The new definition and diagnostic criteria of Parkinson's disease
2016; Elsevier BV; Volume: 15; Issue: 6 Linguagem: Inglês
10.1016/s1474-4422(16)00116-2
ISSN1474-4465
AutoresRonald B. Postuma, Daniela Berg, Charles H. Adler, Bastiaan R. Bloem, Piu Chan, Günther Deuschl, Thomas Gasser, Christopher G. Goetz, Glenda M. Halliday, Lawrence Joseph, Anthony E. Lang, Inga Liepelt‐Scarfone, Irene Litvan, Kenneth Marek, Wolfgang H. Oertel, C. Warren Olanow, Werner Poewe, Matthew Stern,
Tópico(s)Autism Spectrum Disorder Research
ResumoWe thank The Lancet Neurology for highlighting the changes in Parkinson's disease diagnosis given in the new International Parkinson Disease and Movement Disorder Society diagnostic criteria.1The Lancet NeurologyBuilding on 50 years of levodopa therapy.Lancet Neurol. 2016; 15: 1Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar The criteria were created in response to the huge advances in our understanding of Parkinson's disease over the past 20 years, especially the identification of α-synuclein, advances in genetics, recognition of non-motor Parkinson's disease, and the realisation that prodromal stages exist. The Movement Disorder Society recognised that these advances challenge the fundamental definition of Parkinson's disease and created a task force to examine potential changes to the Parkinson's disease definition,1The Lancet NeurologyBuilding on 50 years of levodopa therapy.Lancet Neurol. 2016; 15: 1Summary Full Text Full Text PDF PubMed Scopus (7) Google Scholar develop revised diagnostic criteria,2Postuma RB Berg D Stern M et al.MDS Clinical Diagnostic Criteria for Parkinson's Disease.Mov Disord. 2015; 30: 1591-1601Crossref PubMed Scopus (2918) Google Scholar and develop research criteria for prodromal Parkinson's disease.3Berg D Postuma RB Adler CH et al.MDS Research Criteria for Prodromal Parkinson's Disease.Mov Disord. 2015; 30: 1600-1611Crossref PubMed Scopus (751) Google Scholar The final task force reports were recently published.2Postuma RB Berg D Stern M et al.MDS Clinical Diagnostic Criteria for Parkinson's Disease.Mov Disord. 2015; 30: 1591-1601Crossref PubMed Scopus (2918) Google Scholar, 3Berg D Postuma RB Adler CH et al.MDS Research Criteria for Prodromal Parkinson's Disease.Mov Disord. 2015; 30: 1600-1611Crossref PubMed Scopus (751) Google Scholar But, what has changed and what remains the same? Several key definition decisions were made.4Berg D Postuma RB Bloem B et al.Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson's disease.Mov Disord. 2014; 29: 454-462Crossref PubMed Scopus (311) Google Scholar Parkinson's disease was defined as a synucleinopathy. Despite numerous challenges (rare genetic forms without synuclein deposition, synuclein deposition possibly occurring later than other changes, or inability to document deposition during life), synuclein deposition remains the main final arbiter of diagnosis. However, an exception category was created to include genetic cases (parkin, LRRK-2, etc) that meet clinical Parkinson's disease criteria but have no synuclein deposition on autopsy. Dementia was removed as an exclusion criterion for Parkinson's disease, even if it is the first presenting symptom. Just as many non-motor features of Parkinson's disease might start before motor signs emerge, dementia might also manifest before motor onset. Patients diagnosed with dementia with Lewy bodies should be considered as also having Parkinson's disease if they meet the Movement Disorder Society Parkinson's disease criteria. The task force recognised that Parkinson's disease is highly variable, and therefore should potentially be classified into subtypes. However, we felt that there was still insufficient information to formally delineate a specific subtype classification. Parkinson's disease was, however, divided on the basis of stage of disease into clinical Parkinson's disease (with motor parkinsonism), prodromal Parkinson's disease (motor or non-motor symptoms are present but clinical Parkinson's disease criteria has not yet been met), and preclinical Parkinson's disease (neurodegeneration present, but asymptomatic). The new diagnostic criteria for Parkinson's disease have been published, and constitute the first Parkinson's disease diagnostic criteria of the Movement Disorder Society. Their goal was to help standardise clinical research (entry into clinical trials, etc) and to aid bedside diagnosis. Because there is not yet a reliable objective test for Parkinson's disease, expert opinion still remains the gold standard. So, the clinical criteria were designed to mimic and codify the process of an expert clinician. Several unique features bear special mention.2Postuma RB Berg D Stern M et al.MDS Clinical Diagnostic Criteria for Parkinson's Disease.Mov Disord. 