Approximately only 75% of patients diagnosed with idiopathic Parkinson's disease (PD) actually prove to have the disease at autopsy. Common alternative diagnoses include multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Clinically differentiating parkinsonian syndromes has proved particularly difficult early in the course of the disease.
“There are a lot of different parkinsonian disorders that look like classical Parkinson's disease, but they have a different prognosis. The typical therapeutic strategies, like deep-brain stimulation and even dopamine agonist drugs, don't work for these patients,” said Dr. David Eidelberg of the neurosciences research center of the North Shore-Long Island Jewish Health System in Manhasset, New York. “The prognosis [for the parkinson variant disorders] is uniformly bad. If you have PSP or MSA, for example, not only is your prognosis unfortunately not as good, but surgical treatments are not as effective either,” said Dr. Eidelberg.
A number of studies using [18F]-fluorodeoxyglucose (FDG) positron emission tomography have described characteristic glucose metabolism patterns in patients with PD, MSA, PSP, and CBD. Dr. Eidelberg and his colleague Dr. Thomas Eckert have demonstrated the utility of such imaging as an adjunct to clinical evaluation in differentiating parkinsonian syndromes early in the disease process (Neuroimage 2005;26:912–21).
For this 65-year-old patient and others for whom the clinical diagnosis is uncertain, FDG PET can provide additional information with which to differentiate PD and variant syndromes. Patients at the neurosciences research center are required to fast overnight, and antiparkinsonian medications are withheld at least 12 hours before scanning. Scanning yields 35 two-dimensional image planes with an axial field view of 14.5 cm and a transaxial resolution of 4.2 mm in all directions.
For routine visual reading by experts familiar with typical uptake patterns for the different syndromes, the scans are reconstructed, corrected for attenuation, and smoothed for each subject. Images are displayed as a series of 35 transaxial slices.
Dr. Eidelberg, Dr. Eckert, and their colleagues have developed a computer-supported tool that allows nonexperts to read FDG PET scans. The technique uses statistical parametric mapping for all image processing and analyses. Images are spatially normalized and then a smoothing filter is applied to the images. Template statistical maps have been developed to aid in PET scan interpretation. Any voxels showing increased or decreased metabolism in the patient groups (PD, MSA, PSP, or CBD), compared with a group of healthy controls are overlaid onto T1 magnetic resonance template images. These templates are used to assist in the differential diagnosis of single scans.
Individual patient scans can then be compared statistically with a reference group of healthy control subjects. All voxels showing increased or decreased glucose metabolism above a statistical threshold, compared with that of the control group, also are overlaid into the T1 MRI maps. The hallmark of glucose metabolism in PD patients is increased metabolism in the putamen and globus pallidus and is present bilaterally without regard to the affected side, as seen in this patient's scan. Increased metabolism also is observed in the ventral thalamus, the motor cortex, and the cerebellum. Abnormal reductions in glucose metabolism are present bilaterally in the parietal and occipital association areas and in the dorsolateral prefrontal cortex.
MSA metabolism is characterized by marked bilateral reductions in the putamen and in the cerebellum (see image). Increased metabolism is seen in the frontal and superior parietal and cortical areas and in the thalamus. Hypometabolism is seen in the brainstem.
The distinguishing features of PSP metabolism are the presence of metabolic decrements in midline frontal regions and in the brainstem (see image). Decreased metabolism is also noted bilaterally in the caudate nucleus. Increased metabolism is seen bilaterally in the cortical motor areas, the parietal cortex, and the thalamus.
Glucose metabolism in CBD is characterized by a distinctive asymmetrical cortical activation (relative hypometabolism contralateral to the most affected side) and asymmetrical basal ganglia metabolism (relative hypometabolism contralateral to the most affected side). Hypometabolism is also seen in the paraventricular areas, the brain stem, and the midline frontal areas (see image).
Dr. Eckert, Dr. Eidelberg, and their colleagues used this computer-assisted technique to aid in the differential diagnosis of parkinsonism in a group of 135 patients for whom the clinical diagnosis was uncertain at the time of referral for imaging. The technique was compared with the final clinical diagnosis, which is the preferred diagnostic method.
The computer-assisted reading technique produced the correct diagnosis in 92% of all subjects—98% for early PD. A sensitivity of 100% and a specificity of 86% were obtained in identifying early PD patients (duration of symptoms less than 5 years), as compared with normal controls. A sensitivity of 96% and a specificity of 91% were achieved for PD patients, compared with patients with presumed atypical parkinsonism. This patient was diagnosed with early PD and was started on dopaminergic medication for 6 months after imaging. Symptoms markedly improved.