Jones Katherine E, Graff-Radford Jonathan, Utianski Rene L, Duffy Joseph R, Clark Heather M, Machulda Mary M, Dickson Dennis W, Whitwell Jennifer L, Josephs Keith A, Botha Hugo
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA.
Clin Neurol Neurosurg. 2025 Jun 18;256:109018. doi: 10.1016/j.clineuro.2025.109018.
Patients with progressive apraxia of speech (PAOS) often develop atypical parkinsonian features suggestive of corticobasal syndrome (CBS) or progressive supranuclear palsy (PSP), and typically have an underlying 4-repeat tauopathy at autopsy. We describe three cases of PAOS with underlying Pick's disease, a 3-repeat tauopathy, who lacked CBS or PSP features during life.
We reviewed patients enrolled in the Neurodegenerative Research Group's ongoing studies on speech and language disorders and identified those with PAOS who had autopsy-confirmed Pick's disease. All patients had comprehensive neurologic, speech-language, and neuropsychological assessments, as well as multimodal neuroimaging, during life.
Three female patients presented with phonetic PAOS without parkinsonism. Patient 1 had speech onset at age 54, later developed behavioral variant frontotemporal dementia (bvFTD), and died at 64. Patient 2 had speech onset at 47, early bvFTD features, prominent frontal and temporal involvement, and died at 53. Patient 3 had speech onset at 58, minimal behavioral changes, primarily frontal involvement on imaging, and died at 63.
Our findings highlight that Pick's disease can present with PAOS and may be distinguished from 4R-tau PAOS by an absence of motoric CBS/PSP features and, in some cases, by prominent temporal hypometabolism with bvFTD development. These atypical features may prove useful in the antemortem identification of Pick's disease as a cause of PAOS.
进行性言语失用症(PAOS)患者常出现提示皮质基底节综合征(CBS)或进行性核上性麻痹(PSP)的非典型帕金森特征,且尸检时通常存在潜在的4重复tau蛋白病。我们描述了3例患有潜在匹克病(一种3重复tau蛋白病)的PAOS患者,他们在生前没有CBS或PSP特征。
我们回顾了神经退行性疾病研究组正在进行的关于言语和语言障碍研究中纳入的患者,并确定了那些尸检确诊为匹克病的PAOS患者。所有患者在生前都接受了全面的神经、言语-语言和神经心理学评估以及多模态神经影像学检查。
3例女性患者表现为语音性PAOS,无帕金森症状。患者1在54岁时出现言语问题,后来发展为行为变异型额颞叶痴呆(bvFTD),64岁去世。患者2在47岁时出现言语问题,有早期bvFTD特征,额叶和颞叶受累明显,53岁去世。患者3在58岁时出现言语问题,行为变化轻微,影像学主要表现为额叶受累,63岁去世。
我们的研究结果表明,匹克病可表现为PAOS,且可能通过缺乏运动性CBS/PSP特征与4R-tau PAOS相鉴别,在某些情况下,还可通过伴有bvFTD发展的明显颞叶低代谢来鉴别。这些非典型特征可能有助于生前将匹克病识别为PAOS的病因。