Analysis of the relationship between serum NfL, MIP-1&#x03B1;, LRG1 and neurological sequelae in children with viral encephalitis

doi:10.3877/cma.j.issn.2095-123X.2025.05.005

Abstract

Abstract:

Objective

To analyze the relationship between serum neurofilament light chain protein (NfL), macrophage inflammatory protein-1α (MIP-1α), leucine-rich α-2 glycoprotein 1 (LRG1) and neurological sequelae in children with viral encephalitis (VE).

Methods

One hundred and fifty VE children admitted to Pediatrics Department of Yulin Hospital, First Affiliated Hospital of Xi'an Jiaotong University from February 2020 to January 2023 were selected. After 6 months of follow-up, VE children were divided into sequelae group and non-sequelae group according to whether neurological sequelae occurred or not. Baseline data and the levels of serum NfL, MIP-1α, LRG1 of the two groups of children were compared. The related factors leading to neurological sequelae were analyzed by multivariate Logistic regression analysis, and the clinical value of serum NfL, MIP-1α, LRG1 alone and in combination in predicting neurological sequelae were analyzed by receiver operating characteristic (ROC) curve.

Results

The levels of serum NfL, MIP-1α, LRG1 in sequelae group were higher than those in non-sequelae group (P<0.05). The proportion of children with status epilepticus and alanine aminotransferase >40 U/L in the sequelae group was higher than that in the non-sequelae group, and the PCIS score was lower than that in the non-sequelae group (P<0.05). Moreover, there were statistically significant differences in the distribution of cranial MRI grades and abnormal electroencephalogram conditions between the two groups (P<0.05). Multivariate Logistic regression analysis showed that, status convulsion, serum NfL, MIP-1α and LRG1 were independent influencing factors for neurological sequelae in VE children (P<0.05). ROC curve analysis showed that, the area under the curve (AUC) of serum NfL, MIP-1α and LRG1 alone in predicting neurological sequelae was 0.766, 0.778 and 0.807 respectively, the AUC of combined detection was 0.888, which was significantly higher than that of single detection (P<0.05).

Conclusions

The levels of serum NfL, MIP-1α and LRG1 in VE children are abnormally increase, and the combine detection of serum NfL, MIP-1α and LRG1 is helpful to assist the evaluation of neurological sequelae.

Key words: Viral encephalitis, Neurofilament light chain protein, Macrophage inflammatory protein-1α, Leucine-rich α-2 glycoprotein 1, Neurological sequelae

Shenqin Nie, Yanan Hao, Jie Sun, Diaoyan Gao. Analysis of the relationship between serum NfL, MIP-1α, LRG1 and neurological sequelae in children with viral encephalitis[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2025, 15(05): 281-287.

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References 27

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项目	后遗症组（n=37）	非后遗症组（n=113）	t/χ²/Z值	P值
性别[例（%）]			0.150	0.698
男	21（56.76）	60（53.10）
女	16（43.24）	53（46.90）
年龄[例（%）]			1.309	0.253
>6岁	25（67.57）	87（76.99）
≤6岁	12（32.43）	26（23.01）
发病至入院时间（d，mean±SD）	2.20±0.44	2.05±0.41	1.897	0.060
主要症状[例（%）]
持续高热	33（89.19）	95（84.07）	0.583	0.445
意识障碍	20（54.05）	47（41.59）	1.751	0.186
惊厥持续状态	23（62.16）	29（25.66）	16.394	<0.001
频繁抽搐状态（≥3次）	19（51.35）	41（36.28）	2.637	0.105
精神行为异常	20（54.05）	42（37.17）	2.860	0.091
巴氏征阳性	25（67.57）	68（60.18）	0.646	0.421
脑膜刺激征阳性	14（37.84）	38（33.63）	0.218	0.641
偏瘫	14（37.84）	26（23.01）	3.134	0.077
颅脑MRI分级[例（%）]			2.175	0.030
1级	19（51.35）	77（68.14）
2级	8（21.62）	22（19.47）
3级	7（18.92）	14（12.39）
4级	3（8.11）	0（0.00）
脑电图异常分级[例（%）]			4.203	<0.001
正常	3（8.11）	32（28.32）
轻度	10（27.05）	51（45.13）
中度	19（51.35）	26（23.01）
重度	5（13.51）	4（3.54）
小儿危重病例评分（分，mean±SD）	72.40±8.54	88.92±5.21	14.096	<0.001
脑脊液有核细胞数（×10⁶/L，mean±SD）	108.11±65.22	132.40±84.06	1.605	0.111
脑脊液蛋白质含量>400 mg/L[例（%）]	22（59.46）	52（46.02）	2.015	0.156
C反应蛋白>8 mg/L[例（%）]	25（67.57）	61（53.98）	2.103	0.147
谷丙转氨酶>40 U/L[例（%）]	17（45.95）	23（20.35）	9.335	0.002
肌酸激酶同工酶>24 U/L[例（%）]	16（43.24）	40（35.40）	0.733	0.392
乳酸脱氢酶>245 U/L[例（%）]	25（67.57）	62（54.87）	1.846	0.174

