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Background@#and Purpose Patients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset. @*Methods@#This study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed. @*Results@#The onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD (n=16, 66.7%), AQP4-IgG-seropositive NMOSD (n=7, 29.2%), or multiple sclerosis (n=1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability. @*Conclusions@#Definite NMOSD may be preceded by LF-NMOSD, particularly isolated/ mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.
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Facing the challenge of the COVID-19 epidemic to the classroom teaching, the physiology teaching team of Qiqihar Medical University constructed a blended teaching model based on "small private online course (SPOC)+ live real audio" to carry out online teaching. Through the joint efforts of all team members, the online teaching has been carried out in a stable order for 4 weeks, thus ensuring the teaching effect of physiology. Taking the physiology teaching of 236 nursing undergraduates in Batch 2019 as an example, this paper introduces the teaching design, implementation measures, teaching effect and teaching reflection of carrying out online teaching under the epidemic situation, and provides practical experience for further promoting online teaching in medical colleges and universities during epidemic prevention and control.
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Objective To investigate the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy. Methods We collected and analyzed the clinical and laboratory data and obtained the clinical characteristics of diagnosis and treatment from fifteen patients with positive GFAP antibody tested by cerebrospinal fluid and diagnosed autoimmune GFAP astrocytopathy by the multi-centers. Results The mean age of the first onset of autoimmune GFAP astrocytopathy was 39.73 years old (range 4-65 years), with no significant gender difference. In terms of clinical manifestations, we found the whole brain symptoms including abnormal mental behavior, disturbance of consciousness, epileptic attack accounting for more than 50, , meningitis accounting for 66.7%, myelitis (53.3%), limb tremor (53.3%), vision loss (33.3%); systemic symptoms including fever(100%) and fatigue(86.7%). 46.7% of patients were initially diagnosed with tuberculous meningoencephalitis and were treated with diagnostic antituberculous therapy. The MRI showed 46.7% of patients showed brain linear perivascular radial gadolinium enhancement in the white matter perpendicular to the ventricle. Conclusions Autoimmune GFAP astrocytopathy are acute or subacute dieases and the main clinical features include encephalitis, meningitis, myelitis and optic neuritis. They are likely to be misdiagnosed as tuberculous meningoencephalitis and can manifest progressive loss of consciousness in early phase, which is even life threatening.
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@#Background & Objective: Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are widely used in Western countries. In China, however, the current treatment patterns of MS patients are not well characterized. This is to explore the gap between the current treatments in Guangzhou, Southern China and those given in Western countries. Methods: We performed a survey of MS patients at department of neurology, a tertiary MS referral centre in Guangzhou, concerning treatments of MS in Southern China. The clinical data in patients were collected. The initial treatment, drug withdrawal or switching profile, and therapeutic effect of existing treatments in MS patients were analyzed. Results: The ratio of MS patients who receive DMTs in Guangzhou China is extremely low. Among the 178 patients studied, only 28.09% received initial treatment with DMTs. MS patients who receive initial treatment with first-line DMTs have higher drug withdrawal rates (32.6%) and drug switching rates (30.43%) than those of western populations. The main reasons for withdrawal of first-line DMTs were doctor’s advice (maintenance of remission) (40.00%), economic burden(20.00%), and no channels to buy drugs(13.33%). In MS patients initially treated with first-line DMTs who switched to other drugs, a gap between treatments was common (8/14;57.14%). There were 18 patients with highly active MS receiving treatment with rituximab. Annual relapse rate after treatment significantly decreased than that before treatment (0.74 vs. 1.50 , P < 0.001). Conclusions: DMTs for MS in Guangzhou, Southern China appear to lag behind those in Western countries. Much work is needed to improve drug accessibility and affordability of DMTs in China. Rituximab is an option for highly active MS in limited medical-resource countries.
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Objective To investigate the characteristics of ocular movement disorders in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), and explore the clinical application of videonystagmograph (VNG) exami?nation in the diagnosis and differential diagnosis of MS. Methods Sixteen MS ,10 NMO and 30 control ( sudden deafness ) patients were enrolled prospectively. Ocular movement disorders including saccades, gaze fixation, smooth pursuits, opto?kinetic nystagmus and spontaneous nystagmus were evaluated by using VNG. Results The positive rate of ocular motility disorders in MS patients detected by VGN was 68.75%. The incidences of abnormalities in saccades, smooth pursuits and optokinetic nystagmus were significantly higher in MS than in control groups (P= 0.000, 0.001 and 0.001, respectively). The positive rate of ocular motility disorders in NMO patients detected by VGN was 80.00%. The incidences of abnormal?ities in saccades, gaze fixation, smooth pursuits and optokinetic nystagmus were significantly higher in NMO than control groups (P=0.000, 0.012, 0.000 and 0.002, respectively). The positive rate of ocular motility disorders was not significant? ly different in MS and MS patients (68.5%vs. 80%,P>0.05). Compared with bedside physical examination, VNG showed a notable higher sensitivity in the detection of ocular motility disorders(68.75% vs. 37.50%). Furthermore, VNG disor?ders might indicate brain lesions undetected by MRI. Conclusion This small sample research indicates that VNG is a valuable tool in the detection of ocular motility disorders as well as brain lesions in MS and NMO patients. However, its role in the differential diagnosis between MS and NMO is not confirmed.
