Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system. Patients with FTLD were distributed between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive supranuclear palsy, eight Pick's disease, three frontotemporal dementia with parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one with motor neuron disease, 27 type B including 21 with motor neuron disease, eight type C with right temporal lobe presentations, and 11 unclassifiable including eight with motor neuron disease), FTLD-FUS (eight patients), and one patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy-nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least 'possible' bvFTD diagnostic criteria at first presentation. The frequency of the six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP, suggesting that these features alone cannot be used to separate patients by major molecular class. Voxel-based morphometry revealed that nearly all pathological subgroups and even individual patients share atrophy in anterior cingulate, frontoinsula, striatum, and amygdala, indicating that degeneration of these regions is intimately linked to the behavioural syndrome produced by these diverse aetiologies. In addition to these unifying features, symptom profiles also differed among pathological subtypes, suggesting distinct anatomical vulnerabilities and informing a clinician's prediction of pathological diagnosis. Data-driven classification into one of the 10 most common pathological diagnoses was most accurate (up to 60.2%) when using a combination of known predictive factors (genetic mutations, motor features, or striking atrophy patterns) and the results of a discriminant function analysis that incorporated clinical, neuroimaging, and neuropsychological data.

中文翻译：

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行为变异型额颞叶痴呆的临床病理学相关性。


准确预测行为变异型额颞叶痴呆 (bvFTD) 患者潜在的神经病理学诊断对临床医生来说是一项艰巨的挑战，但对于疾病缓解疗法的成功至关重要。我们试图通过探索大型 bvFTD 队列中的临床病理相关性来改善病理预测。在 438 名 bvFTD 为首要或替代可能临床诊断的患者中，117 名患者有可用的尸检数据，其中 98 名原发性病理诊断为额颞叶变性 (FTLD)，15 名患有阿尔茨海默氏病，4 名患有肌萎缩侧索硬化症。缺乏运动系统之外的神经退行性疾病相关病理学。 FTLD 患者分布在 FTLD-tau 之间（34 名患者：10 名皮质基底节变性、9 名进行性核上性麻痹、8 名皮克病、3 名额颞叶痴呆伴 17 号染色体相关帕金森病、3 名无法分类的 tau 病和 1 名嗜银颗粒病）； FTLD-TDP（55 名患者：9 名 A 型患者，包括 1 名运动神经元疾病患者；27 名 B 型患者，包括 21 名运动神经元疾病患者；8 名 C 型患者，有右颞叶表现；11 名无法分类的患者，包括 8 名运动神经元疾病患者），FTLD-FUS （8 名患者），以及一名 FTLD-泛素蛋白酶体系统阳性包含物 (FTLD-UPS) 的患者，其 tau、TDP-43 和 FUS 染色呈阴性。阿尔茨海默病在随访期间唯一的首要诊断是 bvFTD 的患者中并不常见（6%）。 79% 的 FTLD-tau、86% 的 FTLD-TDP 和 88% 的 FTLD-FUS 在首次就诊时至少满足“可能的”bvFTD 诊断标准。 6 个核心 bvFTD 诊断特征的频率在 FTLD-tau 和 FTLD-TDP 中相似，表明这些特征不能单独用于按主要分子类别区分患者。基于体素的形态测量显示，几乎所有病理亚组甚至个别患者都存在前扣带回、额岛叶、纹状体和杏仁核萎缩，表明这些区域的退化与这些不同病因产生的行为综合征密切相关。除了这些统一的特征之外，病理亚型之间的症状特征也有所不同，表明不同的解剖学脆弱性，并为临床医生对病理诊断的预测提供信息。当结合使用已知的预测因素（基因突变、运动特征或显着的萎缩模式）和判别函数分析的结果时，数据驱动的分类为 10 种最常见的病理诊断之一是最准确的（高达 60.2%）结合了临床、神经影像和神经心理学数据。