脑组织铁沉积病的临床、影像学及遗传学特征分析

Analysis of clinical, imaging and genetic characteristics of bra in iron accumulation

目的 探讨脑组织铁沉积病的临床、影像学、遗传学特征及其关联性。方法 选取2018年4月至2022年3月首都医科大学宣武医院收治的脑组织铁沉积病患者62例。收集患者的临床、影像学和遗传学资料,分析认知障碍、帕金森综合征和共济失调与铁沉积部位和脑代谢异常的关联性。采用全外显子测序或三核苷酸重复序列检测部分遗传性疾病的基因突变。结果 62例患者的常见临床表现依次为认知障碍39例(62.9%),锥体束征37例(59.7%),帕金森综合征36例(58.1%)和共济失调34例(54.8%)。25例完成正电子发射断层成像/CT(positron emission tomography/computed tomography, PET/CT)检查的认知障碍者中,21例(84.0%)显示皮质代谢减低。36例帕金森综合征中,壳核铁沉积16例(44.4%),齿状核铁沉积24例(66.7%),显著高于无帕金森综合征患者壳核铁沉积(5/26,19.2%)与齿状核铁沉积(10/26,38.5%)的比例,差异有统计学意义(P<0.05)。PET/CT显示壳核代谢无异常的11例患者中,有9例对多巴丝肼效果敏感(81.8%),高于PET/CT显示壳核代谢减低者的敏感比例(2/7,28.6%),差异有统计学意义(P<0.05)。有15例患者携带致病基因突变,携带突变患者的发病年龄小于未携带突变患者[(30.0±10.9)岁比(48.6±15.9)岁],差异有统计学意义(P<0.001)。结论 脑组织铁沉积病的病因复杂多样,对于早期出现认知障碍、帕金森综合征等症状的患者,除常规临床和影像学评价,还应完善基因检测、磁敏感加权成像和PET/CT扫描,以完整地评价其病因和病理学机制。

Objective To investigate the clinical, imaging and genetic characteristics of brain iron accumulation and their relationships. Methods A total of 62 patients with brain iron accumulation admitted to Xuanwu Hospital, Capital Medical University from April 2018 to March 2022 were selected. The clinical, imaging and genetic characteristics of the patients were collected to analyze the relationship of cognitive impairment, Parkinson’s syndrome,and ataxia with iron deposition sites and abnormal brain metabolism. Genetic mutations in some diseases were detected by whole-exome sequencing or trinucleotide repeat expansion analysis. Results The common clinical manifestations of the 62 patients were cognitive impairment in 39 cases(62.9%), pyramidal sign in 37 cases(59.7%), Parkinson’s syndrome in 36 cases(58.1%) and ataxia in 34 cases(54.8%). Among the 25 patients with cognitive impairment who received positron emission tomography/computed tomography(PET/CT) examination for brain metabolism, 21(84.0%)showed cortical hypometabolism. In the 36 cases with Parkinson’s syndrome, there were 16 cases(44.4 %) with putamen iron deposition, 24 cases(66.7%) in dentate nuclei, which were more frequent than the cases with iron deposition i n putamen(5/26, 19.2%) and dentate nuclei(10/26, 38.5%) without Parkinson’s syndrome, the differences were statistically significant(P<0.05). Among the 11 patients whose putamen metabolism showed no abnormality in PET/CT, nine patients were sensitive to levodopa/benserazide(81.8%), which was higher than that of patients with hypometabolism in putamen by PET/CT(2/7, 28.6%). There were 15 patients with pathogenic gene mutations, and the onset age of patients with mutations was younger than that of patients without mutations [(30.0±10.9) years vs.(48.6±15.9) years], the difference was statistically significant(P<0.001). Conclusions The etiology of brain iron accumulation is complex and diverse. In addition to routine clinical and imaging eva luation, gene testing, magnetic sensitivity weighted imaging and PET/CT scanning should be improved in order to evaluate the etiology and pathological mechanism of patients with early cognitive impairment and Parkinson’s syndrome.