Clinical analysis of myelin oligodendrocyte glycoprotein antibody-associated inflammatory demyelinationdisease among children

doi:10.3877/cma.j.issn.1673-5250.2021.03.012

Objective

To investigate clinical manifestations, imaging features, treatment and prognosis of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated inflammatory demyelination disease (IDD).

Methods

Seven children with MOG autoantibody-associated IDD diagnosed at the Department of Pediatrics, Sun Yat-Sen Memorial Hospital of Sun Yat-sen University from June 1, 2014 to September 30, 2020 were selected as research subjects, including 2 girls and 5 boys with an average age of 8.3 years old. The clinical features, imaging findings, treatment and prognosis of 7 children with MOG antibody-related IDD were analyzed retrospectively. The procedures followed in this study were in line with the requirements of the World Medical Association Declaration of Helsinki revised in 2013.

Results

①At initial diagnosis, the 7 cases were misdiagnosed as acute disseminated encephalomyelitis (ADEM, 2 cases), optic neuritis (ON, 2 cases), multiple sclerosis (MS, 1 case), meningitis (1 case) and autoimmune encephalitis (AE, 1 case). Among them, the younger children presented with ON symptoms, while the older children presented with ADEM symptoms. ②Among the 7 cases, 2 cases had elevated white blood cell count (WBC) and protein level in cerebrospinal fluid, 6 cases with intracranial pressure >200 mmH₂O (1 mmH₂O=0.098 1 kPa). All the children were positive for MOG antibody in peripheral blood, 6 cases were positive for MOG antibody in cerebrospinal fluid, and 1 case was positive for anti-CASPR-2 antibody in peripheral blood. ③Among the 7 children, the results of laboratory examination showed that WBC increased in 2 cases, and C-reaction protein (CRP) was positive and erythrocyte sedimentation rate (ESR) increased in 1 case in peripheral blood. All the children′s peripheral blood MOG antibody were positive, and 1 child′s peripheral blood anti-CASPR-2 antibody was positive.④The results of imaging examination showed that the lesions involved around the lateral ventricle in 5 cases, basal ganglia in 3 cases, thalamus, spinal cord and optic nerve in 2 cases, brainstem in 1 case and medulla oblongata in 1 case, meningeal enhancement in 1 case. The lesion diameters of 7 cases were larger than 2 cm. In addition, a clear boundary of lesions could be found in 3 children whose ages were more than 5 years old.⑤In the acute phase, 1 child was treated with methylprednisolone [10-30 mg/ (kg·d), dose halved every 3 days] and intravenous immunoglobulin (IVIG) [2 g/(kg·d)×1 d], and 6 children were treated with dexamethasone [initial dose of 0.5 mg/(kg·d) and IVIG 0.4 g/(kg·d)×5 d]. During the maintenance period, all of them were treated with oral prednisone, and 5 of them were treated with IVIG (2 g/kg) every month. 2 recurrent children were treated with methylprednisolone and IVIG again, and 1 of them was treated with rituximab (375 mg/m², once a week for 4 times). After treatment, 5 children recovered completely and 2 children partially recovered. The average annualized relapse rate (ARR) was 0.4 times per year.

Conclusions

MOG antibody-associated IDD has various clinical manifestations and is easy to be misdiagnosed in the early stage. MOG antibody and AE-related antibody can exist at the same time, and most of the imaging findings are multifocal lesions. Although MOG antibody-associated IDD is mediated by antibody, the immunopathogenicity of MOG antigen is closely related to T cells and B cells. MOG-antibody is sensitive to hormones and has a good prognosis even in the case of multiple relapses.

Key words: Demyelinating diseases, Inflammation, Central nervous system, Antibodies, Magnetic resonance imaging, Recurrence, Glucocorticoids, Child

