背景:非典型帕金森病综合征(APS)由于其异质性表型重叠而具有挑战性的神经退行性疾病。到目前为止,没有经过验证的生物标志物可以准确预测疾病进展,和生存研究是高度不同和矛盾的。
目的:研究突尼斯APS患者的临床和分子生存因素。
方法:一项回顾性研究包括突尼斯APS患者。使用临床和分子参数,通过Kaplan-Meier分析探讨生存率.
结果:我们包括409-APS患者,分为166-DLB,112-PSP,81-MSA和50-CBS。突触核蛋白病中的存活率相似,虽然它在tau蛋白病方面有所不同,与CBS相比,PSP更短。DLB的中位生存期因性别而异(p=0.0048),早期帕金森病和认知障碍。在MSA中,MSA-C患者(p=0.012)和喘鸣患者(p=0.0049)的预后较差,动眼神经和神经精神疾病。对于tau蛋白病,PSP-RS的生存期较短(p=0.027),小脑表型,那些有震颤和吞咽问题的人,早期帕金森病和记忆障碍。对于CBS来说,震颤患者预后较差,吞咽和认知问题。在APOE-ε4的APS非携带者(p<0.001)以及MAPT-H1携带者的APS患者的存活率方面注意到显著差异。根据MAPT单倍型携带,PSP患者的生存率较低。此外,拷贝数有影响,因为H1/H2-MAPT谱患者的预后优于H1/H1组.
结论:这项研究确定了APS亚组的生存率,在突触核蛋白病中具有可比性,但PSP较短,CBS较长。它还具有人口统计特征,表型,和遗传档案识别APS亚组中更具侵略性的形式。这些发现解决了临床差距,协助患者和家属咨询,指导临床管理。此外,在以死亡率为结局指标的临床试验中,它们可以促进患者分层.
BACKGROUND: Atypical Parkinsonian Syndromes(APS) are challenging neurodegenerative disorders due to their heterogeneous phenotypic overlaps.So far,there are no validated biomarkers that can accurately predict disease progression,and survival studies were highly different and contradictory.
OBJECTIVE: To investigate clinical and molecular survival factors among Tunisian APS patients.
METHODS: A retrospective study included Tunisian APS-patients.Using clinical and molecular parameters,survival was explored by Kaplan-Meier analysis.
RESULTS: We included 409-APS patients divided into 166-DLB,112-PSP,81-MSA and 50-CBS.Survival rate was similar in synucleinopathies, while it differed in tauopathies,being shorter in PSP compared to CBS.Median survival in DLB was different according to gender(p = 0.0048),early parkinsonism and cognitive disorders. Among MSA, prognosis was worse in MSA-C-patients(p = 0.012) and those with stridor(p = 0.0049),oculomotor and neuropsychiatric disorders. For tauopathies, survival was shorter in PSP-RS(p = 0.027),cerebellar phenotype, those with tremor and swallowing problems at onset, early parkinsonism and memory impairment. For CBS,prognosis was worse in patients with tremor,swallowing and cognitive problems.Significant differences were noted in terms of survival across APS non-carriers of
APOE-ε4(p < 0.001) as well APS patients carriers of MAPT-H1.PSP patients had lower survival rate according to MAPT haplotype carriage. Moreover, the number of copies had an influence as patients with H1/H2-MAPT profile had better prognosis than those with H1/H1.
CONCLUSIONS: This study determined survival rates in APS subgroups,which were comparable across synucleinopathies but shorter in PSP and longer in CBS.It also characterized demographic,phenotypic,and genetic profiles identifying more aggressive forms within APS subgroups.These findings address clinical gaps,aiding counseling for patients and families and guiding clinical management.Furthermore,they could facilitate patient stratification in clinical trials where mortality is an outcome measure.