Serum antinuclear antibodies associate with severe disease activity in neuromyelitis optica spectrum disorder.

BACKGROUND: Studies suggest that antinuclear antibodies (ANAs) may correlate with the long-term prognosis of Neuromyelitis optica spectrum disorder (NMOSD). In this study, we investigated ANAs in Chinese patients with NMOSD and their relationship with disease outcomes. METHODS: We retrospectively collected data from 525 patients diagnosed with NMOSD at West China Hospital between September 1, 2009, and October 1, 2021. Patients were classified into two groups: NMOSD with ANA (+) or without ANA (-). We compared the clinical characteristics, relapse rate, severe attacks, laboratory tests, Expanded Disability Status Scale (EDSS), and prognosis between the two groups. RESULTS: Among the 525 NMOSD patients, those with ANA showed a higher frequency of AQP4-IgG (94.1% vs 79.3%, p < 0.001, false discovery rate (FDR) corrected p < 0.001), and anti-SSA (p < 0.001, FDR corrected p < 0.001), anti-SSB (p < 0.001, FDR corrected p < 0.001), anti-Ro52 antibodies (p < 0.001, FDR corrected p < 0.001), than those without ANA. ANA was detected in 403 patients during the acute phase. Patients with ANA (+) had higher EDSS scores in the acute stage (4.0 vs. 3.75, p = 0.013, FDR corrected p = 0.029) and at final follow-up (p = 0.032, FDR corrected p = 0.064). NMOSD patients with ANA (+) had a higher frequency of severe acute myelitis attack, severe acute myelitis and optic neuritis attack, motor and visual disability, compared to those with ANA (-) (42.1% vs. 27.8%, p = 0.001, FDR corrected p = 0.004, 19.3% vs. 10.3%, p = 0.004, FDR corrected p = 0.018, and 11.1% vs. 4.8%, p = 0.008, FDR corrected p = 0.022 respectively). The two groups had no significant difference in the annual recurrence rate (ARR). CONCLUSION: ANA may be associated with more severe disease activity and disability in NMOSD.

Brain structural and functional connectivity alterations are associated with fatigue in neuromyelitis optica spectrum disorder.

BACKGROUND: Many patients with neurological disorders experience chronic fatigue, but the neural mechanisms involved are unclear. OBJECTIVE: Here we investigated whether the brain structural and functional connectivity alterations were involved in fatigue related to neuromyelitis optica spectrum disorder (NMOSD). METHODS: This prospective pilot study used structural and resting-state functional brain magnetic resonance imaging to compare total cortical thickness, cortical surface area, deep gray matter volume and functional connectivity (FC) between 33 patients with NMOSD and 20 healthy controls (HCs). Patients were subgrouped as low fatigue (LF) and high fatigue (HF). RESULTS: HF patients scored higher on the Hamilton Anxiety Rating Scale and Hamilton Rating Scale for Depression than LF patients and HCs. The two patient subgroups and HC group did not differ significantly in cortical thickness, cortical surface area and volumes of the bilateral caudate nucleus, bilateral putamen, bilateral amygdala, bilateral hippocampus, bilateral thalamus proper or right nucleus accumbens (p > 0.05). However, after correcting for age, sex, years of education, anxiety and depression, HF patients showed larger left pallidum than HCs (0.1573 ± 0.0214 vs 0.1372 ± 0.0145, p = 0.009). Meanwhile, both LF patients (0.0377 ± 0.0052 vs 0.0417 ± 0.0052, p = 0.009) and HF patients (0.0361 ± 0.0071 vs 0.0417 ± 0.0052, p = 0.013) showed smaller left nucleus accumbens than HCs.. Compared with LF patients, HF patients showed significantly decreased FC between the left pallidum and bilateral cerebellar posterior lobes. CONCLUSIONS: This was the first evidence linking structural and functional alterations in the brain to fatigue in NMOSD, and in the future, long term follow-up was necessary.

Association of GTF2IRD1-GTF2I polymorphisms with neuromyelitis optica spectrum disorders in Han Chinese patients.

Variants at the GTF2I repeat domain containing 1 (GTF2IRD1)-GTF2I locus are associated with primary Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders (NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders (odds ratio (OR) = 1.364, 95% confidence interval (CI) 1.019-1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positivity (OR = 1.397, 95% CI 1.021-1.912; P = 0.036) and stratification according to coexisting autoimmune diseases (OR = 1.446, 95% CI 1.072-1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients (OR = 3.15, 95% CI 1.183-8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval number: 2016-31) on March 2, 2016.

[Anxiety and Depression in Patients with Neuromyelitis Optica].

