From the Department of Neurology (J.F.v.d.H., J.M., V.J.G., J.J.v.H.), Leiden University Medical Center, the Netherlands; and National Centre for Epidemiology and CIBERNED (P.M.-M., C.R.-B.), Carlos III Institute of Health, Madrid, Spain.
Neurology. 2016 Jun 14;86(24):2243-50. doi: 10.1212/WNL.0000000000002768. Epub 2016 May 13.
Differences in disease progression in Parkinson disease (PD) have variously been attributed to 2 motor subtypes: tremor-dominant (TD) and postural instability and gait difficulty (PIGD)-dominant (PG). We evaluated the role of these phenotypic variants in severity and progression of nondopaminergic manifestations of PD and motor complications.
Linear mixed models were applied to data from the Profiling Parkinson's disease (PROPARK) cohort (n = 396) to evaluate the effect of motor subtype on severity and progression of cognitive impairment (Scales for Outcomes in Parkinson's disease [SCOPA]-Cognition [SCOPA-COG]), depression (Hospital Anxiety and Depression Scale [HADS]), autonomic dysfunction (SCOPA-Autonomic [SCOPA-AUT]), excessive daytime sleepiness, psychotic symptoms (SCOPA-Psychiatric Complications [SCOPA-PC]), and motor complications. In first analyses, subtype as determined by the commonly used ratio of tremor over PIGD score was entered as a factor, whereas in second analyses separate tremor and PIGD scores were used. Results were verified in an independent cohort (Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP]; n = 365).
The first analyses showed that PG subtype patients had worse SCOPA-COG, HADS, SCOPA-AUT, SCOPA-PC, and motor complications scores, and exhibited faster progression on the SCOPA-COG. The second analyses showed that only higher PIGD scores were associated with worse scores for these variables; tremor score was not associated with severity or progression of any symptom. Analyses in the independent cohort yielded similar results.
In contrast to PIGD, which consistently was associated with greater severity of nondopaminergic symptoms, there was no evidence of a benign effect of tremor. Our findings do not support the use of the TD subtype as a prognostic trait in PD. The results showed that severity of PIGD is a useful indicator of severity and prognosis in PD by itself.
帕金森病(PD)的疾病进展存在差异,其原因可归结为 2 种运动亚型:震颤为主型(TD)和姿势不稳及步态困难为主型(PG)。我们评估了这些表型变异在 PD 非多巴胺能表现和运动并发症的严重程度和进展中的作用。
线性混合模型应用于 Profiling Parkinson's disease(PROPARK)队列(n=396)的数据,以评估运动亚型对认知障碍严重程度和进展的影响(帕金森病结局评分量表-认知分量表[SCOPA-COG])、抑郁(医院焦虑抑郁量表[HADS])、自主神经功能障碍(SCOPA-自主神经[SCOPA-AUT])、日间过度嗜睡、精神病症状(SCOPA-精神病并发症[SCOPA-PC])和运动并发症。在第一次分析中,作为一个因素,根据震颤与 PIGD 评分比确定的亚型被纳入,而在第二次分析中,单独使用震颤和 PIGD 评分。结果在一个独立的队列(Estudio Longitudinal de Pacientes con Enfermedad de Parkinson [ELEP];n=365)中得到验证。
首次分析表明,PG 亚型患者的 SCOPA-COG、HADS、SCOPA-AUT、SCOPA-PC 和运动并发症评分更差,并且 SCOPA-COG 的进展更快。第二次分析表明,只有更高的 PIGD 评分与这些变量的更差评分相关;震颤评分与任何症状的严重程度或进展均无关。独立队列的分析得出了类似的结果。
与 PIGD 一致,后者始终与非多巴胺能症状的严重程度相关,而震颤则没有良性影响的证据。我们的研究结果不支持将 TD 亚型作为 PD 的预后特征。研究结果表明,PG 的严重程度本身就是 PD 严重程度和预后的一个有用指标。