown that the disease extends beyond the substantia nigra pars compacta and involves various non-dopaminergic neurotransmitter systems that mediate both motor and non-motor symptoms that characterise PD. To date, several therapeutic strategies have been proposed to treat such symptoms. However, despite the significant morbidity associated with these symptoms, particularly non-motor symptoms, research into and drug development for problems such as mood and autonomic dysfunction remain scarce. Here, we review novel non-dopaminergic approaches that are in at least phase II clinical development for the treatment of PD.

Lozano AM, Snyder BJ. · Division of Neurosurgery, Toronto Western Hospital, University of Toronto, UHN, 399 Bathurst Street WW 4-447, Toronto, ON, M5T2S8, Canada. · J Neurol. · Pubmed #18821083 No free full text.

Abstract: The cardinal motor manifestation of Parkinson's disease (PD) is being treated with greater and greater efficacy with both newer medications as well as both subthalamic nucleus (STN) and globus pallidus internus (GPI) deep brain stimulation (DBS). The burden of disease is shifting towards the non-dopaminergic disease manifestations including gait and posture. Based on evidence in the literature and in animal models, recent trials are underway to examine the effects of pedunculopontine nucleus DBS on the treatment of parkinsonian gait disorder. We review the rationale behind this treatment and the status of the current trials.

Fox SH, Lang AE. · Division of Neurology, Toronto Western Hospital, Movement Disorders Clinic, University of Toronto, Toronto, Ontario, Canada. · Mov Disord. · Pubmed #18781677 No free full text.

Abstract: Long term levodopa therapy in Parkinson's disease (PD) results in a range of problems. These include fluctuations in FD symptoms termed motor fluctuations, as well as non-motor symptoms, termed non-motor fluctuations. Here we review the phenomenology and methods of assessing these levodopa-related complications.

Fox SH, Chuang R, Brotchie JM. · Movement Disorders Clinic, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada. · Prog Brain Res. · Pubmed #18772047 No free full text.

Abstract: Long-term treatment for Parkinson's disease (PD) with the dopamine-precursor levodopa (l-DOPA) results in the development of motor fluctuations, including involuntary movements, termed l-DOPA-induced dyskinesia (LID). Currently, effective treatments for LID are limited. The neurodegenerative processes underlying PD result in loss of serotonin (5-HT) input from the dorsal raphe nucleus (DRN) to the striatum, but to a lesser extent than loss of dopamine input. l-DOPA may be converted to dopamine in remaining serotonergic neurons and the non-physiological release of dopamine may lead to abnormal dopamine receptor stimulation in the striatopallidal pathways and result in the generation of LID. Suppressing the activity of these 5-HT inputs to the striatum via presynaptic 5-HT(1A) agonists may reduce LID. However, to date, studies with 5-HT(1A) agonists have suggested a reduction in LID, but with worsening PD disability. Postsynaptic 5-HT(2A) and 5-HT(2C) receptors in the striatum may modulate dopamine to reduce LID and the atypical antipsychotic, clozapine is effective at reducing LID without worsening PD. Alternatively, postsynaptic 5-HT(1A), presynaptic 5-HT(1B/1D) receptors and 5-HT(2C) receptors may modulate GABA and glutamate release within other basal ganglia nuclei to reduce LID. Thus, 5-HT ligands can modulate basal ganglia function and hence motor function through several receptor subtypes and locations, with potential therapeutic benefit to the motor complications induced by long-term l-DOPA therapy in PD. Future studies are needed to develop 5-HT selective drugs that can reduce LID without affecting the anti-parkinsonian action of l-DOPA.

Marras C, Lang A. · Toronto Western Hospital, University Health Network and University of Toronto, Ontario, Canada. · Neurology. · Pubmed #18490620 No free full text.