OBJECTIVE: To assess anxiety and depression in patients with neuromyelitis optica (NMO). METHODS: Eligible patients with NMO were assessed with Hamilton anxiety rating scale-14 (HARS-14),Hamilton depression rating scale-21 (HDRS-21) and expanded disability status scale (EDSS). RESULTS: A total of 65 NMO patients [(39.85±10.36) yr., male/female: 5/60) participated in this study. They had a median EDSS score of 2.5 and a mean score of (37.37±20.44) for bodily pain. About 76.9% of patients were NMO-IgG seropositive. The participants had (11.03±6.95) HARS-14 scores and (11.74±7.78) HDRS-21 scores,with 27.69% (18/65) being diagnosed with anxiety and 24.62% (16/65) being depressed. The EDSS scores were correlated with HARS-14 scores (r=0.285, P=0.004) and HDRS-21 scores (r=0.328, P=0.008). Bodily pain was negatively correlated with HARS-14 scores (r=-0.561, P<0.001) and HDRS-21 scores (r=-0.496, P<0.001). Relapse was correlated with anxiety (r=0.285, P=0.022). Age,sex,duration of disease,and serum NMO-IgG were not correlated with HARS-14 scores and HDRS-21 scores. The logistic regression model identified bodily pain as a predictor of anxiety and depression in NMO patients (OR=1.052,1.046,respectively P<0.05). CONCLUSION: Disability and bodily pain are associated with anxiety and depression in NMO patients,while relapse is associated with anxiety only. Bodily pain is a predictor of anxiety and depression in NMO patients.

Different neurologic outcomes of myasthenia gravis with thymic hyperplasia and thymoma after extended thymectomy: A single center experience.

This study aimed to reveal the clinical course and outcomes of myasthenia gravis (MG) in patients with thymic lymphoid hyperplasia and thymoma undergoing extended thymectomy and to identify the clinical prognostic factors of remission for MG. In total, 73 patients undergoing extended thymectomy were divided into two groups: group A with lymphoid hyperplasia (n=39) and group B with thymoma (n=34). According to the MG Foundation of America (MGFA) post-intervention status, the primary endpoint was a composite measure defined as achievement of complete stable remission (CSR), pharmacologic remission (PR), minimal manifestations (MM) or improvement (IM). The secondary endpoint was CSR. The cumulative probabilities of reaching the primary endpoint were 71.8% in group A and 85.3% in group B (p=0.164), respectively. Using Kaplan-Meier survival analysis, the probability of reaching the primary endpoint in group B was remarkably greater than group A (p=0.036). Cox multivariate analysis indicated that pre-operative MGFA class I (HR: 3.019, 95% CI: 1.084-8.410) and MGFA II (2.665, 95% CI: 1.033-6.873) compared to MGFA III and presence of thymoma (HR: 2.229, 95% CI: 1.079-4.606), showed the most consistent association with remission of MG after thymectomy. Finally, thymic lymphoid hyperplasia and severe symptoms may negatively affect prognosis of MG following thymectomy.

Muscle damage in patients with neuromyelitis optica spectrum disorder.

OBJECTIVE: Increasing evidence has shown that skeletal muscle damage plays a role in neuromyelitis optica spectrum disorder (NMOSD). The objective of this study was to compare the serum creatine kinase (sCK) levels in NMOSD patients with different clinical statuses. METHODS: In the observational study, levels of sCK were measured during the acute and stable phases for patients with NMOSD and healthy controls (HCs). RESULTS: We enrolled 168 patients with NMOSD (female:male ratio, 153:15; age: 43.9 ± 13.1 years) in the acute phase, and blood samples were collected from 85 of the patients with NMOSD during both acute and stable phases to determine the sCK levels. The mean log sCK levels of the patients with NMOSD in the acute phase were higher (4.51 ± 1.17, n = 85) than those of the patients with NMOSD in the stable phase (3.85 ± 0.81, n = 85, p = 0.000). Furthermore, the log sCK levels of the patients with NMOSD in the stable phase were lower than those of the HCs (4.31 ± 0.39, n = 200, p = 0.000). In patients with sCK levels within the normal limits, these differences were also observed (p < 0.05). In the multivariable linear regression model performed for the patients with NMOSD in the acute phase, it suggested that a higher estimated glomerular filtration rate (p = 0.026), patients with the core clinical characteristics of optic neuritis (p = 0.005), and serum anti-SSA positivity (p = 0.019) predicted lower log sCK levels. CONCLUSIONS: Muscle damage occurs in patients with NMOSD and is aggravated during the acute phase.

[Correlates of Fatigue in Patients with Neuromyelitis Optica].

OBJECTIVES: To determine clinical characteristics associated with fatigue in patients with neuromyelitis optica (NMO). METHODS: A questionnaire survey was conducted in NMO patients, measuring fatigue using the fatigue impact scale (FIS). RESULTS: A total of 64 NMO patients (mean age: 50.0 years; male/female: 3/61) completed the survey: 71.9% were NMO-IgG seropositive and 43 (67.2%) received immunosuppressive treatments. The patients obtained a global FIS score of 64.8±36.1, with 13.2±8.5, 20.6±11.6 and 31.0±18.7 for the cognitive, physical and social dimensions, respectively. No significant differences were found in global FIS scores ( P=0.294 9), and cognitive ( P=0.467 1), physical ( P=0.472 2) and social ( P=0.212 6) dimensional scores between those with and without immunosuppressive treatments. Age, sex, serum NMO-IgG, duration of disease and annual relapse rates were neither correlated with global FIS scores ( P>0.05), nor with the three dimensional scores ( P>0.05). The Expanded Disability Status Scale score was positively associated with global FIS scores ( P=0.000 5)and cognitive( P=0.018 7), physical( P=0.000 4) and social ( P=0.000 5)dimensional scores. The frequency of attack was also positively correlated with cognitive dimensional scores ( P=0.007 9). CONCLUSIONS: Disability is associated with cognitive, physical and social dimensions of fatigue. High frequency of attack is positively correlated with the cognitive dimension of fatigues.