Journal Article•
Validation of the MDS Clinical Diagnostic Criteria for Parkinson’s Disease (S3.001)
10 Apr 2018-Neurology (Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology)-Vol. 90
TL;DR: In this article, the International Parkinson Disease and Movement Disorders society (MDS) diagnostic criteria against a gold-standard expert clinical diagnosis and to compare concordance/accuracy of the MDS criteria to 1988 United Kingdom brain bank criteria were calculated.
Abstract: Objective: To validate the International Parkinson Disease and Movement Disorders society (MDS) diagnostic criteria against a gold-standard expert clinical diagnosis and to compare concordance/accuracy of the MDS criteria to 1988 United Kingdom brain bank criteria. Background: In 2015, the MDS published the new clinical diagnostic criteria for Parkinson’s disease (PD). These criteria aimed to codify/reproduce the expert clinical diagnostic process, to help standardize diagnosis in research and clinical settings. Their accuracy compared to expert clinical diagnosis has not been tested. Design/Methods: From 8 centers, we recruited 626 patients with parkinsonism (434 with PD and 192 with other causes, diagnosed by an expert treating physician). A second, less experienced neurologist evaluated the presence/absence of each individual item from the diagnostic criteria. The overall accuracy/concordance rate, sensitivity, and specificity of diagnostic criteria were calculated. Results: Of 434 patients diagnosed with PD, 94.5% met MDS criteria for probable PD (i.e. a 5.5% false-negative rate). Of 192 non-PD patients, 88.5% were identified as non-PD by the criteria (i.e. a 11.5% false-positive rate). The overall accuracy for probable PD was 92.6%. For the clinically-established PD category, 59.3% of PD patients and only 1.6% of non-PD patients met MDS criteria. Compared to MDS probable PD criteria, the UK brain bank criteria had significantly lower sensitivity (89.2%, p=0.008), specificity (79.2%, p=0.018), and overall accuracy (86.4%, p Conclusions: The MDS criteria demonstrated high sensitivity and specificity compared to gold-standard expert diagnosis. To meet the unmet gap of specific diagnostic criteria for early PD, we suggest additional ‘Clinically-Established Early PD’ criteria to be used for clinical trials of early PD. Study Supported by: Michael J. Fox Foundation Disclosure: Dr. Postuma has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biotie, Roche/Prothena, Teva Neurosciences, Jazz Pharmaceuticals, Novartis Canada, Theranexus, GE HealthCare, . Dr. Poewe has nothing to disclose. Dr. Litvan has received personal compensation for serving onthe scientific steering committee of the Biotie/Parkinson Study Group clinical trial Dr. Lewis has nothing to disclose. Dr. Lang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Acorda, Avanir Pharmaceuticals, Biogen, Bristol Myers Squibb, Sun Pharma, Cipla, Intekrin, Merck, Medichem, Medtronic, Teva, UCB, and Sunovion, . Dr. Halliday has nothing to disclose. Dr. Goetz has nothing to disclose. Dr. Chan has nothing to disclose. Dr. Slow has nothing to disclose. Dr. Seppi has nothing to disclose. Dr. Schaeffer has nothing to disclose. Dr. Berg has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with UCB Pharma GmbH, Lundbeck, Prexton Therapeutics, GE-Healthcare. Dr. Rios Romenets has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NIA, Genentech/Roche. Dr. Rios Romenets has received research support from NIA, Genentech/Roche. Dr. Mi has nothing to disclose. Dr. Maetzler has nothing to disclose. Dr. Li has nothing to disclose. Dr. Heim has nothing to disclose. Dr. Bledsoe has nothing to disclose.
Citations
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Journal Article•
TL;DR: The International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease as discussed by the authors have been proposed for clinical diagnosis, which are intended for use in clinical research, but may also be used to guide clinical diagnosis.
Abstract: Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.
1,655 citations
TL;DR: Parkinson's disease is evolving from a clinical to a biomarker-supported diagnostic entity, for which earlier identification is possible, different subtypes with diverse prognosis are recognised, and novel disease-modifying treatments are in development.
Abstract: Parkinson's disease is the second most common neurodegenerative disease and its prevalence has been projected to double over the next 30 years. An accurate diagnosis of Parkinson's disease remains challenging and the characterisation of the earliest stages of the disease is ongoing. Recent developments over the past 5 years include the validation of clinical diagnostic criteria, the introduction and testing of research criteria for prodromal Parkinson's disease, and the identification of genetic subtypes and a growing number of genetic variants associated with risk of Parkinson's disease. Substantial progress has been made in the development of diagnostic biomarkers, and genetic and imaging tests are already part of routine protocols in clinical practice, while novel tissue and fluid markers are under investigation. Parkinson's disease is evolving from a clinical to a biomarker-supported diagnostic entity, for which earlier identification is possible, different subtypes with diverse prognosis are recognised, and novel disease-modifying treatments are in development.
262 citations
TL;DR: Clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism are reviewed and the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing are demonstrated.
Abstract: Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson's disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes.
