Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD. METHODS: This multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis. RESULTS: In total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment. CONCLUSIONS: Earlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.

A Pilot Study of Autonomic Function Screening Tests for Differentiating Complex Regional Pain Syndrome Type II and Traumatic Neuropathic Pain.

Background and Objectives: One of the most challenging tasks in a clinical setting is to differentiate between complex regional pain syndrome (CRPS) type II and traumatic neuropathic pain (NeP). CRPS is characterized by several dysautonomic manifestations, such as edema, hyper/hypohidrosis, skin color change, and tachycardia. This study compared the outcomes of autonomic function screening tests in patients with CRPS type II and traumatic NeP for diagnostic differentiation. Materials and Methods: CRPS type II was diagnosed according to the Budapest research criteria, while NeP was diagnosed according to the updated grading system suggested by the International Association for the Study of Pain Special Interest Group on Neuropathic Pain in 2016. Twenty patients with CRPS type II and twenty-five with traumatic NeP were investigated. Results: Twelve patients with CRPS type II presented abnormal results for the quantitative sudomotor axon reflex test (QSART). Abnormal QSART results were more common in the CRPS type II group. Conclusions: Analysis of QSART combined with other ancillary tests can help in the differential diagnosis of CRPS type II and traumatic NeP if factors influencing abnormal QSART are sufficiently controlled.

Efficacy and safety of givosiran for acute hepatic porphyria: 24-month interim analysis of the randomized phase 3 ENVISION study.

BACKGROUND & AIMS: Upregulation of hepatic delta-aminolevulinic acid synthase 1 with accumulation of potentially toxic heme precursors delta-aminolevulinic acid and porphobilinogen is fundamental to the pathogenesis of acute hepatic porphyria. AIMS: evaluate long-term efficacy and safety of givosiran in acute hepatic porphyria. METHODS: Interim analysis of ongoing ENVISION study (NCT03338816), after all active patients completed their Month 24 visit. Patients with acute hepatic porphyria (≥12 years) with recurrent attacks received givosiran (2.5 mg/kg monthly) (n = 48) or placebo (n = 46) for 6 months (double-blind period); 93 received givosiran (2.5 mg or 1.25 mg/kg monthly) in the open-label extension (continuous givosiran, n = 47/48; placebo crossover, n = 46/46). Endpoints included annualized attack rate, urinary delta-aminolevulinic acid and porphobilinogen levels, hemin use, daily worst pain, quality of life, and adverse events. RESULTS: Patients receiving continuous givosiran had sustained annualized attack rate reduction (median 1.0 in double-blind period, 0.0 in open-label extension); in placebo crossover patients, median annualized attack rate decreased from 10.7 to 1.4. Median annualized days of hemin use were 0.0 (double-blind period) and 0.0 (open-label extension) for continuous givosiran patients and reduced from 14.98 to 0.71 for placebo crossover patients. Long-term givosiran led to sustained lowering of delta-aminolevulinic acid and porphobilinogen and improvements in daily worst pain and quality of life. Safety findings were consistent with the double-blind period. CONCLUSIONS: Long-term givosiran has an acceptable safety profile and significantly benefits acute hepatic porphyria patients with recurrent attacks by reducing attack frequency, hemin use, and severity of daily worst pain while improving quality of life.

Subgrouping of Peripheral Neuropathic Pain Patients According to Sensory Symptom Profile Using the Korean Version of the PainDETECT Questionnaire.

BACKGROUND: A culturally validated Korean version of the PainDETECT Questionnaire (PD-Q) was used to identify neuropathic pain components (NeP) in patients suffering from chronic pain. The purpose of this study was to determine if the Korean PD-Q can be used to subgroup patients with peripheral NeP according to sensory symptom profiles. METHODS: This study included 400 Korean patients with peripheral neuropathic pain diagnosed as probable or definite NeP. The total scores and subscores for each item in PD-Q were transformed into a Z-score for standardization. Hierarchical cluster analysis was performed to identify clusters of subjects by PD-Q scores. RESULTS: The mean total PD-Q score of the study participants was 14.57 ± 6.46. A hierarchical cluster analysis identified 5 clusters with distinct pain characteristic profiles. Cluster 1 had relatively severe burning and tingling sensations. The mean total PD-Q score for cluster 2 was the lowest of the 5 clusters. Cluster 3 tended to be vulnerable to pain in response to cold/heat stimulation. Cluster 4 showed relatively severe pain induced by physical stimuli, such as light touch or slight pressure. Cluster 5 had high scores for all NeP symptoms. CONCLUSION: This study demonstrates the ability of patients to cluster by symptoms using the Korean PD-Q. Subgrouping of peripheral neuropathic pain by sensory symptom profile may be useful in making effective drug treatment decisions.

Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis.

BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin. METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters]×albumin level in grams per liter; lower values indicated worse nutritional status). RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (±SD) mNIS+7 at baseline was 80.9±41.5 in the patisiran group and 74.6±37.0 in the placebo group; the least-squares mean (±SE) change from baseline was -6.0±1.7 versus 28.0±2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (±SD) baseline Norfolk QOL-DN score was 59.6±28.2 in the patisiran group and 55.5±24.3 in the placebo group; the least-squares mean (±SE) change from baseline was -6.7±1.8 versus 14.4±2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08±0.02 m per second with patisiran versus -0.24±0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7±9.6 versus -119.4±14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups. CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis. (Funded by Alnylam Pharmaceuticals; APOLLO ClinicalTrials.gov number, NCT01960348 .).

Comparison of MOG and AQP4 antibody seroprevalence in Korean adults with inflammatory demyelinating CNS diseases.

We aimed to compare seroprevalence of anti-myelin oligodendrocyte glycoprotein (MOG) and anti-aquaporin-4 (AQP4) antibodies in Korean adults with inflammatory demyelinating diseases (IDDs) of the central nervous system (CNS), based on a multicenter nationwide database. Sera were analyzed using a live cell-based assay for MOG and AQP4 antibodies. Of 586 Korean adults with IDDs of the CNS, 36 (6.1%) and 185 (31.6%) tested positive for MOG and AQP4 antibodies, respectively. No participant showed double positivity. Seroprevalence of MOG antibodies was about five times lower than that of AQP4 antibodies in a large cohort of Korean adults with IDDs of the CNS.

Serum FAM19A5 in neuromyelitis optica spectrum disorders: Can it be a new biomarker representing clinical status?

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) targets astrocytes and elevates the levels of astrocyte-injury markers during attacks. FAM19A5, involved in reactive gliosis, is secreted by reactive astrocytes following central nervous system (CNS) damage. OBJECTIVE: To investigate the significance of serum FAM19A5 in patients with NMOSD. METHODS: We collected clinical data and sera of 199 patients from 11 hospitals over 21 months. FAM19A5 levels were compared among three groups: NMOSD with positive anti-aquaporin-4 antibody (NMOSD-AQP4), other CNS demyelinating disease, and healthy controls. RESULTS: The median serum FAM19A5 level was higher in the NMOSD-AQP4 (4.90 ng/mL (3.95, 5.79)) than in the other CNS demyelinating (2.35 ng/mL (1.83, 4.07), p < 0.001) or healthy control (1.02 ng/mL (0.92, 1.14), p < 0.001) groups. There were significant differences in the median serum FAM19A5 levels between the attack and remission periods (5.89 ng/mL (5.18, 6.98); 4.40 ng/mL (2.72, 5.13), p < 0.001) in the NMOSD-AQP4 group. Sampling during an attack (p < 0.001) and number of past attacks (p = 0.010) were independently associated with increased serum FAM19A5. CONCLUSION: Serum FAM19A5 was higher in patients with NMOSD-AQP4 and correlated with clinical characteristics. Thus, serum FAM19A5 may be a novel clinical biomarker for NMOSD-AQP4.

Comparison of new-onset and persistent epilepsy in the elderly.

BACKGROUND: Previous studies on elderly epilepsy included only patients with new-onset disease, but there are many patients who developed epilepsy earlier and aged. AIM: We compared the characteristics of new-onset and persistent epilepsy in the elderly. METHODS: We performed a 10-year retrospective analysis of elderly patients with epilepsy divided into two groups according to the onset of seizure: new-onset epilepsy (onset age ≥65) and persistent epilepsy (onset age<65). RESULTS: Nearly half (78/172, 45.3%) of patients in the new-onset group presented as status epilepticus, and one-fourth of these (19/78, 24.4%) died during the initial treatment for status epilepticus. Patients in the new-onset epilepsy group presented more frequently as status epilepticus (59/153 vs 12/78, P < 0.001) and had a past history of status epilepticus (63/153 vs 20/78, P = 0.02). History of stroke (81/153 vs 30/78, P = 0.04), hypertension (83/153 vs 29/78, P = 0.01), and dyslipidemia (53/153 vs 17/78, P = 0.05) was more common in the new-onset group, but patients in the persistent group used more antiepileptic drugs (AEDs; P = 0.036) and total AED drug loads (P = 0.028). CONCLUSIONS: Our study shows that new-onset epilepsy has a higher incidence of status epilepticus and more stroke-related risk factors but may require fewer AEDs for epilepsy control.

