Objective:To explore the clinical characteristics of patients with antibodies against contactin-associated protein-like 2 (CASPR2).Methods:The clinical data of 24 patients with anti-CASPR2 encephalitis diagnosed at the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. According to the age of first onset, the patients were divided into early onset group (10 cases, onset age<45 years) and late onset group (14 cases, onset age≥45 years). The clinical data including clinical manifestations, auxiliary examinations, and treatment response between these 2 groups were compared.Results:Among the 24 patients, there were 13 cases with epilepsy, 13 cases with cognitive decline, 13 cases with mental disorders, 14 cases with autonomic dysfunction, 8 cases with peripheral nerve hyperexcitability, 5 cases with Morvan syndrome, 5 cases with unstable walking, and 8 cases with sleep disorders. Among the 10 cases of the early onset group, 7 cases are females, and 8 cases showed epilepsy. The incidence rate of epilepsy in the early onset group was higher than that in the late onset group (5/14, Fisher exact probability, P=0.047). Among the 14 cases of the late onset group, 6 cases are females, 9 cases showed cognitive impairment and 8 cases presented with mental disorders. There were 6 cases with abnormal brain magnetic resonance imaging (MRI). The cerebrospinal fluid protein of the late onset group [0.37 (0.29, 0.58) g/L] was higher than that in the early onset group [0.22 (0.16, 0.30) g/L; Z=-2.667, P=0.008]. The modified Rankin Scale (mRS) scores before and after treatment were 3.29±0.83 and 1.50 (0.75, 2.25), which were higher than those in the early onset group [mRS scores before and after treatment were 2.10±0.99 and 0 (0, 1.00), t=-3.188, P=0.004; Z=-2.335, P=0.020]. Conclusions:There are various symptoms in patients with anti-CASPR2 encephalitis. The early onset patients are common in women, with a higher incidence of epilepsy. The late onset patients are common in males, with prominent manifestations of cognitive impairment and mental disorders, which have a greater impact on daily living abilities. And abnormal MRI findings are common, and the cerebrospinal fluid protein is higher in late onset patients. Anti-CASPR2 antibody may cause more severe immune damage to the nervous system in elderly patients.

Aim To investigate the levels of krüppel-like factor 2(KLF2)and endothelial nitric oxide synthase 3(NOS3)in the serum of patients with acute cerebral infarction(ACI)of large-artery atherosclerosis(LAA)type,and to analyze their value in the diagnosis and disease assessment of LAA type ACI.Methods A total of 150 patients with LAA type ACI were divided into mild group(n=36),moderate group(n=48),and severe group(n=66)based on their condition.Additionally,a control group(n=150)was selected from health exminers during the same period.The levels of serum KLF2 and NOS3 in each group were compared;receiver operator characteristic(ROC)curve was applied to analyze the diagnostic value of serum KLF2 and NOS3 levels for LAA type ACI and the predictive value for the occurrence of severe LAA type ACI,respectively.Results The serum KLF2 and NOS3 levels were significantly lower in LAA type ACI group than those in control group(P＜0.05).The serum KLF2 and NOS3 levels in the mild,moderate and se-vere groups were significantly decreased in turn(P＜0.05).The area under the curve(AUC)of the combined diagnosis of serum KLF2 and NOS3 for LAA type ACI was 0.858,with a sensitivity of 73.33％and a specificity of 86.00％,which was superior to the individual diagnosis of KLF2 and NOS3(Zcombined detection-KLF2=3.796,Zcombined detection-NOS3=4.689,all P＜0.001).The AUC of combined prediction of serum KLF2 and NOS3 for the occurrence of severe LAA type ACI was 0.878,with a sensitivity of 77.27％and a specificity of 90.48％,which was superior to the independent prediction of KLF2 and NOS3(Zcombineddetection-KLF2=2.401,P=0.016;Zcombined detection-NOS3=3.070,P=0.002).Conclusions The serum levels of KLF2 and NOS3 in patients with LAA type ACI were significantly reduced and negatively correlated with the severity of the disease.The combination of the two has high evaluation efficacy in the diagnosis and disease prediction of LAA type ACI.

