Continuous apomorphine infusion modulates cortical hyperexcitability and abnormal plasticity in Parkinson's disease

BackgroundSeveral studies have demonstrated the clinical benefit of apomorphine subcutaneous infusion in Parkinson's disease (PD). However, it remains unclear whether apomorphine infusion also modulates the abnormal motor cortical excitability and plasticity that contribute to PD pathophysiology and progression.MethodsWe investigated the effects of continuous apomorphine infusion on cortical excitability and plasticity in patients with moderate-advanced PD, assessed at baseline and after 1, 12, and 24 weeks of treatment. Transcranial magnetic stimulation (TMS) was used to evaluate: i) motor cortex excitability (via input-output (I-O) recruitment curves and motor evoked potentials (MEPs) at 100-140% of resting motor threshold); ii) intracortical inhibition/facilitation (SICI; ICF), and plasticity using intermittent theta-burst stimulation (iTBS). Kinematic analysis of finger movements quantified bradykinesia. Eighteen healthy controls (HC) underwent baseline assessments for comparison.ResultsAt baseline, PD patients showed increased cortical excitability and reduced iTBS-induced plasticity compared to HC. After 24 weeks of continuous apomorphine infusion, cortical excitability decreased (reduced I-O slope and MEP amplitudes at 120-140% rMT), and plasticity improved (greater MEP facilitation 30 min post-iTBS). Clinically, motor and non-motor symptoms improved paralleled by a significant reduction in oral levodopa dose. Changes in excitability correlated with changes in motor performance.ConclusionsWe found that continuous apomorphine infusion was associated with progressive modulation of selected cortical markers in PD, in parallel with clinical improvement. These findings also highlight the potential value of cortical markers for monitoring treatment response in advanced PD.