表1 本组7例MOG抗体相关IDD患儿的临床资料比较

病例(No.)	性别	发病年龄(岁)	感染前驱症状	初始合并症状	发病时诊断	急性期治疗方案	维持治疗方案	ARR(次/年)	随访时间(月)	疗效
1	男	5	有	发热、头痛、视物模糊及眼睛疼痛	ON	甲泼尼龙+IVIG	IVIG+泼尼松	0	16	完全恢复
2	女	5	无	性格改变、头晕及疲劳	脑膜炎	地塞米松+IVIG	IVIG+泼尼松	1	37	部分恢复
3	男	12	无	右手小指、无名指肌无力，右手腕部肌无力	ADEM	地塞米松+IVIG	泼尼松	0	26	完全恢复
4	男	13	有	发热、排尿困难、双下肢运动障碍及疼痛	ADEM	地塞米松+IVIG	泼尼松	0	16	完全恢复
5	女	4	无	反复头痛	MS	地塞米松+IVIG	IVIG+泼尼松	1.4	76	部分恢复
6	男	2	无	反复发热、步态不稳、斜颈、呕吐	AE	地塞米松+IVIG	IVIG+泼尼松	0	15	完全恢复
7	男	7	无	右侧肢体麻木、右下肢轻微跛行、左侧眼睑下垂及视物模糊	ON	地塞米松+IVIG	IVIG+泼尼松	-	1	完全恢复

表1 本组7例MOG抗体相关IDD患儿的临床资料比较

病例(No.)	性别	发病年龄(岁)	感染前驱症状	初始合并症状	发病时诊断	急性期治疗方案	维持治疗方案	ARR(次/年)	随访时间(月)	疗效
1	男	5	有	发热、头痛、视物模糊及眼睛疼痛	ON	甲泼尼龙+IVIG	IVIG+泼尼松	0	16	完全恢复
2	女	5	无	性格改变、头晕及疲劳	脑膜炎	地塞米松+IVIG	IVIG+泼尼松	1	37	部分恢复
3	男	12	无	右手小指、无名指肌无力，右手腕部肌无力	ADEM	地塞米松+IVIG	泼尼松	0	26	完全恢复
4	男	13	有	发热、排尿困难、双下肢运动障碍及疼痛	ADEM	地塞米松+IVIG	泼尼松	0	16	完全恢复
5	女	4	无	反复头痛	MS	地塞米松+IVIG	IVIG+泼尼松	1.4	76	部分恢复
6	男	2	无	反复发热、步态不稳、斜颈、呕吐	AE	地塞米松+IVIG	IVIG+泼尼松	0	15	完全恢复
7	男	7	无	右侧肢体麻木、右下肢轻微跛行、左侧眼睑下垂及视物模糊	ON	地塞米松+IVIG	IVIG+泼尼松	-	1	完全恢复

表2 本组7例MOG抗体相关IDD患儿急性期的神经系统体格检查结果

病例(No.)	视神经	体位、步态	四肢肌力、肌张力	共济运动	深、浅感觉	病理反射	脑膜刺激征
1	视力及视野粗测正常，双侧视盘水肿，双侧眼压增高	正常	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	(—)	(—)
2	视力及视野粗测、眼底均正常	正常	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	双侧巴氏征(+)	颈项强直
3	视力及视野粗测、眼底均正常	正常	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	左侧巴氏征(+)	(—)
4	视力及视野粗测、眼底均正常	呈被动卧位	双上肢肌力正常，双下肢肌力Ⅰ级，四肢肌张力正常	双手指鼻试验、轮替试验可，双侧跟膝胫不能配合	正常	双侧巴氏征(+)	颈稍强直
5	视力及视野粗测、眼底均正常	正常	正常	双手指鼻试验、轮替试验欠佳，双侧跟膝胫对称	正常	双侧巴氏征(+)	(—)
6	视力及视野粗测、眼底均正常	体位正常，步态不稳	正常	双手指鼻试验、轮替试验欠佳，双侧跟膝胫不对称	正常	双侧巴氏征(+)	颈项强直
7	视力及视野粗测正常，左侧视盘水肿，双侧眼压增高	体位正常，右下肢轻微跛行	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	(—)	(—)

