East Asian Registry Details Distinct Demyelinating Disease Profile

Shifting Boundaries in Demyelinating Disease

Robust national patient registries are essential tools for epidemiological research, particularly when tracking striking geographic variations in disease prevalence [1, 2]. Diagnostic frameworks across medicine have increasingly shifted from broad syndromal classifications toward precise, biomarker-driven biological definitions [3]. This evolution requires clinicians to continuously update their understanding of disease epidemiology to ensure accurate differential diagnosis and adhere to the latest management guidelines [4]. For central nervous system inflammatory demyelinating diseases, the discovery of specific autoantibodies has fundamentally fractured what was once considered a single clinical spectrum into distinct pathological entities. A new nationwide registry study now offers fresh insights into how these molecular distinctions translate to real-world clinical practice, revealing a unique epidemiological profile in East Asia.

Nationwide Registry Design and Diagnostic Rigor

To establish a clear epidemiological picture of central nervous system inflammatory demyelinating diseases in East Asia, researchers designed a study to provide clinically validated, nationwide estimates of multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in the Republic of Korea. Data collection took place from January to March 2025, drawing on a network of 47 referral hospitals participating in a nationwide hospital-based registry. Participating hospitals identified actively followed patients, strictly defined as those having at least one outpatient visit in the prior six months. Diagnostic rigor was a central focus of the registry design, with all patient diagnoses following established international criteria. To accurately differentiate these overlapping clinical syndromes, patient antibody status was confirmed using validated cell-based assays (a highly specific laboratory technique used to detect autoantibodies targeting cell surface antigens in their natural conformation). Participating centers provided comprehensive clinical profiles for each identified patient, including demographics and detailed treatment data. To assess the clinical burden and neurological impairment across the cohort, the centers also provided scores from the Expanded Disability Status Scale (a standard method of quantifying disability in multiple sclerosis and related diseases). Finally, the researchers calculated prevalence estimates for each condition using national population data, allowing them to extrapolate the findings to the broader population of the Republic of Korea.

A Distinct Epidemiological Profile

The researchers identified a total of 4,196 patients with central nervous system inflammatory demyelinating diseases. Breaking down this nationwide cohort, the registry identified 1,799 patients with MS, alongside 1,616 patients with NMOSD and 781 patients with MOGAD. This distribution yielded a relative ratio of MS to NMOSD to MOGAD of 2.3:2.1:1. Extrapolating these case counts using national population data, the investigators determined the specific disease burdens across the country. The crude prevalence estimate for MS was 3.48 per 100,000. Closely following this, the crude prevalence estimate for NMOSD was 3.13 per 100,000, and the crude prevalence estimate for MOGAD was 1.51 per 100,000. These findings indicate that the nationwide registry demonstrates a distinctive Korean central nervous system inflammatory demyelinating disease profile. Unlike epidemiological data from North America or Europe, the Korean profile shows a relatively higher proportion of NMOSD and MOGAD compared to Western populations. The researchers concluded that the higher relative proportion of NMOSD and MOGAD reflects the low prevalence of MS in East Asia. For clinicians, these numbers highlight the critical importance of routine antibody testing in East Asian patients presenting with demyelinating symptoms. Because antibody-mediated conditions represent nearly half of all cases rather than rare atypical variants, physicians must maintain a high index of suspicion to avoid misdiagnosing these patients with MS and inadvertently prescribing therapies that could exacerbate their condition.

Demographic Divergence: Age and Sex Differences

Beyond prevalence rates, the registry data revealed distinct demographic patterns that can assist clinicians in the differential diagnosis of central nervous system demyelinating diseases. The researchers found that patients with MS typically presented earlier in life, with a mean age at onset of 33.4 ± 12.0 years. In contrast, the antibody-mediated conditions emerged nearly a decade later on average. The mean age at onset for NMOSD was 42.7 ± 14.7 years, while the mean age at onset for MOGAD was 41.7 ± 17.8 years. For practicing physicians, an initial presentation of demyelinating symptoms in a patient over the age of 40 should elevate the clinical suspicion for NMOSD or MOGAD and prompt immediate autoantibody testing. Sex distribution also varied significantly across the three conditions, providing another layer of diagnostic context. While all three diseases showed a female predominance, the extent of this disparity differed markedly. The female-to-male ratio for MS was 2.2:1, and the female-to-male ratio for MOGAD was 1.5:1, reflecting a moderate female bias. However, the registry highlighted a striking sex imbalance in NMOSD, where the overall female-to-male ratio was 5.1:1. This female predominance became even more pronounced when isolating specific biomarker profiles, as the female-to-male ratio in aquaporin-4-IgG positive NMOSD cases was 6.5:1 (aquaporin-4-IgG is an autoantibody targeting water channel proteins on astrocytes, serving as the primary pathogenic driver in most NMOSD cases). Taken together, these demographic clues are highly relevant for the initial clinical assessment of East Asian patients. A young female patient in her early thirties might fit the classic demographic profile for MS, but a middle-aged female patient presenting with optic neuritis or myelitis carries a high pre-test probability for aquaporin-4-IgG positive NMOSD. By integrating these age and sex differences with regional prevalence data, clinicians can better stratify risk and expedite the appropriate diagnostic workup, ensuring that patients with antibody-mediated demyelination receive targeted therapies rapidly.

References

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics, 2002. CA A Cancer Journal for Clinicians. 2005. doi:10.3322/canjclin.55.2.74

2. Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clinical Epidemiology. 2015. doi:10.2147/clep.s91125

3. Jack CR, Bennett DA, Blennow K, et al. NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimer s & Dementia. 2018. doi:10.1016/j.jalz.2018.02.018

4. Galiè N, Humbert M, Vachiéry J, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Respiratory Journal. 2015. doi:10.1183/13993003.01032-2015