项目	后遗症组（n=37）	非后遗症组（n=113）	t/χ²/Z值	P值
性别[例（%）]			0.150	0.698
男	21（56.76）	60（53.10）
女	16（43.24）	53（46.90）
年龄[例（%）]			1.309	0.253
>6岁	25（67.57）	87（76.99）
≤6岁	12（32.43）	26（23.01）
发病至入院时间（d，mean±SD）	2.20±0.44	2.05±0.41	1.897	0.060
主要症状[例（%）]
持续高热	33（89.19）	95（84.07）	0.583	0.445
意识障碍	20（54.05）	47（41.59）	1.751	0.186
惊厥持续状态	23（62.16）	29（25.66）	16.394	<0.001
频繁抽搐状态（≥3次）	19（51.35）	41（36.28）	2.637	0.105
精神行为异常	20（54.05）	42（37.17）	2.860	0.091
巴氏征阳性	25（67.57）	68（60.18）	0.646	0.421
脑膜刺激征阳性	14（37.84）	38（33.63）	0.218	0.641
偏瘫	14（37.84）	26（23.01）	3.134	0.077
颅脑MRI分级[例（%）]			2.175	0.030
1级	19（51.35）	77（68.14）
2级	8（21.62）	22（19.47）
3级	7（18.92）	14（12.39）
4级	3（8.11）	0（0.00）
脑电图异常分级[例（%）]			4.203	<0.001
正常	3（8.11）	32（28.32）
轻度	10（27.05）	51（45.13）
中度	19（51.35）	26（23.01）
重度	5（13.51）	4（3.54）
小儿危重病例评分（分，mean±SD）	72.40±8.54	88.92±5.21	14.096	<0.001
脑脊液有核细胞数（×10⁶/L，mean±SD）	108.11±65.22	132.40±84.06	1.605	0.111
脑脊液蛋白质含量>400 mg/L[例（%）]	22（59.46）	52（46.02）	2.015	0.156
C反应蛋白>8 mg/L[例（%）]	25（67.57）	61（53.98）	2.103	0.147
谷丙转氨酶>40 U/L[例（%）]	17（45.95）	23（20.35）	9.335	0.002
肌酸激酶同工酶>24 U/L[例（%）]	16（43.24）	40（35.40）	0.733	0.392
乳酸脱氢酶>245 U/L[例（%）]	25（67.57）	62（54.87）	1.846	0.174

组别	例数	NfL（g/L）	MIP-1α（pg/L）	LRG1（μg/mL）
后遗症组	37	4.26±1.20	134.40±14.25	14.85±2.61
非后遗症组	113	3.17±0.86	110.24±12.36	9.34±1.95
t值		3.043	9.930	13.661
P值		<0.001	<0.001	<0.001

组别	例数	NfL（g/L）	MIP-1α（pg/L）	LRG1（μg/mL）
后遗症组	37	4.26±1.20	134.40±14.25	14.85±2.61
非后遗症组	113	3.17±0.86	110.24±12.36	9.34±1.95
t值		3.043	9.930	13.661
P值		<0.001	<0.001	<0.001

因素	偏回归系数	标准误	Wald χ²值	P值	OR值	95%CI
惊厥持续状态	1.552	0.375	17.129	<0.001	4.721	2.918~6.779
谷丙转氨酶>40 U/L	0.257	0.219	1.377	0.823	1.293	0.585~2.856
颅脑MRI分级3/4级	0.774	0.652	1.409	0.771	2.168	0.867~5.421
脑电图中/重度异常	0.704	0.682	1.066	0.904	2.022	0.914~4.471
PCIS评分	0.091	0.063	2.086	0.087	1.095	0.968~1.239
NfL	0.521	0.142	13.462	<0.001	1.684	1.105~2.094
MIP-1α	0.698	0.218	10.252	<0.001	2.010	1.642~4.335
LRG1	1.260	0.403	9.775	<0.001	3.525	2.053~6.220

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指标	截断值	敏感度（%）	特异度（%）	约登指数	AUC	95%CI
NfL	3.9 g/L	70.27	80.53	0.508	0.766	0.690~0.831
MIP-1α	17.48 pg/L	81.08	71.68	0.528	0.778	0.702~0.842
LRG1	12.36 μg/mL	72.97	78.76	0.517	0.807	0.734~0.866
联合检测	0.506^*	78.38	96.46	0.748	0.888	0.826~0.934

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[3]	Dandan Liu, Meizhen Sun, Junping Zhao. Relationship between interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in serum and cerebrospinal fluid and acute viral encephalitis with seizures [J]. Chinese Journal of Clinicians(Electronic Edition), 2017, 11(16): 2120-2124.
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