Devenney Emma M, McErlean Kate, Tse Nga Yan, Caga Jashelle, Dharmadasa Thanuja, Huynh William, Mahoney Colin J, Zoing Margaret, Mazumder Srestha, Dobson-Stone Carol, Kwok John B, Halliday Glenda M, Hodges John R, Piguet Olivier, Ahmed Rebekah M, Kiernan Matthew C
Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.
Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.
Front Neurol. 2021 Nov 25;12:743688. doi: 10.3389/fneur.2021.743688. eCollection 2021.
This study aimed to establish (1) the pattern and severity of neuropsychiatric symptoms and other non-motor symptoms of sleep and mood, across ALS phenotypes in comparison to bvFTD and (2) the contribution of non-modifiable factors including age, sex and disease state to the severity of symptoms experienced by ALS patients. Consecutive participants were recruited to the study and underwent a detailed clinical, cognitive, behavioral and neuroimaging assessment. Neuropsychiatric and other non-motor symptoms were determined using the Cambridge Behavioral Inventory, the CBI-R. The scores were converted to define impairment in terms of mild, moderate and severe symptoms for each subscale. Rate, severity and contribution of King's staging and modifiable factors were also determined and a regression model identified predictors of symptom severity. In total, 250 participants (115 ALS, 98 bvFTD, and 37 ALS-FTD patients) were recruited. A similar pattern of neuropsychiatric symptom severity was identified (apathy, disinhibition and stereotypic behavior) for all behavioral phenotypes of ALS compared to bvFTD (all > 0.05). Neuropsychiatric symptoms were also present in cases defined as ALSpure and the cognitive phenotype of ALS (ALSci) although they occurred less frequently and were at the milder end of the spectrum. Disordered sleep and disrupted mood were common across all phenotypes (all < 0.05). The severity of sleep dysfunction was influenced by both sex and age (all < 0.05). Neuropsychiatric symptoms, sleep and mood disorders were common early in the disease process and deteriorated in line with progression on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R; all < 0.05). Diagnostic phenotype, disease duration and global cognition scores were the strongest predictors of non-motor and neuropsychiatric impairments. The current findings reveal strikingly similar patterns of changes across the subgroups of ALS and bvFTD, supporting the concept of the ALS-FTD spectrum. The findings further highlight the impact of non-motor and neuropsychiatric symptoms in patients with ALS, that are often as severe as that seen in ALS-FTD and bvFTD. This study advances understanding across the ALS-FTD spectrum that may accelerate the early identification of patient needs, to ensure prompt recognition of symptoms and thereby to improve clinical awareness, patient care and management.
（1）确定肌萎缩侧索硬化（ALS）各表型与行为变异型额颞叶痴呆（bvFTD）相比，神经精神症状以及睡眠和情绪方面其他非运动症状的模式和严重程度；（2）确定年龄、性别和疾病状态等不可改变因素对ALS患者所经历症状严重程度的影响。连续的参与者被招募到本研究中，并接受详细的临床、认知、行为和神经影像学评估。使用剑桥行为量表（CBI-R）确定神经精神症状和其他非运动症状。分数被转换以根据每个子量表的轻度、中度和重度症状来定义损伤。还确定了King分期和可改变因素的发生率、严重程度及影响，并通过回归模型确定症状严重程度的预测因素。总共招募了250名参与者（115名ALS患者、98名bvFTD患者和37名ALS-FTD患者）。与bvFTD相比，在ALS的所有行为表型中均发现了相似的神经精神症状严重程度模式（冷漠、脱抑制和刻板行为，所有P>0.05）。在定义为ALS纯合型和ALS认知表型（ALSci）的病例中也存在神经精神症状，尽管其发生频率较低且处于症状谱的较轻端。睡眠紊乱和情绪障碍在所有表型中都很常见（所有P<0.05）。睡眠功能障碍的严重程度受性别和年龄两者影响（所有P<0.05）。神经精神症状、睡眠和情绪障碍在疾病过程早期很常见，并随着肌萎缩侧索硬化功能评定量表修订版（ALSFRS-R）的进展而恶化（所有P<0.05）。诊断表型、疾病持续时间和整体认知分数是非运动和神经精神损伤的最强预测因素。当前研究结果揭示了ALS和bvFTD亚组之间惊人相似的变化模式，支持了ALS-FTD谱系的概念。这些结果进一步突出了非运动和神经精神症状对ALS患者的影响，其严重程度通常与ALS-FTD和bvFTD患者所见相当。本研究推进了对ALS-FTD谱系的理解，这可能会加速对患者需求的早期识别，以确保及时识别症状，从而提高临床意识、患者护理和管理水平。