表2 本组7例MOG抗体相关IDD患儿急性期的神经系统体格检查结果

病例(No.)	视神经	体位、步态	四肢肌力、肌张力	共济运动	深、浅感觉	病理反射	脑膜刺激征
1	视力及视野粗测正常，双侧视盘水肿，双侧眼压增高	正常	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	(—)	(—)
2	视力及视野粗测、眼底均正常	正常	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	双侧巴氏征(+)	颈项强直
3	视力及视野粗测、眼底均正常	正常	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	左侧巴氏征(+)	(—)
4	视力及视野粗测、眼底均正常	呈被动卧位	双上肢肌力正常，双下肢肌力Ⅰ级，四肢肌张力正常	双手指鼻试验、轮替试验可，双侧跟膝胫不能配合	正常	双侧巴氏征(+)	颈稍强直
5	视力及视野粗测、眼底均正常	正常	正常	双手指鼻试验、轮替试验欠佳，双侧跟膝胫对称	正常	双侧巴氏征(+)	(—)
6	视力及视野粗测、眼底均正常	体位正常，步态不稳	正常	双手指鼻试验、轮替试验欠佳，双侧跟膝胫不对称	正常	双侧巴氏征(+)	颈项强直
7	视力及视野粗测正常，左侧视盘水肿，双侧眼压增高	体位正常，右下肢轻微跛行	正常	双手指鼻试验、轮替试验可，双侧跟膝胫对称	正常	(—)	(—)

表3 本组7例MOG抗体相关IDD患儿脑脊液检查结果

病例(No.)	WBC(×10⁶/L)	红细胞计数(×10⁶/L)	蛋白质含量(g/L)	氯化物浓度(mmol/L)	葡萄糖浓度(mmol/L)	颅内压(mmH₂O)	单纯疱疹病毒	MOG抗体滴度
1	138	141	0.46	124.2	2.8	210	(—)	1∶32
2	9	814	0.13	123.7	2.9	210	(+)	1∶10
3	4	19	0.30	125.7	4.1	150	(—)	1∶10
4	21	15	0.52	123.0	3.4	220	(—)	1∶10
5	5	4	0.31	125.9	4.6	220	(—)	1∶10
6	2 310	9 910	0.17	125.5	3.7	250	(—)	1∶32
7	14	175	0.23	127.4	3.0	250	(—)	(—)

表3 本组7例MOG抗体相关IDD患儿脑脊液检查结果

病例(No.)	WBC(×10⁶/L)	红细胞计数(×10⁶/L)	蛋白质含量(g/L)	氯化物浓度(mmol/L)	葡萄糖浓度(mmol/L)	颅内压(mmH₂O)	单纯疱疹病毒	MOG抗体滴度
1	138	141	0.46	124.2	2.8	210	(—)	1∶32
2	9	814	0.13	123.7	2.9	210	(+)	1∶10
3	4	19	0.30	125.7	4.1	150	(—)	1∶10
4	21	15	0.52	123.0	3.4	220	(—)	1∶10
5	5	4	0.31	125.9	4.6	220	(—)	1∶10
6	2 310	9 910	0.17	125.5	3.7	250	(—)	1∶32
7	14	175	0.23	127.4	3.0	250	(—)	(—)

表4 本组7例MOG抗体相关IDD患儿外周血实验室检查结果

病例(No.)	血常规			感染指标		细胞因子		淋巴细胞亚群(%)			相关抗体
病例(No.)	WBC(×10⁹/L)	中性粒细胞百分比(%)	淋巴细胞百分比(%)	CRP(mg/L)	ESR(mm/h)	IL-6(pg/mL)	IL-8(pg/mL)	CD4⁺	CD8⁺	CD20	MOG	自身免疫性脑炎
1	23.61	85.4	19.3	29.8	100.0	114	50.0	28.5	34.6	18.8	1∶32	—
2	16.50	83.5	23.5	—	88.0	80	220.0	29.3	32.5	26.5	1∶10	—
3	6.75	52.2	35.3	—	35.0	110	59.5	33.4	25.9	22.0	1∶10	—
4	9.51	72.6	18.6	—	63.8	220	77.2	13.5	18.8	55.2	1∶32	—
5	9.02	40.7	49.8	—	27.0	63	221.0	19.1	30.4	26.4	1∶10	—
6	10.74	46.2	38.3	—	10.0	81	243.0	34.7	24.7	19.9	1∶100	抗CASPR-2抗体为1∶30
7	7.01	61.9	31.8	—	10.0	9	235.0	42.0	24.7	15.7	1∶10	—