2015; 30: 1591-1601Crossref PubMed Scopus (2918) Google Scholar Parkinsonism remains defined as bradykinesia plus rigidity and rest tremor or both. However, postural instability is not a core feature of parkinsonism due to Parkinson's disease (because if present early, it suggests alternate causes). Also, unlike parkinsonism in general, to diagnose bradykinesia due to Parkinson's disease, some decrement in speed or amplitude is also required. Similarly to previous criteria, the Movement Disorder Society criteria combine positive features (supportive criteria) and negative features. However, good clinicians do not only check boxes; rather, they weigh the diagnostic strength of various atypical signs. Therefore, negative features were divided into absolute exclusions (which rule out probable Parkinson's disease) and red flags (which rule out probable Parkinson's disease if numerous or unopposed by supportive features). The criteria permit some flexibility, allowing individual criteria to be interpreted in the context of the whole patient, for example low-dose quetiapine does not merit exclusion for probable drug-induced parkinsonism. Timing was also incorporated because some features argue against Parkinson's disease when present in early Parkinson's disease, but are common in advanced Parkinson's disease. Finally, to account for the long prodromal stage of Parkinson's disease and to set the stage for earlier intervention in the future, the first ever Movement Disorder Society research criteria for prodromal Parkinson's disease were proposed.3Berg D Postuma RB Adler CH et al.MDS Research Criteria for Prodromal Parkinson's Disease.Mov Disord. 2015; 30: 1600-1611Crossref PubMed Scopus (751) Google Scholar The criteria's approach is unique because it uses statistical methods (the Bayesian naive classifier) to estimate the likelihood that a patient has prodromal Parkinson's disease. The Bayesian model has already been used for numerous analyses of different health-related outcomes. However, to our knowledge, use of a mathematical formula to calculate probability of disease has never been incorporated into diagnostic criteria for neurological diseases. The criteria involve three steps: 1The probability of having prodromal Parkinson's disease is estimated based on age (ie, the prior probability).2Diagnostic information is obtained on as many variables as possible. These can include environmental risk variables (eg, sex, smoking, caffeine use), genetic risk variables (from family history or results of genetic testing), prodromal symptoms and signs (eg, constipation, hyposmia, motor testing), or biomarker testing (eg, dopaminergic imaging). The diagnostic strength of each variable is expressed as a likelihood ratio; positive tests have a likelihood ratio of more than 1, and negative tests have a likelihood ratio of less than 1. If information is unavailable, borderline, or uncertain, the likelihood ratio is simply not applied for that test (likelihood ratio=1).3Once all information is collected, all likelihood ratios are multiplied by each other. The total likelihood ratio is then compared with the threshold required to give more than an 80% probability of having prodromal Parkinson's disease (this ranges from likelihood ratio 95–1000, depending on age). If this threshold is met, probable prodromal Parkinson's disease is diagnosed. Why use this method? The essential difficulty frequently encountered when trying to predict disease likelihood is the radical differences in diagnostic accuracy of the various markers. Specificity ranges from 75–80% (depression, constipation) to 99·7% (polysomnogram-proven random eye movement sleep behaviour disorder). The Bayesian naive classifier allows systematic weighting of different diagnostic values. This approach also has the notable advantage of being evidence-based; only markers shown to predict Parkinson's disease in prospective studies with measurable diagnostic accuracy are included. Finally, the field of prodromal Parkinson's disease is still in its relative infancy; the method provides a scaffold upon which results of new diagnostic tests for prodromal Parkinson's disease can be continually added. Because the field of Parkinson's disease is constantly evolving, diagnostic methods need to be constantly updated. The first official Movement Disorder Society clinical criteria provide a framework for a common global clinical diagnostic workup. The research criteria for prodromal Parkinson's disease will allow the systematic diagnosis of this so far prediagnostic phase. Both criteria will no doubt change as future knowledge grows. DB received funds for consultancy/speaking from UCB pharma, Teva, Novartis, and Lundbeck; and grants from the Michael J Fox Foundation, Janssen Pharmaceuticals, the German Parkinsons' disease Association, Parkinson Fonds Deutschland, Teva, and the European Union. RBP received grants from the Fonds de la Recherche en Sante Quebec, the Canadian Institute of Health Research, the Parkinson Society of Canada, the