Accuracy of clinical diagnosis of Parkinson disease
A systematic review and meta-analysis
Abstract
Objective:
To evaluate the diagnostic accuracy of clinical diagnosis of Parkinson disease (PD) reported in the last 25 years by a systematic review and meta-analysis.
Methods:
We searched for articles published between 1988 and August 2014. Studies were included if reporting diagnostic parameters regarding clinical diagnosis of PD or crude data. The selected studies were subclassified based on different study setting, type of test diagnosis, and gold standard. Bayesian meta-analyses of available data were performed.
Results:
We selected 20 studies, including 11 using pathologic examination as gold standard. Considering only these 11 studies, the pooled diagnostic accuracy was 80.6% (95% credible interval [CrI] 75.2%–85.3%). Accuracy was 73.8% (95% CrI 67.8%–79.6%) for clinical diagnosis performed mainly by nonexperts. Accuracy of clinical diagnosis performed by movement disorders experts rose from 79.6% (95% CrI 46%–95.1%) of initial assessment to 83.9% (95% CrI 69.7%–92.6%) of refined diagnosis after follow-up. Using UK Parkinson's Disease Society Brain Bank Research Center criteria, the pooled diagnostic accuracy was 82.7% (95% CrI 62.6%–93%).
Conclusion:
The overall validity of clinical diagnosis of PD is not satisfying. The accuracy did not significantly improve in the last 25 years, particularly in the early stages of disease, where response to dopaminergic treatment is less defined and hallmarks of alternative diagnoses such as atypical parkinsonism may not have emerged. Misclassification rate should be considered to calculate the sample size both in observational studies and randomized controlled trials. Imaging and biomarkers are urgently needed to improve the accuracy of clinical diagnosis in vivo.
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© 2016 American Academy of Neurology.
Publication History
Received: March 5, 2015
Accepted: October 16, 2015
Published online: January 13, 2016
Published in print: February 9, 2016
Disclosure
The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures.
Study Funding
No targeted funding reported.
Authors
Author Contributions
Dr. Giovanni Rizzo: study concept and design, acquisition of data, analysis and interpretation of data, drafting the manuscript. Dr. Massimiliano Copetti: analysis and interpretation of data, drafting the manuscript. Dr. Simona Arcuti: analysis and interpretation of data, drafting the manuscript. Dr. Davide Martino: acquisition of data, revising the manuscript. Dr. Andrea Fontana: analysis and interpretation of data. Dr. Giancarlo Logroscino: study concept and design, analysis and interpretation of data, revising the manuscript for content.
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In a metaanalysis of 20 Parkinson disease (PD) studies, Rizzo et al. reported a pooled diagnostic accuracy of 80.6%, ranging from 61.5-95.7%. [1] The most frequent misdiagnoses among clinic-based studies were multiple system atrophy (MSA) (0-9.8%), Lewy body dementia (LBD) (0-7.9%), vascular encephalopathy (VaE) (0-7.7%), and progresssive supranuclear palsy (PSP) (0-6.5%). [1]
I reexamined a 50-year retrospective series of 604 patients with clinical diagnoses of PD from 900 autopsy-verified cases of parkinsonism in Austria, [2] using current diagnostic criteria. [3, 4] The diagnosis of idiopathic PD was confirmed neuropathologically in 80.3% of the total (25% associated with Alzheimer disease [AD]), whereas 19.7% had the following diagnoses: LBD (6.3%), MSA (4.0%), subcortical arteriosclerotic encephalopathy (SAE) (3.6%), PSP (3.0%), and others (AD, Pick disease, postencephalitic parkinsonism, vascular parkinsonism) (1.8%). [2] These data from a large clinic-based consecutive autopsy series of patients with the clinical diagnosis of PD are comparable with those of previous samples [5] and the systematic review of more than 2000 autopsy-confirmed cases of PD. [1] They all indicate that the currently available validity of a PD clinical diagnosis is still unsatisfactory and emphasize the need for further improvement of clinical criteria for PD using modern biomarkers.
1. Rizzo G, Copetti M, Arcuti S, et al. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology Epub 2016 Jan 13.
2. Jellinger KA. Morphological substrates of parkinsonism with and without dementia: a retrospective clinico-pathological study. J Neural Transm Suppl 2007;72:91-104.
3. Gibb WR, Lees AJ. The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. J Neurol Neurosurg Psychiatry 1988;51:745-752.
4. Jellinger KA. Parkinson's disease. In: Dickson DW, Weller RO, editors. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders, 2nd Edition. Oxford: Wiley-Blackwell, 2011: 194-223.
5. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 1992;55:181-184.
For disclosures, please contact the editorial office at [email protected].
We thank Dr. Jellinger for the comment on our recent article, [1] and for reporting data from such a large population. The results are in line with those obtained by our meta-analysis, [1] and further emphasize the sub-optimal accuracy of the clinical diagnosis of Parkinson disease (PD) until now. Moreover, it is interesting to note that 25% of Dr. Jellinger's reported patients with PD were associated with Alzheimer disease. This is further evidence of the importance of mixed pathology, which will have a growing impact in clinical practice given the progressive increase in the mean age of the population, "tainting" the clinical phenotype and making diagnosis more difficult.
The International Parkinson and Movement Disorder Society recently published new diagnostic criteria for PD based on core supportive and exclusion features, retaining, omitting, or revising many elements of previously published criteria. [2] Future studies will tell us whether these criteria improve the diagnostic accuracy in PD. However, it is likely that a step forward will only be taken when easily accessible biomarkers of disease are available. Promising data have already been derived from studies evaluating total/oligomeric a-synuclein levels in the cerebrospinal fluid and from studies identifying peripheral phosphorylated alpha-synuclein staining, as in the submandibular gland or in the skin. [3-5]
1. Rizzo G, Copetti M, Arcuti S, et al. Accuracy of clinical diagnosis of Parkinson disease: A systematic review and meta-analysis. Neurology 201;86:566-576.
2. Postuma RB, Berg D, Stern M, et al. MDS clinical diagnostic criteria for Parkinson's disease. Mov Disord 2015;30:1591-1601.
3. Parnetti L, Chiasserini D, Persichetti E, et al. Cerebrospinal fluid lysosomal enzymes and alpha-synuclein in Parkinson's disease. Mov Disord 2014;29:1019-1027.
4. Adler CH, Dugger BN, Hentz JG, et al. Peripheral Synucleinopathy in Early Parkinson's Disease: Submandibular Gland Needle Biopsy Findings. Mov Disord 2016;31:250-256.
5. Donadio V, Incensi A, Piccinini C, et al. Skin nerve misfolded a-synuclein in pure autonomic failure and Parkinson disease. Ann Neurol Epub 2015 Nov 25.
For disclosures, please contact the editorial office at [email protected].