麦考酚酸酯治疗AQP4抗体阳性视神经炎疗效观察

目的：评价麦考酚酸酯(MMF)对AQP4抗体阳性视神经脊髓炎谱系障碍(NMOSD)患者预防复发和视力预后的作用。

方法：回顾性病例研究。收集2017-01/2019-12收治的AQP4抗体阳性NMOSD患者11例,其中男3例,女8例。NMOSD特有的重要临床表现为视神经炎。发病平均年龄36.3±6.0(27～47)岁,平均病程3.4±1.4(2.2～6.8)a。在NMOSD缓解期加用MMF 1a或1a以上。记录应用MMF患者的年复发率(ARR)、最佳矫正视力(BCVA)和不良反应。

结果：MMF治疗的中位时间为18(12,36)mo。ARR在基线时为0.66/a,治疗后为0.16/a。91%的患者ARR下降,82%的患者无临床复发。MMF治疗后ARR明显改善(P<0.05)。治疗后平均BCVA与治疗前比较无显著差异(P>0.05)。11例患者中,3例(27%)出现不良反应,其中1例(9%)出现转氨酶升高,2例(18%)出现轻度胃肠道反应。没有因不良反应而停用MMF的情况。

结论：MMF治疗AQP4抗体阳性NMOSD患者能在一定程度上降低其视神经炎的ARR,保护患者的视功能。     

Differentiation of neuromyelitis optica from multiple sclerosis in a cohort from the mainland of China

Background Although there were criteria for diagnosis of neuromyelitis optica （NMO） and multiple sclerosis （MS）,it is still difficult to differentiate NMO from MS,due to the overlapping clinical manifestations.Therefore it is necessary to characterize clinical features of NMO and MS patients in the mainland of China,to simplify the process of disease diagnosis,and to identify criteria for the differential diagnosis of NMO and MS.Methods A total of 138 Chinese Han patients from the mainland of China including 73 NMO,60 MS and 5 MS-like patients with positive NMO-IgG were included in the study.Clinical records were reviewed retrospectively and the results of clinical examination,laboratory experiments,magnetic resonance imaging （MRI） and evoked potentials （EPs） were compared between NMO and MS patients.In addition,the relationship between the NMO-IgG serologic status and clinical characteristics were analyzed.Results Compared with MS patients （1.3∶ 1.0）,more female prevalence was observed in NMO patients （4.2∶ 1.0; P=0.003）.There were also statistically significant differences in visual EPs,oligoclonal bands,brainstem lesions in MRI and longitudinally extensive spinal cord lesions （LESCLs） between NMO and MS patients.Brainstem lesions observed in brain MRI were found in 17.9% of MS patients,over 3.7 times higher than in NMO patients （4.8%,P=0.024）.When stratified NMO patients by NMO-IgG,LESCLs were found in 42.1% of NMO-IgG-negative NMO patients,over 3.5 times higher than in NMO-IgG-positive patients （11.9%,P=0.008）.Statistical difference was also observed in CD4＋/CD8＋ ratios between NMO-IgG-positive and-negative NMO patients.Conclusions Comprehensive analysis of MRI,laboratory and EPs data can facilitate differential diagnosis of MS and NMO.In addition,the combination of LESCLs and brain MRI findings failing to satisfy MRI criteria for MS is highly sensitive and specific for NMO.     

Altered neurovascular coupling in neuromyelitis optica

Neurovascular coupling reflects the close relationship between neuronal activity and cerebral blood flow (CBF), providing a new mechanistic insight into health and disease. Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease of the central nervous system and shows cognitive decline‐related brain gray matter abnormalities besides the damage of optic nerve and spinal cord. We aimed to investigate neurovascular coupling alteration and its clinical significance in NMO by using regional homogeneity (ReHo) to measure neuronal activity and CBF to measure vascular response. ReHo was calculated from functional MRI and CBF was computed from arterial spin labeling (ASL) in 56 patients with NMO and 63 healthy controls. Global neurovascular coupling was assessed by across‐voxel CBF‐ReHo correlations and regional neurovascular coupling was evaluated by CBF/ReHo ratio. Correlations between CBF/ReHo ratio and clinical variables were explored in patients with NMO. Global CBF‐ReHo coupling was decreased in patients with NMO relative to healthy controls (p = .009). Patients with NMO showed decreased CBF/ReHo ratio (10.9%–17.3% reduction) in the parietal and occipital regions and increased CBF/ReHo ratio (8.0%–13.3% increase) in the insular, sensorimotor, temporal and prefrontal regions. Some of these abnormalities cannot be identified by a single CBF or ReHo analysis. Both abnormally decreased and increased CBF/ReHo ratios were correlated with more severe clinical impairments and cognitive decline in patients with NMO. These findings suggested that patients with NMO show abnormal neurovascular coupling, which is associated with disease severity and cognitive impairments.     

Hypothalamic demyelination causing panhypopituitarism

Hypothalamic involvement in multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) is rare and endocrinopathies involving the hypothalamic–pituitary axis in patients with demyelinating conditions have rarely been reported. We present two cases of MS/NMOSD with associated hypothalamic–pituitary involvement and subsequent hypopituitarism, including the first report of a patient with hypothalamic demyelination causing panhypopituitarism. Differential diagnoses, including alemtuzumab‐related and primary pituitary pathology are discussed.     