Weston-Garfield Foundation, the Michael J Fox foundation, and the Webster Foundation; funding for consultancy from Biotie and Roche; and speaker fees from Novartis Canada and Teva Neurosciences. CHA has received research funding from Phytopharm, Avid Radiopharmaceuticals, the Michael J Fox Foundation, the National Institutes of Health, US Department of Defense, and the Arizona Biomedical Research Foundation; and consulting fees from Abbvie, Acadia, Allergan, Impax, Ipsen, Lily, Lundbeck, Merz, Novartis, Teva, and Xenoport. BRB received grant funding from the Netherlands Organization for Scientific Research, Prinses Beatrix Foundation, Stichting Parkinson Fonds, Michael J Fox Foundation, Parkinson Vereniging, and the National Parkinson Foundation; and consultancy/speaker fees from Danone, Zambon, Abbvie, and Teva. PC received grant support from the Ministry of Science and Technology of China. CGG received funds for consultancy from Acadia (Deborah Wood Associates), AstraZeneca, Avanir, Boston Scientific, Ceregene, Clearview, Health Advances, Chelsea Pharmaceuticals (Link Medical Communications), ICON Pricespective LLC, Med-IQ Educational Services, Neurocrine, Pfizer, Pricespective, Teva, and WPP Group Kantor Health LLC; royalties from Oxford University Press, Elsevier Publishers, Wolters Kluwer Health-Lippincott, and Wilkins and Wilkins; grant support from National Institutes of Health, Michael J Fox Foundation, and the Movement Disorders Society; travel support from Ceregene; and is a board member for Acadia and AstraZeneca. CGG directs the Rush Parkinson's Disease Research Center that receives support from the Parkinson's Disease Foundation; he directs the translation programme for the Movement Disorder Society Unified Parkinson's Disease Rating Scale and the Unified Dyskinesia Rating Scale and receives funds from the International Parkinson and Movement Disorder Society for this effort. GH has stock ownership in Cochlear and NIB Holdings; has received consultancy funds from the National Health and Research Council, has received royalties from Academic press, Elsevier, and Oxford University Press; and has grants from National Health and Research Council, Michael J Fox Foundation, Shake-it-Up Australia, Parkinson's NSW, and University of New South Wales. AEL received consultancy from Novartis, Teva, Abbott, Allon Therapeutics, Avanir Pharmaceuticals, Merck, Medtronic, AbbVie, Biogen Idec, Boehringer Ingelheim, NeuroPhage Pharmaceuticals, Centogene, Ceregene; expert testimony regarding welding rods; has grants/grants pending with Canadian Institutes of Health Research, Michael J Fox Foundation, National Parkinson Foundation, Brain Canada, W Garfield Weston Foundation, Parkinson Society Canada, Tourette Syndrome Association, Edmond J Safra Philanthropic Foundation, and Ontario Brain Institute; and has royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press. IL has served on advisory boards for Pfizer, Teva Neuroscience, Merz pharmaceuticals, Northera, Bristol-Myers Squibb, and has been a consultant for UCB pharma; she has received grants the National Institute of Health, the Parkinson Study Group, the Michael J Fox Foundation, CBD solutions-CurePSP, Teva Pharmaceuticals, and AVID Pharmaceuticals. KM received consultancy from Molecular Imaging, Pfizer, GE Healthcare, Merck, Lilly, Bristol-Myers Squibb, Piramal, Prothena, Roche, Oxford Biomedica, Lysosomal Therapeutic. WO is Senior Research Professor of the Charitable Hertie Foundation, Frankfurt/Main Germany. CWO received consultancy from Abbvie, Lilly/Medtronic, LUndbeck, Newron, Novartis, Teva, and Zambon, and owns stock in Clintrex, and has grant support from the Michael J Fox Foundation, the National Space Board Research Institute, and Zambon. WP received personal fees from Abbvie, Allergan, Astra Zeneca, BIAL Pharamaceuticals, Boehringer-Ingelheim, Boston Scientific, GlaxoSmithKline, Ipsen, Lundbeck, Medtronic, MSD Pharmaceuticals, Merck-Serono, Merz, Novartis, Orion Pharma, Teva, University California Berkeley, and Zambon; and received royalties from Wiley Blackwell, Oxford University Press, and Cambridge University Press. MS received consultancy fees from Teva, Merz, Adamas, and Civitas; stock/stock options from Civitas and Adamas; and travel expenses from the International Parkinson and Movement Disorder Society. GD and LJ declare no competing interests. TGasser and IL-S declare no competing interests. Building on 50 years of levodopa therapyAs the movement disorder community enters the 50th anniversary since Birkmayer and Hornykiewicz first documented the clinical benefit of levodopa in patients with Parkinson's disease, it reflects on the advances in the treatment of the disease from the past half century and looks ahead to the developments that are likely to have a substantial effect on the specialty. Full-Text PDF
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