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.

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.

Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma.

Neuroblastoma (NB), which is a subtype of neural-crest-derived malignancy, is the most common extracranial solid tumor occurring in childhood. Despite extensive research, the underlying developmental origin of NB remains unclear. Using single-cell RNA sequencing, we generate transcriptomes of adrenal NB from 160,910 cells of 16 patients and transcriptomes of putative developmental cells of origin of NB from 12,103 cells of early human embryos and fetal adrenal glands at relatively late development stages. We find that most adrenal NB tumor cells transcriptionally mirror noradrenergic chromaffin cells. Malignant states also recapitulate the proliferation/differentiation status of chromaffin cells in the process of normal development. Our findings provide insight into developmental trajectories and cellular states underlying human initiation and progression of NB.