Department of Neurology, St. Olav's University Hospital, Trondheim, Norway.
Parkinsonism Relat Disord. 2011 Aug;17(7):528-32. doi: 10.1016/j.parkreldis.2011.04.014. Epub 2011 Jun 8.
Several non-motor features have been reported to precede the motor signs of Parkinson's disease (PD) by several years. However, the time of onset of non-motor and motor symptoms is still debated. Healthy individuals carrying a PD-related mutation are candidates for studying the earliest disease signs.
To describe clinically healthy family members of PD patients carrying a LRRK2 mutation (LRRK2-PD).
A total of 47 family members of LRRK2-PD patients were included in the present study and were screened for the p.G2019S and p.N1437H substitutions in the LRRK2 gene. A standardized case report form was filled out in each case, including general medical evaluation, neurological examination with UPDRS, an olfaction test, mood, sleep and cognitive questionnaires.
Thirty-two study participants were positive, and 15 were negative for a LRRK2 mutation. Higher UPDRS motor scores, more frequent reports of urinary problems, and fewer hours of sleep were found in mutation carriers compared to non-carriers. The mutation carriers with UPDRS ≥8 were all aged over 50 years, had shorter overall sleeping hours, more frequent urinary and constipation problems, higher mood scores and body mass index. Deterioration of olfaction was not detected in either group.
Healthy LRRK2 mutation carriers presented subclinical parkinsonian motor and non-motor signs in the apparent absence of olfactory loss. Longitudinal studies will determine whether these changes precede alterations detectable by neuroimaging.
已有报道称，几种非运动症状在帕金森病（PD）的运动症状出现前几年就已经出现。然而，非运动和运动症状的发病时间仍存在争议。携带 PD 相关突变的健康个体是研究最早疾病迹象的候选者。
描述携带 LRRK2 突变（LRRK2-PD）的 PD 患者的健康家族成员。
本研究共纳入 47 名 LRRK2-PD 患者的家族成员，并对 LRRK2 基因中的 p.G2019S 和 p.N1437H 取代进行筛查。对每位患者填写标准化病例报告表，包括一般医学评估、UPDRS 神经检查、嗅觉测试、情绪、睡眠和认知问卷。
32 名研究参与者的 LRRK2 基因突变检测结果为阳性，15 名参与者的 LRRK2 基因突变检测结果为阴性。与非携带者相比，突变携带者的 UPDRS 运动评分更高、更频繁地报告出现尿失禁问题、睡眠时间更短。UPDRS≥8 的突变携带者均为 50 岁以上，总睡眠时间较短，尿失禁和便秘问题更频繁，情绪评分和体重指数更高。两组患者的嗅觉恶化均未检测到。
在明显没有嗅觉丧失的情况下，健康的 LRRK2 突变携带者出现亚临床帕金森病的运动和非运动症状。纵向研究将确定这些变化是否早于神经影像学可检测到的改变。
