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In a population based study on the prevalence of Parkinson’s disease in London, Schrag et al reported on the data of a long term clinical evaluation of 202 patients.1 The initial diagnosis of probable Parkinson’s disease was later confirmed in 83%, plus 2% each with atypical features and possible Parkinson’s disease. In 15% the initial diagnosis was later rejected, while 19% of patients not diagnosed as Parkinson’s disease were later found to have the disorder. Their conclusion was that in 15% of the cases the clinical criteria of Parkinson’s disease were not followed, in accordance with previous retrospective clinicopathological studies of parkinsonism, in which the rate of false positive diagnosis ranged between 22–24%2,3 and 15–18%.4,5 Using more strict diagnostic criteria by movement disorder experts, this figure could recently be further reduced to around 10%, with a positive predictive value (PPV) for idiopathic Parkinson’s disease of 98.6%, and for other parkinsonian syndromes 71.4%—for example, for multisystem atrophy (MSA), 85.7%, and for progressive supranuclear palsy (PSP), 80%.6,7
Referring to these data, Schrag et al suggested that at least 10% of the patients with a final clinical diagnosis of Parkinson’s disease may have other disorders.1 In pathological series, the incidence of atypical parkinsonism is substantial; for example, PSP is found in 6–22% of necropsy cases, MSA in 5–11.4%, vascular parkinsonism in 2–3%, and Alzheimer’s disease in demented Parkinson’s disease patients in 2–6%5,6 (see table 1).
Although samples from brain banks and specialised institutions are considered to overrepresent atypical disorders owing to the referral bias inherent in such samples,7 these data are, at least in part, confirmed by a large consecutive clinicopathological study of 260 elderly patients with a clinical diagnosis of parkinsonism derived in the years 1989 to 2001 from three large community hospitals in Vienna, two with acute and one with chronic care facilities (table 1). The concordance of the clinical diagnosis with the necropsy findings in this cohort was much better than in previous series5 (table 2), which, unfortunately, was not considered or quoted by Schrag et al. In our recent necropsy series, the mean incidence of Lewy body disease, including Parkinson’s disease, was 78%; of other neurodegenerative disorders masquerading as Parkinson’s disease (for example, PSP, MSA, and so on), around 12%; while other disorders referred to as secondary parkinsonism (essential tremor, drug induced parkinsonism) accounted for 8.4% (table 1). The initial rate of misdiagnosis in the overall group of 750 cases was around 17%, and, owing to more precise diagnostic criteria, this finally fell to 11.5% (table 2).
A review of the clinical and pathological diagnoses of 160 non-demented patients with parkinsonism (85 men, 75 women; mean (SD) age, 76.6 (8.3) years, range 52 to 96)—the majority of whom had been examined in hospitals by neurologists experienced in movement disorders over a 12 year period from 1990 to the end of 2001—gave the following results: 129 were clinically diagnosed as probable idiopathic Parkinson’s disease without severe dementia, and 21 as having atypical parkinsonian syndromes. The PPV of the clinical diagnosis for the whole group was 89.4% (143/160); for idiopathic Parkinson’s disease, 94.2% (131/139); for PSP, only 50% (4/8); for MSA, 57.1% (4/7); and for vascular parkinsonism, 66.7% (4/6). The sensitivity for idiopathic Parkinson’s disease was 94.2% owing to eight false positive cases, mainly dementia with Lewy bodies (DLB), and two cases of PSP.
The diagnostic accuracy of 89.4% for the whole cohort was higher than in the group described by Hughes et al (85.3%),2 and was similar to that of our own total group of 260 parkinsonian cases without and with dementia, where the rate of false clinical diagnosis was 11.5 % (table 2). This was lower than in previous clinicopathological series from the same hospitals and the same neuropathology department (table 2).
It is of interest that the majority of cases with a false clinical diagnosis of idiopathic Parkinson’s disease in our cohort had a final pathological diagnosis of DLB—mainly “pure” DLB cases which often initially present with parkinsonism.9,10 These were not included or mentioned in either of the British series.1,3,6,7 In our recent consecutive necropsy series of 260 parkinsonian cases, DLB accounted for around 20% which, owing to improved neuropathological techniques and knowledge, was much higher than in previous series (table 1). The reason for the differences between the British series and our own is a matter for debate.
The recent British studies and our own studies imply that neurologists with particular expertise in the field of movement disorders may be best at recognising the clinical syndromes of parkinsonism. However, they also show clearly that neuropathological examination using modern immunohistochemical methods still represents the gold standard for the final diagnosis which, even after examination of the patients by very experienced clinicians, may differ by around 10% from the final clinical diagnosis. Improvement in the clinical consensus criteria and expertise may further reduce the rate of false clinical diagnosis of these devastating disorders—a possible basis for further improvements in treatment strategies.
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