OBJECTIVE To evaluate the correlation between the solid dispersion(SD) powder properties and the relative crystallinity(RC) during SD recrystallization. METHODS Andrographolide was used as model drug, polyvinylpyrrolidone K30, polyethylene glycol 8000, Poloxam 188, Soluplus® as carrier materials, 12 SD powders were prepared by three preparation processes, and then the SD powder properties were determined. Afterwards, the principle component analysis and partial least squares analysis(PLS) were used to evaluate the correlation between the SD powder properties and RC during SD recrystallization. RESULTS The correlation model was successfully established by partial least square method between the SD powder properties and the RC. The VIP value of particle size parameter D(0.5) was >1.2, which indicated that the particle size was the key factor affecting the recrystallization of SD powder. CONCLUSION In practical work, SD powder with different particle size parameters can be obtained by different preparation methods or by adjusting the process parameters of the selected preparation method, so as to improve the recrystallization stability of SD.

Immunoadsorption can selectively remove pathogenic antibodies and has recently achieved good results in neuroimmune diseases. The type and titer of pathogenic antibodies play an important role in the clinical symptoms and severity of patients with autoimmune encephalitis. First-line immunotherapy for autoimmune encephalitis includes steroids, intravenous immunoglobulin, plasma exchange or immunoadsorption. Immunoadsorption selectively and rapidly eliminates autoantibodies and can be an effective therapeutic option as part of multimodal immunotherapy.

Objective:To investigate the clinical characteristics of myelin oligodendrocyte glycoprotein antibody associated disorders (MOGAD) combined with anti- N-methyl- D-aspartate receptor (NMDAR) encephalitis. Methods:Sixty-five patients with MOGAD and 96 patients with anti-NMDAR encephalitis, admitted to our hospital from July 2018 to June 2021, were chosen in our study; 8 patients with MOGAD combined with anti-NMDAR encephalitis were selected as antibody double positive group; 21 patients with MOG antibody(+)/anti-NMDAR antibody(-) and 37 patients with anti-NMDAR antibody(+)/MOG antibody(-) were selected as controls. The differences of clinical characteristics of patients among these groups were compared.Results:(1) In these 8 patients from antibody double positive group, MOGAD and anti-NMDAR encephalitis occurred simultaneously in 6 patients, and anti-NMDAR encephalitis occurred prior to the episode of MOGAD in 2 patients. Autoimmune encephalitis was the dominant phenotype and demyelinating symptoms occurred in some patients. Both MOG antibody and anti-NMDAR antibody were detected in these 8 patients. MRI showed that lesions mostly involved in the cortex and subcortical white matter. Intravenous administration of high-dose methylprednisolone and immunoglobulin was given for patients at acute stage; two patients received mycophenolate mofetil treatment additionally during recurrence. After treatment, syndromes in these 8 patients got improvement. (2) There were no significant differences between patients from antibody double positive group and MOG antibody(+)/anti-NMDAR antibody(-) group in clinical manifestations, auxiliary examinations or treatments ( P>0.05). As compared with patients in antibody double positive group, patients in the anti-NMDAR antibody(+)/MOG antibody(-) group had significantly lower proportion of children and significantly higher modified Rankin scale (mRS) scores at the height of their illness ( P<0.05). As compared with patients in the MOG antibody(+)/anti-NMDAR antibody(-) group, patients in the anti-NMDAR antibody(+)/MOG antibody(-) group had significantly older onset age, significantly lower proportion of children, significantly higher proportion of patients with epilepsy and abnormal psychiatric behavior, significantly higher proportion of patients admitted to Intensive Care Unit, statistically higher mRS scores at the height of their illness, significantly lower proportion of patients with intracranial lesions, and significantly higher proportion of patients used immunoglobulin and plasma exchange ( P<0.05). Conclusion:MOG antibody and anti-NMDAR antibody can cause different clinical symptoms; when MOGAD patients have unusual symptoms, such as abnormal psychiatric behavior and epilepsy, or anti-NMDAR encephalitis patients develope demyelinating features, the possibility of MOGAD combined with anti-NMDAR encephalitis should be considered.

