Journal of neuroimmunology最新文献

Background

Methods

Results

Conclusion

Intravascular large B-cell lymphoma (IVLBCL) is a rare hematological malignancy where its development in the intravascular environment is the main characteristic. Despite its ability to affect multiple organic systems, there is a tropism for the central nervous system, which may be related to several clinical syndromes, making this condition a great mimic and consequently a diagnostic challenge. Rapidly progressive dementia may be one of the presenting phenotypes of IVLBCL. This case report aims to highlight the main red flags, such as sustained elevation of lactate dehydrogenase, organomegaly and specific lesions with vasculitis-like bleeding, all that can be used as clinical clues to direct the differential diagnosis. In addition, it reinforces the role of early brain biopsy in this context, since IVLBCL is a treatable disease.

Rituximab is recommended as the preferred second-line immunotherapy for autoimmune encephalitis (AE). However, Ofatumumab (OFA), a novel fully human anti-CD20 antibody, has been reported infrequently in patients with AE. Among the various forms of AE, anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis is the most common and severe. This study presents three cases of severe anti-NMDAR encephalitis treated with OFA following the failure of first-line immunotherapy. The results indicated that the patients experienced no significant adverse reactions after receiving OFA, and their clinical symptoms improved markedly within one week of treatment. One month post-treatment with OFA, scores on the Glasgow Coma Scale (GCS) and the Barthel Index of Activities of Daily Living (Barthel-ADL) increased, while scores on the modified Rankin Scale (mRS), Clinical Assessment Scale in Autoimmune Encephalitis (CASE), and Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM) decreased. During the three-month and six-month follow-up periods, patients exhibited further symptomatic improvement, suggesting that OFA is a safe and effective treatment option for anti-NMDAR encephalitis. These findings propose a novel therapeutic strategy for severe refractory anti-NMDAR encephalitis.

Agrin is essential for neuromuscular junction (NMJ) formation and maintenance. The C-terminal agrin fragment (CAF), generated by neurotrypsin-mediated cleavage of agrin, has been gaining attention as a potential biomarker for sarcopenia. We investigated serum CAF levels in myasthenia gravis (MG), a NMJ disorder. Compared to healthy controls, serum CAF levels were significantly elevated in acetylcholine receptor antibody-positive MG (AChR-MG) patients, but not in muscle-specific kinase antibody-positive MG patients. In AChR-MG, baseline and post-treatment CAF levels inversely correlated with post-treatment MG activities of daily living scores, suggesting that elevated CAF levels may reflect protective mechanisms against AChR-MG pathogenesis, such as improved NMJ regeneration.

Autoimmune autonomic ganglionopathy (AAG) is a rare disease wherein autoantibodies target the ganglionic acetylcholine receptor (gAChR). Current diagnosis in the United States depends upon clinical symptoms and positive autoantibody detection using a radioimmunoprecipitation assay (RIA). Here we offer a proof-of-principle study on an alternative method, fluorescence-detection size-exclusion-chromatography (FSEC). We show FSEC can detect autoantibodies against gAChR from patient sera but not healthy controls or samples from other autoimmune diseases. We compare FSEC to RIA and find good correlation. We discuss potential advantages of using FSEC as an alternative or as a first-step diagnostic prior to pursuing existing methodologies.

Disease-modifying therapies (DMTs) are used in an increasing number of patients with multiple sclerosis (MS). However, whether DMTs have intrinsic effects on deep gray matter (DGM) microstructure and atrophy is still poorly understood. In this study, we described the quantitative susceptibility values (QSV) and diffusion kurtosis imaging (DKI) metrics of DGM in relapsing–remitting MS (RRMS) patients and their association with cognitive deficits. We recruited 62 patients with RRMS receiving DMTs and 30 patients with RRMS not receiving DMTs underwent MRI on a 3T scanner. Fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), mean diffusivity (MD), mean kurtosis (MK), QSV and volumes of bilateral caudate nucleus (CAU), amygdala (AMYG), putamen (PUT), hippocampus (Hipp), globus pallidus (GP) and thalamus (THA) were measured. Correlation analysis was performed between those image indexes with longitudinal significant changes and clinical neurological scores, including Expanded Disability Status Scale (EDSS), Digit Span Testand (DST), Symbol Digit Modalities Test (SDMT), Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Significant longitudinal increases in FA, KFA and MK values were found in both groups in bilateral CAU, AMYG, PUT, Hipp, GP and THA (all p < 0.005). MD values of the right of CAU in the two groups were significant longitudinal increase (p = 0.009, p = 0.047); MD values of the right of GP (p = 0.042), the left of THA (p = 0.003), the right of THA (p = 0.001) in treated MS were significant longitudinal decrease; There were no significant longitudinal changes between treated and untreated groups in normalized deep gray matter volume. For QSV, longitudinal increase in the right of PUT (p = 0.022) in the treated MS group and in the left of Hipp (p = 0.045) in the untreated MS group. The QSV and DKI measures were highly correlated with cognitive and disability tests. The treated RRMS patients showed different longitudinal changes of MD value and QSV with untreated in several DGM regions, and these differences were correlated with cognitive and microstructural integrity.

Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder where acetylcholine receptor (AChR) antibodies induce membrane attack complex formation at the muscle membrane. The C1-inhibitor (C1-INH) regulates the classical pathway and is a promising marker in other autoimmune disorders. Treatment options for AChR antibody MG include complement inhibitors; nevertheless, the early pathway activation in MG remains unclear. Serum and plasma C1s-C1-INH levels were higher in MG patients than in matched healthy controls, supporting early classical pathway activation in most MG patients. These findings allow prospective validation studies of activated C1s as a putative treatment target and potential accompanying biomarker in MG.

This observational study explored coexisting organ-specific and non-organ-specific autoantibodies in Neuromyelitis optica spectrum disorder(NMOSD) and Myelin oligodendrocyte glycoprotein-IgG-1(MOG-IgG1) associated central nervous system demyelination(MOGAD) in a South Asian cohort from March 2017–2023. Of the 250 cases, 148 were MOGAD(82pediatric) and 102 were NMOSD(15 pediatric). 17.6 % tested positive for ≥1 antibody, with NMOSD showing a higher positivity rate (25.5 %) than MOGAD(12.2 %,p = 0.011). Double antibody positivity occurred more in NMOSD (5.9 %vs.MOGAD,1.4 %,p = 0.045). Three NMOSD cases had Sjogren syndrome with higher Anti-Ro-52 prevalence(12.7 %vs.4.1 %,p = 0.014). NMOSD patients with ≥1 antibody positivity had more constitutional symptoms (45.5 %vs.23.1 %,p = 0.045). Significant associations were found between NMOSD and female gender, having ≥1 antibody-positive status, and testing positive for Anti-Ro-52 and SS-A antibodies (p < 0.05).