Parkinsons Disease Differential Diagnosis And Severity

The Parkinson's-Reversing Breakthrough

Diets for Parkinson Disease

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The initial questions of an imaging ligand are whether it reliably distinguishes between subjects with and without a known pathology (a marker for disease trait) and whether the changes in the imaging outcomes correlate with disease severity (a marker for disease state). In several studies, dopamine and vesicular transporter ligands and 18F-DOPA discriminated between individuals with PD and healthy subjects, with a sensitivity greater than 95% (11,13,20,72-74). These studies take advantage of the relatively greater dopaminergic loss in the putamen to enhance the discriminant function. Furthermore, the reduction in both dopamine and vesicular transporter and 18F-DOPA imaging activity correlated with well-defined clinical rating scales of PD severity (16,20,28,75). Interestingly, when specific PD symptoms were compared, the loss of dopaminergic activity measured by imaging correlated with bradykinesia but not with tremor (20,76). Cross-sectional studies show that severity of bradykinesia measured by clinical scales reflects the severity of the nigrostriatal dopamine neuron loss. Therefore, in vivo dopaminergic imaging provides a biomarker for the presence of disease and for the severity of the pathologic process.

In clinical practice, the diagnosis is most difficult at the onset of symptoms. In studies focused on early PD patients, in vivo imaging demonstrated a 40% to 60% reduction in DAT or F-DOPA activity in the putamen contralateral to the symptomatic side. PD generally presents as a unilateral motor disorder and progresses during a variable period of three to six years to affect both sides, although frequently remaining asymmetric (77). The unilateral motor presentation reflects the asymmetric dopaminergic pathology, which is, in turn, demonstrated by in vivo dopaminergic imaging (11,66,67).

DAT imaging has also been shown to be useful in special diagnostic situations such as psychogenic, drug-induced, traumatic or vascular parkinsonism, in distinguishing these syndromes without a presynaptic dopamine deficit from PD and other related disorders (78,79). A more difficult diagnostic problem is the distinction between the more specific diagnosis of PD and other related neurodegenerative disorders categorized as parkinsonism. The more common etiologies, such as PSP, MSA, CBD, and DLBD, may account for about 15% to 20% of patients with apparent PD. Parkinsonism is characterized by significant nigrostriatal neuronal loss demonstrated by a reduction in in vivo presynaptic dopaminergic imaging. Although the severity of DAT or 18F-DOPA loss does not discriminate between PD and other causes of parkinsonism, the pattern of loss in parkinsonism is less region-specific (putamen and caudate equally affected) and more symmetric than PD. This strategy discriminates between PD and other causes of parkinsonism with a sensitivity of about 75% to 80% (80-82). In addition, the more widespread pathology associated with parkinsonism may be reflected in abnormalities in postsynaptic dopamine receptor imaging and in metabolic imaging, which are not seen in PD. Therefore, the pattern of presynaptic dopaminergic loss may be coupled with post-synaptic dopamine receptor imaging or metabolic imaging to distinguish PD from other parkinsonisms (83,84).

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