Avaliação dos efeitos clínicos e neurofisiológicos do ultrassom transcraniano focal de baixa intensidade em pacientes com doença de Parkinson

Abstract

Transcranial low-intensity focused ultrasound (tFUS) is a novel non-invasive brain stimulation technique with high spatial resolution. tFUS can transiently reduce cortical excitability during sonication (online effect). In theta burst mode (tbFUS), tFUS induces an increase in cortical excitability lasting up to 30 minutes (offline effect), possibly due to a plasticity effect similar to long-term potentiation (LTP). As Parkinson's disease (PD) is known to be associated with altered cortical excitability and plasticity, our goal was to evaluate the clinical and neurophysiological effects of tFUS applied to the primary motor cortex (M1) in PD patients. Twenty PD patients were evaluated (4 females, average age 59.1 ± 8.7 years) both in the 'ON' and 'OFF' states of dopaminergic medication, along with 17 healthy controls (5 females, 63.7 ± 9.2 years). Additionally, 7 newly diagnosed PD patients (PD - denovo) were tested (3 females, 66,4±8,7 years). The online protocol involved sonication of M1 with intensities of 20 W/cm2 (active) and 0 W/cm2 (placebo), with simultaneous measurements of motor-evoked potentials (MEPs) by transcranial magnetic stimulation (TMS). The offline protocol consisted of 80 seconds of tbFUS on M1 with an intensity of 20 W/cm2. Cortical excitability was assessed through MEP amplitudes at baseline (before tbFUS), at 5 minutes ('T5'), T30, and T60 after tbFUS. Wilcoxon's test showed a difference between Active vs. Placebo conditions for the PD-ON group (p=0.03), but not for PD-OFF or controls. The linear mixed-effects (LME) model for PD-ON vs. controls showed a UFBI effect (p=0.048), without a group or UFBI x group interaction effect. LME for PD-OFF vs. controls and LME for PD-ON vs. PD-OFF did not show a significant UFBI, group, or interaction effect. For offline effects, the Wilcoxon test comparing baseline MEP with T5, T30, and T60 showed a difference at T30 in controls (p=0.02) and PD-ON (p=0.042), but not in PD-OFF. LME of MEP amplitudes after sonication, comparing controls with PD-ON, showed a time effect (p=0.002), but no group or interaction effect (group x time). Comparing controls with PD-OFF, there was a group effect (p=0.03), a time effect (p=0.03), and an interaction effect (p=0.02). Comparing PD- ON with PD-OFF, there was a group effect (p=0.03), with no time or interaction effect. The LME for PD-de novo vs. PD-OFF showed a significant time x group interaction effect (p=0.03). Post hoc Mann-Whitney U analysis showed a difference comparing PD-de novo T30-MEP and PD-OFF T30-MEP (p=0.04). There was a significant difference in the bradykinesia score of the mUPDRS between baseline and T60 in PD-ON (p=0.05) and in PD-de novo (p=0.04), but not in PD-OFF. The total score and other tremor and axial sub- scores showed no differences when comparing baseline with T60 in PD-ON, de novo, or OFF. Online tFUS reduced cortical excitability in PD-ON, but not in controls or PD-OFF. tbFUS induced motor cortical plasticity in controls and PD-denovo, but not in PD-OFF patients. However, plasticity was restored in PD-ON patients. PD-ON and denovo patients showed improvement in bradykinesia, highlighting a potential symptomatic effect of tbFUS.