The imbalance between Bregs, Tfh, and Tregs in patients with anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: To detect the alteration of regulatory B cells (Bregs), follicular helper T cells (Tfh), and regulatory T cells (Tregs) frequencies in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Analyze their association with clinical severity and activity, and explore the effects of different immunotherapies on those immune cell subsets. METHODS: We enrolled 21 patients with anti-NMDAR encephalitis, 22 patients with neuromyelitis optica spectrum disorder (NMOSD), 14 patients with idiopathic intracranial hypertension (IIH), and 20 healthy controls (HC) in our study. The frequencies of various immune cell subsets were determined using flow cytometry. RESULTS: Compared to patients with IIH and HC, the frequencies of CD24hiCD38hi transitional B cells as well as Tregs were significantly lower while the frequency of Tfh was significantly higher in patients with anti-NMDAR encephalitis. The frequency of CD24hiCD38hi transitional B cells was significantly lower in the acute stage than in the recovery stage, and was negatively correlated with the modified Rankin scale (mRS) and the clinical assessment scale for autoimmune encephalitis (CASE). The frequency of CD24hiCD38hi transitional B cells at the last follow-up after rituximab (RTX) treatment was significantly higher than those treated with oral immunosuppressants or untreated. There was no clear difference between anti-NMDAR encephalitis and NMOSD in the above immune cell subsets. CONCLUSION: We suggested that the frequencies of CD24hiCD38hi transitional B cells and Tregs were decreased while the frequency of Tfh was increased in patients with anti-NMDAR encephalitis. CD24hiCD38hi transitional B cells frequency may be a potential indicator to estimate the disease activity and severity.

Optic nerve lesion length is a biomarker of visual disability in the pre-chronic phase of Leber's hereditary optic neuropathy.

OBJECTIVE: The current research aims to investigate relationships between the optic nerve (ON) lesion length with visual function in the pre-chronic phase ( illness duration < 12 months) of LHON. METHODS: Orbital MRI was retrospectively analyzed for 45 patients with LHON in the pre-chronic phase. ON lesion length was measured by 2 trained independent readers and it was recorded as multiplication of the number of abnormal MRI slices and slice thickness on T2-STIR sequence in the coronal plane. Decimal visual acuity was converted to the logarithm of minimum angle of resolution. Intra-class correlation coefficients (ICCs) were used to assess intra- and inter-observer agreements. Pearson's correlation analysis and multivariate linear regression models were performed to analyze the correlations of the lesion length with best corrected visual acuity (BCVA) and visual field parameters. RESULTS: 81 afflicted eyes were selected. The ICCs for intra-observer and inter-observer analyses were 0.989 and 0.980 respectively. Both Pearson's correlation analysis and multivariate linear regression models indicated a significant positive correlation between the BCVA or mean deviation (MD) and ON lesion length (rBCVA=0.368, PBCVA=0.001; rMD=-0.269, PMD=0.045) with a coefficient of determination (R2) of 0.152 and 0.114 respectively adjusted for patients' sex, age of onset, onset of vision loss to performance of MRI, mitochondrial DNA mutations. CONCLUSION: ON length with T2-STIR hyperintensities was positively associated with both BCVA and MD, and it was suspected to be a biomarker of visual disability in the pre-chronic phase of LHON.

Coexistence of Charcot-Marie-Tooth 1A and nondystrophic myotonia due to PMP22 duplication and SCN4A pathogenic variants: a case report.

BACKGROUND: Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous hereditary neuropathy, and CMT1A is the most common form; it is caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. Mutations in the transient sodium channel Nav1.4 alpha subunit (SCN4A) gene underlie a diverse group of dominantly inherited nondystrophic myotonias that run the spectrum from subclinical myopathy to severe muscle stiffness, disabling weakness, or frank episodes of paralysis. CASE PRESENTATION: We describe a Chinese family affected by both CMT1A and myotonia with concomitant alterations in both the PMP22 and SCN4A genes. In this family, the affected proband inherited the disease from his father in an autosomal dominant manner. Genetic analysis confirmed duplication of the PMP22 gene and a missense c.3917G > C (p. Gly1306Ala) mutation in SCN4A in both the proband and his father. The clinical phenotype in the proband showed the combined involvement of skeletal muscle and peripheral nerves. Electromyography showed myopathic changes, including myotonic discharges. MRI revealed the concurrence of neurogenic and myogenic changes in the lower leg muscles. Sural nerve biopsies revealed a chronic demyelinating and remyelinating process with onion bulb formations in the proband. The proband's father presented with confirmed subclinical myopathy, very mild distal atrophy and proximal hypertrophy of the lower leg muscles, pes cavus, and areflexia. CONCLUSION: This study reports the coexistence of PMP22 duplication and SCN4A mutation. The presenting features in this family suggested that both neuropathy and myopathy were inherited in an autosomal dominant manner. The proband had a typical phenotype of sodium channel myotonia (SCM) and CMT1A. However, his father with the same mutations presented a much milder clinical phenotype. Our study might expand the genetic and phenotypic spectra of neuromuscular disorders with concomitant mutations.