Objective:To investigate the effects of hippocampal injection of tyrosine kinase receptor binding protein B3(Ephrin-B3) agonist on spontaneous seizures and the expression of hippocampal secretory glycoprotein (Reelin) and phosphorylated adaptor protein (p-Dab1) in epileptic model rats.Methods:Seventy-eight rats were randomly divided into control group and model group according to body mass matching with 39 rats in each group.The rats in control group were fed normaly, and the rats in model group were established epilepsy model by intraperitoneal injection of lithium chloride pilocarpine. The hippocampal tissues were taken in the acute phase (7 days), quiescent phase (14 days) and chronic phase (60 days) after the successful induction of status epilepticus. The levels of Reelin protein and p-Dab1 protein in the hippocampal tissues of epileptic model rats and normal rats were detected by immunohistochemistry and Western blot.And thirteen rats were randomly selected at each time point. Another 48 rats were randomly divided into normal Fc-control group, normal EphB3-Fc group, epilepsy Fc-control group and epilepsy EphB3-Fc group, with 12 rats in each group. Rats in the first two groups were fed normally, and those in the latter two groups were established epileptic model. Seven days after modeling, all rats were injected into bilateral hippocampus with EphB3-Fc (Ephrin-B3 agonist) and FC control (control agent of Ephrin-B3 agonist) according to the grouping, once a day for 7 days. After administration, the changes of behavior and EEG were observed within two weeks. At the same time, the expression of Reelin protein and p-Dab1 protein were detected by immunohistochemistry and Western blot. SPSS 21.0 was used for statistical analysis, One-way ANOVA was used for multi group comparison, and Tukey's test was used for pairwise comparison.Results:The results of immunohistochemistry and Western blot showed that compared with the control group, the levels of Reelin and p-Dab1 protein in hippocampus of model group decreased significantly at 7, 14 and 60 days after epilepsy (all P<0.01). The results of immunohistochemistry showed that compared with epilepsy Fc-control group, the levels of p-Dab1 ((0.41±0.04), (0.58±0.06), P<0.05) in epilepsy EphB3-Fc group increased significantly.Western blot result showed that the level of p-Dab1 in epilepsy EphB3-Fc group increased compared with that of epilepsy Fc-control group (1.34±0.04), (2.26±0.10), P<0.01). Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed less average seizure duration ((39.00±1.79)s, (26.50±1.87)s; t=23.21, P<0.01), less frequencies ((2.00±0.89), (0.50±0.55); t=2.32, P<0.01) and less latent period ((6.33±1.37)day, (12.50±1.87)day; t=2.52, P<0.01) in spontaneous recurrent seizures. Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed lower average amplitude ((37.30±1.21)μV, (29.00±1.41)μV; t=25.14, P<0.01), less average seizure duration ((5.35±0.19)s, (2.35±0.19)s; t=3.13, P<0.01). Conclusion:Ephrin-B3 alleviated spontaneous recurrent seizures by upregulating Reelin and p-Dab1 in temporal lobe epilepsy rat.

Objective　To explore dynamic expression of Ephrin-B3 in hippocampus of pilocarpine induced epileptic rats and the role of Ephrin-B3 in the process of epileptogenesis.Methods　We first established pilocarpine induced epileptic rat model and then detected Ephrin-B3 expression at 7,14 and 60 days post status epilepticus (SE) by real time qPCR,immunohistochemistry and Western blot.Results　After pilocarpine injection,rats showed facial muscles,forelimb and tail clonus and ataxic lurching,head bobbing and wet dog shakes.Real time qPCR revealed that Ephrin-B3 mRNA expression in hippocampus decreased during spontaneous seizure period.Compared with controls,epileptic rats showed decreased Ephrin-B3 expression at 7 days,reached the lowest level at 14 days and then increased slightly at 60 days post-SE (P<0.001).Ephrin-B3 protein in hippocampus also decreased at 7,14 and 60 days detected by Western blot (P<0.001).Immunohistochemistry results showed that Ephrin-B3 mainly expressed in granule cells in dentate gyrus.Analysis of immunohistochemistry revealed decreased Ephrin-B3 expression in epileptic rats compared with controls (P<0.001).Conclusion　The dynamic changes of Ephrin-B3 expression in hippocampus of epileptic rats indicated that Ephrin-B3 may participate in the process of spontaneous recurrent seizures.

Objective:To investigate the clinical characteristics and therapeutic efficacy of spontaneous intracranial hypotension (SIH) complicated with cerebral venous thrombosis (CVT).Methods:The clinical data of 4 patients with SIH complicated with CVT admitted to our hospital from March 2014 to April 2020 were retrospectively analyzed. And the clinical data of 35 patients with SIH complicated with CVT were included for summary analysis through literature retrieval (the databases included PubMed, CNKI and Wanfang; retrieval period was from database construction to December 31, 2020).Results:These 4 patients were with onset of orthostatic headache; one was with recurred orthostatic headache after relief, and the other 3 developed persistent headache and epileptic seizure; case 1 was with superior sagittal sinus and cortical vein thrombosis, case 3 was with superior sagittal sinus thrombosis, and other 2 patients were with isolated cortical vein thrombosis. Twenty-six documented cases demonstrated headache changes: 12 patients (46.15%) developed persistent headache, 12 patients (46.15%) showed orthostatic headache persistently, and 2 patients (7.69%) had disappeared headache. The most common new symptoms were epilepsy in 17 patients (48.57%) and limb weakness in 10 patients (28.57%). Totally, these 31 patients (4 patients from our hospital+27 patients from literature retrieval) had hemorrhage after treatment; the percentage of patients having hemorrhage changes in the 17 patients accepted anticoagulant therapy was significantly increased as compared with that in 14 patients accepted other treatments (7/17 vs. 1/14, P<0.05); there were no bleeding changes in 5 patients accepted epidural blood patch and anticoagulant therapy. Conclusions:The clinical features of SIH complicated with CVT are various, and the change of headache is not a reliable marker. In the course of SIH, it is necessary to be alert to the occurrence of CVT if there are new symptoms such as epileptic attack or limb weakness. The etiological treatment of SIH is essential and the hemorrhage risk after anticoagulant therapy should be concerned in patients with SIH complicated with CVT.

