不宁腿综合征患者脑铁代谢的变化

Changes of brain iron metabolism in patients with restless legs syndrome

目的 探讨不宁腿综合征患者脑铁代谢的变化.方法 连续收集2012年5月至2013年9月在南昌大学第二附属医院神经内科就诊的不宁腿综合征（RLS）患者35例和年龄、性别相匹配的健康志愿者35名.采用3.0T MR系统对RLS患者和健康志愿者进行多回波采集的增强T2加权血管成像（ESWAN）序列扫描,感兴趣区包括红核、黑质致密部、黑质网状部、丘脑、苍白球、壳核、尾状核头部、齿状核和脑脊液共9个部位,应用以年龄为协变量的协方差分析方法对两者之间的脑铁含量进行统计学分析.结果 RLS患者脑内双侧感兴趣区的铁含量明显低于健康对照者,尤其在红核（3.286±0.044与3.260±0.028,F=8.372,P=0.005）、黑质致密部（3.323±0.046与3.296±0.030,F=8.741,P=0.004）、黑质网状部（3.274±0.051与3.247±0.034,F=6.525,P=0.013）、苍白球（3.257±0.044与3.228±0.049,F=6.275,P=0.015）、丘脑（3.382±0.060与3.354±0.039,F =5.084,P=0.027）、齿状核（3.285±0.057与3.261±0.027,F=5.080,P=0.027）的铁含量减少差异有统计学意义,并且与RLS严重程度量表评分呈负相关（r=-0.836～-0.507,P=0.000～0.002）.RLS患者右侧感兴趣区的脑铁含量低于左侧,但左右两侧差异无统计学意义.重度RLS患者的脑铁含量较轻中度RLS患者及健康对照者明显降低（F=3.859～ 30.238;P=0.000～ 0.026）.血清铁蛋白的变化与脑铁代谢变化并不完全一致,虽然血清铁蛋白≥45 μg/L组和＜45 μg/L组与对照组比较,双侧苍白球（F=5.538,P=0.006）、黑质致密部（F=5.309,P=0.007）、黑质网状部（F=3.918,P=0.025）、红核（F =4.651,P=0.013）的铁含量明显降低,差异有统计学意义,但血清铁蛋白≥45 μg/L组与血清铁蛋白＜45 μg/L组比较,除苍白球外,所有感兴趣区脑铁含量差异均无统计学意义.结论 RLS患者脑铁含量明显降低,以红核、黑质、苍白球最为明显,病情严重时脑铁代谢异常的范围更广,并且RLS患者的脑铁含量与RLS严重程度量表评分呈负相关.血清铁蛋白测定在RLS诊治中的价值需进一步评估.

Objective To investigate the changes of brain iron metabolism in patients with restless legs syndrome （RLS）.Methods Thirty-five patients with RLS and thirty-five sex-and age-matched healthy volunteers were consecutively collected in the Department of Neurology of the Second Affiliated Hospital of Nanchang University from May 2012 to Septemper 2013.Patients with RLS and healthy volunteers were analyzed on enhanced T2-star weighted angiography image （3.0 T）,using region of interest （ROI） in red nucleus （RN）,substantia nigra pars compacta （SNc）,substantia nigra pars reticulata （SNr）,thalamus （Th）,globus pallidus （GP）,putamen （PU）,head of caudate nucleus （CN）,dentate nucleus （DN）,cerebrospinal fluid （CSF）.The differences between the two groups were evaluated by analysis of covariance with age as a covariate.Results Brain iron content in the ROI was significantly lower in RLS patients compared with controls,such as RN （3.286 ± 0.044 vs 3.260 ± 0.028,F =8.372,P =0.005）,SNc （3.323 ± 0.046 vs 3.296 ± 0.030,F =8.741,P =0.004）,SNr （3.274 ± 0.051 vs 3.247 ± 0.034,F =6.525,P =0.013）,GP （3.257 ±0.044 vs 3.228 ±0.049,F=6.275,P =0.015）,Th （3.382-±0.060 vs 3.354 ±0.039,F=5.084,P =0.027） and DN （3.285 ±0.057 vs 3.261±0.027,F=5.080,P=0.027）.There was a strong negative correlation between the iron content in the six regions （RN,SNc,SNr,GP,Th,DN） and International RLS Study Group Rating Scale （IRLS） score （ranging from r =-0.507,P =0.002 to r =-0.836,P =0.000）.Brain iron content in the right ROI of RLS patients trended to be lower than that in the left,with no statistically significant difference.Brain iron content was significantly lower in the severe RLS group than either the mild-to-moderate group or controls （ranging from F =3.859,P =0.026 to F =30.238,P =0.000）.Although brain iron content in GP （F =5.538,P =0.006）,SNc （F =5.309,P =0.007）,SNr （F =3.918,P =0.025） and RN （F =4.651,P =0.013） was significantly lower in RLS patients with either serum ferritin ≥ 45 μg/L or 〈 45 μg/L,compared with controls,the change in serum ferritin level was not completely consistent with change of iron metabolism in brain.No significant difference was observed in the ROI （except GP） between the groups with serum ferritin ≥ 45 μg/L and 〈45 μg/L.Conclusions RLS patients present a low iron content in brain,especially in RN,SN and GP,with more regions involved in severer cases.There is a strong negative correlation between brain iron content and IRLS score.The value of serum ferritin in the diagnosis of RLS needs further evaluation.