Treatment patterns of patients with multiple sclerosis in Guangzhou, China

@#Background & Objective: Disease-modifying treatments (DMTs) for multiple sclerosis (MS) are widely used in Western countries. In China, however, the current treatment patterns of MS patients are not well characterized. This is to explore the gap between the current treatments in Guangzhou, Southern China and those given in Western countries. Methods: We performed a survey of MS patients at department of neurology, a tertiary MS referral centre in Guangzhou, concerning treatments of MS in Southern China. The clinical data in patients were collected. The initial treatment, drug withdrawal or switching profile, and therapeutic effect of existing treatments in MS patients were analyzed. Results: The ratio of MS patients who receive DMTs in Guangzhou China is extremely low. Among the 178 patients studied, only 28.09% received initial treatment with DMTs. MS patients who receive initial treatment with first-line DMTs have higher drug withdrawal rates (32.6%) and drug switching rates (30.43%) than those of western populations. The main reasons for withdrawal of first-line DMTs were doctor’s advice (maintenance of remission) (40.00%), economic burden(20.00%), and no channels to buy drugs(13.33%). In MS patients initially treated with first-line DMTs who switched to other drugs, a gap between treatments was common (8/14;57.14%). There were 18 patients with highly active MS receiving treatment with rituximab. Annual relapse rate after treatment significantly decreased than that before treatment (0.74 vs. 1.50 , P < 0.001). Conclusions: DMTs for MS in Guangzhou, Southern China appear to lag behind those in Western countries. Much work is needed to improve drug accessibility and affordability of DMTs in China. Rituximab is an option for highly active MS in limited medical-resource countries.

Myelin Oligodendrocyte Glycoprotein-IgG Contributes to Oligodendrocytopathy in the Presence of Complement, Distinct from Astrocytopathy Induced by AQP4-IgG / 神经科学通报·英文版

Immunoglobulin G against myelin oligodendrocyte glycoprotein (MOG-IgG) is detectable in neuromyelitis optica spectrum disorder (NMOSD) without aquaporin-4 IgG (AQP4-IgG), but its pathogenicity remains unclear. In this study, we explored the pathogenic mechanisms of MOG-IgG in vitro and in vivo and compared them with those of AQP4-IgG. MOG-IgG-positive serum induced complement activation and cell death in human embryonic kidney (HEK)-293T cells transfected with human MOG. In C57BL/6 mice and Sprague-Dawley rats, MOG-IgG only caused lesions in the presence of complement. Interestingly, AQP4-IgG induced astroglial damage, while MOG-IgG mainly caused myelin loss. MOG-IgG also induced astrocyte damage in mouse brains in the presence of complement. Importantly, we also observed ultrastructural changes induced by MOG-IgG and AQP4-IgG. These findings suggest that MOG-IgG directly mediates cell death by activating complement in vitro and producing NMOSD-like lesions in vivo. AQP4-IgG directly targets astrocytes, while MOG-IgG mainly damages oligodendrocytes.

Registry of infl ammatory demyelinating diseases of the central nervous system in the Asia-Pacifi c region

Background and Objective: Comparable data are sparse for infl ammatory demyelinating diseases of the central nervous system (CNS) in the Asia-Pacifi c region, and we aimed to establish a registry of patients with such diseases in the region. Methods: A network of neurologists in the Asia-Pacifi c Region was established to register patients with the targeted diseases. A standardized register form and relevant instructions in English, translated into the local language when needed, were prepared before the study start and used for data collection. Results: Eight study centres from different countries/areas participated in the study. In total, 857 patients with a validated diagnosis of different infl ammatory demyelinating diseases of the CNS were registered, 591 females and 266 males with a female-to-male ratio 2.2. The mean age at onset for all patients was 35.9 (SD: 12.9) years, signifi cantly younger (p = 0.010) for females (35.1 years, SD: 12.6 years) than for males (37.6 years, SD: 13.4 years). Conclusion: Patients with different infl ammatory demyelinating diseases of the CNS were in the fi rst time registered in a multi-centre study from eight countries/areas in the Asia-Pacifi c region. A platform and basis has been established for further study in the fi eld.

Aquaporin-4 IgG: Overview and future perspectives

The discovery of aquaporin-4 IgG in patients with demyelination is an exciting development. Initially associated with the Devic’s phenotype, aquaporin-4 IgG has also been consistently found albeit less frequently in tumefactive disease, encephalopathies, classical MS and by one group in GBS. Curiously the cerebellum has the highest concentration of the target antigen, but remains the only part of the nervous system yet to demonstrate “characteristic lesions” with aquaporin-4 IgG. Moreover there is tantalising evidence that seropositivity is influenced by age, sex, and ancestral immunogenetic haplotypes. There is no exclusive clinical or radiological feature of seropositivity, and prospective cohorts universally find transitional cases. The use of teleological definitions is unhelpful and unscientific. Older detailed pathological studies have documented changes of both neuromyelitis optica and multiple sclerosis in the same individual, with both necrotising and classical lesions. Any hypothesis must accommodate the above observations, amongst other problematic findings. A logical initial conclusion is that demyelinating disease is a complex and extraordinarily heterogeneous process, and that aquaporin-4 IgG provides a new window into the disease. Crucially, the diagnostic and therapeutic implications of aquaporin-4 IgG can only be ascertained with evidence from rigorous prospective clinical study in different immunogenetic populations, and further pathological investigations are necessary.

The Registry of Asia Pacific Inflammatory Demyelination (RAPID Study)

The diversity and heterogeneity of idiopathic central nervous system demyelinating disease in Asia has long been recognised, but there is a dearth of epidemiological work looking at this specific question. Existing data on demyelinating diseases from both the East and the West has been confounded by differences in case ascertainment, selection bias, differing study methodologies and the exclusion of so-called “atypical” cases. This is particularly so in Asia where the application of Western diagnostic criteria may not be appropriate. The RAPID Study is designed to identify the full spectrum of demyelinating disease presentations, including atypical forms, and those associated with other systemic diseases or other disease markers and it is not linked to any form of therapy or medical intervention. The time interval for data collection is finite at twelve months, at which stage the epidemiological data collected will be collated and analysed by the Central Steering Committee. The efforts of all contributors will be recognised in the planned publication derived from this study. Moreover, the data collected will be capable of forming the framework of subsequent clinically isolated syndrome follow up studies and may also form the basis of subsequent sub-studies such as in those centres which are in a position to perform serological and immunogenetic testing. Diagnostic criteria can only be established when a scientific evidence base has been established, and the criteria then tested prospectively. The RAPID data will be pivotal in helping to resolve current controversies surrounding immunological and radiological markers of demyelinating disease.