Diabetic Oculomotor Nerve Palsy Displaying Enhancement of the Oculomotor Nerve in the Orbit and Cavernous Sinus on MRI.

INTRODUCTION: Imaging data were scarce on diabetic oculomotor nerve palsy (ONP). Our study explored the MRI features and their clinical implications for diabetic ONP. METHODS: Fifty-nine patients with a clinical diagnosis of diabetic ONP were recruited from our department between January 2015 and December 2019. Orbital MRI was retrospectively analyzed, and follow-up scans were obtained for 5 patients. Based on the ocular motor nerve palsy scale, the difference in the scores on the first and last hospital days was defined as the improvement score and was used to assess the treatment effects in all. RESULTS: Thirty-eight (64.41%) patients presented thickening and enhancement of the cavernous segment and inferior division of the intraorbital segment of the ipsilateral oculomotor nerve, with the cisternal segment spared in all. After complete resolution of symptoms, follow-up MRI in 5 patients revealed that the enhancement was less obvious compared with the previous images. 6 patients in the enhancement group and 4 patients in the nonenhancement group were treated with 80 mg of methylprednisolone. Significant differences were not detected in the median improvement scores between patients with and those without corticosteroid use (p = 0.240). CONCLUSION: Thickening and enhancement of the unilateral oculomotor nerve were common imaging findings in diabetic ONP, and they persisted after complete resolution of symptoms in some patients. The cavernous segment and the inferior division of the intraorbital segment were simultaneously involved, and the cisternal segment was often spared. Refraining from corticosteroids was recommended even with nerve enhancement.

In silico studies reveal RSc1154 and RhlE as temperature-related pathogenic proteins of Ralstonia solanacearum.

This study aimed to explore the temperature-related pathogenic mechanism of Ralstonia solanacearum infection in tomato (Lycopersicon esculentum Mill.). Based on bioinformatics analysis of microarray dataset (GSE33657), the co-differentially expressed genes (co-DEGs) ribonucleic acids were identified in R. solanacearum GMI1000-infected L. esculentum Mill., which was cultured at 20°C and 28°C, in rich medium containing casamino acids, peptone, and glucose (CPG) and planta. In total, 63 upregulated co-DEGs and 57 downregulated co-DEGs were identified between 20°C and 28°C in the CPG and planta groups. Protein-protein interaction network revealed 70 protein interaction pairs and 59 nodes. Notably, iolG, iolE, ioll and RSc1248 played critical roles in the network. The subcellular localization and functional annotation showed that the increased expressed proteins were mainly localized in the inner cell membrane, while those with decreased expression were localized in the cytoplasm. Furthermore, these proteins were mainly enriched in regulation of DNA-templated transcription. RSc1154 and RhlE were predicted to be temperature-related pathogenic genes for R. solanacearum in tomato. Furthermore, phosphorelay signal transduction system function might play an important role in R. solanacearum infection. The candidate genes were verified by quantitative real-time PCR, and the results were consistent with gene expression profile.

