Barreh Guedi Ali, Sghaier Ikram, Abida Youssef, Gharbi Alya, Nasri Amina, Mrabet Saloua, Souissi Amira, Djebara Mouna Ben, Trabelsi Sameh, Kacem Imen, Gargouri-Berrechid Amina, Gouider Riadh
Neurology Department, LR18SP03, Razi University Hospital, Tunis, Tunisia.
Clinical Investigation Center (CIC) "Neurosciences and Mental Health", Razi University Hospital, Tunis, Tunisia.
J Mov Disord. 2024 Jul;17(3):294-303. doi: 10.14802/jmd.23276. Epub 2024 Apr 23.
LRRK2-G2019S is the most frequent mutation in North African Parkinson's disease (PD) patients. Data on its impact on disease progression and treatment response remain elusive. Therefore, we investigated the clinical features, treatments, and complications of PD in Tunisian patients according to their LRRK2-G2019S profile.
This longitudinal retrospective study was performed in the Department of Neurology, Razi University Hospital. We included clinically diagnosed PD patients according to the Movement Disorders Society criteria and reviewed their medical records for clinical, treatment, and neuropsychological assessments. All patients were screened for the LRRK2-G2019S mutation using Sanger sequencing. The correlation between LRRK2-G2019S and clinical PD features was evaluated.
We included 393 PD patients, 41.5% of whom had LRRK2-G2019S mutations. Patients with mutations were younger (p = 0.017), and female PD patients had a greater mutation frequency (p = 0.008). Mutation carriers exhibited distinct clinical features, with a greater frequency of postural instability gait difficulty forms (adjusted-p < 0.001). During disease progression, carriers showed a faster annual progression in the Unified Parkinson's Disease Rating Scale Section III scores (adjusted-p = 0.009), and significantly higher levodopa equivalent dose values in later stages (1060.81 vs. 877.83 for 6-8 years). Motor complications, such as dyskinesia (adjusted-p < 0.001) and motor fluctuations (31.9% vs. 25.7%, adjusted-p < 0.001), were more prevalent in carriers, particularly in the later stages. LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms, including episodic memory (adjusted-p < 0.001), attention (adjusted-p < 0.001), and dysexecutive disorders (adjusted-p = 0.038), as well as neuropsychiatric symptoms and dysautonomic signs.
The present study demonstrated that the variability of the clinical profile among Tunisian PD patients was explained by the incomplete penetrance of LRRK2-G2019S, which increased with age. Further studies using biomarker and disease progression data are necessary to improve PD management.
LRRK2-G2019S是北非帕金森病（PD）患者中最常见的突变。关于其对疾病进展和治疗反应影响的数据仍然不明确。因此，我们根据突尼斯患者的LRRK2-G2019S基因分型，对其PD的临床特征、治疗及并发症进行了研究。
这项纵向回顾性研究在拉齐大学医院神经科进行。我们纳入了根据运动障碍协会标准临床诊断为PD的患者，并查阅他们的病历以进行临床、治疗及神经心理学评估。所有患者均采用桑格测序法筛查LRRK2-G2019S突变。评估LRRK2-G2019S与临床PD特征之间的相关性。
我们纳入了393例PD患者，其中41.5%携带LRRK2-G2019S突变。携带突变的患者更年轻（p = 0.017），女性PD患者的突变频率更高（p = 0.008）。突变携带者表现出不同的临床特征，姿势性不稳步态困难型的发生率更高（校正p < 0.001）。在疾病进展过程中，携带者在统一帕金森病评定量表第三部分评分中的年进展速度更快（校正p = 0.009），且在疾病后期左旋多巴等效剂量值显著更高（6 - 8年时分别为1060.81和877.83）。运动并发症，如异动症（校正p < 0.001）和运动波动（31.9%对25.7%，校正p < 0.001）在携带者中更常见，尤其是在疾病后期。LRRK2-G2019S携带者非运动症状的患病率也较低，包括情景记忆（校正p < 0.001）、注意力（校正p < 0.001）和执行功能障碍（校正p = 0.038），以及神经精神症状和自主神经功能障碍体征。
本研究表明，突尼斯PD患者临床特征的变异性可由LRRK2-G2019S的不完全外显率来解释，且这种不完全外显率随年龄增加。有必要进一步开展使用生物标志物和疾病进展数据的研究，以改善PD的管理。