Abstract: Recent years have seen major changes in our understanding of Parkinson disease (PD), challenging conventional wisdom, much of which was established during the Decade of the Brain. In this article, we highlight important changes in our understanding of PD in six general categories: definition, etiology, pathology, pathogenesis, clinical features, and therapeutics.

Lee FJ, Liu F. · Department of Neuroscience, Centre for Addiction and Mental Health, Clarke Division, Toronto, Ontario, Canada M5T 1R8. · Brain Res Rev. · Pubmed #18313759 No free full text.

Abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by a loss of nigrostriatal dopaminergic neurons. Recently, PD research has been stimulated by the identification of genes that are implicated in rare familial forms of PD. However, despite these discoveries, the primary cause of PD is still unclear. Various pathogenic mechanisms may be involved including mitochondrial dysfunction, proteasomal dysfunction/protein aggregation, oxidative damage, environmental factors and genetic disposition. Furthermore, dopamine has also been implicated in contributing to the pathogenesis of PD. This review will focus on the genes that have been identified to be associated with PD and how they may impair dopamine metabolism. Understanding the role of these PD-related genes in dopamine neurobiology may provide insight into the underpinning pathogenic mechanisms of PD.

Zand R. · The International Institute of Health Studies, Ottawa, Ont., Canada. · Eur Neurol. · Pubmed #18230877 links to  free full text

Abstract: In recent years, improving the quality of life and the level of functioning in Parkinson's disease patients has become the main challenge of all therapeutic protocols for this chronic disease. Hence, identifying comorbid psychiatric conditions is the ambition of many studies in the field. To date, a few research studies have investigated the development of problem gambling as a potential side effect of dopamine agonist medications. However, there are still controversies among experts in the field. Thus far, published reports have been able to neither demonstrate the extent of risk for gambling-related problems nor study the correlation of dosage with this potential adverse effect among Parkinson's disease patients treated with dopaminergic medications. In fact, prospective epidemiologic studies are needed to technically estimate the incidence rate and the relative risk of pathological gambling among patients with Parkinson's disease and to determine the correlation between dosage of these medications and the development of pathological gambling.

Tauskela JS. · National Research Council, Institute for Biological Sciences, Synaptic Pathophysiology Group, Ottawa, ON K1A 0R6, Canada. · IDrugs. · Pubmed #17642004 No free full text.

Abstract: MitoQ is an orally active antioxidant that has the ability to target mitochondrial dysfunction. The agent is currently under development by Antipodean Pharmaceuticals Inc in phase II clinical trials for Parkinson's disease and liver damage associated with HCV infection. MitoQ has demonstrated encouraging preclinical results in numerous studies in isolated mitochondria, cells and tissues undergoing oxidative stress and apoptotic death. MitoQ aims to not only mimic the role of the endogenous mitochondrial antioxidant coenzyme Q10 (CoQ10), but also to augment substantially the antioxidant capacity of CoQ to supraphysiological levels in a mitochondrial membrane potential-dependent manner. MitoQ represents the first foray into the clinic in an attempt to deliver an antioxidant to an intracellular region that is responsible for the formation of increased levels of potentially deleterious reactive oxygen species. Results from the clinical trials with MitoQ will have important repercussions on the relevance of a mitochondrial-targeted approach.

Hodaie M, Neimat JS, Lozano AM. · Division of Neurosurgery, Toronto Western Hospital, University Health Network and University of Toronto, Toronto, Canada. · Neurosurgery. · Pubmed #17228250 No free full text.

Abstract: For several decades, the clinical study of Parkinson's disease has driven an increasingly sophisticated understanding of the dopaminergic system and its complex role in modulating motor behavior. This article reviews salient areas of research in this field, commencing with the molecular biology of the development of the mesencephalic dopaminergic system. We then discuss events thought to be crucial in the cellular and molecular pathology of Parkinson's disease, proposed mechanisms of cell death, and relevant toxin models. These advancements are used as a template to review emerging therapeutic techniques, including neuroprotection strategies, surgical treatment of trophic factors, gene therapy, and neural transplantation.