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Objective To analyze the association between interleukin-23 receptor (IL23R) gene single nucleotide polymorphisms (SNPs) and multiple sclerosis (MS) in a Southern Han Chinese population.Methods Three SNPs (rs2201841,rs10889677,rs7517847) within the IL23R gene were detected in 178 MS patients and 221 controls using polymerase chain reaction and restriction fragment length polymorphism method (PCR-RFLP).Haplotypes of the IL23R gene were constructed with SHEsis software.Results The frequencies of the genotype or allele in the IL23R gene SNPs(rs2201841:TT,TC,CC in MS patients:5.7％ (10/175),45.7％ (80/175),48.6％ (85/175),in controls:7.4％ (16/217),41.0％ (89/217),51.6％ (112/217),x2 =1.08,P =0.58 ; rs10889677:AA,AC,CC in MS patients:52.0％ (89/171),42.7％ (73/171),5.3％ (9/171),in controls:57.7％ (123/213),36.2％ (77/213),6.1％ (13/213),x2 =1.71,P =0.43 ; rs7517847:GG,GT,TT in MS patients:16.9％ (29/172),51.7％(89/172),31.4％ (54/172),in controls:14.4％ (31/215),49.3％ (106/215),36.3％(78/215),x2=1.15,P =0.56)showed no significant difference between MS patients and controls.The genotype did not influence the age of onset,the duration or disease severity in MS patients.The SNPs rs2201841 and rs10889677 had strong linkage disequlibrium (D' =0.614,r2 =0.327).The haplotype frequencies showed no significant difference between the MS patients and controls.Conclusion There is no evidence in our study to support the association between IL23R SNPs and MS in a Southern Han Chinese population.
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Objective To investigate the associations of aquaporin-4 (AQP4) promoter polymorphisms with anti-AQP4 antibody and genetic susceptibility to multiple sclerosis (MS) and neuromyelitis optica (NMO) in Southern Chinese population.Methods The polymorphisms of AQP4promoter 0 and 1 were analyzed by PCR and DNA sequencing in 18 NMO,38 MS,13 recurrent myelitis (RM),6 recurrent optic neuritis (RON)patients and 39 healthy controls. Results Fourteen polymorphism loci were observed in AQP4-promoter 0,while 6 ones were observed in AQP4-promoter 1.Among them,the incidence rate of polymorphism at position - 1003 bp (A-G) of AQP4-promoter 0 in anti-AQP4 antibody-positive patients was significantly higher than that in anti-AQP4 antibody-negative patients and controls (former:13/18 vs 20/45,P =0.046; latter:13/18 vs 10/39,P =0.001 ).The incidence rates of polymorphism at position between -401 bp and -400 bp ( C inserted) of AQP4-promoter 1 in anti-AQP4 antibody-positive and -negative patients were significantly higher than that in controls( former:5/16 vs 0/28,P =0.008; latter:8/38 vs 0/28,P =0.027 ). The incidence rates of polymorphism at position - 1003 bp (A-G) of AQP4-promoter 0 and position between -401 bp and -400 bp ( C inserted)of AQP4-promoter 1 in patients with NMO and MS were significantly higher than that in controls( NMO:11/18 vs 10/39,P =0.010;4/15 vs 0/28,P =0.020; MS:19/38 vs 10/39,P =0.027;8/34 vs 0/28,P =0.018).Conclusions Polymorphisms loci were observed in AQP4-promoter 0 and AQP4-promoter 1,which may have an influence on the susceptibility to MS and NMO.Polymorphism at position - 1003 bp ( A-G) of AQP4-promoter 0 may be related to the emergence of anti-AQP4 antibody in patients with NMO and MS.