Objective: To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance. Methods: The data about basic clinical features, fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs, 15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected. The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed. The relevance between the diversity of intestinal microbiota and inflammatory index was explored. Results: Compared with healthy controls, the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered. The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls, while their inflammation indexes, including IL-6, IL-10 and transforming growth factor (TGF)-α, in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml, t=4.197, P=0.001; (3.4±2.1) pg/ml vs (0.9±0.2) pg/ml, t=2.265, P=0.037; (21.4±12.7) ng/ml vs (13.7±7.8) ng/ml, t=3.702, P=0.004). Compared with control group, the relative abundance of butyrivibrio, prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8%±3.5% vs 13.0%±4.7%, t=4.941, P<0.001; 3.9%±2.2% vs 6.9%±3.3%, t=3.282, P=0.003; 5.1%±2.5% vs 7.3%±3.0%, t=2.641, P=0.012), while the relative abundance of ackermania was increased obviously (7.0%±3.1% vs 4.4%±2.8%, t=2.802, P=0.008); Besides, the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4%±2.4% vs 5.5%±2.1%, t=2.784, P=0.009; 7.9%±5.4% vs 13.0%±4.7%, t=2.501, P=0.018). In the comparison between subgroups, the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1%±8.9% vs 32.6%±10.4%, t=2.572, P=0.016), while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4%±1.6% vs 1.7%±1.4%, t=2.977, P=0.006). Moreover, there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548, P=0.003). Conclusions The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs. Moreover, there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs, which can be used as an important means of clinical auxiliary examination.

Objective:To investigate the characteristics of magnetic resonance myelography (MRM) and its application in the treatment of spontaneous intracranial hypotension (SIH).Methods:The clinical data, MRM characteristics, and treatment of 15 patients with SIH who underwent MRM examination in the First Affiliated Hospital of Zhengzhou University from August 2014 to August 2019 were retrospectively analyzed. According to treatment methods, nine patients were divided into conservative treatment group and six patients were divided into combined epidural blood patch treatment group. The gender, age, time interval from onset to MRM examination, cerebrospinal fluid pressure and MRM characteristics between the two groups were compared. SPSS 20.0 software was used for statistical description, and independent sample t-test was applied to compare the differences between groups. Results:All of the 15 cases reported orthostatic headache. Their cerebrospinal fluid pressure was (29.67±19.77, range 0-55) mmH 2O (1 mmH 2O=0.009 8 kPa), and onset-MRM interval was (33.07±24.22, range 7-90) days. The MRM characteristics were observed, including all 15 cases with periradicular leaks, four cases with anterior epidural fluid collections, six cases with posterior epidural fluid collections, and eight cases with high cervical (C 1-2 to C 2-3) retrospinal cerebrospinal fluid collections. There were 2 to 32 leak sites with an average of (10.20±7.87) sites. Among the 153 leak sites, 58(37.9%) sites were located at cervical vertebra, 77(50.3%) sites at thoracic vertebra, 18(11.8%) sites at lumbar vertebra, and 61(39.9%) sites at either the cervicothoracic junction (C 7-T 1 to T 1-2) or the upper thoracic region (T 2-3to T 6-7). Five patients responded well to one-time targeted autologous epidural blood patch on the basis of the location of the cerebrospinal fluid leakage. Besides, one patient improved with targeted epidural blood patch twice. There were no statistically significant differences in gender, age, onset-MRM interval, cerebrospinal fluid pressure, number and location of leak sites between the conservative treatment group and combined treatment group. Conclusions:The periradicular leaks of cerebrospinal fluid at cervical vertebra and thoracic vertebra are the most common feature of MRM in patients with SIH. MRM can identify the existence and location of cerebrospinal fluid leakage, assist in the diagnosis of SIH, and guide targeted epidural blood patch.