Data for this review were identified by searches of MEDLINE (up to July, 2005) and references from relevant articles. Other papers for inclusion were identified from the personal files of the authors, from previous reviews of the subject, either by these authors or by other authors, and from our editorial board duties on neurology journals. Only articles in the English language were reviewed.
ReviewThe diagnosis of Parkinson's disease
Introduction
Parkinson's disease is a progressive neurological disorder characterised by tremor, rigidity, and slowness of movements, and is associated with progressive neuronal loss of the substantia nigra and other brain structures. Non-motor features, such as dementia and dysautonomia, occur frequently, especially in advanced stages of disease. Parkinson's disease is not regarded as a single disease entity and the term does not necessarily mean the same for all clinicians and researchers. Some use the term as a strictly clinical diagnosis and might accept different pathological substrates underlying the syndrome. Others will use the term only for those cases of idiopathic parkinsonism associated with Lewy body inclusions in the nigra cells and in cells in other brain regions. Here we use the term Parkinson's disease to refer to a clinical condition—progressive parkinsonism of undetermined cause without features suggestive of an alternative diagnosis responding to dopaminergic treatment—associated with depletion of brainstem neurons and with Lewy body inclusions in some of the remaining nerve cells.1, 2
Although a diagnosis of Parkinson's disease, as defined above, can be a straightforward clinical exercise in patients with typical presentations of cardinal signs and excellent response to levodopa treatment, the differential diagnosis versus other forms of parkinsonism can be challenging, especially early in the disease when signs and symptoms of different forms of parkinsonism have greater overlap. Error rates in clinicopathological series have been as high as 24% even though most of the patients in these studies had been treated by movement-disorder specialists.3 Two studies draw attention to the difficulties in the diagnosis of the disease in the early stages. In a prospective clinicopathological study, Rajput and colleagues4 showed that initial clinical diagnosis within 5 years of disease onset was correct in 65% of cases. After a mean duration of 12 years, the final diagnosis of Parkinson's disease by the clinician was confirmed at autopsy in 76% of cases. Similarly, among 800 patients in the Deprenyl and Tocopherol Antioxidative Therapy for Parkinson Disease5 study with mild early parkinsonism judged to have Parkinson's disease, 8·9% were later reported to have an alternative diagnosis on the basis of multifactorial, clinical diagnostic criteria.
With the use of standard clinical criteria, such as the UK Parkinson's disease brain bank criteria, accuracy of a clinical diagnosis of the disease can be improved significantly; however, up to 10% of patients diagnosed with the disease in life will still have to be reclassified at post-mortem examination.6 Diagnostic specificity and sensitivity of these criteria have been estimated as 98·6% and 91·1%, respectively.7 Diagnostic sensitivity and specificity of criteria used to diagnose atypical parkinsonian disorders, such as multisystem atrophy or progressive supranuclear palsy, are significantly lower than those used for Parkinson's disease.7, 8, 9
Population-based studies have shown that at least 15% of patients with a diagnosis of Parkinson's disease in the population do not fulfil strict clinical criteria for the disease, and about 20% of patients with Parkinson's disease who have already come to medical attention have not been diagnosed with the disease.10 In clinicopathological studies the most common misdiagnoses relate to other forms of degenerative parkinsonism, such as progressive supranuclear palsy, multisystem atrophy, or corticobasal degeneration.7 Clinically based studies have shown that other common errors include essential tremor, drug-induced parkinsonism, and vascular parkinsonism.11 Additionally, there is ongoing debate on the distinction between Parkinson's disease with dementia and dementia with Lewy bodies.12, 13 Here we review published work on the clinical differential diagnosis of the various parkinsonian syndromes and critically assess the role of ancillary tests in the diagnostic work-up of patients with parkinsonism.
Section snippets
Essential tremor
Essential tremor is a monosymptomatic disorder characterised by the presence of bilateral, largely symmetrical, postural or kinetic tremor that affects the hands and forearms and is visible and persistent.14 Bradykinesia, rigidity, and postural instability are not part of the illness, but around 20% of patients with essential tremor are misdiagnosed with Parkinson's disease and vice versa.15 Postural tremor in essential tremor is apparent immediately as the arms are outstretched, whereas a
Ancillary tests in the differential diagnosis of Parkinson's disease
Although some core clinical characteristics differ between the various forms of degenerative parkinsonism, there is broad clinical overlap (table 1).71, 72, 73, 74, 75 Error rates in clinicopathological studies draw attention to the need for additional diagnostic tests to solidify differential diagnostic accuracy. These tests include genetic testing, challenge tests of dopaminergic responsiveness, neurophysiological studies and autonomic function testing, tests of olfactory function, and
Conclusion
A correct diagnosis of Parkinson's disease is a prerequisite for patient counselling and therapeutic management. Despite all recent advances in imaging and genetics of parkinsonian disorders the diagnosis of Parkinson's disease remains a primarily clinical exercise. However, clinical diagnostic uncertainty is high at initial presentation and up to 30% of patients initially diagnosed as having the disease are clinically reclassified, even in specialised units.10 Imaging studies that used
Search strategy and selection criteria
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