Bobba RS, Beattie K, Parkinson B, Kumbhare D, Adachi JD. · Division of Rheumatology, McMaster University, Hamilton, Ontario, Canada. · Drug Saf. · Pubmed #17147460 No free full text.

Abstract: Bisphosphonates are the primary pharmacological agents used for the management of osteoporosis and hypercalcaemia of malignant bone disease. The efficacy of these agents in these two conditions has been demonstrated in many well designed trials published over the past 2 decades. The variety of bisphosphonates currently available to us provides a wide range of tolerability and dosing profiles thus necessitating a thorough comparison of the most recent oral and intravenous bisphosphonates to differentiate the clinical context in which they should be used. Despite the fact that bisphosphonates are generally well accepted, their tolerability is dependent on complications which encompass gastrointestinal (GI) and renal toxicity. Other adverse events include osteonecrosis of the jaw, arthralgias, flu-like symptoms and uveitis. Studies have shown that various dosing regimens are able to modulate these rates of toxicity. To maximise tolerability, the direction of future therapy will likely fall into a pattern of decreasing the frequency of administration of bisphosphonates, whether it is oral or intravenous formulations, thus improving patient adherence. To review the literature on different dosing regimens of various bisphosphonates and their associated tolerability, we searched MEDLINE for articles from 1975 to 2006. Oral bisphosphonates, in particular alendronate and risedronate, have been systematically evaluated with regards to GI toxicity. Overall tolerability with these oral formulations has found GI toxicity to be the primary adverse event of interest. Both alendronate and risedronate have been found to have similar rates of GI toxicity when compared with placebo. Mounting evidence has developed validating the use of intravenous ibandronate and zoledronic acid for the purpose of treating hypercalcaemia secondary to malignancy. Unique to all other bisphosphonates, ibandronate also has an oral form which has a similar GI-toxicity profile to placebo. In addition, no significant differences in renal toxicity have been observed between those receiving intravenous ibandronate compared with placebo. Because of its potency and mode of administration, zoledronic acid has been widely accepted for the treatment of hypercalcaemia secondary to malignancy. However, a decrease in renal function, albeit rare, remains a significant complication of zoledronic acid; therefore, regular renal monitoring is recommended.

Moro E, Lang AE. · University of Toronto, Department of Medicine, Movement Disorders Center, 399 Bathurst Street, McL7 402, Canada. · Expert Rev Neurother. · Pubmed #17144783 No free full text.

Abstract: Deep-brain stimulation is currently the most effective surgical treatment for advanced Parkinson's disease. The relevant targets to date are the subthalamic nucleus and the globus pallidus internus, although the thalamus (ventralis intermedius nucleus) is preferred in tremor-dominant, aged Parkinson's disease patients. Long-term benefit in cardinal parkinsonian signs, motor fluctuations and dyskinesia has been reported in 5-year follow-up studies of subthalamic nucleus deep-brain stimulation. However, some psychiatric consequences have raised important issues and emphasized the need for an experienced deep-brain stimulation surgical team. This team should be multidisciplinary and involve movement disorder neurologists, neurosurgeons, neuropsychologists and psychiatrists. The recent observation that deep-brain stimulation of the pedunculopontine nucleus improves axial signs, possibly even in those less responsive to levodopa, brings new hope to the management of advanced Parkinson's disease.

Giacobbe P, Kennedy SH. · University Health Network, 200 Elizabeth Street, EN8-222, Toronto, Ontario M5G 2C4, Canada. · Curr Psychiatry Rep. · Pubmed #17094923 No free full text.