Eye movement abnormalities in AQP4-IgG positive neuromyelitis optica spectrum disorder.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) has been recognized as a disease characterized by severe visual afferent impairment. Abnormal eye movements, as the other important neuro-ophthalmic manifestation of NMOSD, were commonly overlooked. The aim of our study was to describe the ocular motor manifestations of AQP4-IgG positive NMOSD patients, and explore the value of eye movement abnormalities in the evaluation of the disabled disease. METHODS: Systemic clinical bedside ocular motor examinations and quantitative horizontal saccadic eye movement assessments were performed in 90 patients with AQP4-IgG positive NMOSD. General disability was evaluated by expanded disability status scale (EDSS). Vision-specific functional status was evaluated by the National Eye Institute-Visual Function Questionnaire (NEI-VFQ 25) and the 10-item neuro-ophthalmic supplement. Brain magnetic resonance imaging (MRI) was acquired in all patients. RESULTS: In clinical examination, eye movement abnormalities were found in 38% of NMOSD patients. Abnormalities in the quantitative saccadic test were found in 67% of NMOSD patients, including 48% of patients with clinically normal eye movements. EDSS scores in patients with clinical eye movement abnormality were significantly higher (P<0.001) than those with a normal examination. The 10-item neuro-ophthalmic supplement score was significantly associated with quantitative saccadic eye movement abnormalities (P=0.031). CONCLUSIONS: Eye movement abnormalities were common in AQP4-IgG positive NMOSD patients, and were associated with general disability and specific visual handicap. The systemic clinical eye movement examination combined with the quantitative saccade test was easy to perform, and could provide additional useful information in evaluating NMOSD.

Awake nasotracheal fiberoptic intubation and self-positioning followed by anesthesia induction in prone patients: A pilot observational study.

Anesthesia followed by placement in the prone position takes time and may result in complications. This study aimed to evaluate the feasibility of awake nasotracheal fiberoptic intubation and self-positioning followed by anesthesia induction in prone-positioned patients under general anesthesia.Sixty-two patients (ASA physical status I-II) scheduled for awake nasotracheal fiberoptic intubation and prone self-positioning before surgery under general anesthesia were selected. Patient preparation began with detailed preoperative counseling regarding the procedure. Premedication with sedative and antisialagogue was followed by airway anesthesia with topical lidocaine; then, awake nasotracheal fiberoptic intubation was carried out. The patients then positioned themselves comfortably before induction of general anesthesia. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), incidence of coughing or gagging, and rate pressure product (RPP) were assessed. Statistical analysis was performed with repeated-measures one-way analysis of variance.Fifty-eight of the 62 patients completed prone self-positioning smoothly. Compared with values before intubation, SBP, DBP, HR, and RPP were slightly increased after intubation, although the difference was not statistically significant (P > 0.05). One patient had moderate coughing and 1 patient had gagging during prone self-positioning, which were tolerable.These findings indicated that awake nasotracheal fiberoptic intubation and self-positioning followed by induction of anesthesia is safe and feasible alternative to routine prone positioning after induction of general anesthesia.

[Etiologic analysis of 487 cases of ophthalmoplegia].

OBJECTIVE: To study the etiology of ophthalmoplegia cases. METHODS: A retrospective case series study. We summarized and analyzed etiological diagnosis of 487 ophthalmoplegia patients from January 2005 to September 2010 in Beijing Tongren Hospital of Capital Medical University and Beijing Tongren Eye Center. Clinical data included the case history, clinical manifestations, and results of examinations of neurology, ophthalmology, endocrinology and iconography. The analysis of variance (ANOVA) and Chi-Square test were used in our study. RESULTS: Nineteen different kinds of causes were identified. In terms of age onset, microvascular ischemic (MVI) patients were the oldest (60.38 +/- 11.16) in all groups. It significantly distinguished from myasthenia gravis (MG) and local non-specific inflammation (F = 24.46, P = 0.000). From the view of ophthalmoplegia characters, bilateral asymmetry ophthalmoplegia was the character of MG. We also found that all MVI patients had lesions in unilateral single ocular movement nerve. Unilateral multiple nerves or muscles lesions were the main feature of local non-specific inflammation. In addition, from the view of concomitant symptoms, local aching was very frequent in local non-specific inflammation (all 60 cases) and MVI (44 cases) patients (Chi2 = 36.346, P = 0.000). The mild pupil changing could be found in about one half patients of the two diseases (Chi2 = 0.026, P = 0.875). CONCLUSIONS: The causes of ophthalmoplegia are very complicate. MG, MVI and local non-specific inflammation are the most frequent causes. In more than half of patients, the lesions are located in neurological system, about one third located in neuromuscular junction and the least in the muscles.

[Preparation and identification of monoclonal antibody against hMOF].

