Tambasco Nicola, Muti Marco, Chiarini Pietro, Tarducci Roberto, Caproni Stefano, Castrioto Anna, Nigro Pasquale, Parnetti Lucilla, Floridi Pietro, Rossi Aroldo, Calabresi Paolo
Clinica Neurologica, Azienda Ospedaliera-Università di Perugia, Perugia, Italy.
Servizio di Fisica Sanitaria, Azienda Ospedaliera di Terni, Terni, Italy.
PLoS One. 2014 May 15;9(5):e96806. doi: 10.1371/journal.pone.0096806. eCollection 2014.
Wearing-off is one of the most frequent problems encountered by levodopa-treated patients. Entacapone, a peripheral inhibitor of catechol-O-methyltransferase (COMT), reduces this motor complication by prolonging the effect of levodopa. We sought to understand the impact of COMT-inhibition on movement execution in PD patients with wearing-off by comparing functional magnetic resonance imaging (f-MRI) activation patterns prior to and during entacapone treatment. Our hypothesis was to determine whether changes in cortical activation are associated to COMT-inhibitor treatment.
Nine levodopa-treated non-demented PD patients with wearing-off were prospectively studied in two f-MRI session, prior to and during entacapone treatment. A group of control subjects were also studied for comparison.
The patients significantly improved under COMT-inhibitor treatment based on home diaries. F-MRI results showed that at baseline the patients presented a bilateral activation of the primary motor, controlateral premotor cortex and supplementary motor area, as well as ipsilateral cerebellum. During treatment with entacapone, PD patients showed reductions in the activations of these cortical areas and a decreased activation in the ipsilateral cerebellum.
Our preliminary findings indicate that f-MRI is able to detect cortical activation changes during long-term modulation of dopaminergic treatment in PD patients with wearing-off, and thus, this technique could be further investigated in advanced PD patients.
疗效减退是左旋多巴治疗患者最常遇到的问题之一。儿茶酚-O-甲基转移酶（COMT）外周抑制剂恩他卡朋可通过延长左旋多巴的作用来减轻这种运动并发症。我们试图通过比较恩他卡朋治疗前和治疗期间的功能磁共振成像（f-MRI）激活模式，来了解COMT抑制对出现疗效减退的帕金森病（PD）患者运动执行的影响。我们的假设是确定皮质激活的变化是否与COMT抑制剂治疗有关。
对9名接受左旋多巴治疗且出现疗效减退的非痴呆PD患者进行前瞻性研究，在恩他卡朋治疗前和治疗期间各进行一次f-MRI检查。还研究了一组对照受试者以作比较。
根据家庭日记，患者在COMT抑制剂治疗下有显著改善。f-MRI结果显示，在基线时，患者双侧初级运动皮质、对侧运动前区皮质和辅助运动区以及同侧小脑均有激活。在恩他卡朋治疗期间，PD患者这些皮质区域的激活减少，同侧小脑的激活也减少。
我们的初步研究结果表明，f-MRI能够检测出出现疗效减退的PD患者在多巴胺能治疗长期调节过程中的皮质激活变化，因此，可在晚期PD患者中进一步研究该技术。