表4 本组7例MOG抗体相关IDD患儿外周血实验室检查结果

病例(No.)	血常规			感染指标		细胞因子		淋巴细胞亚群(%)			相关抗体
病例(No.)	WBC(×10⁹/L)	中性粒细胞百分比(%)	淋巴细胞百分比(%)	CRP(mg/L)	ESR(mm/h)	IL-6(pg/mL)	IL-8(pg/mL)	CD4⁺	CD8⁺	CD20	MOG	自身免疫性脑炎
1	23.61	85.4	19.3	29.8	100.0	114	50.0	28.5	34.6	18.8	1∶32	—
2	16.50	83.5	23.5	—	88.0	80	220.0	29.3	32.5	26.5	1∶10	—
3	6.75	52.2	35.3	—	35.0	110	59.5	33.4	25.9	22.0	1∶10	—
4	9.51	72.6	18.6	—	63.8	220	77.2	13.5	18.8	55.2	1∶32	—
5	9.02	40.7	49.8	—	27.0	63	221.0	19.1	30.4	26.4	1∶10	—
6	10.74	46.2	38.3	—	10.0	81	243.0	34.7	24.7	19.9	1∶100	抗CASPR-2抗体为1∶30
7	7.01	61.9	31.8	—	10.0	9	235.0	42.0	24.7	15.7	1∶10	—

表5 本组7例MOG抗体相关IDD患儿发病时头颅和脊柱MRI检查结果

病例(No.)	头颅MRI										脊柱MRI
病例(No.)	脑皮质	脑皮质下白质	侧脑室周围白质病变	基底节	丘脑或下丘脑	脑干	小脑	胼胝体	大病灶(>2 cm轴向)	划分界限清晰的病变	延髓受累	颈髓受累	胸髓受累	腰髓受累
1	+	+	—	—	—	—	—	—	+	+	—	—	—	—
2	+	—	+	+	—	+	—	—	+	+	—	—	—	—
3	+	—	+	—	—	—	—	—	+	—	+	+	+	—
4	—	+	—	—	—	—	—	—	+	—	—	+	+	—
5	—	+	+	—	+	—	—	—	+	—	—	—	—	—
6	—	—	+	+	—	—	+	—	+	—	—	—	—	—
7	—	+	+	+	+	—	—	—	+	+	—	—	—	—

表5 本组7例MOG抗体相关IDD患儿发病时头颅和脊柱MRI检查结果

病例(No.)	头颅MRI										脊柱MRI
病例(No.)	脑皮质	脑皮质下白质	侧脑室周围白质病变	基底节	丘脑或下丘脑	脑干	小脑	胼胝体	大病灶(>2 cm轴向)	划分界限清晰的病变	延髓受累	颈髓受累	胸髓受累	腰髓受累
1	+	+	—	—	—	—	—	—	+	+	—	—	—	—
2	+	—	+	+	—	+	—	—	+	+	—	—	—	—
3	+	—	+	—	—	—	—	—	+	—	+	+	+	—
4	—	+	—	—	—	—	—	—	+	—	—	+	+	—
5	—	+	+	—	+	—	—	—	+	—	—	—	—	—
6	—	—	+	+	—	—	+	—	+	—	—	—	—	—
7	—	+	+	+	+	—	—	—	+	+	—	—	—	—

图2 1例MOG抗体相关IDD患儿(No.2，女性，5岁)头颅MRI检查结果(白色箭头示侧脑室后角旁白质多发病灶)

图3 1例MOG抗体相关IDD患儿(No.3，男性，12岁)头颅、全脊柱MRI检查结果[图3A：头颅MRI检查结果(白色箭头示左侧侧脑室后角旁白质及右卵圆中心脑白质异常信号)；图3B：全脊柱MRI检查结果(白色箭头示脊髓内脱髓鞘)]

图4 1例MOG抗体相关IDD患儿(No.4，男，13岁)头颅、全脊柱MRI检查结果[图4A：头颅MRI检查结果(白色箭头示双侧大脑半球皮质下病变)；图4B：全脊柱MRI检查结果(白色箭头示胸段脊髓内病变)]

图6 1例MOG抗体相关IDD患儿(No.6，男性，2岁)头颅常规MRI检查结果(白色箭头示双侧侧脑室旁白质、双侧小脑脚及中脑右部多发异常病变)

图7 1例MOG抗体相关IDD患儿(No.7，男性，7岁)头颅常规MRI检查结果[图7A：头颅MRI横断面(白色箭头示左侧基底节区异常信号)；图7B：头颅MRI冠状面(白色箭头示左侧中脑异常信号)]

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