Extremely Early Onset Transthyretin Familial Amyloid Polyneuropathy with a Leu55Pro Mutation: A Pediatric Case Report and Literature Review.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a life-threatening autosomal dominant disease caused by the deposition of amyloid fibrils composed of TTR proteins. Symptoms of this disease include progressive sensorimotor neuropathy, cardiomyopathy, and involvement of other organs. We described a pediatric case of extremely early onset TTR-FAP with a TTR Leu55Pro mutation. A 17-year-old boy began to suffer from lower limb weakness, gait disturbance, and decreased sensation from 14 years of age onward. He presented with hypertrophic cardiomyopathy, periorbital and scleral ecchymosis, anhidrosis, orthostatic intolerance, and gastrointestinal autonomic dysfunction including nausea, vomiting, and diarrhea alternating with constipation. The patient's older sister had developed similar gastrointestinal symptoms from 20 years of age onward and was diagnosed as having hypertrophic cardiomyopathy. The boy's biopsy results showed infiltrated amyloid deposition on subcutaneous fat tissue and endocardium. Genetic analysis of the TTR gene demonstrated that both the patient and his sister had a pathogenic mutation, c.224T > C (Leu55Pro). Both patients were prescribed tafamidis, a TTR stabilizing agent. Although a majority of TTR-FAPs occur during adulthood, it should be suspected, even in pediatric populations, when symmetric length dependent neuropathy occurs in conjunction with a family history of neuropathy, autonomic neuropathy, and/or cardiomyopathy.

A genetic risk score is associated with polycystic ovary syndrome-related traits.

STUDY QUESTION: Is a genetic risk score (GRS) associated with polycystic ovary syndrome (PCOS) and its related clinical features? SUMMARY ANSWER: The GRS calculated by genome-wide association studies (GWASs) was significantly associated with PCOS status and its related clinical features. WHAT IS KNOWN ALREADY: PCOS is a heterogeneous disorder and is characterized by oligomenorrhea, hyperandrogenism and polycystic ovary morphology. Although recent GWASs have identified multiple genes associated with PCOS, a comprehensive genetic risk study of these loci with PCOS and related traits (e.g. free testosterone, menstruation number/year and ovarian morphology) has not been performed. STUDY DESIGN, SIZE, DURATION: This study was designed as a cross-sectional case-control study. We recruited 862 women with PCOS and 860 controls. Women with PCOS were divided into four subgroups: (1) oligomenorrhea + hyperandrogenism + polycystic ovary, (2) oligomenorrhea + hyperandrogenism, (3) oligomenorrhea + polycystic ovary and (4) hyperandrogenism + polycystic ovary. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Genomic DNA was genotyped for the PCOS susceptibility loci using the HumanOmni1-Quad v1 array. Venous blood was drawn in the early follicular phase to measure baseline metabolic and hormonal parameters. A GRS was calculated by summing the number of risk alleles from 11 single-nucleotide polymorphisms (SNPs) that were identified in previous GWASs on PCOS. A weighted GRS (wGRS) was calculated by multiplying the number of risk alleles for each SNP by its estimated effect (beta) obtained from the association analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The GRS was higher in women with PCOS than in controls (8.8 versus 8.2, P < 0.01) and was significantly associated with PCOS after adjusting for age and BMI. An analysis of GRS quartiles (Q1 = 3-5, Q2 = 6-8, Q3 = 9-11, Q4 = 12-15) revealed that the subjects in the highest quartile showed a remarkable increased risk of PCOS compared with those in the lowest quartile (odds ratio = 6.28, P < 0.001). Free testosterone level, menstruation number per year, ovarian volume and ovarian follicle numbers were significantly associated with the GRS (in all cases, P < 0.01). The wGRS yielded similar results. LIMITATIONS, REASONS FOR CAUTION: We used 11 loci for the calculation of GRS, but a higher number of PCOS risk alleles was reported in previous studies. Therefore, further studies should assess the value of GRS including the additional SNPs related to PCOS. Although a GRS of ≥12 was significantly associated with PCOS, the GRS showed a poor predictive value; therefore, the use of genetic information based on current GWAS data only may present problems. WIDER IMPLICATIONS OF THE FINDINGS: The GRS could be used to identify asymptomatic individuals among people at risk and stratify them into accurate risk categories for the purpose of individualizing treatment approaches, which could potentially improve health outcomes. STUDY FUNDING/COMPETING INTERESTS: None of the authors have any conflicts of interest to declare. No funding was obtained for the study.

Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome.

STUDY QUESTION: Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women. WHAT IS KNOWN ALREADY: PCOS is a highly complex disorder with significant contributions from both genetic and environmental factors. Previous genome-wide association studies (GWAS) in the Han Chinese population identified several risk loci for PCOS. However, GWAS studies on PCOS remain very few. The aim of this study was to identify novel markers of susceptibility to PCOS through GWAS. STUDY DESIGN, SIZE, DURATION: A two-stage GWAS was conducted. The initial discovery set for GWAS consisted of 976 PCOS cases and 946 controls. The second stage (replication study) included 249 PCOS cases and 778 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were diagnosed according to the Rotterdam criteria. Genomic DNAs were genotyped using the HumanOmni1-Quad v1 array. In the replication stage, the 21 most promising signals selected from the discovery stage were tested for their association with PCOS. MAIN RESULTS AND THE ROLE OF CHANCE: One novel locus with genome-wide significance and seven moderately associated loci for PCOS were identified. The strongest association was on chromosome 8q24.2 (rs10505648, OR = 0.52, P = 5.46 × 10(-8)), and other association signals were located at 4q35.2, 16p13.3, 4p12, 3q26.33, 9q21.32, 11p13 and 1p22 (P = 5.72 × 10(-6)-6.43 × 10(-5)). The strongest signal was located upstream of KHDRBS3, which is associated with telomerase activity, and could drive PCOS and related phenotypes. LIMITATIONS, REASONS FOR CAUTION: The limitation of our study is the modest sample size used in the replication cohort. The limited sample size may contribute to a lack of statistical power to detect an association or show a trend in severity. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide new insight into the genetics and biological pathways of PCOS and could contribute to the early diagnosis and prevention of metabolic and reproductive morbidities. STUDY FUNDING/COMPETING INTERESTS: This work was supported in part by the grant from the Korea Centers for Disease Control and Prevention (2009-E00591-00). The work was also supported by the Ewha Global Top5 Grant 2013 of Ewha Womans University. None of the authors has any conflict of interest to declare.

Clinical implications of menstrual cycle length in oligomenorrhoeic young women.

OBJECTIVE: Although menstrual irregularity is associated with insulin resistance and hyperandrogenism, the relationship between the severity of menstrual infrequency and clinical phenotypes in young women with oligomenorrhoea (OM) is unclear. We evaluated whether a longer menstrual cycle length is associated with less favourable metabolic features. DESIGN/PATIENTS/MEASUREMENTS: A total of 1174 young women (aged 19-39 years) with a menstrual cycle length over 40 days and 1430 women with regular menstrual cycles participated voluntarily. Metabolic parameters, insulin sensitivity index (ISI) and testosterone were measured. Oligomenorrhoeic women were divided into three groups: (i) polycystic ovary syndrome (PCOS) by National Institute of Health criteria, (ii) severe OM (menstrual cycle length >60 days), and (iii) mild OM (menstrual cycle length 40-60 days). RESULTS: In normal-weight women (BMI < 23 kg/m(2)), the degrees of insulin resistance and hyperandrogenaemia are the highest in PCOS and higher in severe OM compared with mild OM. In overweight or obese women, PCOS was more insulin resistant and hyperandrogenaemic, but there was no difference between severe and mild OM. After excluding PCOS, women with severe OM showed a twofold increased risk of metabolic syndrome compared with regular cycling women (odds ratio 2·4, 95% confidence interval 1·1-5·6). By linear regression analysis, a longer menstrual cycle length was associated with ISI after adjustment for age, BMI, metabolic risk factors and testosterone. CONCLUSIONS: Women with a menstrual cycle length over 60 days should be more closely monitored for the metabolic syndrome than women with a menstrual cycle length of 40-60 days, even if they have no PCOS.