Abstract: Traditionally, the therapeutic approach to treatment-resistant depression (TRD) has relied on pharmacotherapy in various sequences and combinations, in addition to evidence-based psychotherapy or electroconvulsive therapy. Despite refinements to the existing therapeutic modalities, there remains a significant subpopulation of severely ill patients with refractory mood disorders who fail to achieve a clinical response despite aggressive psychosocial and biological treatments. Interest in the use of deep brain stimulation (DBS) for treatment-resistant psychiatric illness has emerged in recent years for a number of reasons: 1) as part of a general re-evaluation of both noninvasive and invasive brain stimulation techniques, 2) because of the demonstrated clinical efficacy of DBS for movement disorders, and 3) as a logical consequence of studies defining the functional neurocircuitry of several psychiatric disorders. This review will examine the progress of DBS in the treatment of Parkinson's disease and the potential implications for its use in TRD, as well as the role of the psychiatrist in selection and ongoing management of patients who receive this procedure.

Hamani C, Neimat J, Lozano AM. · Division of Neurosurgery, University of Toronto, Toronto Western Hospital, Toronto, Canada. · J Neural Transm Suppl. · Pubmed #17017558 No free full text.

Abstract: Approximately 30,000 patients have been treated throughout the world with deep brain stimulation for Parkinson's disease and other conditions. With accumulating experience, there has been an appreciation of the important benefits of this procedure, including the alleviation of disability and improvement in the quality of life. We have also become aware of some limitations of DBS surgery. Among the important issues that remain to be resolved are the timing of surgery, whether early or late in the course of the disease, and the best target for the individual patient, including a reassessment of the relative merits of globus pallidus versus subthalamic nucleus surgery. A better understanding of the symptoms that are resistant to both levodopa therapy and DBS surgery is also required.

Miksys S, Tyndale RF. · Department of Pharmacology, Centre for Addiction and Mental Health, University of Toronto, Ontario, Canada. · J Neural Transm Suppl. · Pubmed #17017527 No free full text.

Abstract: Brain expression of cytochromes P450 2B6, 2D6 and 2E1 is higher in smokers, and is induced by nicotine in animals. These enzymes can metabolize many of the neurotoxins associated with Parkinson's disease. Since smoking is known to be protective against Parkinson's disease, we hypothesise that nicotine-induced elevation of brain CYPs in smokers may contribute to neuroprotection against Parkinson's disease. This supports the therapeutic use of nicotine to delay the progress of this disease.

Crizzle AM, Newhouse IJ. · Department of Public Health, Lakehead University, Thunder Bay, Ontario, Canada. · Clin J Sport Med. · Pubmed #17016120 No free full text.

Abstract: OBJECTIVE: To review existing studies evaluating the effectiveness of physical exercise on mortality, strength, balance, mobility, and activities of daily living (ADL) for sufferers of Parkinson's disease (PD). DATA SOURCES: The following databases were searched (1) Cochrane Database of Systematic Reviews, (2) Cumulative Index to Nursing and Allied Health Literature (CINAHL), (3) PubMed and (4) Medline/NARIC (National Rehabilitation Information Center) using combinations of key words Parkinson's disease and physical exercise. Only articles written in English were included. References cited were also examined. STUDY SELECTION: Studies were eligible if (1) only patients with PD were included in the intervention study (there were many studies that evaluated the benefits of exercise after stroke, cardiac arrest, sports injuries, surgery, and arthritis, but only a few for patients with PD), (2) the intervention included some form of physical or therapeutic exercise, (3) the effects of the physical exercise were evaluated, and (4) the studies were published in a refereed journal. Because few studies were found that dealt with PD patients exclusively, all studies that evaluated the effectiveness of physical exercise for only PD patients were included. Seven studies met our criteria and were selected. Three of the selected studies were randomized controlled studies, 1 was an open trial, and the other 3 relied on patients' own assessments. DATA SYNTHESIS: Outcomes in the studies were measured in terms of physical improvements in patients with PD, such as improved axial rotation, functional reach, flexibility, balance, muscle strength, short-step gait, and mobility. All studies reviewed show that exercise improves overall performance in PD patients. Improvements were measured using standardized tests and other measurement scales. CONCLUSIONS: The results of the present research synthesis support the hypothesis that patients with PD improve their physical performance and activities of daily living through exercise. Future studies should include the development of standardized exercise programs specific for problems associated with PD as well as standardized testing methods for measuring improvements in PD patients. There is also a need for longer term studies (over 1 year) to assess if improvements achieved during the intervention stage are retained long term.

