■进行性核上性麻痹(PSP)是一种罕见的神经退行性疾病,包括几种具有各种运动和认知缺陷的表型。我们旨在研究PSP表型的运动和认知特征,并评估载脂蛋白E(APOE)基因变体对PSP表型表达的影响。
■在20年的横断面研究中,我们回顾性回顾了所有分类为PSP的患者的图表,并使用MDS-2017标准将其重新分类为表型.根据症状发作后的前3年的临床表现,将表型分为三个亚组。定义了疾病的早期阶段:理查森综合征(PSP-RS),PSP-皮层(PSP-F+PSP-SL+PSP-CBS)和PSP-皮层下(PSP-P+PSP-PGF+PSP-PI+PSP-OM+PSP-C+PSP-PLS)。收集临床和神经心理学评估数据。使用RFLP-PCR进行APOE的基因分型并通过Sanger测序进行验证。
■我们纳入了112名PSP患者,包括10种表型,分为48PSP-RS,34PSP-皮质(17.6%PSP-CBS,9.4%PSP-F,8.2%PSP-SL)和30PSP-皮层下(11.6%PSP-P,8%PSP-PI,2.6%PSP-OM,1.8%PSP-PGF,1.8%PSP-C,0.9%PSP-PLS)亚组。PSP-RS病例的发病年龄较大(p=0.009),运动障碍僵硬和左旋多巴耐药的帕金森病(p=0.006),而PSP-皮质病例有更多的震颤和不对称和/或左旋多巴反应性帕金森病(p=0.025)。PSP-皮质下亚组的认知结构域改变明显较少。总的来说,PSP-APOEε4携带者较早发展为帕金森病(p=0.019),有较早的动眼功能障碍(p=0.052)和更多的认知改变。这也与PSP-RS表型中帕金森病发病的年龄较小有关(p=0.026)。
■这项研究证明了突尼斯人中PSP的广泛表型谱。后期的疾病发作和运动障碍-刚性和左旋多巴抗性帕金森病是PSP-RS表型的标志,而轻度认知障碍是PSP-皮质下亚组的特征。APOEε4等位基因与早期的帕金森病和动眼功能障碍有关,似乎在定义PSP患者的认知特征中发挥作用。
OBJECTIVE: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder encompassing several phenotypes with various motor and cognitive deficits. We aimed to
study motor and cognitive characteristics across PSP phenotypes and to assess the influence of apolipoprotein E (APOE) gene variants on PSP phenotypic expression.
METHODS: In this 20-year cross-sectional
study, we retrospectively reviewed the charts of all patients classified as PSP patients and recategorized them according to phenotype using the Movement Disorder Society criteria (2017). Phenotypes were divided into three subgroups, Richardson\'s syndrome (PSP-RS), PSP-cortical (PSP with predominant frontal presentation [PSP-F] + PSP with predominant speech/language disorder [PSP-SL] + PSP with predominant corticobasal syndrome [PSP-CBS]) and PSP-subcortical (PSP with predominant parkinsonism [PSP-P] + PSP with progressive gait freezing [PSP-PGF] + PSP with predominant postural instability [PSP-PI] + PSP with predominant ocular motor dysfunction [PSP-OM] + PSP with cerebellar ataxia [PSP-C] + PSP with primary lateral sclerosis [PSP-PLS]), based on clinical presentation during the first 3 years after symptom onset, which defines the early disease stage. Clinical and neuropsychological assessment data were collected. Genotyping of APOE was performed using restriction fragment length polymorphism polymerase chain reaction and verified by Sanger sequencing.
RESULTS: We included 112 PSP patients comprising 10 phenotypes classified into 48 PSP-RS, 34 PSP-cortical (PSP-CBS, 17.6%; PSP-F, 9.4%; PSP-SL, 8.2%) and 30 PSP-subcortical (PSP-P, 11.6%; PSP-PI, 8%; PSP-OM, 2.7%; PSP-PGF, 1.8%; PSP-C, 1.8%; PSP-PLS, 0.9%) subgroups. PSP-RS patients were older at disease onset (p = 0.009) and had more akinetic-rigid and levodopa-resistant parkinsonism (p = 0.006), while PSP-cortical patients had more tremors and asymmetric and/or levodopa-responsive parkinsonism (p = 0.025). Cognitive domains were significantly less altered in the PSP-subcortical subgroup. Overall, PSP-APOEε4 carriers developed parkinsonism earlier (p = 0.038), had earlier oculomotor dysfunction (p = 0.052) and had more altered cognitive profiles. The APOEε4 allele was also associated with a younger age of parkinsonism onset in the PSP-RS phenotype group (p = 0.026).
CONCLUSIONS: This
study demonstrated the wide phenotypic spectrum of PSP among Tunisians. Disease onset and akinetic-rigid and levodopa-resistant parkinsonism were the hallmarks of the PSP-RS phenotype, while milder cognitive impairment was characteristic of the PSP-subcortical subgroup. The APOEε4 allele was associated with earlier parkinsonism and oculomotor dysfunction and seemed to play a role in defining a more altered cognitive profile in PSP patients.