Incidence of cancer in chronic inflammatory demyelinating polyneuropathy: a nationwide cohort study in South Korea.

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare disease, and the potential risk of cancer in patients with CIDP remains an important concern during treatment. However, a comprehensive epidemiological study examining this association is yet to be conducted. This study aimed to investigate the incidence of cancer in patients with CIDP in South Korea using data from the Korean Health Insurance Review and Assessment Service (HIRA) database. Methods: Data from the HIRA database between January 2016 and June 2021 were analyzed. The actual incidence of cancer in patients with CIDP was compared with the expected incidence based on the general population statistics in South Korea, with adjustments for age. Results: In total, 888 patients with CIDP were included in the analysis, of whom 50 (5.63% of malignancy incidence) were newly diagnosed with cancer during the study period. Among the patients with CIDP diagnosed with cancer, 32 (64.00%) were aged 60 years or older, and 36 (72.00%) were male. The observed number of cancer diagnoses corresponded to an incidence rate of 5.63%, with a standardized incidence ratio (SIR) of 2.83 (95% confidence interval [CI]: 1.89-4.39) compared to the expected cancer incidence rate of 2.00%. Notably, the SIR for malignancies of lymphoid, hematopoietic, and related tissues, excluding malignant immunoproliferative diseases, multiple myeloma, and plasma cell neoplasms (C81-96, except C88 and C90), was the highest at 8.51 (95% CI: 4.18-19.83). Conclusion: Our study shows a potential association between CIDP and an increased risk of hematological malignancies, which is consistent with previous investigations. Further studies are required to better understand the relationship between CIDP and cancer.

Serial Nerve Conduction Studies in Guillain-Barré Syndrome: Its Usefulness and Precise Timing.

PURPOSE: Nerve conduction study (NCS) is essential for subclassifying Guillain-Barré syndrome (GBS). It is well known that the GBS subclassification can change through serial NCSs. However, the usefulness of serial NCSs is debatable, especially in patients with early stage GBS. METHODS: Follow-up NCS data within 3 weeks (early followed NCS, EFN) and within 3 to 10 weeks (late-followed NCS, LFN) were collected from 60 patients with GBS who underwent their first NCS (FN) within 10 days after symptom onset. Each NCS was classified into five subtypes (normal, demyelinating, axonal, inexcitable, and equivocal), according to Hadden's and Rajabally's criteria. We analyzed the frequency of significant changes in classification (SCCs) comprising electrodiagnostic aggravation and subtype shifts between demyelinating and axonal types according to follow-up timing. RESULTS: Between FN and EFN, 33.3% of patients with Hadden's criteria and 18.3% with Rajabally's criteria showed SCCs. Between FN and LFN, 23.3% of patients with Hadden's criteria and 21.7% with Rajabally's criteria showed SCCs, of which 71.4% (Hadden's criteria) and 46.2% (Rajabally's criteria) already showed SCCs from the EFN. The conditions of delayed SCCs between EFN and LFN were very early FN, mild symptoms at the FN, or persistent electrophysiological deterioration 3 weeks after symptom onset. CONCLUSIONS: A substantial proportion of patients with GBS showed significant changes in neurophysiological classification at the early stage. Serial NCS may be helpful for precise neurophysiological classification. This study suggests that follow-up NCSs should be performed within 3 weeks of symptom onset in patients with GBS in whom FN was performed within 10 days of symptom onset.

Establishment of a registry of clinical data and bioresources for rare nervous system diseases.

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.

Quality of life in patients with myelin oligodendrocyte glycoprotein antibody associated disease compared to patients with AQP4-IgG positive neuromyelitis optica spectrum disorders: A Korean multicenter study.