Frank C, Pari G, Rossiter JP. · St Mary's of the Lake Hospital, Kingston, ON. · Can Fam Physician. · Pubmed #16893149 links to  free full text

Abstract: OBJECTIVE: To review the clinical features of Parkinson disease (PD) and other causes of motor parkinsonism with an emphasis on diagnosis in elderly patients. SOURCES OF INFORMATION MEDLINE: and Google Scholar were searched for original research articles describing clinical diagnosis of parkinsonism. Consensus statements and articles summarizing diagnostic criteria for parkinsonian syndromes were also reviewed. Most evidence was levels II or III. MAIN MESSAGE: Diagnosis of PD is made clinically and can be challenging. In older patients, PD can present with general functional decline and nonspecific symptoms. Clinical criteria for diagnosing PD and the TRAP mnemonic can be helpful. A 2-week trial of levodopa-carbidopa treatment can be considered. Specific signs and a minimal response to levodopa treatment suggest other causes of parkinsonism. Clinical features of other causes of parkinsonism are reviewed in the article. CONCLUSION: Parkinsonism and PD are common in older patients. Family physicians should consider parkinsonism in the differential diagnosis of patients who have falls and exhibit general functional decline.

Voon V, Kubu C, Krack P, Houeto JL, Tröster AI. · Department of Psychiatry, Toronto Western Hospital, Toronto, Canada. · Mov Disord. · Pubmed #16810676 No free full text.

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor, cognitive, neuropsychiatric, autonomic, and other nonmotor symptoms. The efficacy of deep brain stimulation (DBS) for the motor symptoms of advanced PD is well established. However, the effects of DBS on the cognitive and neuropsychiatric symptoms are less clear. The neuropsychiatric aspects of DBS for PD have recently been of considerable clinical and pathophysiological interest. As a companion to the preoperative and postoperative sections of the DBS consensus articles, this article reviews the published literature on the cognitive and neuropsychiatric aspects of DBS for PD. The majority of the observed neuropsychiatric symptoms are transient, treatable, and potentially preventable. Outcome studies, methodological issues, pathophysiology, and preoperative and postoperative management of the cognitive and neuropsychiatric aspects and complications of DBS for PD are discussed.

Zadikoff C, Rochon P, Lang A. · Morton and Gloria Shulman Movement Disorders Center, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. · Can J Neurol Sci. · Pubmed #16583718 No free full text.

Abstract: OBJECTIVE: To review the risk of pergolide associated cardiac valvulopathy in patients with Parkinson's disease. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library. Reference lists were reviewed and librarians were consulted to identify additional trials. STUDY SELECTION: All studies and case reports in the English literature on pergolide and cardiac valvulopathy. Data extraction: Demographics of patients, study duration, dose and duration of pergolide use, echocardiogram results, length of follow-up, and clinical outcome. RESULTS: Twenty-two published articles were identified. There were no randomized controlled trials. Follow-up time varied between a few months and four years. Three case reports and four studies (three case control and one observational) assessed 246 patients. Evidence for valvulopathy was found in all studies. Variable methods were used to assess the degree of valvular regurgitation making comparisons between studies difficult. Little clinical correlation is available for echocardiogram results. Variable improvement was shown in the few patients in whom the drug was stopped. There is insufficient data to determine whether dose and duration or other comorbities have an effect on the risk of developing cardiac valvulopathy. CONCLUSION: Pergolide therapy is associated with an increased risk of developing cardiac valvulopathy but the true incidence and importance of this remains unknown. Further prospective studies are needed with standardized assessments of echocardiograms.