logopenic型原发性进行性失语患者临床、影像及基因学特征

Characteristics of clinical presentation, neuroimaging and genetics in a patient with logopenic variant primary progressive aphasia

目的 探讨logopenic型原发性进行性失语（1vPPA）患者的临床、影像和基因学特征。方法报道1例通过临床表现、神经心理评估、神经影像及基因检测明确诊断的lvPPA患者，并总结其临床、神经影像学及基因学特点。结果本例lvPPA患者以进行性语言功能障碍起病，神经心理量表检测示自发语言中命名和复述功能严重受损、智能减退，日常生活能力和精神行为正常。神经影像检查示左侧大脑额叶、颞顶叶和外侧裂局部皮质、左侧海马结构显著萎缩及低灌注，左侧萎缩额叶皮质下白质区域FLAIR序列呈高信号，DWI与磁敏感加权成像未见异常信号，磁共振血管造影示左侧大脑中动脉血管远端较右侧明显纤细、分支稀疏，18氟标记的2-（氟-18）-2-脱氧葡萄糖正电子发射体层成像检查示左侧额、颞、顶叶及海马区域代谢水平较右侧明显降低。基因检测示颗粒蛋白前体（GRN）基因内含子区域1处已报道为可致病的剪切位点突变c．708＋1G〉A（鸟嘌呤〉腺嘌呤），及凝溶胶蛋白基因外显子区域2处尚未见报道的杂合突变点C．241A〉C（腺嘌呤〉胞嘧啶）、c．242G〉C（鸟嘌呤〉胞嘧啶）。结论lvPPA患者以自发语言中命名和复述功能障碍为特征性表现，伴有智能减退。脑萎缩及低灌注，主要累及左侧额叶、颞顶叶、外侧裂局部皮质、左侧海马结构，并伴有萎缩皮质下白质区域损害，左侧大脑中动脉血管较对侧纤细。GRN基因致病位点突变的检测有助于进一步明确lvPPA的诊断。

Objective To discuss the characteristics of clinical presentation, neuroimaging and genetics in a patient with logopenic variant primary progressive aphasia （lvPPA）. Methods A case of lvPPA diagnosed with clinical presentation, neuropsychological tests, neuroimaging and genetic testing was reported, and the clinical characteristics of lvPPA were summarized. Results The initial symptom of lvPPA was progressive language impairment. A series of neuropsychological tests showed impaired spontaneous naming, repetition and intelligence with normal daily life ability and mental behavior. Neuroimaging examination showed muhiple atrophy and hypo-perfusion in left frontal lobe, temporo-parietal lobe, lateral fissure and hippocampus. Moreover, high signal was revealed in left atrophic frontal subcortical white matter regions on FLAIR, which was normal on DWI and susceptibility weighted imaging. MR angiography showed slender left middle cerebral artery with sparse branches in distal, and lSF-fluorodeoxyglucose positron emission tomography showed hypometabolism in left frontal lobe, temporo-parietal lobe and hippocampus. Genetic testing revealed a pathogenic intron splicing mutation e. 708 ＋ 1G 〉 A reported before in progrannlin （GRN） gene, and two novel extron hybrid mutations c. 241A 〉 C and c. 242G 〉 C in gelsolin gene. Conclusions lvPPA prominently manifested with impaired spontaneous naming and repetition in progressive language disorder, accompanied with slight intelligent impairment. Atrophy and hypoperfusion regions were mainly distributed in left frontal lobe, temporo-parietal lobe, lateral fissure and hippocampus, with involvement of subcortieal white matter and slender left middle cerebral artery. Genetic testing for pathogenic mutation in GRN gene was helpful for diagnosis of IvPPA.