BACKGROUND: Little is known about the quality of life (QOL) of patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). We compared QOL and associated factors in patients with MOGAD and aquaporin4 IgG (AQP4-IgG) positive neuromyelitis optica spectrum disorder (NMOSD). METHODS: This multicenter questionnaire study compared the QOL of 41 patients with MOGAD and 78 with AQP4-IgG positive NMOSD. Patients who were positive for AQP4-IgG or MOG antibodies were included. WHO Quality of Life Scale Brief Version was used to assess QOL in physical, psychological, social, and environmental domains. QOL, sleep quality, pain, fatigue, and depression were compared between the two groups. The factors associated with QOL in each group and the entire cohort were analyzed. RESULTS: The proportion of patients with poor QOL was not significantly different between MOGAD (51.22 %) and AQP4-IgG positive NMOSD (58.97 %, p = 0.054). In the MOGAD group, the pain score (ß=-1.032, p = 0.001) and depression score (ß=-0.694, p = 0.007) were negatively associated with physical and psychological QOL, respectively. Sleep quality was negatively associated with physical (ß=-1.506, p = 0.034) and psychological (ß =-2.064, p = 0.033) QOL. When the entire cohort was analyzed, a positive MOG antibody was independently associated with worse psychological QOL (ß=-8.998, p = 0.013) compared to positive AQP4-Ab after adjustment for sleep quality, depression, fatigue, and pain. CONCLUSIONS: The overall QOL of the patients of MOGAD was comparable to that of AQP4-IgG positive NMOSD. Patients with MOGAD were experiencing sleep disorder, fatigue, and depression at similar degrees to those of patients with AQP4-IgG positive NMOSD. Further consideration of sleep quality and psychological QOL is required to improve QOL in patients with MOGAD.

Potential prognostic value of rheumatoid factor in anti-aquaporin 4-immunoglobin G-positive neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is the central nervous system demyelinating disease differentiated from multiple sclerosis by the presence of anti-aquaporin 4-antibody (AQP4-ab), which is sometimes accompanied by non-organ-specific autoantibodies. METHODS: We prospectively collected clinical information and profiles of non-organ-specific autoantibodies such as fluorescent antinuclear (FANA), anti-Sjögren's syndrome A (SSA)/Ro, anti-SS B (SSB)/La, anti-neutrophil cytoplasmatic (ANCA), lupus anticoagulant (LA), anti-cardiolipin (ACA), anti-double-stranded DNA (dsDNA), rheumatoid factor (RF), anti-thyroperoxidase, and anti-thyroglobulin antibodies in patients with NMOSD. Clinical characteristics and laboratory findings of patients with NMOSD with or without autoantibodies were analyzed. Cox proportional hazard models were used to identify independent risk factors predicting high disability in patients with NMOSD. RESULTS: A total of 158 patients with NMOSD (Female: Male = 146:12; age, 36.11 ± 14.7) were included. FANA was observed most frequently (33.3 %), followed by anti-SSA (28.6 %), anti-SSB (10.0 %), RF (8.5 %), anti-dsDNA (7.0 %), LA (4.7 %), ACA (4.8 %), and ANCA (2.4 %). High disability (Expanded Disability Status Scale (EDSS) score ≥ 6) was observed more frequently in patients with RF (45.5 %) than in those without RF (14.5 %) (p = 0.02). RF was a significant predictive factor for the high disability (hazard ratio [HR], 3.763; 95 % confidence interval [CI], 1.086-13.038; p = 0.037), age at onset (HR, 1.093; 95 % CI, 1.05-1.14; p ≤0.001), and annual relapse rate (ARR) (HR, 4.212; 95 % CI, 1.867-9.503; p = 0.001). CONCLUSION: Organ-specific and non-organ-specific autoantibodies are frequently observed in Korean patients with AQP4-ab-positive NMOSD. RF may be an independent predictor of high disability, along with age at onset and ARR.

Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder.

Background: Myelin oligodendrocyte glycoprotein antibody (MOG) immunoglobulin G (IgG)-associated disease (MOGAD) has clinical and pathophysiological features that are similar to but distinct from those of aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (AQP4-NMOSD). MOG-IgG and AQP4-IgG, mostly of the IgG1 subtype, can both activate the complement system. Therefore, we investigated whether the levels of serum complement components, regulators, and activation products differ between MOGAD and AQP4-NMOSD, and if complement analytes can be utilized to differentiate between these diseases. Methods: The sera of patients with MOGAD (from during an attack and remission; N=19 and N=9, respectively) and AQP4-NMOSD (N=35 and N=17), and healthy controls (N=38) were analyzed for C1q-binding circulating immune complex (CIC-C1q), C1 inhibitor (C1-INH), factor H (FH), C3, iC3b, and soluble terminal complement complex (sC5b-9). Results: In attack samples, the levels of C1-INH, FH, and iC3b were higher in the MOGAD group than in the NMOSD group (all, p<0.001), while the level of sC5b-9 was increased only in the NMOSD group. In MOGAD, there were no differences in the concentrations of complement analytes based on disease status. However, within AQP4-NMOSD, remission samples indicated a higher C1-INH level than attack samples (p=0.003). Notably, AQP4-NMOSD patients on medications during attack showed lower levels of iC3b (p<0.001) and higher levels of C3 (p=0.008), C1-INH (p=0.004), and sC5b-9 (p<0.001) compared to those not on medication. Among patients not on medication at the time of attack sampling, serum MOG-IgG cell-based assay (CBA) score had a positive correlation with iC3b and C1-INH levels (rho=0.764 and p=0.010, and rho=0.629 and p=0.049, respectively), and AQP4-IgG CBA score had a positive correlation with C1-INH level (rho=0.836, p=0.003). Conclusions: This study indicates a higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD. On the other hand, the production of terminal complement complexes (TCC) was found to be more substantial in AQP4-NMOSD than in MOGAD. These findings suggest a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.

