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Progression and prognosis in multiple system atrophy presenting with REM behavior disorder.
表现为 REM 行为障碍的多系统萎缩的进展和预后。
- 影响因子:3.85
- DOI:10.1212/WNL.0000000000009372
- 作者列表:"Giannini G","Mastrangelo V","Provini F","Droghini A","Cecere A","Barletta G","Mignani F","Guaraldi P","Cortelli P","Calandra-Buonaura G
- 发表时间:2020-03-31
Abstract
OBJECTIVES:To investigate (1) the prevalence of REM sleep behavior disorder (RBD) as mode of disease onset in a cohort of patients with multiple system atrophy (MSA) and (2) disease progression and prognosis in patients with MSA with RBD predating (pre-RBD) and following (post-RBD) disease onset. METHODS:We retrospectively identified all patients with a clinical diagnosis of MSA evaluated at least once a year during the disease course. Type of onset was defined by the first reported motor or autonomic symptom/sign related to MSA. The occurrence of symptoms/signs and milestone of disease progression, and their latency from disease onset, were collected. Survival data were calculated. RBD was confirmed by video-polysomnography. RESULTS:Of a total of 158 patients, pre-RBD represented the mode of disease onset in 27% of patients, preceding disease onset according to the international criteria with a median of 3 (2-5) years. Comparing pre-RBD and post-RBD patients, the first group showed an increased prevalence of autonomic onset of disease, a reduced prevalence of parkinsonism, an earlier onset of stridor, pyramidal signs, symptomatic orthostatic hypotension, urinary dysfunction, severe dysphagia, and wheelchair dependency. The risk of death was higher in patients with pre-RBD. CONCLUSIONS:In our MSA cohort, RBD represented the most frequent mode of disease presentation. A more rapid progression of disease was observed in the pre-RBD group. These findings suggested a careful assessment of sleep disorders to early recognize RBD and a closer follow-up of autonomic dysfunction and stridor in patients with pre-RBD.
摘要
目的: 调查 (1) 多系统萎缩 (MSA) 患者队列中快速眼动睡眠行为障碍 (RBD) 作为发病模式的患病率 (2) RBD 发病前 (pre-RBD) 和发病后 (post-RBD) MSA 患者的疾病进展和预后。 方法: 我们回顾性确定了所有临床诊断为 MSA 的患者,在病程中每年至少评估一次。发病类型由首次报告的与 MSA 相关的运动或自主神经症状/体征定义。收集疾病进展的症状/体征和里程碑的发生情况,以及疾病发作的潜伏期。计算生存数据。RBD 通过视频多导睡眠图确诊。 结果: 在总共 158 例患者中,pre-RBD 代表了 27% 患者的发病模式,根据国际标准在疾病发作前,中位数为 3 (2-5) 年。比较 RBD 前和 RBD 后患者,第一组显示自主发病患病率增加,帕金森综合征患病率降低,喘鸣、锥体束征发病较早,症状性直立性低血压、排尿功能障碍、严重吞咽困难和轮椅依赖。RBD 前期患者的死亡风险较高。 结论: 在我们的 MSA 队列中,RBD 代表了最常见的疾病表现模式。在 RBD 前组中观察到疾病进展更快。这些发现建议仔细评估睡眠障碍以早期识别 RBD,并对 RBD 前期患者的自主神经功能障碍和喘鸣进行更密切的随访。
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METHODS:BACKGROUND:Neuroinflammation has been recognized as an important factor in the pathogenesis of Alzheimer's disease (AD). One of the most recognized pathways in mediating neuroinflammation is the prostaglandin E2-EP1 receptor pathway. OBJECTIVE:Here, we examined the efficacy of the selective EP1 antagonist ONO-8713 in limiting amyloid-β (Aβ), lesion volumes, and behavioral indexes in AD mouse models after ischemic stroke. METHODS:Transgenic APP/PS1, 3xTgAD, and wildtype (WT) mice were subjected to permanent distal middle cerebral artery occlusion (pdMCAO) and sham surgeries. Functional outcomes, memory, anatomical outcomes, and Aβ concentrations were assessed 14 days after surgery. RESULTS:pdMCAO resulted in significant deterioration in functional and anatomical outcomes in the transgenic mice compared with the WT mice. No relevant differences were observed in the behavioral tests when comparing the ONO-8713 and vehicle-treated groups. Significantly lower cavitation (p = 0.0373) and percent tissue loss (p = 0.0247) were observed in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 mice. However, the percent tissue injury was significantly higher in APP/PS1 + ONO-8713 mice compared with WT + ONO-8713 group (p = 0.0373). Percent tissue loss was also significantly lower in the 3xTgAD + ONO-8713 mice than in the WT + ONO-8713 mice (p = 0.0185). ONO-8713 treatment also attenuated cortical microgliosis in APP/PS1 mice as compared with the vehicle (p = 0.0079); however, no differences were observed in astrogliosis across the groups. Finally, APP/PS1 mice presented characteristic Aβ load in the cortex while 3xTgAD mice exhibited very low Aβ levels. CONCLUSION:In conclusion, under the experimental conditions, EP1 receptor antagonist ONO-8713 showed modest benefits on anatomical outcomes after stroke, mainly in APP/PS1 mice.