Objective: Aim of the study is to investigate neuroanatomical correlates of Long-Duration Response using structural magnetic resonance imaging (MRI) and voxel-based morphometry analysis.

Background: Parkinson disease (PD) is a neurodegenerative disorder characterized by the response to L-dopa, that still remains the best available symptomatic treatment for PD. The therapeutic response to L-dopa consists of two components: the short-duration response (SDR), an improvement of the clinical condition following the administration of a single dose of L-dopa, and the long-duration response (LDR), a sustained benefit deriving from prolonged administration of L-dopa.

Method: Drug-naïve patients with a new diagnosis of PD according to Brain Bank criteria were consecutively enrolled. They underwent an acute challenge with 250/25 mg of L-dopa. Then, a treatment with 250/25 mg every 24 hours was started and, after two weeks, LDR was evaluated. Structural brain MRI data were acquired using a 3D T1-weighted sequence and VBM analysis of MRI data was performed.

Results: Twenty-four patients were enrolled (table). After two weeks of therapy, 15 patients (62.5%) showed LDR (PD-LDR+), while 9 patients (37.5%) showed no LDR (PD-LDR-). VBM analysis between PD-LDR+ and PD-LDR- showed decreased GM density in left putamen and in superior frontal gyrus in PD-LDR+ (p<0.001 uncorrected) (figure).

Conclusion: This study showed the presence of atrophy in cortical and subcortical areas in PD patients who showed LDR after two weeks of continuative levodopa therapy with 250/25 mg every 24 hours. The presence of basal ganglia atrophy could induce a compensation mechanism, improving connectivity and leading to a sustained response to dopaminergic therapy.

References: Zappia M, Oliveri RL, Bosco D, Nicoletti G, Branca D, Caracciolo M, Napoli ID, Gambardella A, Quattrone A. The long-duration response to L-dopa in the treatment of early PD. Neurology. 2000 May 23;54(10):1910-5. Esposito F, Tessitore A, Giordano A, De Micco R, Paccone A, Conforti R, Pignataro G, Annunziato L, Tedeschi G. Rhythm-specific modulation of the sensorimotor network in drug-naive patients with Parkinson’s disease by levodopa. Brain. 2013 Mar;136(Pt 3):710-25.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/grey-matter-atrophy-in-parkinsons-disease-with-long-duration-response/