The Parkinson's-Reversing Breakthrough

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Abbreviations: CT, computed tomography; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD, Parkinson's disease.

Abbreviations: CT, computed tomography; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; PD, Parkinson's disease.

The first clinicopathological study found that only 69% to 75% of the patients with an autopsy-confirmed diagnosis of PD had at least two of the three cardinal manifestations of PD: tremor, rigidity, and bradykinesia (141). Furthermore, 20% to 25% of patients who showed two of these cardinal features had a pathological diagnosis other than PD. Even more concerning, 13% to 19% of patients who demonstrated all the three cardinal features typically associated with a clinical diagnosis of PD had another pathological diagnosis. Rajput et al. (142) reported autopsy results in 59 patients with parkinsonian syndromes. After a long-term followup period, the clinical diagnosis of PD was retained in 41 of 59 patients. However, only 31 of 41 (75%) patients with clinically determined PD showed histopathological signs of PD at autopsy examination.

A third series (143) comprised 100 patients with a clinical diagnosis of PD, who had been examined during their life by different neurologists using poorly defined diagnostic criteria. When autopsies were performed (mean interval between symptom-onset and autopsy 11.9 years), PD was found in 76 patients. The authors reviewed the charts of these patients and applied the United Kingdom Parkinson's Disease Society Brain Bank clinical criteria for PD requiring bradykinesia and at least one other feature, including rigidity, resting tremor, or postural instability, and focusing on clinical progression, asymmetry of onset, and levodopa response. Sixteen additional exclusion criteria were also applied (Table 7). With the application of these diagnostic criteria, 89 of the original 100 patients were considered to have PD, but again only 73 (82%) were confirmed to have PD at autopsy. When the authors reex-amined the patients with all the three cardinal features (excluding the postural instability), only 65% of patients with an autopsy diagnosis of PD fit this clinical category.

These authors (144) studied another 100 patients with a clinical diagnosis of PD that came to neuropathological examination. Ninety fulfilled pathologic criteria for PD. Ten were misdiagnosed: MSA (six), PSP (two), postencephalitic parkinsonism (one), and vascular parkinsonism (one). They next examined the accuracy of diagnosis of parkinsonian disorders in a specialist movement disorders service (145). They reviewed the clinical and pathological features of 143 cases of parkinsonism, likely including many of the patients previously reported (144). They found a surprisingly high positive predictive value (98.6%) of clinical diagnosis of PD among the specialists. In fact, only 1 of 73 patients diagnosed with PD during life was found to have an alternate diagnosis. This study demonstrated that the clinical diagnostic accuracy of PD may be improved by utilizing stringent criteria and a prolonged followup. A retrospective study (146) showed that the hallucinations are very predictive of Lewy body pathology, either PD or DLB. Further refinements in neuroimaging are likely to improve the clinical accuracy of early PD in the future.

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