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ObjectiveTo construct expressing vector of microRNA with molecular cloning methods which target CD4 and electroporating the vector to the MT4 cell to determine its effect to CD4 expression.MethodsPredict a microRNA can target CD4.Linking the pre-mir-181a PCR products to T vector,then cloning into the pEGFP-N1 vector after enzyme digestion.To test the integrity through the colony PCR and sequencing analysis.Electroporating the vector to MT4 cell,using FACS to test the CD4 expression.ResultsHsa-mir-181a is able to target CD4.The sequence of the construct was correct.The hsa-mir-181a is stable expressing in MT4 after electroporating with the vector and MT4 cell CD4 was down-regulated.ConclusionThe construct can be stable expressing hsa-mir-181a in MT4 cell and down-regulating the CD4 expressing.This method can be utilized as a novel intervention to the HIV fusion,it shows potential as a gene therapy tool in vitro.
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Objective To compare the efficiency of original neuromyelitis optica(NMO)-IgG assay of detecting NMO-IgG with a new anti-aquaporin-4(AQP4)assay of detecting AQP4,and to explore the accuracy of the method in the diagnosis of NMO and multiple sclerosis(MS).Methods The sera were obtained from 44 patients with NMO and 46 patients with MS and were tested by both NMO-IgG and antiAOP4 assays.NMO-IgG was identified by original NMO-IgG assay with a substrate from mouse brain.AntiAQIP4 was detected by anti-AQP4 antibody assay.The results from the two assays were statistically analyzed to compare accuracy and specificity of the methods.Results The results of the two assays were concordant in 45 testing negative cases and 36 positive cases(Kappa=0.798.P=0.000).The McNemar test showed that the positive rate of the two assays were not significantly different(P=1.000).The NMO-IgG assay showed 77.3% sensitivity,87% specificity,82.2% diagnosis accuracy,85%positive predictive value,87% negative predictive value.and 74.3%Younden index. The anti-AOP4 antibody assay showed 88.6% sensitivity,95.7%specificity,92.2% diagnosis accuracy,98.1% positive predictive value,89.8% negative predictive value.and 84.3% Younden index.Conclusions This study demonstrated that NMO-IgG and AQP4 antibody detection have high sensitivity and specificity to detect NMO and MS.Anti-AQP4 detected by anti-AQP4 antibody assay may be more useful for NMO diagnosis.
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Objective To investigate the asseciation of 1188A/C polyrnorphism of Interlenkin-12B gene (IL-12B) with remit-relapse multiple sclerosis (RRMS) in the southern Chinese population.Methods Ninety-four patients with RRMS and 145 age- and-sex-matched normal controls were recnfited in this study.The polymorphism was detected by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) assay in these subjects.The frequencies of the alleles in each group were statistically analyzed.Results The frequency of the allele A increased significantly in RRMS patients (64.4%) compared with that in healthy controls (53.8%, χ2=5.228, P=0.022).An increased risk for MS was suggested in carriers of the A allele (OR=1.551, 95% CI=1.064-2.262).Conclusions The A allele in 1188A/C polymorphism of IL-12B gene may be a risk factor for RRMS in southern Chinese population.
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Objective To investigate brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) concentrations in serum and cerebrospinal fluid (CSF) in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO),and their neuroprotective effects.Methods Sixty-two patients (49 patients were MS and 13 patients were NMO) and 21 controls were investigated in our studies.The disability severity in MS and NMO patients in their relapse period was assessed by the Expanded Disability Status Scale (EDSS).MRI scanning of brain,spinal cord or optic nerve was examined and the oligoclonal band in serum and CSF were detected.BDNF and GDNF concentrations in serum and CSF were assessed by Liquid Assay.Results There were no significant differences of BDNF (μg/L,5.616±0.650 in serum and 0.186±0.012 in CSF of MS patients;6.584±0.929 in serum and 0.176± 0.006 in CSF of NMO patients) and GDNF (μg/L,0.039 in serum and 0.080 in CSF of MS patients;0.029 in serum and 0.050 in CSF of NMO patients) concentrations in serum and CSF in patients with MS and NMO in relapse,compared with those in controls.There was a positive correlation between BDNF and GDNF concentrations in CSF (r=0.756,P=0.000),and a negative correlation between BDNF and GDNF concentrations in serum (r=-0.329,P=0.018).There were no correlations of BDNF and GDNF concentrations in serum and CSF with EDSS,blood brain barrier index,Delpech index and Tourtellotte synthesis rate.There were no significant differences of BDNF and GDNF concentration in serum and CSF between NMO/MS patients with and without atrophy.Conclusions The level of BDNF in patients with MS and NMO is correlated with that of GDNF,which may have a synergistic neurotrophic effect on MS and NMO.BDNF and GDNF are not associated with the blood-brain harrier destruction and lgG synthesis in central nervous system.However,associations of BDNF and GDNF with functional disability and neuron atrophy in NMO and MS patients still need further studies.