Yanyu Chang

Serum uric acid and anti-N-methyl-d-aspartate receptor encephalitis

Background: Uric acid (UA) levels are associated with autoimmune and neurodegenerative disorders, but their relationship with anti‐N‐methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis is unknown. Methods: UA levels were evaluated in 58 patients with anti‐NMDAR encephalitis, and 58 age‐ and sex‐matched healthy controls (CTLs). Follow‐up evaluations of 30 out of the 58 patients with anti‐NMDAR encephalitis were conducted 3 months after admission. Modified Rankin scale (mRS) scores and clinical and cerebrospinal fluid parameters were evaluated in all anti‐NMDAR encephalitis patients. Results: Serum UA levels were significantly lower in patients with anti‐NMDAR encephalitis than those in CTLs (p < 0.001), and this was especially evident in patients with severe impairments (mRS ≥ 4 vs. <4, p = 0.004) or with limited response to treatment (vs. favourable outcome, p = 0.002). Follow‐up evaluations revealed that serum UA levels normalized after treatment, with significantly increased serum UA levels (p < 0.001), and that mRS scores were significantly lower (p < 0.001) than those before treatment. In addition, serum UA levels were significantly associated with mRS scores (r = −0.463, p < 0.001). Conclusion: Our results showed that serum UA levels in patients with anti‐NMDAR encephalitis are reduced during attacks compared with those in CTLs, are normalized after treatment, and are associated with disease severity. HighlightsSerum UA levels in patients with anti‐NMDAR encephalitis are reduced during attacks.Treatment normalizes serum UA levels in anti‐NMDAR encephalitis.Patients with mRS scores <4 have higher serum UA levels than those with scores ≥4.Patients with favourable rather than limited outcomes have higher serum UA levels.Serum UA levels are significantly associated with mRS scores.

Serum concentration of CD40L is elevated in inflammatory demyelinating diseases

It is believed that auto-inflammatory activity, including cellular and humoral immunity responses, especially T cell-B cell collaboration, is one of the most important components of the pathogenesis of inflammatory demyelinating disease. CD40L is critical for T cell-B cell collaboration. Actually, serum CD40L levels have been shown to increase in MS. In the present study, serum CD40L levels were measured by an enzyme-linked immunosorbent assay (ELISA) in NMO (n=27) and MS (n=19) patients and controls (n=14). We revealed elevation of CD40L in NMO patients, and discovered a correlation between CD40L and humoral immunity in inflammatory demyelinating disease.

B cell depleting therapy for multiple sclerosis overlapping with neuromyelitis optica spectrum disorder

Multiple sclerosis and neuromyelitis optica spectrum disorder are currently thought to be independent entities. Some patients display intermediate manifestations that fit the criteria for both diseases without positive relevant serobiomarkers. An overall standard and consensus for the diagnosis and treatment of these overlapping patients have not been reached. We describe a patient with frequently relapsing demyelinating episodes and repeatedly adjusted treatment regimens due to diagnostic difficulties. This case did not respond adequately to glucocorticoid plus azathioprine or to interferon. Benefits were finally obtained by using rituximab, an anti-CD20 specific monoclonal antibody targeting B cells. Treatments targeting B cell mediated humoral immunity such as rituximab, may be a safe and appropriate choice for these challenging demyelinating cases, especially in Asian population.

Study of the placentae of patients with neuromyelitis optica spectrum disorder

Previous studies have shown that circulating AQP4-IgG may lead to negative consequences during pregnancy in patients with neuromyelitis optica spectrum disorder (NMOSD). The objective of this study was to explore whether AQP4-IgG influences pregnancy by affecting AQP4 expression and inducing placental inflammation in patients with NMOSD. We prospectively collected clinical data from six pregnant AQP4-IgG-seropositive NMOSD patients and their infants, and investigated AQP4 expression and placental inflammatory infiltration by comparing hematoxylin and eosin and immunohistochemical (AQP1, AQP4, C5b-9, IgG, CD3, CD8, CD20, and CD68) staining results with three normal controls. Four patients were term pregnant and their infants were normal for development, serum AQP4-IgG was positive at the time of birth, and three infants were negative for AQP4-IgG after 3 months. Two patients underwent induced abortion; one because of NMOSD relapse and another because of fetal malformation. Histological investigation showed normal structure of the chorionic villi, and no significant difference in the intensity of the immunohistochemical staining for AQP1, AQP4, and inflammatory markers in placentae of patients and the controls. Our results showed that there was no significant decrease in placental AQP4 expression, and no obvious placental inflammation or signs of damage in term placentae of NMOSD patients seropositive for AQP4-IgG.

Serum cystatin C and anti-N-methyl-D-aspartate receptor encephalitis

Cystatin C (CysC) is associated with many neurodegenerative disorders and autoimmune diseases, but its relationship with anti‐N‐Methyl‐D‐aspartate receptor (anti‐NMDAR) encephalitis is unknown.