OBJECTIVE: To prepare and identify the monoclonal antibody (mAb) against hMOF. METHODS: BALB/C mice were immunized with protein from the spleen cells isolated and fused with SP2/0 cells. After several rounds of screening and cloning, the hybridoma cell strain secreting anti-hMOF mAb was obtained. Its specificity was evaluated with ELISA and Western blot, and the titer, immunoglobulin subtype and affinity of the mAb were measured. RESULTS: One cell strains of hybridoma were obtained and named as 4C1C8. The anti-hMOF mAb secreted by the hybridoma cell strain was identified as IgG1 subtype. The mAb titers in ascitic fluid were 1 409600, as determined with ELISA with an affinity reaching to 7.65 x 10(6) L/mol. Western blot demonstrated that the antibodies could specifically recognize the immunogen. The cell immunohistochemistry proved that the antibody could recognize the hMOF antigens expressed on the normal cells HL7702. CONCLUSION: The success in anti-hMOF mAb preparation provides the basis for further study of hMOF.

[Childhood-onset myasthenia gravis: the analysis of influencing factors of therapeutic effect and prognosis].

OBJECTIVE: Though myasthenia gravis (MG) is a typical autoimmune disorder, there was some controversy on the treatment of the childhood-onset MG. By observing the efficacy of different therapies, the authors analyzed the affecting factors of prognosis in childhood-onset MG. METHOD: The retrospective data of 155 patients with childhood-onset MG (age of MG onset was less than 15 years) were collected from Department of Neurology, Beijing Tongren Hospital (January 2000 - February 2010). The patients were non-randomly divided according to their treatment into 3 groups (glucocorticoid, thymectomy and glucocorticoid combined with thymectomy groups). Postintervention status meeting the criteria of Myasthenia Gravis Foundation of America (MGFA) "complete stable remission, CSR", "pharmacologic remission, PR", "minimal manifestations, MM", or "Improved, I" was regarded as desirable response, which was used as primary indicator of observation. The authors assessed the efficacy of three therapies and analyzed the influencing factors of prognosis by using Chi-square test and Logistic regression. RESULT: At 3 months of treatment, glucocorticoid group showed the highest effective rate. At the end of 1 year or 2 years of treatment, glucocorticoid combined with thymectomy group showed the highest effective rate respectively. The generalization rate of MG at 2 years, 10 years and 20 years in childhood-onset ocular MG patients were 4.3%, 10.7%, and 41.5%, respectively. Of patients with generalization of MG, 48.1% occurred within 2 years, 92.6% within 20 years. Univariate analysis showed that in childhood-onset ocular MG patients, variables such as age at onset (> 10 years), LG-MG and with chronic fatigue were significantly associated with general MG conversion. Whereas multivariate analysis showed that patients with age at onset (> 10 years) and chronic muscle fatigue were apt to convert to generalized MG. CONCLUSION: Glucocorticoid appeared to have an effect that leads to early remission of symptoms in childhood-onset MG patients and glucocorticoid combined with thymectomy appeared to have better long-term effect. For those childhood-onset ocular MG patients with longer course of disease, older age of onset, chronic fatigue, or LG-MG, physicians should try to prevent the generalization of MG by immunosuppressive therapies.

[Analysis of characteristics of ocular manifestations of benign intracranial hypertension].

OBJECTIVE: To investigate the ocular manifestation of benign intracranial hypertension (BIH). METHODS: It was a retrospective case series study. Clinical data of BIH patients were investigated retrospectively, including symptom, fundus findings, visual acuity and visual field. RESULTS: It was a retrospective case series study. The majority of 67 patients were female (46 cases, 87%), of which 71.7% were over-weight. While ocular symptoms were reported in 94.0% (63 cases) of cases in whole disease course, 28 cases (41.8%) primarily presented with ocular symptoms, including transient bilateral loss of vision, visual deterioration and diplopia. Papilledema was found in 65 cases (97.0%), of which 54 cases (80.6%) were bilateral. Some patients showed unilateral papilledema (11 cases, 16.4%)and optic atrophy. Abnormal visual acuity was found in 95 eyes (70.9%), of which 35 eyes (26.4%) were below 20/200. Visual field abnormality was found in 89.8% of 49 tested cases. The most common visual field lesion was the enlargement of the blind spot (82 eyes, 83.7%), followed by general constriction in 24 eyes (24.5%), nasal step in 17 eyes (25.4%), central scotoma in 9 eyes (9.2%), Bjerrum scotoma in 22 eyes (22.4%) and arcuate scotoma in 14 eyes (14.3%). CONCLUSION: BIH is not really "benign", especially from the viewpoint of optic nerve function.