Symptom-led staging for primary progressive aphasia.
Symptom-led staging for primary progressive aphasia.
复制标题
原发性进行性失语症的症状主导分期。
DOI：
10.1101/2023.03.13.23286972
复制
发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Wood,Oli
中科院分区：
文献类型：
--
作者：
Hardy,ChrisJd;Taylor-Rubin,Cathleen;Taylor,Beatrice;Harding,Emma;Gonzalez,AidaSuarez;Jiang,Jessica;Thompson,Laura;Kingma,Rachel;Chokesuwattanaskul,Anthipa;Walker,Ffion;Barker,Suzie;Brotherhood,Emilie;Waddington,Claire;Wood,Oli
原发性进行性失语症(PPA)在诊断、治疗和预后方面面临复杂而多样的挑战。临床知情的PPA综合征分期系统将朝着迎接这些挑战迈出实质性的一步。这项研究通过对大型国际PPA队列中有生活经验的人进行详细的、多领域混合方法的症状调查来解决这一需求。我们对患有典型PPA综合征变体(非流利/无语法(NvPPA)、语义(SvPPA)或逻辑开放(LvPPA))的患者的照顾者进行了结构化的在线调查。在一项探索性调查中，英国国家PPA支持小组的118名照顾者接受了一份关于语言交流和非语言功能(非语言思维、行为和健康、身体)症状的推定清单和顺序。根据反馈，我们扩展了症状列表，并为每种PPA亚型创建了六个临时临床阶段。在一项“巩固”调查中，这些阶段被呈现给英国和澳大利亚PPA支持小组的110名照顾者成员，并根据定量和定性反馈进行细化。如果代表PPA综合征的大多数受访者(至少50%)将症状评为“存在”，则保留症状，并根据多数人的共识将其分配到一个综合阶段；根据受访者与该症状的最终分期一致的比例，估计对每个症状的分配的可信度。定性回答使用框架分析进行分析。对于每个PPA综合征，确定了从1(非常轻微)到6(严重)的6个阶段；早期以沟通障碍的综合征特征症状区分，后期跨症状趋同和对基本日常生活活动的依赖增加。在所有综合征的早期阶段都报告了拼写错误、听力变化和非语言行为特征。随着疾病的发展，nfvPPA患者比其他症状更早出现吞咽和活动障碍，而识别以svPPA为特征的熟悉的人和家庭物品的困难，以及视觉空间症状在lvPPA患者中更加突出。SvPPA的症状分期总体置信度高于其他证候。在所有症状中，功能里程碑被确定为预测主要日常生活影响和相关管理需求的顺序的关键缺陷。定性地，我们确定了五个主要主题，包括15个副主题，反映了受访者对PPA的经验和对分阶段实施的建议。这项工作介绍了典型的PPA综合征的一个典型的、以症状为导向的分期方案：PPA进展计划辅助(PPA2)。我们的发现对诊断和护理路径指南、试验设计以及对患有这些疾病的人的个性化预后和治疗具有重要意义。
The primary progressive aphasias (PPA) present complex and diverse challenges of diagnosis, management and prognosis. A clinically-informed, syndromic staging system for PPA would take a substantial step toward meeting these challenges. This study addressed this need using detailed, multi-domain mixed-methods symptom surveys of people with lived experience in a large international PPA cohort. We administered structured online surveys to caregivers of patients with a canonical PPA syndromic variant (nonfluent/agrammatic (nvPPA), semantic (svPPA) or logopenic (lvPPA)). In an ‘exploratory’ survey, a putative list and ordering of verbal communication and nonverbal functioning (nonverbal thinking, conduct and wellbeing, physical) symptoms was administered to 118 caregiver members of the UK national PPA Support Group. Based on feedback, we expanded the symptom list and created six provisional clinical stages for each PPA subtype. In a ‘consolidation’ survey, these stages were presented to 110 caregiver members of UK and Australian PPA Support Groups, and refined based on quantitative and qualitative feedback. Symptoms were retained if rated as ‘present’ by a majority (at least 50%) of respondents representing that PPA syndrome, and assigned to a consolidated stage based on majority consensus; the confidence of assignment was estimated for each symptom as the proportion of respondents in agreement with the final staging for that symptom. Qualitative responses were analysed using framework analysis. For each PPA syndrome, six stages ranging from 1 (‘Very mild’) to 6 (‘Profound’) were identified; earliest stages were distinguished by syndromic hallmark symptoms of communication dysfunction, with increasing trans-syndromic convergence and dependency for basic activities of daily living at later stages. Spelling errors, hearing changes and nonverbal behavioural features were reported at early stages in all syndromes. As the illness evolved, swallowing and mobility problems were reported earlier in nfvPPA than other syndromes, while difficulty recognising familiar people and household items characterised svPPA and visuospatial symptoms were more prominent in lvPPA. Overall confidence of symptom staging was higher for svPPA than other syndromes. Across syndromes, functional milestones were identified as key deficits that predict the sequence of major daily life impacts and associated management needs. Qualitatively, we identified five major themes encompassing 15 subthemes capturing respondents’ experiences of PPA and suggestions for staging implementation. This work introduces a prototypical, symptom-led staging scheme for canonical PPA syndromes: the PPA Progression Planning Aid (PPA2). Our findings have implications for diagnostic and care pathway guidelines, trial design and personalised prognosis and treatment for people living with these diseases.