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Positron emmission tomography (PET) imaging improved diagnostic accuracyin Parkinson's disease.

Metabolic brain imaging  improved diagnostic accuracy by about 20% in patients with features of early parkinsonism but an uncertain clinical diagnosis, international researchers reported.

In comparison to these high values, published clinicopathologic data suggest that the positive predictive value of a clinical diagnosis, even by a specialist, is only about 75%. Many neurodegenerative diseases share common signs and symptoms, and some 80% of patients misdiagnosed as having Parkinson's disease actually have multiple system atrophy or progressive supranuclear palsy.

These conditions have a much worse prognosis than idiopathic Parkinson's disease, which does not substantially shorten lifespan.

Moreover, treatments differ for these conditions, so more accurate diagnostic techniques have been needed. So Tang and colleagues employed an imaging technique known as fluorine-18-labeled-fluorodeoxyglucose (FDG)-PET to identify specific disease-related metabolic patterns for the three conditions.

They noted that Parkinson's disease was characterized by increased pallidothalamic and pontocerebellar metabolic activity. Multiple system atrophy had bilateral reductions in putamen and cerebellar activity, and supranuclear palsy showed metabolic deficits in the upper brain stem, medial frontal cortex, and medial thalamus.

Among 167 patients with parkinsonian features but uncertain clinical diagnosis who underwent FDG-PET, 96 were classified as having Parkinson's disease, 41 with multiple system atrophy, and 30 with progressive supranuclear palsy.

Patients also were assessed clinically by blinded movement disorders specialists and followed for a mean of 2.6 years before a final clinical diagnosis was made. The investigators employed a multiple-pattern analytical technique to compute a patient's likelihood of having each disease, and calculated the discriminative measures for each.

They found that the imaging classifications were accurate not only for idiopathic Parkinson's disease, but also for multiple system atrophy:

• Sensitivity, 85%

• Specificity, 96%

• Positive predictive value, 97%

• Negative predictive value, 83%

And for progressive supranuclear palsy:

• Sensitivity, 88%

• Specificity, 94%

• Positive predictive value, 91%

• Negative predictive value, 92%

They also calculated these discriminative values for patients with short duration of disease (less than two years), when it can be particularly difficult to make a diagnosis clinically because disease-specific features have not yet appeared. Patients with short duration of disease also would be "ideal participants in clinical trials of potential disease-modifying drugs," the investigators noted.

Among 55 patients with short-duration disease, the positive predictive values for idiopathic Parkinson's disease and atypical parkinsonian syndrome were 92% and 95%, respectively. And among 33 of these patients who were then followed for at least two years after imaging, the positive predictive values rose to 94% and 100%.

This ability to make an imaging classification accurately several years before the final clinical diagnosis "is especially relevant when considering treatment options for patients with medically refractory parkinsonism because invasive surgical approaches such as deep brain stimulation are generally ineffective for patients with atypical parkinsonian syndrome," the investigators wrote.

Moreover, for patients with atypical parkinsonism, the high sensitivity and specificity "will be of particular advantage when assessing potential participants in clinical trials of drugs to treat these progressive disorders."

An accompanying editorial noted that the different types of parkinsonism cannot be classified with available techniques such as imaging of dopamine transporters with single-photon emission CT or of fluorodopa uptake with PET.

"Neuroprotective and disease-modifying drug research is intensifying and results mostly rely on accurate early diagnosis. If neuronal loss in Parkinson's disease follows a linear or exponential pattern, early treatment is crucial," Antonini argued.

But advanced imaging should not be considered a replacement for thorough clinical investigation by movement disorder neurologists, and prospective multicenter studies are needed to confirm the accuracy of this metabolic pattern-based approach, he cautioned.

Source: Lancet Neurology

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