Epidemiology of Chronic Inflammatory Demyelinating Polyneuropathy in South Korea: A Population-Based Study.

BACKGROUND AND PURPOSE: We performed a population-based study to determine the prevalence and incidence of chronic inflammatory demyelinating polyneuropathy (CIDP) in South Korea using data from the Korean Health Insurance Review and Assessment Service (HIRA) database. METHODS: Data recorded in the HIRA database between January 2016 and December 2020 were analyzed. The inclusion criteria in this study for patients with CIDP were a diagnostic code of G61.8 in the seventh and eighth revision of the Korean Standard Classification of Disease and a >3-month history of oral immunosuppressant use. The age-adjusted incidence rate and prevalence of CIDP in South Korea were also analyzed. RESULTS: CIDP was newly diagnosed in 953 patients during the study period. The mean age at diagnosis was 58.36 years, and the male-to-female ratio was 1.74. The age-adjusted incidence rates were 0.22, 0.21, 0.23, 0.30, and 0.25 per 100,000 person-years in 2016, 2017, 2018, 2019, and 2020, respectively. The age-adjusted prevalence was estimated at 1.16 per 100,000 persons in 2020. Age and the Elixhauser Comorbidity Index were associated with the in-hospital mortality of patients with CIDP. Infection and cardiovascular disease (CVD) were also significantly associated with the in-hospital mortality of those patients. Acute-onset CIDP was initially diagnosed in an estimated 101 out of 953 patients with CIDP. CONCLUSIONS: The prevalence and incidence rates of CIDP in South Korea were comparable between this nationwide cohort study and previous studies. Common comorbidities such as CVD and diabetes should be appropriately monitored in patients with CIDP to prevent a poor prognosis and socioeconomic burden.

Residents need competence not confidence: A retrospective evaluation of the new competency education program for Korean neurology residents.

The objective of our study was to scrutinize the learning experiences of Korean neurology residents, with an emphasis on the implications of the novel competency-based curriculum implemented in 2021. We hypothesized that this revised curriculum could modulate residents' cognitive conduct, primarily the manifestation of overconfidence, in distinctive ways across different stages of training. Our investigative framework was three-fold. Initially, we began with a qualitative inquiry involving in-depth interviews with a purposively selected cohort of eight residents from four training sites. This approach facilitated comprehensive insight into their perceptions of their competence and confidence across the continuum of a four-year residency program. Subsequently, we incorporated the K-NEPA13 assessment instrument, administered to the residents and their overseeing supervisors. This stage aimed to dissect potential cognitive biases, particularly overconfidence and consistency, within the resident population. The final study involved a comprehensive survey administered to a group of 97 Korean neurology residents, allowing us to consolidate and validate our preceding findings. Our findings revealed that junior residents portrayed heightened confidence in their clinical capabilities compared to their senior peers. Intriguingly, junior residents also displayed a stronger inclination towards reevaluating their clinical judgments, a behavior we hypothesize is stimulated by the recently introduced competency-based curriculum. We identified cognitive divergence between junior and senior residents, with the latter group favoring more consistent and linear cause-and-effect reasoning, while the former demonstrated receptiveness to introspection and reconsideration. We speculate this adaptability might be engendered by the supervisor assignment protocol intrinsic to the new curriculum. Our study highlights the essentiality of incorporating cognitive behaviors when devising medical education strategies. Acknowledging and addressing these diverse cognitive biases, and instilling a spirit of adaptability, can nurture a culture that persists in continuous learning and self-reflection among trainee doctors.