Structural MRI substrate of long-duration response to levodopa in Parkinson’s disease: an exploratory study

OBJECTIVE: The long-duration response (LDR) to L-dopa is a sustained benefit deriving from chronic administration of therapy to patients with Parkinson’s disease (PD). Almost all patients with early PD may develop the LDR to L-dopa, even if some patients could not at given dosages of the drug. Aim of this exploratory study is to investigate whether a neuroanatomical substrate may underlie the development of the of LDR using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analysis. METHODS: Twenty-four drug-naïve PD patients were enrolled and underwent a baseline 3D T1-weighted structural brain MRI. Then, a treatment with 250/25 mg of L-dopa/carbidopa every 24 h was started and, after 2 weeks, LDR was evaluated by movement time recordings. RESULTS: After 2 weeks of continuative therapy, 15 patients (62.5%) showed a sustained LDR (LDR +), while nine patients (37.5%) did not develop a sustained LDR (LDR −). VBM analysis on MRI executed before treatment showed changes of gray matter in precentral and middle frontal gyri in patients subsequently developing a sustained LDR with respect to those patients who will not achieve LDR. CONCLUSIONS: Parkinsonian patients who will develop a LDR to L-dopa may present, before starting treatment, peculiar structural conditions in cortical areas involved in motor control. Our exploratory study suggests that some cortical structural changes may predispose individual patients for developing the LDR to L-dopa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-021-10550-5.