Association of serum gamma-glutamyltransferase and C-reactive proteins with neuromyelitis optica and multiple sclerosis

BACKGROUND Many studies have demonstrated that serum gamma glutamyltransferase (GGT) within normal range might be an early marker of oxidative stress. However the role of GGT in neuromyelitis optica (NMO) and multiple sclerosis (MS) is unknown. METHODS We assessed the correlations among GGT and C-reactive protein (CRP) levels, as well as clinical characteristics of NMO and MS. Serum GGT and CRP levels were measured in 106 NMO patients, 87 MS patients, 79 patients with non-inflammatory neurological diseases (Parkinson disease) and 80 healthy controls (HC). Clinical parameters, blood-brain barrier (BBB) index and Delpech index of MS and NMO were also investigated. RESULTS We found that NMO patients had higher serum GGT and CRP levels within their normal ranges compared to MS, PD, healthy controls. NMO patients exhibited significantly higher EDSS scores than MS patients. The BBB index in NMO patients was significantly higher than that in MS patients. Significant correlations existed between serum GGT and CRP levels and EDSS scores, BBB index in NMO and MS patients. CONCLUSION Elevated GGT and CRP levels within their normal ranges in NMO and MS may be associated with inflammatory response, oxidative stress and BBB disturbance in the diseases. Further study into the underlying pathophysiology of this relationship is warranted.

Brain Immunohistopathology in a Patient with Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy

Background: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a novel meningoencephalomyelitis. However, the pathogenesis of this disease is unclear. We therefore examined a brain biopsy from a patient with autoimmune GFAP astrocytopathy by immunohistopathology. Methods: We examined brain biopsy sections from a patient with autoimmune GFAP astrocytopathy using hematoxylin and eosin (HE) and Luxol fast blue (LFB) staining, and immunostaining with antibodies for CD4, CD8, CD3, CD20, CD68, CD138, Neu-N, GFAP, myelin oligodendrocyte glycoprotein (MOG), and aquaporin-4 (AQP4). Results: HE staining revealed extensive inflammatory cells (marked lymphocytes) around brain vessels, and LFB showed no signs of demyelination or axon loss. Immunohistochemical analysis showed CD3+ and CD4+ T cells cuffing around brain vessels, accompanied by CD8+ T cells, CD20+ B cells, and CD138+ plasma cells, while some macrophages (CD68+) were scattered throughout the brain parenchyma. There was no loss of AQP4 or MOG expression in this patient, while GFAP was abundantly expressed. Conclusions: These findings suggest that inflammatory cells, including T cells, B cells, plasma cells, and macrophages, are involved in autoimmune GFAP astrocytopathy. Demyelination and astrocyte loss may not necessarily occur in this disease.

Ectrodactyly in a Chinese patient born to a mother with neuromyelitis optica spectrum disorder

NMOSD develops primarily in women of childbearing age, and several previous studies have shown that the disorder may increase the risk of miscarriage. However, there are no reports, to our knowledge, of fetal malformation, other than neonatal hydrocephalus, related to NMOSD. We report a 30-year-old woman who experienced recurrent neuritis and who was seropositive for AQP4-IgG. She became pregnant, and the fetus was found to have ectrodactyly. Histological analysis of the placenta showed moderate inflammatory infiltration; however, whether fetal malformation in NMOSD is related to inflammation and AQP4-IgG remains to be determined.

Different features between pediatric-onset and adult-onset patients who are seropositive for MOG-IgG: A multicenter study in South China

BACKGROUND Immunoglobulin against myelin oligodendrocyte glycoprotein (MOG-IgG) is a potential demyelinating disease-associated autoantibody. Whether clinical features of MOG antibody-associated demyelinating diseases change with age remains unclear. OBJECT To investigate the different clinical features between pediatric-onset and adult-onset MOG-IgG-seropositive patients in a relatively large cohort. METHODS A total of 816 consecutive patients with suspected demyelinating disease were prospectively enrolled from three tertiary academic centers in South China from February 2016 to December 2016. Sixteen pediatric-onset cases (≤14 years old) and 34 adult-onset cases (>14 years old) seropositive for MOG-IgG were identified. Differences in clinical features between the two groups were investigated. RESULTS There was a significant difference in the cumulative incidence of first relapse among the two groups (P = .008). Cerebral symptoms were significantly higher in pediatric-onset patients than in adult-onset patients, either at disease onset (pediatric-onset group, 10/16(62.5%); adult-onset group, 8/34(23.53%); P = .007) or throughout the course of disease (pediatric-onset group, 11/16(68.8%); adult-onset group, 10/34(29.4%); P = .009). Optic nerve symptoms were more common in adult-onset groups, but no significant difference was found between the two groups. A significantly higher rate of pediatric-onset patients (9/16, 56.3%) met the acute disseminated encephalomyelitis criteria compared with adult-onset patients (2/34, 5.9%) (P = .0003), and isolated optic neuritis was mainly diagnosed in adult-onset patients (pediatric-onset group, 2/16(12.5%); adult-onset group, 14/34(41.2%); P = .043). The MOG-IgG titer showed a significant positive correlation with total protein levels in cerebrospinal fluid, but only in adult-onset patients (r = 0.95; P = .0004). On magnetic resonance imaging, extensive white matter lesions were observed in both groups, and the number was much higher in pediatric-onset (7/15, 46.7%) than in adult-onset patients (4/29, 13.8%) (P = .043). At the last follow-up, more pediatric-onset patients (10/16, 62.5%) experienced complete recovery (EDSS 0.0 at last follow up) compared with adult-onset patients (9/34, 26.5%) (P = .014). CONCLUSIONS Distinctive features are present between pediatric-onset and adult-onset patients with MOG-IgG. Further studies are required to determine the different underlying pathogenesis of MOG antibody at different ages.

Serum complement levels in anti-N-methyl-d-aspartate receptor encephalitis.

This study aimed to evaluate the relationship between serum complement and anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis.