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Issue Date: 2-May-2011
Authors: Contrafatto, Donatella
Title: Asymmetry of nigral dopaminergic neurons' depletion in parkinson's disease
Abstract: Parkinson's disease (PD) is a neurological disorder characterized by the lateralization of motor manifestations, that is still evident late in the course of disease, corresponding to the unilateral predominance of the nigrostriatal degenerative process. The diagnosis is essentially clinical, supported by the evidence of a good clinical dopaminergic response. However the diagnosis is sometimes difficult also in a movement disorders' specialist setting, especially with vascular parkinsonism (VP) due to the overlap in clinical presentation and the lack of specificity at neuroimaging. We studied 20 PD, 20 VP and 20 Essential Tremor (ET) patients as control group, who had undergone a cerebral [123I] FP-CIT SPECT that is the best tecnique, to date, for in vivo assessment of dopaminergic depletion. On SPECT results a semiquantitative analisis has been performed; the binding of the ligand in the most affected side resulted significantly lower in VP than in ET patients but higher compared to PD patients. We calculate also the Striatal Asymmetry Index (SAI), that resulted significantly higher in PD compared to VP (p<0.001) and ET (p<0.001) groups. We found that a cut-off of SAI greater than 14.08 could differentiate PD from VP with a 100% specificity and a 60% sensitivity. Our work has provided an important glimpse about the possible role of functional imaging in differentiating with a good degree of certainty VP from PD, suggesting that SAI detected using [123I]FP-CIT SPECT could be used to this purpose. Moving from this consideration, we wondered if asymmetry can be predictive also of the response to levodopa (LD) at short term LD-test. In fact, up to 40% of drug nave patients are initially not responsive to dopaminergic drugs, but LD responsiveness is one of the best predictors of a correct diagnosis of PD. We performed a study enrolling 20 PD patients never previously exposed to levodopa, who had undergone a short term LD-test with levodopa/carbidopa 250/25 mg to quantify the clinical response to dopaminergic therapy, and a [123I] FP-CIT SPECT. We estimated the amplitude (mean percentual reduction of UPDRS motor score) and the duration (time necessary for the UPDRS motor score to return to the 50% of the maximal improvement) of the response at acute LD-test. At SPECT study, as expected, mean caudate and putamen uptake were lower controlaterally to the most affected side. A significant correlation between the Striatal Asymmetry Index and the magnitude of the response was found (r 0.64, p <0.002). Asymmetry appeared to predict the responsiveness to levodopa, that can be crucial in the management of therapy, helping phisicians in the choice of best therapy.
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