【In Press】 Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica

AIM: To determine the thickness of the retinal ganglion cell-inner plexiform layer (GCIPL) and the retinal nerve fiber layer (RNFL) in patients with neuromyelitis optica (NMO). METHODS: We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis (ON), subjects were divided into either the NMO-ON group (30 eyes) or the NMO-ON contra group (10 eyes). A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using high-definition optical coherence tomography (OCT). RESULTS: In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 ?m, the minimum GCIPL thickness was 66.02±10.02 ?m, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 ?m in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±78.03 ?m, the minimum GCIPL thickness was 25.39±25.1 ?m, and the RNFL thicknesses were 148.33±23.22, 136.36±23.45, 82.21±22.30 and 83.36±31.28 ?m in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 ?m, the minimum GCIPL thickness was 85.28±10.75 ?m, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 ?m in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group (P<0.05); additionally, the RNFL was thinner in the inferior quadrant in the NMO-ON group than in the control group (P<0.05). Significant correlations were observed between the GCIPL and RNFL thickness measurements as well as between thickness measurements and the two visual field parameters of mean deviation (MD) and corrected pattern standard deviation (PSD) in the NMO-ON group (P<0.05). CONCLUSION: The thickness of the GCIPL and RNFL, as measured using OCT, may indicate optic nerve damage in patients with NMO.     

视神经脊髓炎患者血浆纤维蛋白原水平及临床相关性分析

目的探讨视神经脊髓炎患者血浆纤维蛋白原(FIB)水平并分析其与临床特点的相关性。方法选择59例NMO患者、56例MS患者、9例AM患者,以19例良性发作性位置性眩晕(BPPV)患者为对照组,采用扩展残疾状态量表(EDSS)评估疾病严重程度,测定并比较各组血浆凝血酶原时间(PT),活化部分凝血酶时间(APTT)、FIB水平、凝血酶时间(TT)及其与临床特点的相关性。结果 NMO急性期患者血浆FIB水平高于MS组(F=18.857,P0.01)及对照组(F=12.238,P0.01)。NMO组血浆FIB水平与EDSS分值相关(r=0.561,P0.01),与患者发病年龄正相关(r=0.340,P=0.008);MS组血浆FIB水平与EDSS分值显著相关(r=0.302,P=0.0024),与疾病病程正相关(r=0.329,P=0.013)。结论视神经脊髓炎发病急性期血浆FIB水平增高并与疾病严重程度呈正相关。     

视神经脊髓炎转基因(2D2)鼠的繁殖和鉴定

目的建立视神经脊髓炎转基因(2D2)小鼠的繁育方法,并对其子代鼠进行基因鉴定。方法将雌雄2D2转基因小鼠各1只与C57BL/6野生型小鼠(1∶1)进行交配,由鼠尾血提取基因组DNA,应用PCR技术扩增,电泳后观察2D2转基因传代小鼠的基因表型。结果共繁育产生56只子代小鼠,其中36只子代小鼠基因组DNA扩增出657bp的2D2条带,阳性率为64.3%。结论成功利用杂交方式有效繁殖2D2转基因鼠和应用PCR技术进行基因鉴定,为后续视神经脊髓炎的实验研究奠定了基础。     

核转录因子κB涉及水通道蛋白-4抗体阳性血清对星形胶质细胞的毒性作用

目的探讨核转录因子κB(nuclear factor kappa B,NF-κB)在水通道蛋白4(aquaporin-4,AQP4)抗体诱导的星形胶质细胞损伤中的作用。方法纯化培养新生SD大鼠大脑皮质星形胶质细胞,按随机数字表法分为对照组、吡咯醛二硫氨基甲酸(PDTC)组、AQP4抗体阳性血清组(AQP4抗体组)和AQP4抗体+PDTC组,其中对照组加入10%(体积分数)健康人血清,PDTC组给予10μmol/L PDTC预处理1h后加入等量健康人血清;抗体组加入AQP4抗体阳性血清;AQP4抗体+PDTC组先用PDTC预处理1h后再加入AQP4抗体阳性血清。细胞培养12h后采用免疫细胞化学荧光法观察各组NF-κB p65入核情况,MTS比色法检测细胞存活度,免疫印迹法检测细胞内p65蛋白、磷酸化p65(p-p65)蛋白的表达。结果 AQP4抗体组可见明显NF-κB p65入核,其余三组均未见明显入核;AQP4抗体+PDTC组细胞存活度高于AQP4抗体组(吸光度值分别为0.4380±0.005、0.3897±0.045,F=133.355,P0.05);各组间NF-κB p65蛋白表达水平比较差异无统计学意义(P0.05);AQP4抗体+PDTC组p-p65蛋白表达水平较AQP4抗体组明显减少(分别为0.7027±0.020,0.8197±0.027,F=10.794,P0.05)。结论 AQP4抗体阳性血清可能通过激活NF-κB途径促进星形胶质细胞损伤,抑制NF-κB活性对星形胶质细胞具有保护作用。