Murakami Aya, Koga Shunsuke, Sekiya Hiroaki, Nakamura Masataka, Yakushiji Yusuke, Dickson Dennis W
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Department of Neurology, Kansai Medical University, Osaka, Japan.
Acta Neuropathol Commun. 2025 Jul 9;13(1):151. doi: 10.1186/s40478-025-02058-0.
Frontotemporal lobar degeneration with TDP-43 pathology (FTLD) usually presents with frontotemporal dementia, semantic aphasia or progressive nonfluent aphasia. Corticobasal syndrome and atypical parkinsonism have been occasionally reported, but progressive supranuclear palsy (PSP) syndrome (also known as Richardson syndrome (RS)) has not been reported in patients with FTLD-TDP. In this study we report clinical and pathologic characteristics of FTLD-TDP, clinically diagnosed as PSP syndrome (FTLD-TDP-PSP).
We reviewed clinical information of 270 patients with FTLD-TDP from the Mayo Clinic brain bank and identified 5 patients with FTLD-TDP-PSP. As a control group, we selected ten consecutive patients of pathologically confirmed PSP with clinical presentations of PSP syndrome (PSP-RS). We compared the clinical and pathological features of FTLD-TDP-PSP and PSP-RS.
The most common clinical symptoms in FTLD-TDP-PSP were memory loss (100%) followed by parkinsonism (80%), early falls (60%), and behavioral variant FTD (60%). All patients with PSP-RS met the Movement Disorder Society's criteria for probable PSP, while only one FTLD-TDP-PSP met the probable PSP. Two of the five patients with FTLD-TDP-PSP had moderate or severe neuronal loss in the substantia nigra and one had moderate or severe neuronal loss in the putamen and globus pallidus.
A small subset of patients with FTLD-TDP can, in rare instances, present with symptoms associated with PSP. Therefore, FTLD-TDP may be considered in differential diagnosis, especially in patients who do not meet the diagnostic criteria. Our findings emphasize the need for further clinical and biomarker studies of FTLD-TDP.
伴有TDP-43病理改变的额颞叶变性（FTLD）通常表现为额颞叶痴呆、语义性失语或进行性非流畅性失语。偶尔有关于皮质基底节综合征和非典型帕金森病的报道，但FTLD-TDP患者中尚未有进行性核上性麻痹（PSP）综合征（也称为理查森综合征（RS））的报道。在本研究中，我们报告了临床上诊断为PSP综合征（FTLD-TDP-PSP）的FTLD-TDP的临床和病理特征。
我们回顾了梅奥诊所脑库中270例FTLD-TDP患者的临床信息，确定了5例FTLD-TDP-PSP患者。作为对照组，我们连续选取了10例经病理证实为PSP且临床表现为PSP综合征（PSP-RS）的患者。我们比较了FTLD-TDP-PSP和PSP-RS的临床和病理特征。
FTLD-TDP-PSP最常见的临床症状是记忆力减退（100%），其次是帕金森综合征（80%）、早期跌倒（60%）和行为变异型额颞叶痴呆（60%）。所有PSP-RS患者均符合运动障碍协会可能的PSP标准，而只有1例FTLD-TDP-PSP符合可能的PSP标准。5例FTLD-TDP-PSP患者中有2例黑质存在中度或重度神经元丢失，1例壳核和苍白球存在中度或重度神经元丢失。
一小部分FTLD-TDP患者在极少数情况下可出现与PSP相关的症状。因此，在鉴别诊断中应考虑FTLD-TDP，尤其是那些不符合诊断标准的患者。我们的研究结果强调了对FTLD-TDP进行进一步临床和生物标志物研究的必要性。
