Carandina Angelica, Lazzeri Giulia, Rodrigues Gabriel Dias, Franco Giulia, Monfrini Edoardo, Arienti Federica, Frattini Emanuele, Trezzi Ilaria, da Silva Soares Pedro Paulo, Bellocchi Chiara, Furlan Ludovico, Montano Nicola, Di Fonzo Alessio, Tobaldini Eleonora
Department of Internal Medicine, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Neurology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
Front Neurosci. 2022 Mar 15;16:842498. doi: 10.3389/fnins.2022.842498. eCollection 2022.
Evidence from clinical practice suggests that PD patients with the Glucocerebrosidase gene mutations (GBA-PD) are characterized by more severe dysautonomic symptoms than patients with idiopathic PD (iPD). Therefore, an accurate assessment of cardiovascular autonomic control (CAC) is necessary to clarify the role of GBA mutations in the pathophysiology of PD. We evaluated the CAC at rest and during orthostatic challenge of 15 iPD, 15 GBA-PD and 15 healthy controls (CTR). ECG and respiration were recorded in supine position and during active standing. The analysis of Heart Rate Variability (HRV) was performed on ECG recordings using two different approaches, linear spectral analysis and non-linear symbolic analysis. GBA-PD patients presented more frequently an akinetic-rigid phenotype and cognitive dysfunction than iPD patients. Both iPD and GBA-PD group were characterized by a lower spectral HRV than CTR group. At rest, the GBA-PD group was characterized by a lower parasympathetic modulation and a shift of the sympathovagal balance toward a sympathetic predominance compared to the CTR group. Moreover, the GBA-PD patients presented a lower HR increment and a lower or absent reduction of the vagal modulation in response to the active standing than iPD patients. Lastly, the cardiovascular autonomic dysfunction in PD patients was associated with longer disease duration, and with the occurrence of REM sleep behavior disorder and constipation. Our findings suggest a more severe impairment of the CAC in PD patients with GBA mutations. These results and further studies on the role of GBA mutations could allow a stratification based on cardiovascular risk in PD patients and the implementation of specific prevention programs.
临床实践证据表明，与特发性帕金森病（iPD）患者相比，携带葡萄糖脑苷脂酶基因突变的帕金森病（GBA-PD）患者具有更严重的自主神经功能障碍症状。因此，准确评估心血管自主神经控制（CAC）对于阐明GBA突变在帕金森病病理生理学中的作用至关重要。我们评估了15例iPD患者、15例GBA-PD患者和15例健康对照者（CTR）在静息状态和直立位挑战期间的CAC。在仰卧位和主动站立期间记录心电图和呼吸。使用两种不同方法，即线性频谱分析和非线性符号分析，对心电图记录进行心率变异性（HRV）分析。与iPD患者相比，GBA-PD患者更频繁地出现运动不能-强直型表型和认知功能障碍。iPD组和GBA-PD组的频谱HRV均低于CTR组。静息时，与CTR组相比，GBA-PD组的特点是副交感神经调制较低，交感-迷走神经平衡向交感神经占优势转变。此外，与iPD患者相比，GBA-PD患者在主动站立时心率增加较低，迷走神经调制降低较低或无降低。最后，帕金森病患者的心血管自主神经功能障碍与病程延长、快速眼动睡眠行为障碍和便秘的发生有关。我们的研究结果表明，携带GBA突变的帕金森病患者的CAC受损更严重。这些结果以及对GBA突变作用的进一步研究可能有助于根据帕金森病患者的心血管风险进行分层，并实施特定的预防方案。