97 citations
University of Kiel1, Mayo Clinic2, Radboud University Nijmegen3, Capital Medical University4, Rush University Medical Center5, University of New South Wales6, Toronto Western Hospital7, University of Sydney8, German Center for Neurodegenerative Diseases9, University of California, San Diego10, University of Navarra11, University of Marburg12, Icahn School of Medicine at Mount Sinai13, Innsbruck Medical University14, Montreal General Hospital15, University of Pennsylvania16, University of California, San Francisco17
TL;DR: A clinical diagnostic criteria for Parkinson's disease (PD) is published and one unmet need is for highly specific criteria for clinical trials in early/de novo PD.
Abstract: Author(s): Berg, Daniela; Adler, Charles H; Bloem, Bastiaan R; Chan, Piu; Gasser, Thomas; Goetz, Christopher G; Halliday, Glenda; Lang, Anthony E; Lewis, Simon; Li, Yuan; Liepelt-Scarfone, Inga; Litvan, Irene; Marek, Kenneth; Maetzler, Corina; Mi, Taomian; Obeso, Jose; Oertel, Wolfgang; Olanow, C Warren; Poewe, Werner; Rios-Romenets, Silvia; Schaffer, Eva; Seppi, Klaus; Heim, Beatrice; Slow, Elizabeth; Stern, Matthew; Bledsoe, Ian O; Deuschl, Gunther; Postuma, Ronald B | Abstract: BACKGROUND:In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD. OBJECTIVES:The objective of this study was to generate and test a PD diagnostic criteria termed "clinically established early PD." METHODS:We modified the Movement Disorder Society criteria to increase specificity for early PD by removing all disease duration components and changing red flags to absolute exclusions. We then estimated the sensitivity/specificity of clinically established early PD criteria in patients with disease duration l5 years, selected from a 626-patient validation study. RESULTS:After documentation of parkinsonism, 18 individual exclusion criteria are assessed that preclude the diagnosis of "clinically established early PD." Among 212 PD and 152 non-PD patients, the estimated specificity was 95.4%, with 69.8% sensitivity. CONCLUSIONS:We describe high-specificity criteria for de novo PD, which are freely available for use in clinical trials. © 2018 International Parkinson and Movement Disorder Society.
89 citations
TL;DR: This study compared the accuracy and specificity of the new criteria for the diagnosis of PSP with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times.
Abstract: Background In 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times. Methods Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cutoff. Results A total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes. Conclusion The International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society.
83 citations
References
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9,528 citations
TL;DR: The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported, and these observations call into question current concepts of Parkinson's Disease as a single distinct morbid entity.
Abstract: Few detailed clinico-pathological correlations of Parkinson's disease have been published. The pathological findings in 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic Parkinson's disease are reported. Seventy six had nigral Lewy bodies, and in all of these Lewy bodies were also found in the cerebral cortex. In 24 cases without Lewy bodies, diagnoses included progressive supranuclear palsy, multiple system atrophy, Alzheimer's disease, Alzheimer-type pathology, and basal ganglia vascular disease. The retrospective application of recommended diagnostic criteria improved the diagnostic accuracy to 82%. These observations call into question current concepts of Parkinson's disease as a single distinct morbid entity.
9,411 citations
TL;DR: Associated pathological findings suggest that cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease.
Abstract: The Lewy body is a distinctive neuronal inclusion that is always found in the substantia nigra and other specific brain regions in Parkinson's disease. It is mainly composed of structurally altered neurofilament, and occurs wherever there is excessive loss of neurons. It occurs in some elderly individuals and rarely in other degenerative diseases of the central nervous system. In 273 brains of patients dying from disorders other than Parkinson's disease, the age-specific prevalence of Lewy bodies increased from 3.8% to 12.8% between the sixth and ninth decades. Associated pathological findings suggest that these cases of incidental Lewy body disease are presymptomatic cases of Parkinson's disease, and confirm the importance of age (time) in the evolution of the disease. In view of the common and widespread occurrence of this disorder we propose that endogenous mechanisms operating in early life may be more important than environmental agents in the pathogenesis of Lewy bodies and Parkinson's disease.
3,223 citations
TL;DR: 'Sniffin'
Abstract: 'Sniffin' Sticks' is a new test of nasal chemosensory performance based on pen-like odor dispensing devices. It comprises three tests of olfactory function, namely tests for odor threshold (n-butanol, testing by means of a single staircase), odor discrimination (16 pairs of odorants, triple forced choice) and odor identification (16 common odorants, multiple forced choice from four verbal items per test odorant). After extensive preliminary investigations the tests were applied to a group of 104 healthy volunteers (52 female, 52 male, mean age 49.5 years, range 18-84 years) in order to establish test-retest reliability and to compare them with an established measure of olfactory performance (the Connecticut Chemosensory Clinical Research Center Test, CCCRC). Performance decreased with increasing age of the subjects (P < 0.001). Coefficients of correlation between sessions 1 and 2 were 0.61 for thresholds, 0.54 for discrimination and 0.73 for identification. Butanol thresholds as obtained with the CCCRC increased as a function of age; this relation to the subjects' age was not found for the CCCRC odor identification task. The test-retest reliability for CCCRC thresholds was 0.36, for odor identification it was 0.60. It is concluded that 'Sniffin' Sticks' may be suited for the routine clinical assessment of olfactory performance.
2,046 citations
Journal Article•
TL;DR: The International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease as discussed by the authors have been proposed for clinical diagnosis, which are intended for use in clinical research, but may also be used to guide clinical diagnosis.
Abstract: Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.
1,655 citations