脑脊液NF-L pNF-H与脊髓性肌萎缩症患者病情严重程度及治疗的相关性

Correlation of cerebrospinal fluid NF-L and pNF-H with the condition and treatment of patients with spinal muscular atrophy

目的探讨脑脊液神经丝蛋白轻链(NF-L)及磷酸化神经丝蛋白重链(pNF-H)水平与脊髓性肌萎缩症(SMA)患者病情及治疗的相关性。方法选取2022-02—2023-08蚌埠医科大学第一附属医院儿科确诊为脊髓性肌萎缩(SMA)并接受诺西那生钠治疗的22例患儿为研究对象,收集患儿性别、基因检测结果、疾病分型、开始治疗的年龄、发病年龄、开始治疗前疾病持续时间等基本信息,于诺西那生钠鞘内注射前收集脑脊液标本并检测脑脊液NF-L、pNF-H水平,采用汉默史密斯功能性运动量表扩展版(HFMSE)及上肢模块修订版(RULM)对SMA患儿进行运动功能评估,比较SMA患儿开始治疗时脑脊液NF-L、pNF-H水平,分析脑脊液NF-L、pNF-H水平与开始治疗的年龄、治疗前疾病持续时间及运动功能的相关性,对比治疗期间脑脊液NF-L、pNF-H水平。结果Ⅱ型与Ⅲ型SMA患儿脑脊液NF-L水平(438.15±163.41比283.47±108.11)存在统计学差异(t=2.123,P=0.047),与Ⅱ型、Ⅲ型SMA患儿HFMSE评分(r=-0.521,P=0.15)及RULM评分(r=-0.528,P=0.014)呈负相关,接受诺西那生钠治疗后差异有统计学意义(381.21±166.80比284.94±150.08比194.53±91.09)(Z=23.684,P<0.001);Ⅱ型与Ⅲ型SMA患儿脑脊液pNF-H水平(335.04±110.30比251.64±146.64)差异无统计学意义(P>0.05),与Ⅱ型、Ⅲ型SMA患儿HFMSE评分(r=-0.471,P=0.31)及RULM评分(r=-0.577,P=0.006)呈负相关,接受诺西那生钠治疗后差异有统计学意义(306.71±128.85比179.64±69.28比130.85±49.60)(Z=22.842,P<0.001)。结论脑脊液NF-L、pNF-H水平与SMA患儿病情严重程度呈负相关,并在接受诺西那生钠修正治疗后降低。

Objective To investigate the correlation between cerebrospinal fluid neurofilament protein light chain(NF-L)and phosphorylated neurofilament protein heavy chain(pNF-H)levels and the condition and treatment of SMA patients.Methods Twenty-two children diagnosed with spinal muscular atrophy(SMA)and treated with sodium nusinersen(Nusinersen)in the Department of Paediatrics of the First Affiliated Hospital of Bengbu Medical College were selected as the study subjects between February 2022 and August 2023.Basic information such as gender,genetic test results,disease typing,age of treatment initiation,age of onset of disease,and duration of disease before treatment initiation were collected.Cerebrospinal fluid(CSF)specimens were collected before intrathecal injection of Nusinersen sodium and cerebrospinal fluid NF-L and pNF-H levels were measured,and the motor function in children with SMA was assessed by the Hammersmith functional motor scale expanded(HFMSE)and revised upper limb module(RULM).The variability of cerebrospinal fluid NF-L and pNF-H levels at the start of treatment in children with SMA were compared,and the correlation between the levels of cerebrospinal fluid NF-L and pNF-H and the age at the beginning of treatment,the duration of disease before treatment and motor function was analyzed,and the variability of CSF NF-L,pNF-H levels during treatment were compared.Results CSF NF-L levels were differentiated between children with typeⅡversus typeⅢSMA(438.15±163.41 vs 283.47±108.11,t=2.123,P=0.047),which was negatively correlated with HFMSE score(r=-0.521,P=0.15)and RULM score(r=-0.528,P=0.014)in children with typeⅡand typeⅢSMA,and produced a difference after treatment with nociceptive sodium(381.21±166.80 vs 284.94±150.08 vs 194.53±91.09,Z=23.684,P<0.001).CSF pNF-H levels did not differ statistically between patients with typeⅡand typeⅢSMA(335.04±110.30 vs 251.64±146.64,P>0.05),and were negatively correlated with HFMSE score(r=-0.471,P=0.31)and RULM score(r=-0.577,P=0.006)in children with typeⅡand typeⅢSMA,and produced a difference in the children treated with nocinafosine sodium(306.71±128.85 vs 179.64±69.28 vs 130.85±49.60,Z=22.842,P<0.001).Conclusion The levels of NF-L and pNF-H in cerebrospinal fluid is negatively correlated with the severity of SMA and decrease after treatment with nusinersen.